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1. Time in Target Blood Pressure Range and Dementia.

Author: Glodzik L and Tzourio C
Subjects: Humans, Blood Pressure physiology, Dementia diagnosis, Hypertension diagnosis
Abstract: Competing Interests: Disclosures None.
Published: 2023
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2. Blood pressure lowering and prevention of dementia: an individual patient data meta-analysis.

Author: Peters R, Xu Y, Fitzgerald O, Aung HL, Beckett N, Bulpitt C, Chalmers J, Forette F, Gong J, Harris K, Humburg P, Matthews FE, Staessen JA, Thijs L, Tzourio C, Warwick J, Woodward M, and Anderson CS
Subjects: Humans, Blood Pressure, Antihypertensive Agents therapeutic use, Antihypertensive Agents pharmacology, Randomized Controlled Trials as Topic, Hypertension complications, Hypertension drug therapy, Stroke drug therapy, Dementia epidemiology, Dementia prevention & control
Abstract: Aims: Observational studies indicate U-shaped associations of blood pressure (BP) and incident dementia in older age, but randomized controlled trials of BP-lowering treatment show mixed results on this outcome in hypertensive patients. A pooled individual participant data analysis of five seminal randomized double-blind placebo-controlled trials was undertaken to better define the effects of BP-lowering treatment for the prevention of dementia., Methods and Results: Multilevel logistic regression was used to evaluate the treatment effect on incident dementia. Effect modification was assessed for key population characteristics including age, baseline systolic BP, sex, and presence of prior stroke. Mediation analysis was used to quantify the contribution of trial medication and changes in systolic and diastolic BP on risk of dementia. The total sample included 28 008 individuals recruited from 20 countries. After a median follow-up of 4.3 years, there were 861 cases of incident dementia. Multilevel logistic regression reported an adjusted odds ratio 0.87 (95% confidence interval: 0.75, 0.99) in favour of antihypertensive treatment reducing risk of incident dementia with a mean BP lowering of 10/4 mmHg. Further multinomial regression taking account of death as a competing risk found similar results. There was no effect modification by age or sex. Mediation analysis confirmed the greater fall in BP in the actively treated group was associated with a greater reduction in dementia risk., Conclusion: The first single-stage individual patient data meta-analysis from randomized double-blind placebo-controlled clinical trials provides evidence to support benefits of antihypertensive treatment in late-mid and later life to lower the risk of dementia. Questions remain as to the potential for additional BP lowering in those with already well-controlled hypertension and of antihypertensive treatment commenced earlier in the life-course to reduce the long-term risk of dementia., Classification of Evidence: Class I evidence in favour of antihypertensive treatment reducing risk of incident dementia compared with placebo., Competing Interests: Conflict of interest: The authors report no targeted funding. R.P. is funded by the Australian National Health and Medical Research Centre Australian Dementia Centre for Research Collaboration, and Neuroscience Research Australia; Y.X. is funded by NHMRC Project Grant (APP1160373); M.W. and C.S.A. are supported by Investigator Grants (APP1174120 and GNT1175861 respectively) from the National Health and Medical Research Council (NHMRC) of Australia, and together with J.C. receive funding from an NHMRC Program Grant (APP1149987); M.W. is a consultant to Amgen, Kyowa Kirin, and Freeline; J.C. has received research grants from Servier, and from the NHMRC for both PROGRESS and ADVANCE, and honoraria from Servier for speaking about them at Scientific meetings; C.S.A. has received research grants from Penumbra, Takeda, Credit, and Genesis paid to his institution., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Published: 2022
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3. Association Between Blood Pressure Variability With Dementia and Cognitive Impairment: A Systematic Review and Meta-Analysis.

Author: de Heus RAA, Tzourio C, Lee EJL, Opozda M, Vincent AD, Anstey KJ, Hofman A, Kario K, Lattanzi S, Launer LJ, Ma Y, Mahajan R, Mooijaart SP, Nagai M, Peters R, Turnbull D, Yano Y, Claassen JAHR, and Tully PJ
Subjects: Humans, Risk, Blood Pressure physiology, Cognitive Dysfunction etiology, Dementia etiology, Hypertension complications
Abstract: [Figure: see text].
Published: 2021
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4. Impact of Model Choice When Studying the Relationship Between Blood Pressure Variability and Risk of Stroke Recurrence.

Author: de Courson H, Ferrer L, Barbieri A, Tully PJ, Woodward M, Chalmers J, Tzourio C, and Leffondré K
Subjects: Aged, Female, Humans, Hypertension physiopathology, Male, Middle Aged, Proportional Hazards Models, Recurrence, Risk Factors, Blood Pressure physiology, Hypertension complications, Stroke etiology
Abstract: [Figure: see text].
Published: 2021
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5. Combination blood pressure lowering in the presence or absence of background statin and aspirin therapy: a combined analysis of PROGRESS and ADVANCE Trials.

Author: Wang N, Harris K, Chalmers J, Harrap S, Mancia G, Marre M, Poulter N, Tzourio C, Williams B, Zoungas S, Woodward M, and Rodgers A
Subjects: Antihypertensive Agents therapeutic use, Aspirin pharmacology, Blood Pressure, Drug Combinations, Humans, Perindopril pharmacology, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hypertension drug therapy, Indapamide pharmacology
Abstract: Objectives: To assess the effects of combination BP lowering on cardiovascular events and mortality in the presence of aspirin and/or statin therapy in a combined analysis of the ADVANCE and PROGRESS trials., Methods: We conducted an analysis of 14 682 participants allocated combination therapy with perindopril and indapamide or placebo followed up for a mean of 4.2 years. Participants were stratified into four groups defined by background use of medications at baseline: statin, aspirin, both or neither. Linear mixed effect models were used to assess differences in BP and Cox proportional hazard models were used to estimate the risks of major cardiovascular events, all-cause mortality and treatment discontinuation., Results: At baseline, 14% of patients were on both aspirin and statin, 35% on aspirin, 9% on statins and 42% on neither aspirin/statins. Compared with placebo, combination BP therapy reduced mean SBP by 5.7 mmHg in ADVANCE and 12.1 mmHg in PROGRESS, with no difference (P > 0.447) between patients by baseline use of aspirin/statin. Combination BP therapy reduced the risk of major cardiovascular events (hazard ratio 0.78, 95% CI 0.71-0.86), with no significant difference (P = 0.600) between aspirin/statin subgroups. Rates of treatment discontinuation were similar with combination BP therapy compared with placebo (18.4 versus 18%), with no evidence of difference across the subgroups (P = 0.340)., Conclusion: BP lowering with perindopril and indapamide reduces the risk of major cardiovascular events independent of baseline use of aspirin and/or statins., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2021
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6. Short-term blood pressure variability, arterial stiffness, and cardiovascular events: results from the Bordeaux cohort.

Author: Cremer A, Doublet J, Boulestreau R, Gaudissard J, Tzourio C, and Gosse P
Subjects: Adolescent, Blood Pressure, Blood Pressure Monitoring, Ambulatory, Cohort Studies, Humans, Risk Factors, Hypertension diagnosis, Hypertension epidemiology, Vascular Stiffness
Abstract: Objective: Short-term blood pressure variability derived from 24-h ambulatory monitoring is associated with poor cardiovascular prognosis. However, previous analyses of this have clearly been influenced by clinical cofounders, particularly blood pressure (BP) level. Arterial stiffness is a powerful marker of cardiovascular risk, which may influence BP variability. In this study, we assessed the prognostic value of BP variability based on 24-h ambulatory measurements and adjusted for arterial stiffness., Methods: Population: Bordeaux cohort of hypertensive patients. Inclusion criteria were 24-h ambulatory BP monitoring at baseline with measurements every 15' day and night, determination of wake-up time and bedtime, and assessment of arterial stiffness with monitoring of Korotkoff sound arrival time. A total of 969 patients (age 54 ± 14 years) with an average follow up of 120 ± 78 months and 178 cardiovascular recorded events were included., Results: In univariate survival analyses, the standard deviations of day, night, and 24-h SBP were associated with the occurrence of cardiovascular events. The standard deviation of night-time SBP showed the strongest association with the outcome variable and was entered into multivariate analyses. In multivariate analyses, night-time SBP variability remained significantly associated with the occurrence of cardiovascular events after adjusting for major cardiovascular risk factors, 24-h SBP, and arterial stiffness. BP variability and arterial stiffness showed no significant association., Conclusion: Our results suggest that variability of night-time SBP is an important marker of the risk of cardiovascular events in hypertensive patients, independently of average 24-h BP and arterial stiffness., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2021
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7. Blood Pressure Variability and Dementia: A State-of-the-Art Review.

Author: Ma Y, Tully PJ, Hofman A, and Tzourio C
Subjects: Cerebrovascular Circulation, Endothelium, Vascular physiopathology, Humans, Hypertension physiopathology, Hypotension physiopathology, Vascular Stiffness, Blood Pressure physiology, Cognitive Dysfunction epidemiology, Dementia epidemiology, Hypertension epidemiology, Hypotension epidemiology
Abstract: Accumulating evidence demonstrates that blood pressure variability (BPV) may contribute to target organ damage, causing coronary heart disease, stroke, and renal disease independent of the level of blood pressure (BP). Several lines of evidence have also linked increased BPV to a higher risk of cognitive decline and incident dementia. The estimated number of dementia cases worldwide is nearly 50 million, and this number continues to grow with increasing life expectancy. Because there is no effective treatment to modify the course of dementia, targeting modifiable vascular factors continues as a top priority for dementia prevention. A clear understanding of the role of BPV in dementia may shed light on the etiology, early prevention, and novel therapeutic targets of dementia, and has therefore gained substantial attention from researchers and clinicians. This review summarizes state-of-art evidence on the relationship between BPV and dementia, with a specific focus on the epidemiological evidence, the underlying mechanisms, and potential intervention strategies. We also discuss challenges and opportunities for future research to facilitate optimal BP management and the clinical translation of BPV for the risk assessment and prevention of dementia., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Published: 2020
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8. Cerebral small vessel disease genomics and its implications across the lifespan.

Author: Sargurupremraj M, Suzuki H, Jian X, Sarnowski C, Evans TE, Bis JC, Eiriksdottir G, Sakaue S, Terzikhan N, Habes M, Zhao W, Armstrong NJ, Hofer E, Yanek LR, Hagenaars SP, Kumar RB, van den Akker EB, McWhirter RE, Trompet S, Mishra A, Saba Y, Satizabal CL, Beaudet G, Petit L, Tsuchida A, Zago L, Schilling S, Sigurdsson S, Gottesman RF, Lewis CE, Aggarwal NT, Lopez OL, Smith JA, Valdés Hernández MC, van der Grond J, Wright MJ, Knol MJ, Dörr M, Thomson RJ, Bordes C, Le Grand Q, Duperron MG, Smith AV, Knopman DS, Schreiner PJ, Evans DA, Rotter JI, Beiser AS, Maniega SM, Beekman M, Trollor J, Stott DJ, Vernooij MW, Wittfeld K, Niessen WJ, Soumaré A, Boerwinkle E, Sidney S, Turner ST, Davies G, Thalamuthu A, Völker U, van Buchem MA, Bryan RN, Dupuis J, Bastin ME, Ames D, Teumer A, Amouyel P, Kwok JB, Bülow R, Deary IJ, Schofield PR, Brodaty H, Jiang J, Tabara Y, Setoh K, Miyamoto S, Yoshida K, Nagata M, Kamatani Y, Matsuda F, Psaty BM, Bennett DA, De Jager PL, Mosley TH, Sachdev PS, Schmidt R, Warren HR, Evangelou E, Trégouët DA, Ikram MA, Wen W, DeCarli C, Srikanth VK, Jukema JW, Slagboom EP, Kardia SLR, Okada Y, Mazoyer B, Wardlaw JM, Nyquist PA, Mather KA, Grabe HJ, Schmidt H, Van Duijn CM, Gudnason V, Longstreth WT Jr, Launer LJ, Lathrop M, Seshadri S, Tzourio C, Adams HH, Matthews PM, Fornage M, and Debette S
Subjects: Adult, Aged, Aged, 80 and over, Alzheimer Disease epidemiology, Cerebral Small Vessel Diseases complications, Cerebral Small Vessel Diseases diagnosis, Diffusion Tensor Imaging, Female, Genetic Loci, Genome-Wide Association Study, Humans, Hypertension epidemiology, Male, Medical History Taking, Mendelian Randomization Analysis, Middle Aged, Risk Assessment, Risk Factors, Stroke epidemiology, White Matter diagnostic imaging, Young Adult, Alzheimer Disease genetics, Cerebral Small Vessel Diseases genetics, Hypertension genetics, Stroke genetics
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
Published: 2020
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9. Heterogeneity in the reporting of blood pressure variability: high time for methodological consensus.

Author: Tully PJ and Tzourio C
Subjects: Blood Pressure, Blood Pressure Determination, Consensus, Humans, Cardiovascular Diseases, Hypertension
Published: 2020
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10. Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis.

Author: Peters R, Yasar S, Anderson CS, Andrews S, Antikainen R, Arima H, Beckett N, Beer JC, Bertens AS, Booth A, van Boxtel M, Brayne C, Brodaty H, Carlson MC, Chalmers J, Corrada M, DeKosky S, Derby C, Dixon RA, Forette F, Ganguli M, van Gool WA, Guaita A, Hever AM, Hogan DB, Jagger C, Katz M, Kawas C, Kehoe PG, Keinanen-Kiukaanniemi S, Kenny RA, Köhler S, Kunutsor SK, Laukkanen J, Maxwell C, McFall GP, van Middelaar T, Moll van Charante EP, Ng TP, Peters J, Rawtaer I, Richard E, Rockwood K, Rydén L, Sachdev PS, Skoog I, Skoog J, Staessen JA, Stephan BCM, Sebert S, Thijs L, Trompet S, Tully PJ, Tzourio C, Vaccaro R, Vaaramo E, Walsh E, Warwick J, and Anstey KJ
Subjects: Aged, Aged, 80 and over, Cognitive Dysfunction epidemiology, Cognitive Dysfunction etiology, Female, Humans, Male, Middle Aged, Antihypertensive Agents therapeutic use, Dementia epidemiology, Dementia etiology, Hypertension complications, Hypertension drug therapy
Abstract: Objective: High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data., Methods: To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data., Results: Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age., Conclusion: Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals., Clinical Trials Registration: The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454., (© 2019 American Academy of Neurology.)
Published: 2020
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11. Association Between Blood Pressure Variability and Cerebral Small-Vessel Disease: A Systematic Review and Meta-Analysis.

Author: Tully PJ, Yano Y, Launer LJ, Kario K, Nagai M, Mooijaart SP, Claassen JAHR, Lattanzi S, Vincent AD, and Tzourio C
Subjects: Aged, Cerebral Small Vessel Diseases diagnostic imaging, Cerebral Small Vessel Diseases physiopathology, Female, Humans, Hypertension diagnosis, Hypertension physiopathology, Male, Prognosis, Risk Assessment, Risk Factors, Blood Pressure, Cerebral Small Vessel Diseases epidemiology, Hypertension epidemiology
Abstract: Background Research links blood pressure variability (BPV) with stroke; however, the association with cerebral small-vessel disease (CSVD) remains unclear. As BPV and mean blood pressure are interrelated, it remains uncertain whether BPV adds additional information to understanding cerebrovascular morphological characteristics. Methods and Results A systematic review was performed from inception until March 3, 2019. Eligibility criteria included population, adults without stroke (<4 weeks); exposure, BPV quantified by any metric over any duration; comparison, (1) low versus high or mean BPV and (2) people with versus without CSVD; and outcomes, (1) CSVD as subcortical infarct, lacunae, white matter hyperintensities, cerebral microbleeds, or enlarged perivascular spaces; and (2) standardized mean difference in BPV. A total of 27 articles were meta-analyzed, comprising 12 309 unique brain scans. A total of 31 odds ratios (ORs) were pooled, indicating that higher systolic BPV was associated with higher odds for CSVD (OR, 1.27; 95% CI, 1.14-1.42; I 2 =85%) independent of mean systolic pressure. Likewise, higher diastolic BPV was associated with higher odds for CSVD (OR, 1.30; 95% CI, 1.14-1.48; I 2 =53%) independent of mean diastolic pressure. There was no evidence of a pairwise interaction between systolic/diastolic and BPV/mean ORs ( P =0.47), nor a difference between BPV versus mean pressure ORs ( P =0.58). Fifty-four standardized mean differences were pooled and provided similar results for pairwise interaction ( P =0.38) and difference between standardized mean differences ( P =0.70). Conclusions On the basis of the available studies, BPV was associated with CSVD independent of mean blood pressure. However, more high-quality longitudinal data are required to elucidate whether BPV contributes unique variance to CSVD morphological characteristics.
Published: 2020
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12. Exploiting Drug-Apolipoprotein E Gene Interactions in Hypertension to Preserve Cognitive Function: The 3-City Cohort Study.

Author: Tully PJ, Helmer C, Peters R, and Tzourio C
Subjects: Aged, Alzheimer Disease, Antihypertensive Agents administration & dosage, Female, Follow-Up Studies, Health Status, Humans, Male, Prospective Studies, Renin-Angiotensin System drug effects, Apolipoproteins E genetics, Cognition drug effects, Drug Interactions genetics, Hypertension drug therapy
Abstract: Objectives: The objective was to test the hypothesis that antihypertensive drugs have a differential effect on cognition in carriers and noncarriers of the apolipoprotein ε4 (APOE4) polymorphism., Design: Prospective population-based cohort, France., Setting and Participants: A total of 3359 persons using antihypertensive drugs (median age 74 years, 62% women) were serially assessed up to 10 years follow-up., Measures: Exposure to antihypertensive drug use was established in the first 2 years. Cognitive function was assessed at baseline, 2, 4, 7, and 10 years with a validated test battery covering global cognition, verbal fluency, immediate visual recognition memory, processing speed, and executive function. Clinically significant change in cognitive function was determined using reliable change indices represented as z scores and analyzed with linear mixed-models., Results: From 3359 persons exposed to antihypertensive drugs, 653 were APOE4 carriers (5.1% homozygous, 94.9% heterozygous) and median follow-up was 5.2 years (interquartile range 3.7-8.0). In APOE4 carriers, improved general cognitive function over time was associated with exposure to angiotensin converting enzyme inhibitors [β = .14; 95% confidence interval (CI) .06-.23, P = .001] and angiotensin receptor blockers (β = .11; 95% CI .02-.21, P = .019). Improved verbal fluency was associated with angiotensin converting enzyme inhibitors (β = .11; 95% CI .03-.20, P = .012)., Conclusions: Renin-angiotensin-system blockade was associated with improved general cognitive function in APOE4 carriers. Findings did not support renin-angiotensin-system drugs' lipophilicity or ability to cross the blood-brain barrier as potential mechanisms. The findings have implications for selecting the optimal antihypertensive drug in older populations at risk of cognitive decline and dementia., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)
Published: 2019
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13. Blood pressure variability and risk of cardiovascular event: is it appropriate to use the future for predicting the present?

Author: de Courson H, Leffondré K, and Tzourio C
Subjects: Blood Pressure, Blood Pressure Determination, Humans, Hypertension
Published: 2018
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14. Effect of SSRI and calcium channel blockers on depression symptoms and cognitive function in elderly persons treated for hypertension: three city cohort study.

Author: Tully PJ, Peters R, Pérès K, Anstey KJ, and Tzourio C
Subjects: Affect drug effects, Aged, Aged, 80 and over, Cognition drug effects, Cognitive Dysfunction complications, Depression complications, Female, France, Humans, Hypertension complications, Logistic Models, Male, Memory drug effects, Mental Status and Dementia Tests, Prospective Studies, Treatment Outcome, Calcium Channel Blockers therapeutic use, Cognitive Dysfunction drug therapy, Depression drug therapy, Hypertension drug therapy, Selective Serotonin Reuptake Inhibitors therapeutic use
Abstract: ABSTRACTBackground:Emerging genetic, ex-vivo, and clinical trial evidence indicates that calcium channel blockers (CCB) can improve mood and cognitive function. The objective of this study was to examine the effect of selective serotonin reuptake inhibitor (SSRI) therapy augmented with CCB on depression and cognitive decline in an elderly population with hypertension., Methods: Prospective study of 296 persons treated with SSRI and antihypertensive drugs. Baseline and two year clinic assessments were used to categorize participants as users of SSRI + CCB (n = 53) or users of SSRI + other antihypertensives (n = 243). Clinic visits were performed up to four times in a ten-year period to assess depression and cognitive function., Results: The sample mean age was 75.2 ± 5.47 years and 78% of participants were female. At two year follow-up there was a significant group by time interaction showing lower Center for Epidemiological Studies-Depression (CESD) scores in the SSRI + CCB group, F(1,291) = 4.13, p = 0.043, η2p = 0.014. Over ten-years follow-up, SSRI + CCB use was associated with improved general cognitive function (Mini-Mental State Examination: β = 0.97; 95% CI 0.14 to 1.81, p = 0.023) and immediate visual memory (Boston Visual Retention Test: β = 0.69; 95% CI 0.06 to 1.32, p = 0.033)., Conclusion: The findings provide general population evidence that SSRI augmentation with CCB may improve depression and cognitive function.
Published: 2018
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15. Impact of home blood pressure monitoring on blood pressure control in older individuals: a French randomized study.

Author: Tzourio C, Hanon O, Godin O, Soumaré A, and Dufouil C
Subjects: Aged, Aged, 80 and over, Diastole, Female, France, Humans, Male, Self Care, Systole, Blood Pressure, Blood Pressure Monitoring, Ambulatory, Hypertension physiopathology, Office Visits
Abstract: Objective: Home blood pressure (BP) monitoring is one of the tools recommended in hypertension management. However, its influence in older adults is seldom investigated. We aimed to assess whether regular home BP monitoring leads to a reduction of BP and an improvement in hypertension control in older adults., Methods: In a 24-month trial, individuals aged 73-97 years were randomized in a control (office and home BP measured at 0, 12, and 24 months) or an intervention (office measured at 0, 12, and 24 months; home BP measured every 3 months) group. The primary outcome was the difference in means office BP over 24 months in hypertensive patients. Secondary outcomes included differences in mean home BP over follow-up in hypertensive patients, and frequency of hypertension and of drug use at 24 months in the total sample. Intention-to-treat analyses comprised 1733 persons, among which 1043 were hypertensive., Results: Hypertensive patients in the intervention group experienced a significantly greater fall in office systolic BP (SBP) [mean between-group difference -2.1 mmHg, 95% confidence interval (CI) -4.1; -0.2, P = 0.03], home SBP (mean between-group difference -3.4, 95% CI -4.8; -2.1, P < 0.0001), and home diastolic BP (mean between-group difference -1.1, 95% CI -1.8; -0.4, P = 0.002) than those in the control group, in the main model. No overall differences were observed for office diastolic BP (P = 0.74), frequency of hypertension (P = 0.92), or drug use (P = 0.51) over time. Similar results were observed after adjustment for known predictors of BP though attenuated for office SBP (P = 0.07)., Conclusion: Regular home BP monitoring every 3 months without co-intervention results in small but greater reductions of BP over time. Further research in large trials focused on older adults is needed to confirm the effectiveness of this intervention in a variety of settings.
Published: 2017
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16. Response to Letter Regarding Article, "Antihypertensive Drug Use, Blood Pressure Variability, and Stroke Risk in Older Adults: Three-City Cohort Study".

Author: Tully PJ, Debette S, and Tzourio C
Subjects: Adult, Blood Pressure drug effects, Cohort Studies, Humans, Stroke, Antihypertensive Agents, Hypertension
Published: 2016
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17. Antihypertensive Drug Use, Blood Pressure Variability, and Incident Stroke Risk in Older Adults: Three-City Cohort Study.

Author: Tully PJ, Debette S, Dartigues JF, Helmer C, Artero S, and Tzourio C
Subjects: Aged, Aged, 80 and over, Cohort Studies, Female, France epidemiology, Humans, Hypertension epidemiology, Incidence, Male, Risk, Stroke epidemiology, Adrenergic beta-Antagonists adverse effects, Angiotensin Receptor Antagonists adverse effects, Antihypertensive Agents adverse effects, Blood Pressure drug effects, Hypertension drug therapy, Stroke chemically induced
Abstract: Background and Purpose: The aim was to determine the association between antihypertensive drug class and incident stroke controlling for long-term blood pressure (BP) variability (BPV) in people aged ≥65 years., Methods: The sample included 5951 participants (median age 74 years, 60% women) taking at least 1 drug for hypertension (3727/5951) or with systolic BP >140 mm Hg or diastolic BP >90 mm Hg. Participants were evaluated for incident fatal and nonfatal stroke to 12 years follow-up. BPV was calculated with the coefficient of variation method and regressed against 9 antihypertensive drug classes (BPVreg). Hazard models were used to determine hazard ratios for incident stroke risk attributable to drug class, adjusted for BP, BPVreg, covariates, and delayed entry bias., Results: There were 273 incident strokes over a median of 9.1 years (interquartile range 6.4-10.4). Stroke risk was generally not reduced by BP-lowering drugs. Angiotensin receptor blockers (hazard ratio 1.56; 95% confidence interval 1.06-2.28; P=0.02) and β-blockers (hazard ratio 1.41; 95% confidence interval 1.03-1.92; P=0.03) were associated with an increased total stroke risk. Angiotensin receptor blockers and β-blockers were also associated with ischemic strokes after adjustment for systolic BPV. Diastolic BPV was associated with stroke risk in analyses stratified by systolic BP 140 to 160 mm Hg (per 0.10 increase in coefficient of variation, hazard ratio 1.59; 95% confidence interval 1.05-2.40; P=0.03)., Conclusions: The angiotensin receptor blocker and β-blocker drug classes were associated with incident stroke and ischemic stroke in older adults. BPV was generally not associated with incident stroke., (© 2016 American Heart Association, Inc.)
Published: 2016
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18. Kidney Function Decline and Apparent Treatment-Resistant Hypertension in the Elderly.

Author: Kaboré J, Metzger M, Helmer C, Berr C, Tzourio C, Massy ZA, and Stengel B
Subjects: Age Factors, Aged, Aged, 80 and over, Albuminuria epidemiology, Albuminuria etiology, Antihypertensive Agents therapeutic use, Causality, Comorbidity, Creatinine blood, Diabetes Mellitus epidemiology, Disease Progression, Drug Resistance, Drug Therapy, Combination, Follow-Up Studies, France epidemiology, Glomerular Filtration Rate, Humans, Hypercholesterolemia epidemiology, Hypertension epidemiology, Hypertension etiology, Hypertension, Renal diagnosis, Hypertension, Renal epidemiology, Middle Aged, Obesity epidemiology, Odds Ratio, Prevalence, Renal Insufficiency, Chronic physiopathology, Sensitivity and Specificity, Sex Factors, Hypertension drug therapy, Renal Insufficiency, Chronic complications
Abstract: Background: Cross-sectional studies show a strong association between chronic kidney disease and apparent treatment-resistant hypertension, but the longitudinal association of the rate of kidney function decline with the risk of resistant hypertension is unknown., Methods: The population-based Three-City included 8,695 participants older than 65 years, 4265 of them treated for hypertension. We estimated the odds ratios (OR) of new-onset apparent treatment-resistant hypertension, defined as blood pressure ≥ 140/90 mmHg despite use of 3 antihypertensive drug classes or ≥ 4 classes regardless of blood pressure, associated with the mean estimated glomerular filtration rate (eGFR) level and its rate of decline over 4 years, compared with both controlled hypertension and uncontrolled nonresistant hypertension with ≤ 2 drugs. GFR was estimated with three different equations., Results: Baseline prevalence of apparent treatment-resistant hypertension and of controlled and uncontrolled nonresistant hypertension, were 6.5%, 62.3% and 31.2%, respectively. During follow-up, 162 participants developed apparent treatment-resistant hypertension. Mean eGFR decline with the MDRD equation was 1.5±2.9 mL/min/1.73 m² per year: 27.7% of the participants had an eGFR ≥3 and 10.1% ≥ 5 mL/min/1.73 m² per year. After adjusting for age, sex, obesity, diabetes, and cardiovascular history, the ORs for new-onset apparent treatment-resistant hypertension associated with a mean eGFR level, per 15 mL/min/1.73 m² drop, were 1.23 [95% confidence interval 0.91-1.64] compared to controlled hypertension and 1.10 [0.83-1.45] compared to uncontrolled nonresistant hypertension; ORs associated with a decline rate ≥ 3 mL/min/1.73 m² per year were 1.89 [1.09-3.29] and 1.99 [1.19-3.35], respectively. Similar results were obtained when we estimated GFR with the CKDEPI and the BIS1 equations. ORs tended to be higher for an eGFR decline rate ≥ 5 mL/min/1.73 m² per year., Conclusion: The speed of kidney function decline is associated more strongly than kidney function itself with the risk of apparent treatment-resistant hypertension in the elderly.
Published: 2016
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19. Hippocampal perivascular spaces are related to aging and blood pressure but not to cognition.

Author: Yao M, Zhu YC, Soumaré A, Dufouil C, Mazoyer B, Tzourio C, and Chabriat H
Subjects: Aged, Aged, 80 and over, Cognition, Cohort Studies, Dilatation, Pathologic, Female, Humans, Hypertension physiopathology, Logistic Models, Magnetic Resonance Imaging methods, Male, Proportional Hazards Models, Risk Factors, Aging pathology, Blood Pressure physiology, Hippocampus pathology, Hypertension pathology
Abstract: The risk factors of hippocampal dilated perivascular spaces (H-dPVS), their radiological relevance and their impact on cognitive performance remain under investigation. These aspects were evaluated in 1818 stroke- and dementia-free participants enrolled in the 3C-Dijon MRI study, using logistic regression, multiple linear regression, and Cox models. At study entry, the load of H-dPVS was found strongly associated with age and hypertension (degree 2 vs. degree 0: odds ratio: 1.16; 95% confidence interval: 1.02-1.33 and odds ratio: 1.98; 95% confidence interval: 1.39-2.81, respectively) and positively related to the presence of lacunar infarcts, white-matter hyperintensities volume, and hippocampal volume (p ≤ 0.024). Load of H-dPVS was not related to baseline cognitive performance (p > 0.05). Cox regression modeling did not show a significant relationship between the load of H-dPVS and incident dementia risk (p > 0.05). The present results support that both aging and blood pressure do play a key role in the development of H-dPVS in the older population. In contrast with the dilated perivascular spaces located in white matter or basal ganglia, the load of H-dPVS does not appear associated with occurrence of dementia., (Copyright © 2014 Elsevier Inc. All rights reserved.)
Published: 2014
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20. Is hypertension associated with an accelerated aging of the brain?

Author: Tzourio C, Laurent S, and Debette S
Subjects: Aging, Premature pathology, Aging, Premature physiopathology, Antihypertensive Agents therapeutic use, Brain pathology, Cerebrovascular Trauma diagnosis, Cerebrovascular Trauma prevention & control, Cognition Disorders diagnosis, Cognition Disorders epidemiology, Cognition Disorders prevention & control, Dementia diagnosis, Dementia epidemiology, Dementia prevention & control, Humans, Hypertension drug therapy, Hypertension physiopathology, Magnetic Resonance Imaging, Mass Screening, Risk Factors, Aging, Premature etiology, Blood Pressure physiology, Brain physiopathology, Cerebrovascular Trauma epidemiology, Hypertension complications
Published: 2014
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21. Categories of hypertension in the elderly and their 1-year evolution. The Three-City Study.

Author: Cacciolati C, Hanon O, Dufouil C, Alpérovitch A, and Tzourio C
Subjects: Aged, Cohort Studies, Home Care Services, Humans, Office Visits, Risk Factors, Hypertension classification, White Coat Hypertension complications
Abstract: Objective: To assess the 1-year risk of developing sustained hypertension in untreated elderly with white-coat hypertension (WCHT) or masked hypertension (MHT), and the 1-year risk of developing uncontrolled hypertension in treated elderly with office or home uncontrolled hypertension (OUHT or HUHT)., Methods: We studied the 1-year risk of developing sustained or uncontrolled hypertension in a community-based cohort of 1481 individuals aged at least 73 years. The same BP device was used throughout the entire study. WCHT was defined as high blood pressure (BP) at office and normal home BP without antihypertensive intake, OUHT as high office BP and normal home BP with antihypertensive intake, MHT as high BP at home and normal office BP without antihypertensive intake, and HUHT as high home BP and normal office BP with antihypertensive intake. Sustained hypertension was defined as high office and home BP without antihypertensive intake and uncontrolled hypertension as high office and home BP with antihypertensive intake., Results: Sustained or uncontrolled hypertension at 1 year was diagnosed in 13% of participants with high office BP and in 26% of those with high home BP. Compared to participants with normal office and home BP, risk of sustained/uncontrolled hypertension was increased about three-fold in individuals with high office BP [OR = 2.9; 95% confidence interval (CI) = 1.5-5.5; P = 0.002] and about seven-fold in those with high home BP (OR = 6.8; 95% CI = 3.8-12.2; P < 0.0001). These risks were higher in individuals not treated by antihypertensive (OR(WCHT) = 4.3, P = 0.03; OR(MHT) = 16.8, P < 0.0001)., Conclusion: In this community-based study, elderly individuals with high office or home BP had an increased risk of hypertension 1 year later. This risk was higher among individuals not treated by antihypertensive and particularly in those with MHT. As these high-risk individuals would be otherwise undetected our results strongly support the large use of home blood pressure measurement in the elderly.
Published: 2013
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22. Blood pressure variability in elderly persons with white-coat and masked hypertension compared to those with normotension and sustained hypertension.

Author: Cacciolati C, Tzourio C, and Hanon O
Subjects: Aged, Aged, 80 and over, Blood Pressure Monitoring, Ambulatory, Cardiovascular Diseases etiology, Female, Humans, Male, Risk Factors, Blood Pressure physiology, Hypertension physiopathology, Masked Hypertension physiopathology, White Coat Hypertension physiopathology
Abstract: Background: The relationship between blood pressure (BP) measured, its variability, and risk of cardiovascular events is well established; however, it is not well known whether there is a difference of variability between the four categories of BP status obtained by the comparison of office and home BP measurements: normotension and masked, white-coat, and sustained hypertension. Here, we assessed BP variability (BPV) according to BP status in the elderly., Methods: The study population consisted of 1,701 individuals aged ≥73 years drawn from the general population. Office and home BP measurements were obtained with the same device. At home, 18 measures were taken (3 in the morning, 3 in the evening, for 3 consecutive days). BP statuses were defined according to European Society of Hypertension recommendations. To assess BPV, seven indexes were defined (e.g., standard deviation of the 18 measures, day-to-day variability, triplet-to-triplet variability, and coefficient of variation)., Results: Subjects with white-coat hypertension and normotension had similar BPV, and the variability among those with masked hypertension was very close to that in those with sustained hypertension. Overall, BPV was much higher in subjects with masked hypertension than in those with white-coat hypertension, in both treated and untreated groups., Conclusions: In elderly individuals, the short-term variability of BP is similar in masked and sustained hypertension and higher than in normotension and white-coat hypertension. This result suggests the hypothesis that BPV among persons with masked hypertension may contribute to the elevated cardiovascular risk observed in this BP pattern.
Published: 2013
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23. Feasibility of home blood pressure measurement in elderly individuals: cross-sectional analysis of a population-based sample.

Author: Cacciolati C, Tzourio C, Dufouil C, Alpérovitch A, and Hanon O
Subjects: Age Factors, Aged, Aged, 80 and over, Chi-Square Distribution, Cross-Sectional Studies, Educational Status, Female, France, Health Knowledge, Attitudes, Practice, Humans, Hypertension physiopathology, Logistic Models, Male, Multivariate Analysis, Odds Ratio, Patient Education as Topic, Patient Satisfaction, Personal Autonomy, Predictive Value of Tests, Risk Factors, Self Report, Time Factors, Blood Pressure, Blood Pressure Monitoring, Ambulatory, Hypertension diagnosis
Abstract: Background: Home blood pressure measurement (HBPM) is recommended by hypertension guidelines, particularly in the elderly. However, feasibility of HBPM in this age group has not been fully established. Our objective was therefore to assess HBPM feasibility in elderly individuals of the general population., Methods: After minimal training, 1,814 individuals aged ≥ 73 years were asked to measure their blood pressure (BP) at home six times per day (three in the morning and three in the evening) during 3 days, with the validated device OMRON M6 (exam 1). Measures of BP were self-reported by the participants on a booklet. The same procedure was applied 1-year later (exam 2). HBPM was considered as successful when at least 12 measures of the 18 were performed. Participants were also asked to complete a questionnaire intended to assess difficulties met performing HBPM., Results: Rate of success for HBPM was 96% at exam 1 and 97% at exam 2. We analyzed pattern of individuals who failed HBPM examination and found that age >80, low education level, and non-autonomy were independently associated with an increased risk of HBPM failure. HBPM was considered nonrestrictive by 89% of participants and 97% declared that HBPM was simple to perform., Conclusions: In this population-based sample of elderly, rate of success of HBPM was high and maintained at 1-year after minimal training. Moreover, HBPM acceptance was excellent. These results suggest that HBPM is feasible and can be largely diffused to the elderly of general population. However, particular care must be given to very old, nonautonomous, and low educated individuals.
Published: 2012
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24. Masked hypertension in the elderly: cross-sectional analysis of a population-based sample.

Author: Cacciolati C, Hanon O, Alpérovitch A, Dufouil C, and Tzourio C
Subjects: Aged, Aged, 80 and over, Female, France epidemiology, Humans, Hypertension epidemiology, Male, Blood Pressure Determination, Blood Pressure Monitoring, Ambulatory methods, Hypertension diagnosis
Abstract: Background: Masked hypertension (MHT), defined as normal blood pressure (BP) at office associated with high BP at home, has been shown to be associated with an increased risk of vascular events. However, MHT is poorly known in the elderly, although this age segment is at high risk of hypertension-related vascular events. Our objectives were to assess frequency and determinants of MHT in the elderly., Methods: We studied MHT in a community-based sample of 1,814 participants aged 75 years or older, whose office BP and home BP measurements (HBPM) were both taken with the same device (Omron M6; Omron Healthcare, Kyoto, Japan).Hypertension was defined as a systolic BP (SBP) ≥ 140 mm Hg and/or a diastolic BP (DBP) ≥ 90 mm Hg for office BP, and SBP ≥ 135 mm Hg and/or DBP ≥ 85 mm Hg for HBPM., Results: Frequency of MHT was 16% in the overall sample and 41% in participants with a normal office BP. Multivariable analyses revealed that male subjects, >80 years of age, with diabetes, on antihypertensive medication, and with office SBP >120 mm Hg were independently associated with a higher risk of MHT., Conclusion: MHT is frequent in the elderly and is associated with a high vascular profile. These results should encourage a more widespread use of home BP monitoring in this age segment.
Published: 2011
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25. Antihypertensive treatment and change in blood pressure are associated with the progression of white matter lesion volumes: the Three-City (3C)-Dijon Magnetic Resonance Imaging Study.

Author: Godin O, Tzourio C, Maillard P, Mazoyer B, and Dufouil C
Subjects: Aged, Aged, 80 and over, Aging, Cross-Sectional Studies, Disease Progression, Female, Follow-Up Studies, Humans, Leukoencephalopathies pathology, Longitudinal Studies, Magnetic Resonance Imaging methods, Male, Predictive Value of Tests, Risk Factors, Antihypertensive Agents therapeutic use, Blood Pressure drug effects, Hypertension drug therapy, Hypertension epidemiology, Leukoencephalopathies epidemiology
Abstract: Background: Blood pressure (BP) is recognized as a major risk factor for white matter lesions (WMLs), but longitudinal data are scarce, and there is insufficient evidence for the benefit of antihypertensive therapy on WML progression. We studied the relationship between BP change and WML volume progression over time in a sample of 1319 elderly individuals who had 2 cerebral magnetic resonance imaging examinations 4 years apart. We also examined the impact of antihypertensive treatment on WML progression., Methods and Results: Subjects were participants from the Three-City (3C)-Dijon Magnetic Resonance Imaging Study, a prospective population-based cohort of elderly ≥ 65 years of age. WML volumes and their progression were estimated with the use of a fully automatic procedure. We performed ANCOVA models first to assess the association between BP change and WML progression and second to estimate the relation between antihypertensive treatment and WML load progression. Baseline and change in BP were significant predictors of higher WML progression over time after controlling for potential confounders. Among subjects with high SBP (≥ 160 mm Hg) at baseline not treated by antihypertensive medication, antihypertensive treatment started within 2 years was related to a smaller increase in WML volume at a 4-year follow-up (0.24 cm³; SE=0.44 cm³) than no hypertensive treatment (1.60 cm³; SE = 0.26 cm³; P = 0.0008) on multivariable modeling., Conclusions: Our findings reinforce the hypothesis that hypertension is a strong predictor of WML and that adequate treatment may reduce the course of WML progression. Because WMLs are linked to both dementia and stroke risks, these results could have implications for future preventive trials.
Published: 2011
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26. Severity of dilated Virchow-Robin spaces is associated with age, blood pressure, and MRI markers of small vessel disease: a population-based study.

Author: Zhu YC, Tzourio C, Soumaré A, Mazoyer B, Dufouil C, and Chabriat H
Subjects: Aged, Aging physiology, Basal Ganglia Cerebrovascular Disease diagnosis, Basal Ganglia Cerebrovascular Disease physiopathology, Blood Pressure physiology, Cohort Studies, Dilatation, Pathologic diagnosis, Dilatation, Pathologic pathology, Dilatation, Pathologic physiopathology, Female, Humans, Hypertension physiopathology, Logistic Models, Magnetic Resonance Imaging, Male, Microvessels physiopathology, Predictive Value of Tests, Prognosis, Retrospective Studies, Risk Factors, Aging pathology, Basal Ganglia Cerebrovascular Disease pathology, Hypertension pathology, Microvessels pathology, Severity of Illness Index
Abstract: Background and Purpose: Little is known about the risk factors of dilated Virchow-Robin spaces (dVRS) and their relation with other markers of brain small vessel disease. We investigated both issues in a large population-based sample of elderly individuals., Methods: Severity of dVRS was semiquantitatively graded in both white matter and basal ganglia using high-resolution 3-dimensional MRI images taken from 1818 stroke- and dementia-free subjects enrolled in the Three-City Dijon MRI study. Multinomial logistic regression models were used to model the association of cardiovascular risk factors, APOE genotype, brain atrophy, and MRI markers of small vessel disease with the degree of dVRS., Results: Severity of dVRS was found to be strongly associated with age in both basal ganglia (degree 4 versus 1: OR, 2.1; 95% CI, 1.4 to 3.2) and white matter (OR, 1.5; 95% CI, 1.2 to 1.9). The proportion of hypertensive subjects increased with the degrees of dVRS in both basal ganglia (P = 0.02) and white matter (P = 0.048). Men presented a higher risk of severe dVRS in basal ganglia than women, particularly degree 4 (OR, 6.0; 95% CI, 1.8 to 19.8). The degree of dVRS was associated with the volume of white matter hyperintensities and the prevalence of lacunes, but not with brain atrophy., Conclusions: In this large cohort study of elderly subjects, the degree of dVRS appears independently associated with age, hypertension, volume of white matter hyperintensities, and lacunar infarctions. dVRS should be considered as another MRI marker of cerebral small vessel disease in the elderly with regional variations in their severity.
Published: 2010
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27. Hypertension and lower walking speed in the elderly: the Three-City study.

Author: Dumurgier J, Elbaz A, Dufouil C, Tavernier B, and Tzourio C
Subjects: Aged, Brain, Female, Humans, Magnetic Resonance Imaging, Male, Risk Factors, Hypertension physiopathology, Walking physiology
Abstract: Objective: The brain is one of the main targets of hypertension. However, little is known about the relation between hypertension and motor performances. We studied the association between hypertension and walking speed in a cohort of elderly people., Methods: Analyses are based on participants (65-85 years) from the Dijon (France) center of the Three-City study (n = 3604), followed every 2 years. Persistent hypertension was defined by the use of antihypertensive drugs at baseline or at first follow-up, or by high blood pressure (> or =140/90 mmHg) at baseline and first follow-up. Walking speed was measured over 6 m, at baseline and fourth follow-up (n = 1774) after a mean (SD) duration of 7.0 (0.5) years. Brain MRI was performed in 1590 participants. Generalized linear models were used to assess the relation between hypertension and baseline walking speed or walking speed change., Results: At baseline, mean (SD) walking speed (m/s) was lower in hypertensive patients [1.51 (0.31)] than in nonhypertensive individuals [1.59 (0.30), P < 0.001]. During follow-up, hypertensive patients had a higher mean annual decline in walking speed [cm/s per year; 2.30 (3.4)] than nonhypertensive individuals [1.87 (3.3), P = 0.004]. The number of antihypertensive drugs was associated with lower walking speed at baseline and higher walking speed decline. Adjustment for MRI white matter abnormalities attenuated these relations., Conclusion: Persistent hypertension was associated with both lower walking speed and higher decline in walking speed in the elderly. These results may be partly explained by white matter abnormalities and support the hypothesis of a contribution of vascular risk factors to motor dysfunction., Competing Interests: There are no conflicts of interest.
Published: 2010
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28. Effects of perindopril-based lowering of blood pressure on intracerebral hemorrhage related to amyloid angiopathy: the PROGRESS trial.

Author: Arima H, Tzourio C, Anderson C, Woodward M, Bousser MG, MacMahon S, Neal B, and Chalmers J
Subjects: Aged, Antihypertensive Agents administration & dosage, Blood Pressure drug effects, Blood Pressure physiology, Cerebral Amyloid Angiopathy physiopathology, Cerebral Arteries drug effects, Cerebral Arteries metabolism, Cerebral Arteries physiopathology, Cerebral Hemorrhage prevention & control, Comorbidity, Female, Humans, Hypertension physiopathology, Male, Middle Aged, Placebos, Risk Factors, Risk Reduction Behavior, Treatment Outcome, Cerebral Amyloid Angiopathy complications, Cerebral Hemorrhage drug therapy, Cerebral Hemorrhage etiology, Hypertension complications, Hypertension drug therapy, Perindopril administration & dosage
Abstract: Background and Purpose: Patients with cerebral amyloid angiopathy (CAA) are at high risk for intracerebral hemorrhage (ICH), but no effective prevention strategies have been established. The objective is to determine whether lowering of blood pressure (BP) provides protection for this high-risk patient group., Methods: This study is a subsidiary analysis of the PROGRESS trial-a randomized, placebo-controlled trial that established the beneficial effects of BP lowering in patients with cerebrovascular disease; 6105 patients were randomly assigned to either active treatment (perindopril for all participants plus indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo. Outcomes were probable CAA-related ICH as defined by the Boston criteria, probable hypertension-related ICH, and unclassified ICH., Results: Over a mean follow-up of 3.9 years, 16 probable CAA-related ICH, 51 probable hypertension-related ICH, and 44 unclassified ICH occurred. Active treatment reduced the risk of CAA-related ICH by 77% (95% CI, 19%-93%), that of hypertension-related ICH by 46% (95% CI, 4%-69%), and that of unclassified ICH by 43% (95% CI, -5%-69%). There was no evidence of differences in the magnitude of the effects of treatment among different types of ICH (P homogeneity=0.4)., Conclusions: BP-lowering treatment is likely to provide protection against all types of ICH.
Published: 2010
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29. Changes in blood pressure in a large cohort of elderly individuals: Study 3C.

Author: Lachouri M, Gourlet V, D'Athis P, Tzourio C, and Quantin C
Subjects: Age Factors, Aged, Aged, 80 and over, Blood Pressure Determination, Female, Follow-Up Studies, France, Humans, Hypertension physiopathology, Male, Multivariate Analysis, Predictive Value of Tests, Reproducibility of Results, Time Factors, Aging, Antihypertensive Agents therapeutic use, Blood Pressure drug effects, Hypertension drug therapy
Abstract: Objective: Analysis of changes in blood pressure with a two-year interval, and of factors associated with this change, in a large cohort of elderly individuals., Methods: Follow-up of a cohort of 9294 individuals aged 65 years and over recruited from the general population for Study 3C. Changes in blood pressure are defined as the difference in its averages between the inclusion visit and the follow-up visit at 2 years. The factors associated with changes in systolic blood pressure were identified by univariate and multivariate analyses., Results: Systolic and diastolic blood pressure decreased on average by 7.60 mmHg and 4.45 mmHg respectively in 7659 individuals included in the study between the initial measurement and the follow-up at 2 years. The analyses revealed that the initial high blood pressure level was the main factor for this decrease that would be explained by a phenomenon of regression towards the mean., Conclusion: These results confirm the importance of repeating blood pressure measurements during several examinations for a good estimate of individual blood pressure values in this age range. It is also important to consider this phenomenon in studies including specific blood pressure estimates only.
Published: 2009
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30. Relationship between blood pressure and outdoor temperature in a large sample of elderly individuals: the Three-City study.

Author: Alpérovitch A, Lacombe JM, Hanon O, Dartigues JF, Ritchie K, Ducimetière P, and Tzourio C
Subjects: Age Factors, Aged, 80 and over, Antihypertensive Agents administration & dosage, Blood Pressure physiology, Blood Pressure Determination, Cohort Studies, Female, Humans, Hypertension drug therapy, Male, Probability, Prospective Studies, Risk Assessment, Sampling Studies, Sensitivity and Specificity, Sex Factors, Urban Population, Geriatric Assessment, Hypertension physiopathology, Seasons, Temperature
Abstract: Background: Seasonal variations of blood pressure-related diseases have been described in several populations. However, few studies have examined the seasonal variations of blood pressure in the elderly, a segment of the population particularly exposed to vascular diseases. The association of blood pressure with season and outdoor temperature was examined in 8801 subjects 65 years or older from the Three-City study, a population-based longitudinal study., Methods: Blood pressure was measured at baseline and 2-year follow-up examinations. Daily outdoor temperature measured at 11 am was provided by the local meteorological offices., Results: Both systolic and diastolic blood pressure values differed significantly across the 4 seasons and across the quintiles of the distribution of outdoor temperature. Systolic blood pressure decreased with increasing temperature, with an 8.0-mm Hg decrease between the lowest (< 7.9 degrees C) and the highest (> or = 21.2 degrees C) temperature quintile. Intraindividual differences in blood pressure between follow-up and baseline examinations were strongly correlated with differences in outdoor temperature. The higher the temperature at follow-up compared with baseline, the greater the decrease in blood pressure. Longitudinal changes in blood pressure according to difference in outdoor temperature were larger in subjects 80 years or older than in younger participants., Conclusions: Outdoor temperature and blood pressure are strongly correlated in the elderly, especially in those 80 years or older. During periods of extreme temperatures, a careful monitoring of blood pressure and antihypertensive treatment could contribute to reducing the consequences of blood pressure variations in the elderly.
Published: 2009
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31. Relationship between blood pressure and depression in the elderly. The Three-City Study.

Author: Lenoir H, Lacombe JM, Dufouil C, Ducimetière P, Hanon O, Ritchie K, Dartigues JF, Alpérovitch A, and Tzourio C
Subjects: Aged, Antihypertensive Agents therapeutic use, Cross-Sectional Studies, Depression diagnosis, Depression drug therapy, Female, France epidemiology, Humans, Hypertension drug therapy, Linear Models, Male, Psychotropic Drugs therapeutic use, Urban Population statistics & numerical data, Aging, Blood Pressure, Depression epidemiology, Hypertension epidemiology, Hypertension psychology
Abstract: Objective: To examine the relationship between blood pressure and depression in a large sample of noninstitutionalized elderly people., Methods: Cross-sectional community-based study in 9294 participants aged 65 years and over, living at home, in three French cities (Bordeaux, Dijon and Montpellier). Participants were categorized as depressive, based on three different markers of depression. Multiple linear regression analyses of the relation between depression and mean systolic and diastolic blood pressure values were conducted, taking into account potential confounders like age, sex, education, smoking, alcohol consumption, body mass index and history of cardiovascular events., Results: Our working sample had a mean age (SD) of 73.7 (5.0) years, and included 60.7% of women. Overall, 31% of participants met the criteria for depression, 77.5% had hypertension, and 49.5% were on antihypertensive drugs. Analyses showed lower systolic and diastolic blood pressure values in depressive individuals compared with nondepressive ones, in both men (systolic blood pressure 148.2 versus 151.8 mmHg, P < 0.002; diastolic blood pressure 83.0 versus 84.7 mmHg, P = 0.003) and women (systolic blood pressure 141.7 versus 144.7 mmHg, P < 0.0001; diastolic blood pressure 80.7 versus 81.4 mmHg, P < 0.02). These associations were independent of age and of use of antihypertensive or psychotropic agents., Conclusion: In a large sample of elderly individuals from the general population, depressive individuals had lower blood pressure values than nondepressive ones, independent of medications and of history of cardiovascular events.
Published: 2008
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32. Hypertension, cognitive decline, and dementia: an epidemiological perspective.

Author: Tzourio C
Subjects: Alzheimer Disease drug therapy, Alzheimer Disease epidemiology, Alzheimer Disease physiopathology, Antihypertensive Agents pharmacology, Antihypertensive Agents therapeutic use, Brain blood supply, Brain pathology, Brain physiopathology, Cerebral Arteries drug effects, Cerebral Arteries pathology, Cerebral Arteries physiopathology, Cognition Disorders drug therapy, Comorbidity, Dementia drug therapy, Humans, Prevalence, Cognition Disorders epidemiology, Cognition Disorders physiopathology, Dementia epidemiology, Dementia physiopathology, Hypertension epidemiology, Hypertension physiopathology
Abstract: Hypertension is a known risk factor for stroke, and thus for vascular dementia. However, recent large observational studies have suggested that high blood pressure may also play a role in Alzheimer's disease. The mechanisms linking hypertension to Alzheimer's disease remain to be elucidated, but white matter lesions seen on cerebral magnetic resonance imaging appear to be a good marker of this association. It is not yet clearly established whether lowering blood pressure reduces the risk of white matter lesions and dementia, so large trials dealing with this question are eagerly awaited. These future trials could confirm the hope that, by lowering blood pressure, we may have a preventive treatment for dementia. This issue is of major importance, as the number of cases of dementia is expected to rise
Published: 2007

33. [Lowering blood pressure permits limiting cerebral microangiopathy].

Author: Tzourio C, Dufouil C, and Tzourio-Mazoyer N
Subjects: Blood Pressure, Brain Ischemia etiology, Cerebral Infarction etiology, Clinical Trials as Topic, Dementia, Vascular etiology, Dementia, Vascular prevention & control, Humans, Hypertension complications, Intracranial Arteriosclerosis complications, Magnetic Resonance Imaging, Multicenter Studies as Topic, Antihypertensive Agents therapeutic use, Brain Ischemia prevention & control, Cerebral Infarction prevention & control, Cerebrovascular Circulation drug effects, Hypertension drug therapy
Published: 2006
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34. Prevalence, awareness, treatment, and control of hypertension in the elderly: the Three City study.

Author: Brindel P, Hanon O, Dartigues JF, Ritchie K, Lacombe JM, Ducimetière P, Alpérovitch A, and Tzourio C
Subjects: Aged, Aged, 80 and over, Antihypertensive Agents therapeutic use, Blood Pressure drug effects, Blood Pressure physiology, Cardiovascular Diseases drug therapy, Cardiovascular Diseases epidemiology, Cardiovascular Diseases physiopathology, Data Interpretation, Statistical, Diabetes Mellitus epidemiology, Diabetes Mellitus physiopathology, Female, Humans, Hypertension physiopathology, Male, Obesity epidemiology, Obesity physiopathology, Office Visits statistics & numerical data, Prevalence, Aging physiology, Health Knowledge, Attitudes, Practice, Hypertension drug therapy, Hypertension epidemiology
Abstract: Objective: To study management of hypertension in the elderly in a large population-based study and to evaluate the prevalence of hypertension and factors related to awareness, treatment, and control., Design: The Three City study, a population-based study among 9693 non-institutionalized individuals aged 65 years and over., Methods: Blood pressure was measured with an automated electronic device, and treatment assessed, during home interview. Hypertension was defined by a mean blood pressure of two measurements superior to or equal to 160/95 mmHg and/or the intake of antihypertensive medications., Results: In the final working sample of 9090 people, 62% were hypertensive. More than two-thirds were aware of their hypertension and 81% were treated with antihypertensive drugs. Among 4573 treated hypertensive participants, 35% had a blood pressure over 160/95 mmHg and 69% over 140/90 mmHg. Women were more frequently aware of their hypertension, more frequently treated, and more frequently controlled than men. A history of cardiovascular disease, high body mass index, diabetes and high frequency of visits to the general practitioner were related to higher percentages of awareness and treatment. Among treated hypertensive patients, those with a history of cardiovascular events or who visited their general practitioner more often or who more often had their blood pressure measured were more frequently controlled. Awareness was strongly associated with treatment, but was inversely related to control of hypertension among treated hypertensive patients., Conclusions: Management of hypertension, and particularly its control among treated hypertensive patients, needs to be improved in people aged 65 years and over.
Published: 2006
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35. The ACE gene I/D polymorphism is not associated with the blood pressure and cardiovascular benefits of ACE inhibition.

Author: Harrap SB, Tzourio C, Cambien F, Poirier O, Raoux S, Chalmers J, Chapman N, Colman S, Leguennec S, MacMahon S, Neal B, Ohkubo T, and Woodward M
Subjects: Adult, Cognition Disorders complications, Dementia complications, Female, Genotype, Humans, Hypertension complications, Hypertension physiopathology, Male, Middle Aged, Mutagenesis, Insertional, Perindopril therapeutic use, Randomized Controlled Trials as Topic, Risk Factors, Sequence Deletion, Statistics as Topic, Stroke complications, Survival Analysis, Time Factors, Treatment Outcome, Vascular Diseases complications, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Blood Pressure drug effects, Hypertension drug therapy, Peptidyl-Dipeptidase A genetics, Polymorphism, Genetic
Abstract: The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene might have consequences for the risks of vascular diseases. We examined the ACE genotype and the effects of a perindopril-based blood pressure-lowering regimen on macrovascular events, dementia, and cognitive decline among hypertensive and nonhypertensive patients with a history of cerebrovascular disease. ACE I/D genotypes were measured in 5688 of 6105 individuals with previous stroke or transient ischemic attack who participated in the PROGRESS trial. The DD genotype was significantly (P<0.0001) less frequent in Asian subjects (Chinese and Japanese, 14.7%) than in non-Asian subjects (32.0%). Controlling for racial background, there were no associations between ACE genotypes and cerebrovascular disease history or cardiovascular risk factors, including baseline blood pressure. The ACE genotype was not associated with the long-term risks of stroke, cardiac events, mortality, dementia, or cognitive decline; neither did the ACE genotype predict the blood pressure reduction associated with the use of the ACE inhibitor perindopril. Similarly, there was no evidence that the ACE genotype modified the relative benefits of ACE inhibitor-based therapy over placebo. This study provides no evidence that in patients with cerebrovascular disease, knowledge of ACE genotype is useful for predicting either the risk of disease or the benefits of perindopril-based blood pressure-lowering treatment.
Published: 2003
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36. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease.

Author: Tzourio C, Anderson C, Chapman N, Woodward M, Neal B, MacMahon S, and Chalmers J
Subjects: Aged, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Antihypertensive Agents administration & dosage, Blood Pressure drug effects, Cerebrovascular Disorders etiology, Cognition Disorders etiology, Dementia etiology, Diuretics therapeutic use, Double-Blind Method, Female, Humans, Hypertension complications, Indapamide administration & dosage, Male, Middle Aged, Perindopril administration & dosage, Risk, Treatment Outcome, Antihypertensive Agents therapeutic use, Cerebrovascular Disorders complications, Cognition drug effects, Cognition Disorders prevention & control, Dementia prevention & control, Hypertension drug therapy, Indapamide therapeutic use, Perindopril therapeutic use
Abstract: Background: High blood pressure and stroke are associated with increased risks of dementia and cognitive impairment. This study aimed to determine whether blood pressure lowering would reduce the risks of dementia and cognitive decline among individuals with cerebrovascular disease., Methods: The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, double-blind, placebo-controlled trial conducted among 6105 people with prior stroke or transient ischemic attack. Participants were assigned to either active treatment (perindopril for all participants and indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo(s). The primary outcomes for these analyses were dementia (using DSM-IV criteria) and cognitive decline (a decline of 3 or more points in the Mini-Mental State Examination score)., Results: During a mean follow-up of 3.9 years, dementia was documented in 193 (6.3%) of the 3051 randomized participants in the actively treated group and 217 (7.1%) of the 3054 randomized participants in the placebo group (relative risk reduction, 12% [95% confidence interval, -8% to 28%]; P =.2). Cognitive decline occurred in 9.1% of the actively treated group and 11.0% of the placebo group (risk reduction, 19% [95% confidence interval, 4% to 32%]; P =.01). The risks of the composite outcomes of dementia with recurrent stroke and of cognitive decline with recurrent stroke were reduced by 34% (95% confidence interval, 3% to 55%) (P =.03) and 45% (95% confidence interval, 21% to 61%) (P<.001), respectively, with no clear effect on either dementia or cognitive decline in the absence of recurrent stroke., Conclusions: Active treatment was associated with reduced risks of dementia and cognitive decline associated with recurrent stroke. These findings further support the recommendation that blood pressure lowering with perindopril and indapamide therapy be considered for all patients with cerebrovascular disease.
Published: 2003
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37. Impact of interventions scenarios targeting three main vascular risk factors on the future burden of dementia in France

Author: Jacqmin-Gadda, Hélène, Philipps, Viviane, Guillet, Florian, Tzourio, Christophe, Helmer, Catherine, and Joly, Pierre
Published: 2023
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38. Multiethnic Genome-Wide Association Study of Cerebral White Matter Hyperintensities on MRI

Author: Verhaaren, Benjamin FJ, Debette, Stéphanie, Bis, Joshua C, Smith, Jennifer A, Ikram, M Kamran, Adams, Hieab H, Beecham, Ashley H, Rajan, Kumar B, Lopez, Lorna M, Barral, Sandra, van Buchem, Mark A, van der Grond, Jeroen, Smith, Albert V, Hegenscheid, Katrin, Aggarwal, Neelum T, de Andrade, Mariza, Atkinson, Elizabeth J, Beekman, Marian, Beiser, Alexa S, Blanton, Susan H, Boerwinkle, Eric, Brickman, Adam M, Bryan, R Nick, Chauhan, Ganesh, Chen, Christopher PLH, Chouraki, Vincent, de Craen, Anton JM, Crivello, Fabrice, Deary, Ian J, Deelen, Joris, De Jager, Philip L, Dufouil, Carole, Elkind, Mitchell SV, Evans, Denis A, Freudenberger, Paul, Gottesman, Rebecca F, Guðnason, Vilmundur, Habes, Mohamad, Heckbert, Susan R, Heiss, Gerardo, Hilal, Saima, Hofer, Edith, Hofman, Albert, Ibrahim-Verbaas, Carla A, Knopman, David S, Lewis, Cora E, Liao, Jiemin, Liewald, David CM, Luciano, Michelle, van der Lugt, Aad, Martinez, Oliver O, Mayeux, Richard, Mazoyer, Bernard, Nalls, Mike, Nauck, Matthias, Niessen, Wiro J, Oostra, Ben A, Psaty, Bruce M, Rice, Kenneth M, Rotter, Jerome I, von Sarnowski, Bettina, Schmidt, Helena, Schreiner, Pamela J, Schuur, Maaike, Sidney, Stephen S, Sigurdsson, Sigurdur, Slagboom, P Eline, Stott, David JM, van Swieten, John C, Teumer, Alexander, Töglhofer, Anna Maria, Traylor, Matthew, Trompet, Stella, Turner, Stephen T, Tzourio, Christophe, Uh, Hae-Won, Uitterlinden, André G, Vernooij, Meike W, Wang, Jing J, Wong, Tien Y, Wardlaw, Joanna M, Windham, B Gwen, Wittfeld, Katharina, Wolf, Christiane, Wright, Clinton B, Yang, Qiong, Zhao, Wei, Zijdenbos, Alex, Jukema, J Wouter, Sacco, Ralph L, Kardia, Sharon LR, Amouyel, Philippe, Mosley, Thomas H, Longstreth, WT, DeCarli, Charles C, van Duijn, Cornelia M, Schmidt, Reinhold, Launer, Lenore J, Grabe, Hans J, and Seshadri, Sudha S
Subjects: Aging, Brain Disorders, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Biotechnology, Human Genome, Genetics, Acquired Cognitive Impairment, Clinical Research, Dementia, Alzheimer's Disease, Prevention, Stroke, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, Aged, Aged, 80 and over, Chromosomes, Human, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Meta-Analysis as Topic, Middle Aged, Models, Genetic, Racial Groups, White Matter, cerebral small vessel diseases, cerebrovascular disorders, genome-wide association study, hypertension, leukoencephalopathies, polymorphisms, single nucleotide, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology
Abstract: BackgroundThe burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies.Methods and resultsWe included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7×10(-19)) and identified novel loci on chr10q24 (P=1.6×10(-9)) and chr2p21 (P=4.4×10(-8)). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0×10(-8)) and chr2p16 (P=1.5×10(-8)). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16).ConclusionsWe identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.
Published: 2015

39. 20-Year prevalence projections for dementia and impact of preventive policy about risk factors

Author: Jacqmin-Gadda, Hélène, Alperovitch, Annick, Montlahuc, Claire, Commenges, Daniel, Leffondre, Karen, Dufouil, Carole, Elbaz, Alexis, Tzourio, Christophe, Ménard, Joël, Dartigues, Jean-François, and Joly, Pierre
Published: 2013
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40. Association between blood pressure variability with dementia and cognitive impairment: a systematic review and meta-analysis

Author: DE HEUS, Rianne A. A., Tzourio, Christophe, LEE, Emily Jo Lynn, OPOZDA, Melissa, VINCENT, Andrew D., ANSTEY, Karrin J., Hofman, Albert, Kario, Kazuomi, LATTANZI, Simona, Launer, Lenore J., Ma, Yuan, MAHAJAN, Rajiy, MOOIJAART, Simon P., NAGAI, Michiaki, Peters, Ruth, TURNBULL, Deborah, Yano, Yuichiro, CONSORTIUM, Variable Brain, CLAASSEN, Jahr, TULLY, Phillip J., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Risk, medicine.medical_specialty, Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1], Hemodynamics, 030204 cardiovascular system & hematology, hemodynamics, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Internal Medicine, medicine, Dementia, Humans, Cognitive Dysfunction, Association (psychology), Stroke, business.industry, blood pressure, Cognition, cerebrovascular disorders, Original Articles, medicine.disease, stroke, 3. Good health, meta-analysis, Blood pressure, Meta-analysis, Hypertension, Cardiology, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Alzheimer's disease, Alzheimer disease, business, 030217 neurology & neurosurgery, dementia
Abstract: Supplemental Digital Content is available in the text., Research links high blood pressure variability (BPV) with stroke and cerebrovascular disease, however, its association with cognition remains unclear. Moreover, it remains uncertain which BP-derived parameter (ie, variability or mean) holds more significance in understanding vascular contributions to cognitive impairment. We searched PubMed, Embase, PsycINFO, and Scopus and performed a meta-analysis of studies that quantified the association between resting BPV with dementia or cognitive impairment in adults. Two authors independently reviewed all titles, abstracts, and full-texts and extracted data, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Study quality was assessed using the (modified) Newcastle-Ottawa Scale. A multilevel meta-analysis was used, which included effect sizes for both BPV and mean BP, with a combined end point of dementia or cognitive impairment as primary outcome. In the primary analysis, 54 effect sizes were extracted from 20 studies, with a total analytical sample of n=7 899 697. Higher systolic BPV (odds ratio [OR], 1.25 [95% CI, 1.16–1.35]), mean systolic pressure (OR, 1.12 [95% CI, 1.02–1.29]), diastolic BPV (OR, 1.20 [95% CI, 1.12–1.29]), and mean diastolic pressure (OR, 1.16 [95% CI, 1.04–1.29]) were associated with dementia and cognitive impairment. A direct comparison showed that mean BP effect sizes were less strong than BPV effect sizes (OR, 0.92 [95% CI, 0.87–0.97], P
Published: 2021

41. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors

Author: Bakker, Mark K., van der Spek, Rick A.A., van Rheenen, Wouter, Morel, Sandrine, Bourcier, Romain, Hostettler, Isabel C., Alg, Varinder S., van Eijk, Kristel R., Koido, Masaru, Akiyama, Masato, Terao, Chikashi, Matsuda, Koichi, Walters, Robin G., Lin, Kuang, Li, Liming, Millwood, Iona Y., Chen, Zhengming, Rouleau, Guy A., Zhou, Sirui, Rannikmäe, Kristiina, Sudlow, Cathie L.M., Houlden, Henry, van den Berg, Leonard H., Dina, Christian, Naggara, Olivier, Gentric, Jean-Christophe, Shotar, Eimad, Eugène, François, Desal, Hubert, Winsvold, Bendik S., Børte, Sigrid, Johnsen, Marianne Bakke, Brumpton, Ben M., Sandvei, Marie Søfteland, Willer, Cristen J., Hveem, Kristian, Zwart, John-Anker, Verschuren, W. M. Monique, Friedrich, Christoph M., Hirsch, Sven, Schilling, Sabine, Dauvillier, Jérôme, Martin, Olivier, Martinsen, Amy E, Aamodt, Anne Hege, Skogholt, Anne Heidi, Sandset, Else Charlotte, Kristoffersen, Espen S, Ellekjaer, Hanne, Heuch, Ingrid, Nielsen, Jonas Bille, Hagen, Knut, Fritsche, Lars, Thomas, Laurent F., Pedersen, Linda, Gabrielsen, Maiken E, Vigeland, Maria Dehli, Holmen, Oddgeir, Zhou, Wei, Chen, Junshi, Chen (PI), Zhengming, Clarke, Robert, Collins, Rory, Guo, Yu, Li (PI), Liming, Liu, Depei, Lv, Jun, Peto, Richard, Walters, Robin, Avery, Daniel, Boxall, Ruth, Bennett, Derrick, Chang, Yumei, Chen, Yiping, Du, Huaidong, Gan, Wei, Gilbert, Simon, Hacker, Alex, Hill, Michael, Holmes, Michael, Iona, Andri, Kartsonaki, Christiana, Kerosi, Rene, Kong, Ling, Lancaster, Garry, Lewington, Sarah, McDonnell, John, Millwood, Iona, Nie, Qunhua, Ryder, Paul, Sansome, Sam, Schmidt-Valle, Dan, Sherliker, Paul, Sohoni, Rajani, Stevens, Becky, Turnbull, Iain, Wang, Lin, Wright, Neil, Yang, Ling, Yang, Xiaoming, Yao, Pang, Bian, Zheng, Han, Xiao, Hou, Can, Pei, Pei, Liu, Chao, Yu, Canqing, Pang, Zengchang, Gao, Ruqin, Li, Shanpeng, Wang, Shaojie, Liu, Yongmei, Du, Ranran, Cheng, Liang, Tian, Xiaocao, Zhang, Hua, Zhai, Yaoming, Ning, Feng, Sun, Xiaohui, Li, Feifei, Lv, Silu, Wang, Junzheng, Hou, Wei, Zou, Mingyuan, Yan, Shichun, Zhou, Xue, Yu, Bo, Li, Yanjie, Xu, Qinai, Kang, Quan, Guo, Ziyan, Wang, Dan, Hu, Ximin, Chen, Jinyan, Fu, Yan, Wang, Xiaohuan, Weng, Min, Guo, Zhendong, Wu, Shukuan, Li, Yilei, Li, Huimei, Wu, Ming, Zhou, Yonglin, Zhou, Jinyi, Tao, Ran, Yang, Jie, Su, Jian, liu, Fang, Zhang, Jun, Hu, Yihe, Lu, Yan, Ma, Liangcai, Tang, Aiyu, Hua, Yujie, Jin, Jianrong, Liu, Jingchao, Tang, Zhenzhu, Chen, Naying, Huang, Ying, Li, Mingqiang, Meng, Jinhuai, Pan, Rong, Jiang, Qilian, Lan, Jian, Liu, Yun, Wei, Liuping, Zhou, Liyuan, Chen, Ningyu, Wang, Ping, Meng, Fanwen, Qin Sisi Wang, Yulu, Wu, Xianping, Zhang, Ningmei, Chen, Xiaofang, Zhou, Weiwei, Luo, Guojin, Li, Jianguo, Zhong, Xunfu, Liu, Jiaqiu, Sun, Qiang, Ge, Pengfei, Ren, Xiaolan, Dong, Caixia, Zhang, Hui, Mao, Enke, Wang, Xiaoping, Wang, Tao, Zhang, Xi, Zhou, Ding Zhang, Zhou, Gang, Feng, Shixian, Chang, Ling, Fan, Lei, Gao, Yulian, He, Tianyou, Sun, Huarong, He, Pan, Hu, Chen, Zhang, Xukui, Wu, Huifang, Yu, Min, Hu, Ruying, Wang, Hao, Gong, Weiwei, Wang, Meng, Xie, Kaixu, Chen, Lingli, Pan, Dongxia, Gu, Qijun, Huang, Yuelong, Chen, Biyun, Yin, Li, Liu, Huilin, Fu, Zhongxi, Xu, Qiaohua, Xu, Xin, Zhang, Hao, Long, Huajun, Zhang, Libo, Nagai, Akiko, Muto, Kaori, Hirata, Makoto, Morisaki, Takayuki, Yamashita, Yasushi, Kamatani, Yoichiro, Kambara, Yoko, Murakami, Yoshinori, Masumoto, Akihide, Nagayama, Satoshi, Miki, Yoshio, Yoshimori, Kozo, Fujioka, Tomoaki, Takata, Ryo, Yamaji, Ken, Takahashi, Kazuhisa, Asai, Satoshi, Takahashi, Yasuo, Minami, Shiro, Yamaguchi, Hiroki, Koretsune, Yukihiro, Nishizawa, Yasuko, Kodama, Ken, Kutsumi, Hiromu, Suzuki, Takao, Sinozaki, Nobuaki, Murayama, Shigeo, Furukawa, Yoichi, Yamanashi, Yuji, Papagiannaki, Chrisanthi, Piotin, Michel, Trystram, Denis, Edjlali-Goujon, Myriam, Boulouis, Grégoire, Rodriguez, Christine, Hassen, Waghi Ben, Saleme, Suzanna, Mounayer, Charbel, Rouchaud, Aymeric, Levrier, Olivier, Aguettaz, Pierre, Combaz, Xavier, Pasco, Anne, l’Allinec, Vincent, Bintner, Marc, Molho, Marc, Pascale, Gauthier, Chivot, Cyril, Costalat, Vincent, Darganzil, Cyril, Bonafé, Alain, Januel, Anne Christine, Michelozzi, Caterina, Cognard, Christophe, Bonneville, Fabrice, Tall, Philippe, Darcourt, Jean, Biondi, Alessandra, Iosif, Cristina, Ferre, Jean Christophe, Gauvrit, Jean Yves, Eugene, François, Raoult, Hélène, Gentric, Jean Christophe, Ognard, Julien, Anxionnat, René, Gory, Benjamin, Bracard, Serge, Derelle, Anne Laure, Tonnelet, Romain, Spelle, Laurent, Ikka, Léon, Ozanne, Augustin, Gallas, Sophie, Caroff, Jildaz, Achour, Nidal Ben, Moret, Jacques, Chabert, Emmanuel, Berge, Jérôme, Marnat, Gaultier, Barreau, Xavier, Gariel, Florent, Clarencon, Frédéric, Aggour, Mohammed, Ricolfi, Frédéric, Chavent, Adrien, Thouant, Pierre, Lebidinsky, Pablo, Lemogne, Brivael, Herbreteau, Denis, Bibi, Richard, Janot, Kevin, Pierot, Laurent, Soize, Sébastien, Labeyrie, Marc Antoine, Vandendries, Christophe, Kazemi, Appoline, Leclerc, Xavier, Pruvo, Jean Pierre, Bricout, Nicolas, Velasco, Stéphane, Boucebci, Samy, Lemmens, Robin, Pandolfo, Massimo, Bodenant, Marie, Louillet, Fabien, Mas, Jean-Louis, Deltour, Sandrine, Leder, Sara, Léger, Anne, Canaple, Sandrine, Godefroy, Olivier, Giroud, Maurice, Jacquin, Agnès, Moulin, Thierry, Vuillier, Fabrice, Tzourio, Christophe, Santos, Michael Dos, Malik, Rainer, Hausser, Ingrid, Thomas-Feles, Constanze, Weber, Ralf, Grond-Ginsbach, Caspar, Hacke, Werner, Giossi, Alessia, Volonghi, Irene, Costa, Paolo, del Zotto, Elisabetta, Morotti, Andrea, Poli, Loris, Muiesan, Maria Lorenza, Salvetti, Massimo, Rosei, Enrico Agabiti, Lanfranconi, Silvia, Baron, Pierluigi, Ferrarese, Carlo, Susani, Emanuela, Giacalone, Giacomo, Paolucci, Stefano, Palmirotta, Raffaele, Guadagni, Fiorella, Paciaroni, Maurizio, Ballabio, Elena, Parati, Eugenio A., Fluri, Felix, Hatz, Florian, Gisler, Dominique, Amort, Margareth, Bevan, Steve, James, Tom, Olsson, Sandra, Holmegaard, Lukas, Altintas, Ayse, Martin, Juan José, Kittner, Steven, Mitchell, Braxton, Stine, Colin, O’Connell, Jeff, Dueker, Nicole, Koudstaal, Peter J., de Lau, Lonneke M.L., Hofman, Albert, Verhaaren, Benjamin F, Uitterlinden, Andre G, Montaner, Joan, Mendioroz, Maite, Yadav, Sunaina, Khan, Muhammad Saleem, Wilder, Michael, van Dijk, Ewoud, Maaijwee, Noortje, Rutten-Jacobs, Loes, Kramer, Jamie, Malik, Shaneela, Brott, Thomas G, Brown, Robert D, Singleton, Andrew, Hardy, John, Rich, Stephen S, Tanislav, Christian, Jungehülsing, Jan, Werring, David, Alg, Varinder, Hostettler, Isabel, Bonner, Stephen, Walsh, Daniel, Bulters, Diederik, Kitchen, Neil, Brown, Martin, Grieve, Joan, Roberts, Gareth, Jones, Timothy, Critchley, Giles, Sharma, Pankaj, Nelson, Richard, Whitfield, Peter, Ross, Stuart, Patel, Hiren, Eldridge, Paul, Saastamoinen, Kari, Patel, Umang, Lawrance, Enas, Vandabona, Subha, Mendelow, David, Teal, Rachel, Warner, Orlando, Kirkpatrick, Peter, Seshadri, Sudha, Kilarski, Laura, Hyacinth, Hyacinth I, Oliveira, Jamary, Marini, Sandro, Nyquist, Paul, Lewis, Cathryn, Norrving, Bo, Smith, Gustav, Rosand, Jonathan, Biffi, Alessandro, Kourkoulis, Christina, Anderson, Chris, Giese, Anne-Katrin, Bang, Oh Young, Chung, Jong-Won, Kim, Gyeong-Moon, Zhuang, Qishuai, Sheu, Wayne, Smalley, June, Howson, Joanna, Granata, Alessandra, Markus, Hugh, Wardlaw, Joanna, Cole, John, Thalamuthu, Anbupalam, Hopewell, Jemma, Worrall, Bradford, Bis, Josh, Tirschwell, David, Reiner, Alex, Dhar, Raj, Lee, Jin-Moo, Mortenson, Janne, Wassertheil-Smoller, Sylvia, Prasad, Kameshwar, Fisher, Mark, Traenka, Christopher, Wang, Xingwu, Wang, Yongjun, Rouanet, Francois, Sibon, Igor, Sarnowski, Chloé, Maillard, Pauline, Aparicio, Hugo Javier, Dupuis, Josee, Yang, Qiong, Luvizutto, Gustavo, Chasman, Daniel, Rexrode, Kathryn, Harriot, Andrea, Phuah, Chia-Ling, Santo, Gustavo, Gerard, Jen, Liu, Guiyou, Aaron, Sanjith, Christudass, Christhunesa S., Salomi, BSB, Sanghera, Dharambir, Boehme, Amelia, Elkind, Mitchell, Gretarsdottir, Solveig, Lange, Leslie, Rost, Natalia, James, Michael, Stewart, Jill, Goldstein, Larry, Waddy, Salina, Vojinovic, Dina, Ikram, Arfan, Thijs, Vincent, Parati, Eugenio, Boncoraglio, Giorgio, Kooperberg, Charles, Abboud, Sherrine, Zand, Ramin, Bijlenga, Philippe, Selim, Magdy, Happola, Olli, Strbian, Daniel, Tomppo, Liisa, Pathak, Abhishek, Pfeiffer, Dorothea, Aires, de Buenos, de Carvalho, Joao Jose Freitas, Ribeiro, Priscila, Torres, Nuria, Barboza, Miguel, Plomaritoglou, Androniki, Bjorkegren, Johan, Chan, Yu-Feng Yvonne, Gudnason, Villi, Jimenez-Conde, Jordi, Soriano, Carolina, Roquer, Jaume, Bentley, Paul, Tournier-Lasserve, Elisabeth, Dufouil, Carole, Debette, Stephanie, Mishra, Aniket, Wee, Lawrence, Siddiqi, Saima, Wu, Jer-Yuarn, Ko, Tai-Ming, Bione, Silvia, Jood, Katarina, Tatlisumak, Turgut, Arauz, Antonio, Korostynski, Michal, Launer, Lenore, Yue, Suo, bersano, anna, Juchniewicz, Karol Józef, Mateusz, Adamski, Pera, Joanna, Wnuk, Marcin, Levi, Christopher, Gusdon, Aaron, Kostulas, Konstantinos, Maxwell, Jessye, Duering, Marco, Jagiella, Jeremiasz, Hata, Jun, Ninomiya, Toshiharu, Nguyen, Vinh, Thorarinsson, Bjorn Logi, Lee, Tsong-Hai, Rakitko, Alexandr, Dichgans, Martin, Lindgren, Arne, Wasselius, Johan, Drake, Mattias, Stenman, Martin, Ilinca, Andreea, Staals, Julie, Sadr-Nabavi, Ariane, Crawford, Katherine, Lena, Umme, Mateen, Farrah, Ay, Hakan, Wu, Ona, Schirmer, Markus, Romero, Javier, Cramer, Steve, Golland, Polina, Mueller, Bertram, Brown, Robert, Meschia, James, Ross, Owen A., Pare, Guillaume, Chong, Mike, mansour, Ossama yassin, Karaszewski, Bartosz, Enzinger, Christian, Schmidt, Reinhold, Seiler, Stephan, Pichler, Alexander, Ovbiagele, Bruce, Yamada, Yoshiji, Rundek, Tatjana, Blanton, Susan, P, John, Chern, Joseph, O'Donnell, Chris, Corriveau, Roderick, Bhattacharya, Pallab, Gwinn, Katrina, CHANDRA, BHARATENDU, Chen, Christopher, Kalaria, Raj, Koenig, Jim, Singh, Om Prakash, Olugbodi, Akintomi, Giralt, Eva, Saleheen, Danish, de Leeuw, Frank-Erik, Klijn, Karin, Olesen, Jes, Kubo, Michiaki, Spence, David, Pedersen, Annie, Olsson, Maja, Martín, Juan José, Braga, Gabriel, Xu, Huichun, Assimes, Tim, Raskurazhev, Anton, Lee, Wei Ling, Burri, Philippe, Frid, Petrea, GmbH, Heilbronn, Deng, Zhen, Habibi-koolaee, Mahdi, Vijayan, Murali, Leung, Thomas, Wong, Lawrence, Mok, Vincent, Choy, Richard, Jern, Christina, Lebedeva, Elena, Farrall, Martin, Jiayuan, Xu, Loo, Keat Wei, Rinkel, Gabriel, Magnus, Rudolf, Goncalves, Anderson, Franca, Paulo, Cendes, Iscia, Carrera, Caty, Fernandez-Cadenas, Israel, Kim, Helen, Rolfs, Arndt, Owolabi, Mayowa, Bakker, Mark, Ruigrok, Ynte, Hauer, Allard, Pulit, Sara L., Algra, Ale, van der Laan, Sander W., Macleod, Mary, Howard, George, Tiwari, Hemant, Irvin, Ryan, Albright, Karen C., Perry, Rodney, Kidwell, Chelsea, Pavlovic, Aleksandra, Sargurupremraj, Murali, Schilling, Sabrina, Pezzini, Alessandro, Abd-Allah, Foad, DeCarli, Charles, Liebeskind, David, Traylor, Matthew, Tan, Rhea, Danesh, John, Larsson, Susanna C., Rutten, Loes, Donatti, Amanda, Avelar, Wagner, Broderick, Joseph, Woo, Daniel, Kissela, Brett, Ibenez, Laura Garcia, Salman, Rustam, Sudlow, Cathie, McDonough, Caitrin Wheeler, Silliman, Scott, Magvanjav, Oyunbileg, van Agtmael, Tom, Walters, Matthew, Lorentzen, Erik, Stanne, Tara, Olsson, Martina, Nakagawa, Kazuma, Akinyemi, Rufus, Cotlatciuc, Ioana, O'Connell, Jeff, Sparks, Mary, Sorkin, John, Dave, Tushar, Naylor, Jill, Brown, Devin, Du, Rose, Kulik, Tobias B., Attia, John, Faber, James E, Rothwell, Peter, Márquez, Elsa Valdés, Mancuso, Michelangelo, Souza, Doralina Brum, de Silva, Ranil, Vibo, Riina, Korv, Janika, Maguire, Jane, Fornage, Myriam, Illoh, Kachikwu, Milewicz, Dianna, Majersik, Jennifer, DeHavenon, Adam, Kalani, Yashar, Alexander, Matthew, Cushman, Mary, Sale, Michele, Owens, Debra, Keene, Keith, Rich, Stephe, Psaty, Bruce, Longstreth, Will, Atadzhanov, Masharip, Wolfe, Stacey Quintero, Langefeld, Carl, Bushnell, Cheryl, Cruchaga, Carlos, Konrad, Jan, Liu, Junfeng, Sheth, Kevin, Falcone, Guido, Donahue J, Kathleen, Jones, Gregory T., Bown, Matthew J., Ko, Nerissa U., Coleman, Jonathan R.I., Breen, Gerome, Zaroff, Jonathan G., Klijn, Catharina J.M., Sargurupremraj, Muralidharan, Amouyel, Philippe, Debette, Stéphanie, Rinkel, Gabriel J.E., Worrall, Bradford B., Slowik, Agnieszka, Gaál-Paavola, Emilia I., Niemelä, Mika, Jääskeläinen, Juha E., von Und Zu Fraunberg, Mikael, Lindgren, Antti, Broderick, Joseph P., Werring, David J., Redon, Richard, Veldink, Jan H., Ruigrok, Ynte M., Stroke, HUNT All-In, Group, China Kadoorie Biobank Collaborative, Consortium, BioBank Japan Project, Group, ICAN Study, Group, CADISP, investigators, Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study, (ISGC), International Stroke Genetics Consortium, Morel, Sandrine, and Bijlenga, Philippe Alexandre Pierre
Subjects: genetics [Blood Pressure], Medizin, Genome-wide association study, Blood Pressure, Disease, ddc:616.07, Bioinformatics, 616: Innere Medizin und Krankheiten, 0302 clinical medicine, Risk Factors, physiopathology [Hypertension], genetics [Genetic Predisposition to Disease], Genetic risk factor, Stroke, 0303 health sciences, Smoking, genetics [Smoking], genetics [Intracranial Aneurysm], Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Cerebrovascular disorder, 3. Good health, genetics [European Continental Ancestry Group], Hypertension, genetics [Polymorphism, Single Nucleotide], Subarachnoid hemorrhage, pathology [Intracranial Aneurysm], genetics [White People], Biology, Genetic correlation, pathology [Endothelial Cells], Polymorphism, Single Nucleotide, Article, White People, 03 medical and health sciences, Aneurysm, Asian People, ddc:570, Genetics, medicine, Humans, Genetic Predisposition to Disease, cardiovascular diseases, 030304 developmental biology, genetics [Subarachnoid Hemorrhage], genetics [Asian Continental Ancestry Group], 572: Biochemie, genetics [Asian People], pathology [Subarachnoid Hemorrhage], adverse effects [Smoking], Endothelial Cells, Subarachnoid Hemorrhage, medicine.disease, Intracranial aneurysm, Genetic architecture, ddc:616.8, Case-Control Studies, genetics [Hypertension], 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: An author correction to this article published in December 2020 is available at https://doi.org/10.1038/s41588-020-00760-4. Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.
Published: 2021

42. Cerebral small vessel disease genomics and its implications across the lifespan

Author: Sargurupremraj, Muralidharan, Suzuki, Hideaki, Zhao, Wei, Okada, Yukinori, Mazoyer, Bernard, Wardlaw, Joanna M, Nyquist, Paul A, Mather, Karen A, Grabe, Hans, Schmidt, Helena, Van Duijn, Cornelia M, Gudnason, Vilmundur, Longstreth, William T, Armstrong, Nicola J, Launer, Lenore J, Lathrop, Mark, Seshadri, Sudha, Tzourio, Christophe, Adams, Hieab H, Matthews, Paul M, Fornage, Myriam, Debette, Stéphanie, Amouyel, Philippe, de Andrade, Mariza, Hofer, Edith, Basu, Saonli, Berr, Claudine, Brody, Jennifer A, Chasman, Daniel I, Dartigues, Jean-Francois, Folsom, Aaron R, Germain, Marine, de Haan, Hugoline, Heit, John, Houwing-Duitermaat, Jeanine, Yanek, Lisa R, Kabrhel, Christopher, Kraft, Peter, Legal, Grégoire, Lindström, Sara, Monajemi, Ramin, Morange, Pierre-Emmanuel, Psaty, Bruce M, Reitsma, Pieter H, Ridker, Paul M, Rose, Lynda M, Hagenaars, Saskia P, Rosendaal, Frits R, Saut, Noémie, Slagboom, Eline, Smadja, David, Smith, Nicholas L, Suchon, Pierre, Tang, Weihong, Taylor, Kent D, Trégouët, David-Alexandre, Kumar, Rajan B, de Visser, Marieke C H, van Hylckama Vlieg, Astrid, Weng, Lu-Chen, Wiggins, Kerri L, Gormley, Padhraig, Anttila, Verneri, Winsvold, Bendik S, Palta, Priit, Esko, Tonu, Pers, Tune H, van den Akker, Erik B, Farh, Kai-How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A, Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Terwindt, Gisela M, Kallela, Mikko, McWhirter, Rebekah E, Freilinger, Tobias M, Ran, Caroline, Gordon, Scott G, Stam, Anine H, Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H H, Lehtimäki, Terho, Trompet, Stella, Sarin, Antti-Pekka, Wedenoja, Juho, Hinds, David A, Buring, Julie E, Schürks, Markus, Gudlaug Hrafnsdottir, Maria, Stefansson, Hreinn, Ring, Susan M, Hottenga, Jouke-Jan, Mishra, Aniket, Penninx, Brenda W J H, Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C, Madden, Pamela A F, Martin, Nicholas G, Montgomery, Grant W, Jian, Xueqiu, Saba, Yasaman, Kurki, Mitja, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E, Franke, Lude, Huang, Jie, Stergiakouli, Evie, Satizabal, Claudia L, Lee, Phil H, Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefanie, Meitinger, Thomas, Eriksson, Johan G, Salomaa, Veikko, Heikkilä, Kauko, Beaudet, Gregory, Loehrer, Elizabeth, Uitterlinden, Andre G, Hofman, Albert, van Duijn, Cornelia M, Cherkas, Lynn, Pedersen, Linda M, Stubhaug, Audun, Nielsen, Christopher S, Männikkö, Minna, Mihailov, Evelin, Petit, Laurent, Milani, Lili, Göbel, Hartmut, Esserlind, Ann-Louise, Francke Christensen, Anne, Folkmann Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J, Raitakari, Olli, Ikram, M Arfan, Tsuchida, Ami, Spector, Tim, Järvelin, Marjo-Riitta, Metspalu, Andres, Kubisch, Christian, Strachan, David P, Ferrari, Michel D, Belin, Andrea C, Dichgans, Martin, Wessman, Maija, van den Maagdenberg, Arn M J M, Zago, Laure, Zwart, John-Anker, Boomsma, Dorret I, Davey Smith, George, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J, Neale, Benjamin M, Olesen, Jes, Nyholt, Dale R, Schilling, Sabrina, Palotie, Aarno, Sigurdsson, Sigurdur, Gottesman, Rebecca F, Lewis, Cora E, Sarnowski, Chloé, Aggarwal, Neelum T, Lopez, Oscar L, Smith, Jennifer A, Valdés Hernández, Maria C, van der Grond, Jeroen, Wright, Margaret J, Knol, Maria J, Dörr, Marcus, Thomson, Russell J, Bordes, Constance, Evans, Tavia E, Le Grand, Quentin, Duperron, Marie-Gabrielle, Smith, Albert V, Knopman, David S, Schreiner, Pamela J, Evans, Denis A, Rotter, Jerome I, Beiser, Alexa S, Maniega, Susana Muñoz, Beekman, Marian, Bis, Joshua C, Trollor, Julian, Stott, David J, Vernooij, Meike W, Wittfeld, Katharina, Niessen, Wiro J, Soumaré, Aicha, Boerwinkle, Eric, Sidney, Stephen, Turner, Stephen T, Davies, Gail, Eiriksdottir, Gudny, Thalamuthu, Anbupalam, Völker, Uwe, van Buchem, Mark A, Bryan, R Nick, Dupuis, Josée, Bastin, Mark E, Ames, David, Teumer, Alexander, Kwok, John B, Sakaue, Saori, Bülow, Robin, Deary, Ian J, Schofield, Peter R, Brodaty, Henry, Jiang, Jiyang, Tabara, Yasuharu, Setoh, Kazuya, Miyamoto, Susumu, Yoshida, Kazumichi, Nagata, Manabu, Terzikhan, Natalie, Kamatani, Yoichiro, Matsuda, Fumihiko, Bennett, David A, De Jager, Philip L, Mosley, Thomas H, Sachdev, Perminder S, Schmidt, Reinhold, Warren, Helen R, Evangelou, Evangelos, Habes, Mohamad, Thrombosis, International Network against, Consortium, International Headache Genomics, Ikram, Mohammad A, Wen, Wei, DeCarli, Charles, Srikanth, Velandai K, Jukema, J Wouter, Slagboom, Eline P, Kardia, Sharon L R, Equipe VINTAGE - Inserm U1219 [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Adult, Male, epidemiology [Alzheimer Disease], genetics [Alzheimer Disease], diagnosis [Cerebral Small Vessel Diseases], epidemiology [Hypertension], Genome-wide association studies, behavioral disciplines and activities, Risk Assessment, Article, diagnostic imaging [White Matter], Young Adult, Alzheimer Disease, Risk Factors, White matter disease, mental disorders, Humans, Medical History Taking, Aged, Aged, 80 and over, [SCCO.NEUR]Cognitive science/Neuroscience, Mendelian Randomization Analysis, Middle Aged, White Matter, Stroke, Diffusion Tensor Imaging, Genetic Loci, Cerebral Small Vessel Diseases, complications [Cerebral Small Vessel Diseases], Hypertension, genetics [Stroke], genetics [Cerebral Small Vessel Diseases], Female, genetics [Hypertension], ddc:500, epidemiology [Stroke], Genome-Wide Association Study
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials., White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.
Published: 2020

43. Longitudinal follow-up of individual white matter hyperintensities in a large cohort of elderly

Author: Maillard, Pauline, Crivello, Fabrice, Dufouil, Carole, Tzourio-Mazoyer, Nathalie, Tzourio, Christophe, and Mazoyer, Bernard
Published: 2009
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44. An automated procedure for the assessment of white matter hyperintensities by multispectral (T1, T2, PD) MRI and an evaluation of its between-centre reproducibility based on two large community databases

Author: Maillard, Pauline, Delcroix, Nicolas, Crivello, Fabrice, Dufouil, Carole, Gicquel, Sebastien, Joliot, Marc, Tzourio-Mazoyer, Nathalie, Alpérovitch, Annick, Tzourio, Christophe, and Mazoyer, Bernard
Published: 2008
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45. Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

Author: Yiallouros, Panayiotis K., Escobedo-de la Peña, Jorge, Zhou, Bin, Bentham, James, Di Cesare, Mariachiara, Bixby, Honor, Danaei, Goodarz, Hajifathalian, Kaveh, Taddei, Cristina, Carrillo-Larco, Rodrigo M., Djalalinia, Shirin, Khatibzadeh, Shahab, Lugero, Charles, Peykari, Niloofar, Zhang, Wan Zhu, Bennett, James, Bilano, Ver, Stevens, Gretchen A., Cowan, Melanie J., Riley, Leanne M., Chen, Zhengming, Hambleton, Ian R., Jackson, Rod T., Kengne, Andre Pascal, Khang, Young-Ho, Laxmaiah, Avula, Liu, Jing, Malekzadeh, Reza, Neuhauser, Hannelore K., Sorić, Maroje, Starc, Gregor, Sundström, Johan, Woodward, Mark, Ezzati, Majid, Abarca-Gómez, Leandra, Abdeen, Ziad A., Abu-Rmeileh, Niveen M., Acosta-Cazares, Benjamin, Adams, Robert J., Aekplakorn, Wichai, Afsana, Kaosar, Aguilar-Salinas, Carlos A., Agyemang, Charles, Ahmad, Noor Ani, Ahmadvand, Alireza, Ahrens, Wolfgang, Ajlouni, Kamel, Akhtaeva, Nazgul, Al-Raddadi, Rajaa, Ali, Mohamed M., Ali, Osman, Alkerwi, Ala'a, Aly, Eman, Amarapurkar, Deepak N., Amouyel, Philippe, Amuzu, Antoinette, Andersen, Lars Bo, Anderssen, Sigmund A., Ängquist, Lars H., Anjana, Ranjit Mohan, Ansong, Daniel, Aounallah-Skhiri, Hajer, Araújo, Joana, Ariansen, Inger, Aris, Tahir, Arlappa, Nimmathota, Arveiler, Dominique, Aryal, Krishna K., Aspelund, Thor, Assah, Felix K., Assunção, Maria Cecília F., Avdicová, Mária, Azevedo, Ana, Azizi, Fereidoun, Babu, Bontha V., Bahijri, Suhad, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Bandosz, Piotr, Banegas, José R., Barbagallo, Carlo M., Barceló, Alberto, Barkat, Amina, Barros, Aluisio J. D., Barros, Mauro V., Bata, Iqbal, Batieha, Anwar M., Batyrbek, Assembekov, Baur, Louise A., Beaglehole, Robert, Romdhane, Habiba Ben, Benet, Mikhail, Benson, Lowell S., Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloisa, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K., Bi, Yufang, Bikbov, Mukharram, Bista, Bihungum, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B., Björkelund, Cecilia, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boeing, Heiner, Boggia, Jose G., Boissonnet, Carlos P., Bongard, Vanina, Borchini, Rossana, Bovet, Pascal, Braeckman, Lutgart, Brajkovich, Imperia, Branca, Francesco, Breckenkamp, Juergen, Brenner, Hermann, Brewster, Lizzy M., Bruno, Graziella, Bueno-de-Mesquita, H. B(as), Bugge, Anna, Burns, Con, Bursztyn, Michael, de León, Antonio Cabrera, Cacciottolo, Joseph, Cai, Hui, Cameron, Christine, Can, Günay, Cândido, Ana Paula C., Capuano, Vincenzo, Cardoso, Viviane C., Carlsson, Axel C., Carvalho, Maria J., Casanueva, Felipe F., Casas, Juan-Pablo, Caserta, Carmelo A., Chamukuttan, Snehalatha, Chan, Angelique W., Chan, Queenie, Chaturvedi, Himanshu K., Chaturvedi, Nishi, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Shuohua, Cheng, Ching-Yu, Dekkaki, Imane Cherkaoui, Chetrit, Angela, Chiolero, Arnaud, Chiou, Shu-Ti, Chirita-Emandi, Adela, Chirlaque, María-Dolores, Cho, Belong, Cho, Yumi, Christofaro, Diego G., Chudek, Jerzy, Cifkova, Renata, Cinteza, Eliza, Claessens, Frank, Clays, Els, Concin, Hans, Cooper, Cyrus, Cooper, Rachel, Coppinger, Tara C., Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Craig, Cora L., Crujeiras, Ana B., Cruz, Juan J., D'Arrigo, Graziella, d'Orsi, Eleonora, Dallongeville, Jean, Damasceno, Albertino, Dankner, Rachel, Dantoft, Thomas M., Dauchet, Luc, Davletov, Kairat, De Backer, Guy, De Bacquer, Dirk, de Gaetano, Giovanni, De Henauw, Stefaan, de Oliveira, Paula Duarte, De Smedt, Delphine, Deepa, Mohan, Dehghan, Abbas, Delisle, Hélène, Deschamps, Valérie, Dhana, Klodian, Di Castelnuovo, Augusto F., Dias-da-Costa, Juvenal Soares, Diaz, Alejandro, Dickerson, Ty T., Do, Ha T. P., Donfrancesco, Chiara, Donoso, Silvana P., Döring, Angela, Dorobantu, Maria, Doua, Kouamelan, Drygas, Wojciech, Dulskiene, Virginija, Džakula, Aleksandar, Dzerve, Vilnis, Dziankowska-Zaborszczyk, Elzbieta, Eggertsen, Robert, Ekelund, Ulf, El Ati, Jalila, Elliott, Paul, Elosua, Roberto, Erasmus, Rajiv T., Erem, Cihangir, Eriksen, Louise, Eriksson, Johan G., Evans, Alun, Faeh, David, Fall, Caroline H., Farzadfar, Farshad, Felix-Redondo, Francisco J., Ferguson, Trevor S., Fernandes, Romulo A., Fernández-Bergés, Daniel, Ferrante, Daniel, Ferrari, Marika, Ferreccio, Catterina, Ferrieres, Jean, Finn, Joseph D., Fischer, Krista, Föger, Bernhard, Foo, Leng Huat, Forslund, Ann-Sofie, Forsner, Maria, Fouad, Heba M., Francis, Damian K., do Carmo Franco, Maria, Franco, Oscar H., Frontera, Guillermo, Fuchs, Flavio D., Fuchs, Sandra C., Fujita, Yuki, Furusawa, Takuro, Gaciong, Zbigniew, Galvano, Fabio, Garcia-de-la-Hera, Manoli, Gareta, Dickman, Garnett, Sarah P., Gaspoz, Jean-Michel, Gasull, Magda, Gates, Louise, Geleijnse, Johanna M., Ghasemian, Anoosheh, Ghimire, Anup, Giampaoli, Simona, Gianfagna, Francesco, Gill, Tiffany K., Giovannelli, Jonathan, Goldsmith, Rebecca A., Gonçalves, Helen, Gonzalez-Gross, Marcela, González-Rivas, Juan P., Gorbea, Mariano Bonet, Gottrand, Frederic, Graff-Iversen, Sidsel, Grafnetter, Dušan, Grajda, Aneta, Grammatikopoulou, Maria G., Gregor, Ronald D., Grodzicki, Tomasz, Grøntved, Anders, Grosso, Giuseppe, Gruden, Gabriella, Grujic, Vera, Gu, Dongfeng, Guan, Ong Peng, Gudmundsson, Elias F., Gudnason, Vilmundur, Guerrero, Ramiro, Guessous, Idris, Guimaraes, Andre L., Gulliford, Martin C., Gunnlaugsdottir, Johanna, Gunter, Marc, Gupta, Prakash C., Gupta, Rajeev, Gureje, Oye, Gurzkowska, Beata, Gutierrez, Laura, Gutzwiller, Felix, Hadaegh, Farzad, Halkjær, Jytte, Hardy, Rebecca, Hari Kumar, Rachakulla, Hata, Jun, Hayes, Alison J., He, Jiang, He, Yuna, Elisabeth, Marleen, Henriques, Ana, Cadena, Leticia Hernandez, Herrala, Sauli, Heshmat, Ramin, Hihtaniemi, Ilpo Tapani, Ho, Sai Yin, Ho, Suzanne C., Hobbs, Michael, Hofman, Albert, Dinc, Gonul Horasan, Horimoto, Andrea R. V. R., Hormiga, Claudia M., Horta, Bernardo L., Houti, Leila, Howitt, Christina, Htay, Thein Thein, Htet, Aung Soe, Than Htike, Maung Maung, Hu, Yonghua, Huerta, José María, Huisman, Martijn, Husseini, Abdullatif S., Huybrechts, Inge, Hwalla, Nahla, Iacoviello, Licia, Iannone, Anna G., Ibrahim, Mohsen M., Wong, Norazizah Ibrahim, Ikeda, Nayu, Ikram, M. Arfan, Irazola, Vilma E., Islam, Muhammad, al-Safi Ismail, Aziz, Ivkovic, Vanja, Iwasaki, Masanori, Jacobs, Jeremy M., Jaddou, Hashem, Jafar, Tazeen, Jamrozik, Konrad, Janszky, Imre, Jasienska, Grazyna, Jelaković, Ana, Jelaković, Bojan, Jennings, Garry, Jeong, Seung-lyeal, Jiang, Chao Qiang, Joffres, Michel, Johansson, Mattias, Jokelainen, Jari J., Jonas, Jost B., Jørgensen, Torben, Joshi, Pradeep, Jóźwiak, Jacek, Juolevi, Anne, Jurak, Gregor, Jureša, Vesna, Kaaks, Rudolf, Kafatos, Anthony, Kajantie, Eero O., Kalter-Leibovici, Ofra, Kamaruddin, Nor Azmi, Karki, Khem B., Kasaeian, Amir, Katz, Joanne, Kauhanen, Jussi, Kaur, Prabhdeep, Kavousi, Maryam, Kazakbaeva, Gyulli, Keil, Ulrich, Boker, Lital Keinan, Keinänen-Kiukaanniemi, Sirkka, Kelishadi, Roya, Kemper, Han C. G., Kengne, Andre P., Kerimkulova, Alina, Kersting, Mathilde, Key, Timothy, Khader, Yousef Saleh, Khalili, Davood, Khateeb, Mohammad, Khaw, Kay-Tee, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Killewo, Japhet, Kim, Jeongseon, Kim, Yeon-Yong, Klumbiene, Jurate, Knoflach, Michael, Kolle, Elin, Kolsteren, Patrick, Korrovits, Paul, Koskinen, Seppo, Kouda, Katsuyasu, Kowlessur, Sudhir, Koziel, Slawomir, Kriemler, Susi, Kristensen, Peter Lund, Krokstad, Steinar, Kromhout, Daan, Kruger, Herculina S., Kubinova, Ruzena, Kuciene, Renata, Kuh, Diana, Kujala, Urho M., Kulaga, Zbigniew, Krishna Kumar, R., Kurjata, Pawel, Kusuma, Yadlapalli S., Kuulasmaa, Kari, Kyobutungi, Catherine, Laatikainen, Tiina, Lachat, Carl, Lam, Tai Hing, Landrove, Orlando, Lanska, Vera, Lappas, Georg, Larijani, Bagher, Laugsand, Lars E., Le Nguyen Bao, Khanh, Le, Tuyen D., Leclercq, Catherine, Lee, Jeannette, Lee, Jeonghee, Lehtimäki, Terho, León-Muñoz, Luz M., Levitt, Naomi S., Li, Yanping, Lilly, Christa L., Lim, Wei-Yen, Lima-Costa, M. Fernanda, Lin, Hsien-Ho, Lin, Xu, Lind, Lars, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Lorbeer, Roberto, Lotufo, Paulo A., Lozano, José Eugenio, Luksiene, Dalia, Lundqvist, Annamari, Lunet, Nuno, Lytsy, Per, Ma, Guansheng, Ma, Jun, Machado-Coelho, George L. L., Machi, Suka, Maggi, Stefania, Magliano, Dianna J., Magriplis, Emmanuella, Majer, Marjeta, Makdisse, Marcia, Malhotra, Rahul, Mallikharjuna Rao, Kodavanti, Malyutina, Sofia, Manios, Yannis, Mann, Jim I., Manzato, Enzo, Margozzini, Paula, Marques-Vidal, Pedro, Marques, Larissa Pruner, Marrugat, Jaume, Martorell, Reynaldo, Mathiesen, Ellisiv B., Matijasevich, Alicia, Matsha, Tandi E., Mbanya, Jean Claude N., Mc Donald Posso, Anselmo J., McFarlane, Shelly R., McGarvey, Stephen T., McLachlan, Stela, McLean, Rachael M., McLean, Scott B., McNulty, Breige A., Mediene-Benchekor, Sounnia, Medzioniene, Jurate, Meirhaeghe, Aline, Meisinger, Christa, Menezes, Ana Maria B., Menon, Geetha R., Meshram, Indrapal I., Metspalu, Andres, Meyer, Haakon E., Mi, Jie, Mikkel, Kairit, Miller, Jody C., Minderico, Cláudia S., Francisco, Juan, Miranda, J. 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McLachlan, Stela, McLean, Rachael M, McLean, Scott B, McNulty, Breige A, Mediene-Benchekor, Sounnia, Medzioniene, Jurate, Meirhaeghe, Aline, Meisinger, Christa, Menezes, Ana Maria B, Menon, Geetha R, Meshram, Indrapal I, Metspalu, Andre, Meyer, Haakon E, Mi, Jie, Mikkel, Kairit, Miller, Jody C, Minderico, Cláudia S, Francisco, Juan, Miranda, J Jaime, Mirrakhimov, Erkin, Mišigoj-Durakovic, Marjeta, Modesti, Pietro A, Mohamed, Mostafa K, Mohammad, Kazem, Mohammadifard, Noushin, Mohan, Viswanathan, Mohanna, Salim, Mohd Yusoff, Muhammad Fadhli, Møllehave, Line T, Møller, Niels C, Molnár, Déne, Momenan, Amirabba, Mondo, Charles K, Monyeki, Kotsedi Daniel K, Moon, Jin Soo, Moreira, Leila B, Morejon, Alain, Moreno, Luis A, Morgan, Karen, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mota, Jorge, Esmaeel Motlagh, Mohammad, Motta, Jorge, Msyamboza, Kelias P, Mu, Thet Thet, Muiesan, Maria L, Müller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Musil, Vera, Nabipour, Iraj, Nagel, Gabriele, Naidu, Balkish M, Nakamura, Harunobu, Námešná, Jana, Nang, Ei Ei K, Nangia, Vinay B, Narake, Sameer, Nauck, Matthia, Navarrete-Muñoz, Eva Maria, Ndiaye, Ndeye Coumba, Neal, William A, Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang Ngoc, Nguyen, Quang V, Nieto-Martínez, Ramfis E, Niiranen, Teemu J, Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A, Noorbala, Ahmad Ali, Norat, Teresa, Noto, Davide, Al Nsour, Mohannad, O'Reilly, Dermot, Oda, Eiji, Oehlers, Glenn, Oh, Kyungwon, Ohara, Kumiko, Olinto, Maria Teresa A, Oliveira, Isabel O, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, Pedro, Ornelas, Rui, Osmond, Clive, Ostojic, Sergej M, Ostovar, Afshin, Otero, Johanna A, Overvad, Kim, Owusu-Dabo, Elli, Paccaud, Fred Michel, Padez, Cristina, Pahomova, Elena, Pajak, Andrzej, Palli, Domenico, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Panza, Francesco, Papandreou, Dimitrio, Park, Soon-Woo, Parnell, Winsome R, Parsaeian, Mahboubeh, Patel, Nikhil D, Pecin, Ivan, Pednekar, Mangesh S, Peer, Nasheeta, Peeters, Petra H, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C, Peters, Annette, Petersmann, Astrid, Petkeviciene, Janina, Pham, Son Thai, Pigeot, Iri, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pitakaka, Freda, Piwonska, Aleksandra, Plans-Rubió, Pedro, Polašek, Ozren, Porta, Miquel, Portegies, Marileen L P, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Prashant, Mathur, Price, Jacqueline F, Puder, Jardena J, Puiu, Maria, Punab, Margu, Qasrawi, Radwan F, Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricarda, Rahman, Mahfuzar, Raitakari, Olli, Raj, Manu, Ramachandra Rao, Sudha, Ramachandran, Ambady, Ramos, Elisabete, Rampal, Lekhraj, Rampal, Sanjay, Rangel Reina, Daniel A, Redon, Josep, Reganit, Paul Ferdinand M, Ribeiro, Robespierre, Riboli, Elio, Rigo, Fernando, Rinke de Wit, Tobias F, Ritti-Dias, Raphael M, Robinson, Sian M, Robitaille, Cynthia, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Rojas-Martinez, Rosalba, Romaguera, Dora, Ronkainen, Kimmo, Rosengren, Annika, Roy, Joel G R, Rubinstein, Adolfo, Sandra Ruiz-Betancourt, Blanca, Rutkowski, Marcin, Sabanayagam, Charumathi, Sachdev, Harshpal S, Saidi, Olfa, Sakarya, Sibel, Salanave, Benoit, Salazar Martinez, Eduardo, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Sánchez-Abanto, Jose, Sans, Susana, Santos, Diana A, Santos, Ina S, Nunes dos Santos, Renata, Santos, Rute, Saramies, Jouko L, Sardinha, Luis B, Sarganas, Giselle, Sarrafzadegan, Nizal, Saum, Kai-Uwe, Savva, Savva, Scazufca, Marcia, Schargrodsky, Herman, Schipf, Sabine, Schmidt, Carsten O, Schöttker, Ben, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sharma, Sanjib K, Shaw, Jonathan E, Shibuya, Kenji, Shin, Dong Wook, Shin, Youchan, Si-Ramlee, Khairil, Siantar, Rosalynn, Sibai, Abla M, Santos Silva, Diego Augusto, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöström, Michael, Skovbjerg, Sine, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, Smith, Margaret C, Snijder, Marieke B, So, Hung-Kwan, Sobngwi, Eugène, Söderberg, Stefan, Solfrizzi, Vincenzo, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild I A, Soric, Maroje, Jérome, Charles Sossa, Soumare, Aicha, Staessen, Jan A, Stathopoulou, Maria G, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stronks, Karien, Strufaldi, Maria Wany, Sun, Chien-An, Sung, Yn-Tz, Suriyawongpaisal, Paibul, Sy, Rody G, Shyong Tai, E, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarqui-Mamani, Carolina B, Tautu, Oana-Florentina, Taylor, Anne, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thuesen, Betina H, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Tormo, María José, Torrent, Matie, Traissac, Pierre, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh T H, Trivedi, Atul, Tshepo, Lechaba, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Tynelius, Per, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice E, Ulmer, Hanno, Uusitalo, Hannu M T, Valdivia, Gonzalo, Valvi, Damaskini, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, van Rossem, Lenie, Van Schoor, Natasja M, van Valkengoed, Irene G M, Vanderschueren, Dirk, Vanuzzo, Diego, Vatten, Lar, Vega, Toma, Velasquez-Melendez, Gustavo, Veronesi, Giovanni, Monique Verschuren, W M, Verstraeten, Roosmarijn, Victora, Cesar G, Viet, Lucie, Viikari-Juntura, Eira, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vlasoff, Tiina, Vollenweider, Peter, Voutilainen, Sari, Wade, Alisha N, Wagner, Aline, Walton, Janette, Wan Bebakar, Wan Mohamad, Wan Mohamud, Wan Nazaimoon, Wanderley, Rildo S, Wang, Ming-Dong, Wang, Qian, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Wedderkopp, Niel, Weerasekera, Deepa, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wijga, Alet H, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Emmanuel A, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Justin Y Y, Wong, Tien Yin, Woo, Jean, Giwercman Wu, Aleksander, Wu, Frederick C, Wu, Shouling, Xu, Haiquan, Yan, Weili, Yang, Xiaoguang, Ye, Xingwang, Yiallouros, Panayiotis K, Yoshihara, Akihiro, Younger-Coleman, Novie O, Yusoff, Ahmad Faudzi, Zainuddin, Ahmad Ali, Zambon, Sabina, Zampelas, Antoni, Zdrojewski, Tomasz, Zeng, Yi, Zhao, Dong, Zhao, Wenhua, Zheng, Wei, Zheng, Yingfeng, Zhu, Dan, Zhussupov, Baurzhan, Zimmermann, Esther, Cisneros, Julio Zuñiga, The State Key Laboratory of Cell Biology [Shanghai, China] (CAS Center for Excellence in Molecular Cell Science), Shanghai Institute of Biochemistry and Cell Biology [Shanghai, China]-University of Chinese Academy of Sciences [Shanghai, China], Imperial College London, University of Kentucky, Middlesex University, Cleveland Clinic, Universidad Peruana Cayetano Heredia (UPCH), Brandeis University, Mulago Hospital [Kampala, Ouganda], Department of Epidemiology and Public Health, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), World Health Organisation (WHO), Al-Quds University, Discipline of Medicine, University of South Australia [Adelaide], Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Centre for Industrial Management, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institute of Preventive Medicine, Copenhagen University Hospitals, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Dept. Atherosclerose, University of Iceland [Reykjavik], Institute for Biotechnology and Bioengineering (IBB), Technical University of Lisbon, Medical University of Łódź (MUL), Department of Preventive Medicine and Public Health, Universidad Autónoma de Madrid (UAM), Faculté de Médecine de Tunis, Université de Tunis El Manar (UTM), Sunder Lal Jain Hospital, Ufa Eye Research Institute [Bashkortostan], National Institute of Public Health, Department of Epidemiology, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association-Leibniz Association, CHU Toulouse [Toulouse], Institute of Social and Preventive Medicine, Lausanne university hospital, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Medical Sciences [Turin, Italy] (DMS), Università degli studi di Torino = University of Turin (UNITO), ASU - School for Engineering of Matter, Transport and Energy, Arizona State University [Tempe] (ASU), Universidade do Porto = University of Porto, University of Oxford [Oxford], Cancer & Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), 2nd Department of Internal Medicine, Molecular Medicine, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-IRC KULAK, Department of Public Health, State University of Ghent, MRC Lifecourse Epidemiology Unit [Southampton, UK], University of Southampton, Réseau International des Instituts Pasteur (RIIP), Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Sahlgrenska University Hospital [Gothenburg], Institute of Metabolic Science, MRC, Institut National de Nutrition et de Technologie Alimentaire (INNTA), University of Huddersfield, IMIM-Hospital del Mar, Generalitat de Catalunya, Medstar Research Institute, Queen's University [Belfast] (QUB), Medical Research Council, Applied Sciences, National Research Institute on Food and Nutrition, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Innsbruck Medical University [Austria] (IMU), Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Laboratoire d'Etude des Mammifères Marins (LEMM), Océanopolis [Brest], Faculté de Médecine Henri Warembourg - Université de Lille, Institute of Sport Science and Clinical Biomechanics, University of Southern Denmark (SDU), Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Centro Investig Quim Aplicada, Coahuila, Mexico, Centro Investigacion en Quimica Aplicada, Coahuila, Mexico, University of Geneva [Switzerland], Department of Civil Engineering [Hamirpur], National Institute of Technology [Hamirpur], Health Services Research Unit, Danish Cancer Society, Institute of Cancer Epidemiology, London School of Hygiene and Tropical Medicine (LSHTM), University College of London [London] (UCL), The Georges Institute for International Health, The University of Sydney, School of Information Technology, Deakin University Waurn Ponds, Faculté de Médecine, Université Djilali Liabès [Sidi-Bel-Abbès], Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), CIBER de Epidemiología y Salud Pública (CIBERESP), VU University Medical Center [Amsterdam], Universiteit Gent = Ghent University [Belgium] (UGENT), Faculty of Agricultural and Food Science, American University of Beirut [Beyrouth] (AUB), Åbo Akademi University [Turku], Department of Public Health Sciences, Karolinska Institutet [Stockholm], Great Lakes Institute for Environmental Research, University of Windsor [Ca], Universität Heidelberg [Heidelberg], Research Center for Prevention and Health, University of Ljubljana, Division of Cancer Epidemiology, University of Crete School of medicine, School of Public Health and Clinical Nutrition, University of Eastern Finland, Institute of Epidemiology and Social Medicine, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Research Institute of Child Nutrition Dortmund, Rheinische Friedrich-Wilhelms-Universität Bonn, Cancer Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Department of Oncology, University of Tampere Medical School, University of Tampere, Wageningen University and Research [Wageningen] (WUR), Centre for Environmental Health, National Institue of Public Health, School of Public Health, The University of Hong Kong (HKU), Tehran University of Medical Sciences, Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione (INRAN), INRAN, National University of Singapore (NUS), Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Uppsala Universitet [Uppsala], Department of Public Health and Community Medicine, University of Gothenburg (GU), Institute of Earthquake Science, CEA, Beijing, CEA, Beijing, University of Porto Medical School, Laboratoire de Chimie Physique D'Orsay (LCPO), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aging Program, National research council, Padua, Italy, Baker IDI Heart and Diabetes Institute, Institute of Internal Medicine, Russian Academy of Medical Sciences, Department of Nutrition and Dietetics, Harokopio University, Emory University [Atlanta, GA], Départment of Biotechnology, Faculty of Science, University of Oran Es-Senia [Oran] | Université d'Oran Es-Senia [Oran], Institut National de la Santé et de la Recherche Médicale (INSERM), University of Tartu, Department of Community, Université Ain Shams-Faculty of Medicine-Environmental and Occupational Medicine, Pécsi Tudemányegyetem, Department of Community, Environmental and Occupational Medicine, Université Ain Shams, Research Centre in Physical Activity, Health and Leisure, Nutrition and Metabolism Section, International Agency for Research on Cancer, Bushehr University of Medical Sciences, Institute of Epidemiology and Medical Biometry [Ulm, Allemagne], Universität Ulm - Ulm University [Ulm, Allemagne], Università degli studi di Palermo - University of Palermo, MRc Environmental Epidemiology Unit, Department of Cardiology and Department of Clinical Epidemiology, Aarhus University Hospital, Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Department of Epidemiology and Population Studies, Jagiellonian University, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Social Robotics Laboratory, University of Freiburg, Freiburg im Breisgau, Department of Ophthalmology, Universitätsklinikum Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, University of Bari Aldo Moro (UNIBA), Department of Cardiology, Eastbourne General Hospital, Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Laboratoire d'Innovation pour les Technologies des Energies Nouvelles et les nanomatériaux (LITEN), Institut National de L'Energie Solaire (INES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), King‘s College London, Public Health Sciences, University of Edinburgh, Movement Disorders and Tourette Centre, Genetica medicala, Victor Babeş University of Medicine and Pharmacy (UMFT), Andrology Unit, United Laboratories of Tartu University Clinics, Tampere University Hospital, Department of Hygiene and Epidemiology, Dept of Epidemiology and Public Health, Department of Epidemiology and Biostatistics, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, Institut de Veille Sanitaire (INVS), Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain, parent, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], University of São Paulo (USP), Institut de Recherche pour le Développement (IRD [France-Sud]), Institute for plasma research, Institute for Plasma Research, Department of Biosciences and Nutrition, Department of Reproductive Endocrinology, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC - Academic medical center, Central Hospital and Faculty of medicine and biomedical sciences university, University of Yaoundé [Cameroun], Department of Clinical Sciences, Lund University [Lund]-Lund University Diabetes Centre, School of Computing [Leeds], University of Leeds, Copenhagen University Hospital, Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maastricht University [Maastricht], Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Applied Food Science, Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, University of Amsterdam, Dept. of Social Medecine, Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University Hospital, Africa Centre for Health and Population Studies, University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN)-Medical Research Council of South Africa, Center for Family and Community Medicine, Department of Neurobiology, Care Sciences and Society, Department of Cardiovascular Sciences [Leuven], Cancer Epidemiology Institute, Department of Epidemiology and Health Promotion (MONICA Data Centre), National Public Health Institute, Nutrition et Alimentation des Populations aux Suds (NutriPass), Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Havard School of Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], University of Kuopio, Tampere University, University Medical Centre Utrecht, Department of Social Medicine, Amsterdam, Center for Metabolic Bone Diseases, Catholic University of Leuven, Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Universidad Miguel Hernández [Elche] (UMH), Institute of Public Health and Clinical Nutrition [Kuopio, Finland], Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Division of Community Health Sciences, St George's University of London, Medizinische Universität Wien = Medical University of Vienna, Medical University of Silesia (SUM), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of Innsbruck, National Institute of Hygiene Warsaw, Johns Hopkins University School of Medicine [Baltimore], Food Science and Technology, Beijing Forestry University, College of Automation Engineering, Nanjing University of Aeronautics and Astronautics (CAE-NUAA), NUAA, Chinese Center for Disease Control and Prevention, Department of Applied Mathematics, School of Science, Northwestern Polytechnical University, Xi’an, Shaanxi 710072, Siemens Corporate Research, Siemens AG [Munich], Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), This work was supported by the Wellcome Trust [101506/Z/13/Z]., NCD Risk Factor Collaboration (NCD-RisC). We thank WHO country and regional offices and the World Heart Federation for support in data identification and access., Universidad Autonoma de Madrid (UAM), University of Turin, Universidade do Porto, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Lille 2 - Faculté de Médecine, Westfälische Wilhelms-Universität Münster (WWU), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of KwaZulu-Natal (UKZN)-Medical Research Council of South Africa, Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Lund University Diabetes Centre-Lund University [Lund], Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Medical University of Silesia, Katowice, Apollo - University of Cambridge Repository, University of Kentucky (UK), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Lausanne University Hospital, University of Oxford, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Université de Genève = University of Geneva (UNIGE), Deakin University [Waurn Ponds], Universiteit Gent = Ghent University (UGENT), Universität Heidelberg [Heidelberg] = Heidelberg University, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Universidade de São Paulo = University of São Paulo (USP), Lund University [Lund], Laboratoire Chrono-environnement (UMR 6249) (LCE), Leopold Franzens Universität Innsbruck - University of Innsbruck, National Institute of Public Health - National Institute of Hygiene [Poland], Yiallouros, Panayiotis K. [0000-0002-8339-9285], Giampaoli, Simona [0000-0002-6679-1488], Moschonis, George [0000-0003-3009-6675], Papandreou, Dimitrios [0000-0002-4923-484X], Stathopoulou, Maria G. [0000-0003-4376-2083], Stergiou, George S. [0000-0002-6132-0038], Trichopoulou, Antonia [0000-0002-7204-6396], Valvi, Damaskini [0000-0003-4633-229X], Chen, Z, Woodward, M, Key, T, and Smith, M
Subjects: systolic blood pressure, Settore MED/09 - Medicina Interna, blood pressure measurement, HEALTH EXAMINATION SURVEYS, Blood Pressure, Hypertension, Population Health, Global Health, Non-communicable Disease, Epidemiology, [SDV]Life Sciences [q-bio], global health, South Asia, purl.org/pe-repo/ocde/ford#3.03.09 [https], kohonnut verenpaine, Medicine and Health Sciences, middle income country, measurement method, skin and connective tissue diseases, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Kardiologi: 771, Public, Environmental & Occupational Health, adult, Population health, public health, blood pressure regulation, Public Health, Global Health, Social Medicine and Epidemiology, Non-communicable disease, kansainvälinen vertailu, health survey, aged, female, priority journal, Blood pressure, mean arterial pressure, GLOBAL TRENDS, SODIUM-INTAKE, Life Sciences & Biomedicine, survey design, hypertension, prevalence, Global health, UNITED-STATES, URBAN COMMUNITIES, Article, SECULAR TRENDS, Middle East, Central Asia, male, disease prevalence, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, kansanterveys, blood, SYSTEMATIC ANALYSIS, human, verenpainetauti, non-communicable disease, Science & Technology, Pacific Ocean, high income country, diastolic blood pressure, Pacific Rim, Blood Pressure - Epidemiology - Population, North Africa, major clinical study, HYPERTENSION PREVALENCE, verenpaine, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, ARTERIAL-HYPERTENSION, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, POTASSIUM INTAKE, sense organs, trend analysis, trend study, population research, population health, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, low income country
Abstract: Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probit-transformed) prevalence of raised blood pressure and age-group-and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the high-income Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups., This work was supported by the Wellcome Trust [101506/Z/13/Z].
Published: 2018

46. Exploiting Drug-Apolipoprotein E Gene Interactions in Hypertension to Preserve Cognitive Function: The 3-City Cohort Study

Author: TULLY, P. J., Helmer, C., Peters, R., Tzourio, Christophe, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Adelaide, Australian National University (ANU), Imperial College London, and CCSD, Accord Elsevier
Subjects: mild cognitive impairment, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Hypertension, renin-angiotensin system, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Alzheimer's disease, antihypertensive agents, cognitive function
Abstract: International audience; OBJECTIVES: The objective was to test the hypothesis that antihypertensive drugs have a differential effect on cognition in carriers and noncarriers of the apolipoprotein epsilon4 (APOE4) polymorphism. DESIGN: Prospective population-based cohort, France. SETTING AND PARTICIPANTS: A total of 3359 persons using antihypertensive drugs (median age 74 years, 62% women) were serially assessed up to 10 years follow-up. MEASURES: Exposure to antihypertensive drug use was established in the first 2 years. Cognitive function was assessed at baseline, 2, 4, 7, and 10 years with a validated test battery covering global cognition, verbal fluency, immediate visual recognition memory, processing speed, and executive function. Clinically significant change in cognitive function was determined using reliable change indices represented as z scores and analyzed with linear mixed-models. RESULTS: From 3359 persons exposed to antihypertensive drugs, 653 were APOE4 carriers (5.1% homozygous, 94.9% heterozygous) and median follow-up was 5.2 years (interquartile range 3.7-8.0). In APOE4 carriers, improved general cognitive function over time was associated with exposure to angiotensin converting enzyme inhibitors [beta = .14; 95% confidence interval (CI) .06-.23, P = .001] and angiotensin receptor blockers (beta = .11; 95% CI .02-.21, P = .019). Improved verbal fluency was associated with angiotensin converting enzyme inhibitors (beta = .11; 95% CI .03-.20, P = .012). CONCLUSIONS: Renin-angiotensin-system blockade was associated with improved general cognitive function in APOE4 carriers. Findings did not support renin-angiotensin-system drugs' lipophilicity or ability to cross the blood-brain barrier as potential mechanisms. The findings have implications for selecting the optimal antihypertensive drug in older populations at risk of cognitive decline and dementia.
Published: 2019

47. Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: a pooled analysis of 1018 population-based measurement studies with 88.6 million participants NCD Risk Factor Collaboration (NCD-RisC) Members are listed at the end of the paper

Author: Zhou, Bin, Bentham, James, Di Cesare, Mariachiara, Bixby, Honor, Danaei, Goodarz, Hajifathalian, Kaveh, Taddei, Cristina, Carrillo-Larco, Rodrigo M., Djalalinia, Shirin, Khatibzadeh, Shahab, Lugero, Charles, Peykari, Niloofar, Zhang, Wan Zhu, Bennett, James, Bilano, Ver, Stevens, Gretchen A., Cowan, Melanie J., Riley, Leanne M., Chen, Zhengming, Hambleton, Ian R., Jackson, Rod T., Kengne, Andre Pascal, Khang, Young-Ho, Laxmaiah, Avula, Liu, Jing, Malekzadeh, Reza, Neuhauser, Hannelore K., Soric, Maroje, Starc, Gregor, Sundstrom, Johan, Woodward, Mark, Ezzati, Majid, Abarca-Gomez, Leandra, Abdeen, Ziad A., Abu-Rmeileh, Niveen M., Acosta-Cazares, Benjamin, Adams, Robert J., Aekplakorn, Wichai, Afsana, Kaosar, Aguilar-Salinas, Carlos A., Agyemang, Charles, Ahmad, Noor Ani, Ahmadvand, Alireza, Ahrens, Wolfgang, Ajlouni, Kamel, Akhtaeva, Nazgul, Al-Raddadi, Rajaa, Ali, Mohamed M., Ali, Osman, Alkerwi, Ala'a, Aly, Eman, Amarapurkar, Deepak N., Amouyel, Philippe, Amuzu, Antoinette, Andersen, Lars Bo, Anderssen, Sigmund A., Angquist, Lars H., Anjana, Ranjit Mohan, Ansong, Daniel, Aounallah-Skhiri, Hajer, Araujo, Joana, Ariansen, Inger, Aris, Tahir, Arlappa, Nimmathota, Arveiler, Dominique, Aryal, Krishna K., Aspelund, Thor, Assah, Felix K., Assuncao, Maria Cecilia F., Avdicova, Maria, Azevedo, Ana, Azizi, Fereidoun, Babu, Bontha V., Bahijri, Suhad, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Bandosz, Piotr, Banegas, Jose R., Barbagallo, Carlo M., Barcelo, Alberto, Barkat, Amina, Barros, Aluisio J. D., Barros, Mauro V., Bata, Iqbal, Batieha, Anwar M., Batyrbek, Assembekov, Baur, Louise A., Beaglehole, Robert, Ben Romdhane, Habiba, Benet, Mikhail, Benson, Lowell S., Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloisa, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K., Bi, Yufang, Bikbov, Mukharram, Bista, Bihungum, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B., Bjorkelund, Cecilia, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boeing, Heiner, Boggia, Jose G., Boissonnet, Carlos P., Bongard, Vanina, Borchini, Rossana, Bovet, Pascal, Braeckman, Lutgart, Brajkovich, Imperia, Branca, Francesco, Breckenkamp, Jürgen, Brenner, Hermann, Brewster, Lizzy M., Bruno, Graziella, Bueno-de-Mesquita, Bueno-de-Mesquita, Bugge, Anna, Burns, Con, Bursztyn, Michael, Cabrera de Leon, Antonio, Cacciottolo, Joseph, Cai, Hui, Cameron, Christine, Can, Gunay, Candido, Ana Paula C., Capuano, Vincenzo, Cardoso, Viviane C., Carlsson, Axel C., Carvalho, Maria J., Casanueva, Felipe F., Casas, Juan-Pablo, Caserta, Carmelo A., Chamukuttan, Snehalatha, Chan, Angelique W., Chan, Queenie, Chaturvedi, Himanshu K., Chaturvedi, Nishi, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Shuohua, Cheng, Ching-Yu, Cherkaoui Dekkaki, Imane, Chetrit, Angela, Chiolero, Arnaud, Chiou, Shu-Ti, Chirita-Emandi, Adela, Chirlaque, Maria-Dolores, Cho, Belong, Cho, Yumi, Christofaro, Diego G., Chudek, Jerzy, Cifkova, Renata, Cinteza, Eliza, Claessens, Frank, Clays, Els, Concin, Hans, Cooper, Cyrus, Cooper, Rachel, Coppinger, Tara C., Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Craig, Cora L., Crujeiras, Ana B., Cruz, Juan J., D'Arrigo, Graziella, d'Orsi, Eleonora, Dallongeville, Jean, Damasceno, Albertino, Dankner, Rachel, Dantoft, Thomas M., Dauchet, Luc, Davletov, Kairat, De Backer, Guy, De Bacquer, Dirk, de Gaetano, Giovanni, De Henauw, Stefaan, de Oliveira, Paula Duarte, De Smedt, Delphine, Deepa, Mohan, Dehghan, Abbas, Delisle, Helene, Deschamps, Valerie, Dhana, Klodian, Di Castelnuovo, Augusto F., Dias-da-Costa, Juvenal Soares, Diaz, Alejandro, Dickerson, Ty T., Do, Ha T. P., Dobson, Annette J., Donfrancesco, Chiara, Donoso, Silvana P., Doering, Angela, Dorobantu, Maria, Doua, Kouamelan, Drygas, Wojciech, Dulskiene, Virginija, Dzakula, Aleksandar, Dzerve, Vilnis, Dziankowska-Zaborszczyk, Elzbieta, Eggertsen, Robert, Ekelund, Ulf, El Ati, Jalila, Elliott, Paul, Elosua, Roberto, Erasmus, Rajiv T., Erem, Cihangir, Eriksen, Louise, Eriksson, Johan G., Escobedo-de la Pena, Jorge, Evans, Alun, Faeh, David, Fall, Caroline H., Farzadfar, Farshad, Felix-Redondo, Francisco J., Ferguson, Trevor S., Fernandes, Romulo A., Fernandez-Berges, Daniel, Ferrante, Daniel, Ferrari, Marika, Ferreccio, Catterina, Ferrieres, Jean, Finn, Joseph D., Fischer, Krista, Foger, Bernhard, Foo, Leng Huat, Forslund, Ann-Sofie, Forsner, Maria, Fouad, Heba M., Francis, Damian K., Franco, Maria do Carmo, Franco, Oscar H., Frontera, Guillermo, Fuchs, Flavio D., Fuchs, Sandra C., Fujita, Yuki, Furusawa, Takuro, Gaciong, Zbigniew, Galvano, Fabio, Garcia-de-la-Hera, Manoli, Gareta, Dickman, Garnett, Sarah P., Gaspoz, Jean-Michel, Gasull, Magda, Gates, Louise, Geleijnse, Johanna M., Ghasemian, Anoosheh, Ghimire, Anup, Giampaoli, Simona, Gianfagna, Francesco, Gill, Tiffany K., Giovannelli, Jonathan, Goldsmith, Rebecca A., Goncalves, Helen, Gonzalez-Gross, Marcela, Gonzalez-Rivas, Juan P., Bonet Gorbea, Mariano, Gottrand, Frederic, Graff-Iversen, Sidsel, Grafnetter, Dusan, Grajda, Aneta, Grammatikopoulou, Maria G., Gregor, Ronald D., Grodzicki, Tomasz, Grontved, Anders, Grosso, Giuseppe, Gruden, Gabriella, Grujic, Vera, Gu, Dongfeng, Guan, Ong Peng, Gudmundsson, Elias F., Gudnason, Vilmundur, Guerrero, Ramiro, Guessous, Idris, Guimaraes, Andre L., Gulliford, Martin C., Gunnlaugsdottir, Johanna, Gunter, Marc, Gupta, Prakash C., Gupta, Rajeev, Gureje, Oye, Gurzkowska, Beata, Gutierrez, Laura, Gutzwiller, Felix, Hadaegh, Farzad, Halkjaer, Jytte, Hardy, Rebecca, Kumar, Rachakulla Hari, Hata, Jun, Hayes, Alison J., He, Jiang, He, Yuna, Hendriks, Marleen Elisabeth, Henriques, Ana, Hernandez Cadena, Leticia, Herrala, Sauli, Heshmat, Ramin, Hihtaniemi, Ilpo Tapani, Ho, Sai Yin, Ho, Suzanne C., Hobbs, Michael, Hofman, Albert, Dinc, Gonul Horasan, Horimoto, Andrea R. V. R., Hormiga, Claudia M., Horta, Bernardo L., Houti, Leila, Howitt, Christina, Htay, Thein Thein, Htet, Aung Soe, Htike, Maung Maung Than, Hu, Yonghua, Maria Huerta, Jose, Huisman, Martijn, Husseini, Abdullatif S., Huybrechts, Inge, Hwalla, Nahla, Iacoviello, Licia, Iannone, Anna G., Ibrahim, Mohsen M., Wong, Norazizah Ibrahim, Ikeda, Nayu, Ikram, M. Arfan, Irazola, Vilma E., Islam, Muhammad, Ismail, Aziz al-Safi, Ivkovic, Vanja, Iwasaki, Masanori, Jacobs, Jeremy M., Jaddou, Hashem, Jafar, Tazeen, Jamrozik, Konrad, Janszky, Imre, Jasienska, Grazyna, Jelakovic, Ana, Jelakovic, Bojan, Jennings, Garry, Jeong, Seung-lyeal, Jiang, Chao Qiang, Joffres, Michel, Johansson, Mattias, Jokelainen, Jari J., Jonas, Jost B., Jorgensen, Torben, Joshi, Pradeep, Jozwiak, Jacek, Juolevi, Anne, Jurak, Gregor, Juresa, Vesna, Kaaks, Rudolf, Kafatos, Anthony, Kajantie, Eero O., Kalter-Leibovici, Ofra, Kamaruddin, Nor Azmi, Karki, Khem B., Kasaeian, Amir, Katz, Joanne, Kauhanen, Jussi, Kaur, Prabhdeep, Kavousi, Maryam, Kazakbaeva, Gyulli, Keil, Ulrich, Boker, Lital Keinan, Keinanen-Kiukaanniemi, Sirkka, Kelishadi, Roya, Kemper, Han C. G., Kengne, Andre P., Kerimkulova, Alina, Kersting, Mathilde, Key, Timothy, Khader, Yousef Saleh, Khalili, Davood, Khateeb, Mohammad, Khaw, Kay-Tee, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Killewo, Japhet, Kim, Jeongseon, Kim, Yeon-Yong, Klumbiene, Jurate, Knoflach, Michael, Kolle, Elin, Kolsteren, Patrick, Korrovits, Paul, Koskinen, Seppo, Kouda, Katsuyasu, Kowlessur, Sudhir, Koziel, Slawomir, Kriemler, Susi, Kristensen, Peter Lund, Krokstad, Steinar, Kromhout, Daan, Kruger, Herculina S., Kubinova, Ruzena, Kuciene, Renata, Kuh, Diana, Kujala, Urho M., Kulaga, Zbigniew, Kumar, R. Krishna, Kurjata, Pawel, Kusuma, Yadlapalli S., Kuulasmaa, Kari, Kyobutungi, Catherine, Laatikainen, Tiina, Lachat, Carl, Lam, Tai Hing, Landrove, Orlando, Lanska, Vera, Lappas, Georg, Larijani, Bagher, Laugsand, Lars E., Khanh Le Nguyen Bao, Khanh Le Nguyen Bao, Le, Tuyen D., Leclercq, Catherine, Lee, Jeannette, Lee, Jeonghee, Lehtimaki, Terho, Leon-Munoz, Luz M., Levitt, Naomi S., Li, Yanping, Lilly, Christa L., Lim, Wei-Yen, Fernanda Lima-Costa, M., Lin, Hsien-Ho, Lin, Xu, Lind, Lars, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Lorbeer, Roberto, Lotufo, Paulo A., Eugenio Lozano, Jose, Luksiene, Dalia, Lundqvist, Annamari, Lunet, Nuno, Lytsy, Per, Ma, Jun, Machado-Coelho, George L. L., Machi, Suka, Maggi, Stefania, Magliano, Dianna J., Magriplis, Emmanuella, Majer, Marjeta, Makdisse, Marcia, Malhotra, Rahul, Rao, Kodavanti Mallikharjuna, Malyutina, Sofia, Manios, Yannis, Mann, Jim I., Manzato, Enzo, Margozzini, Paula, Marques-Vidal, Pedro, Marques, Larissa Pruner, Marrugat, Jaume, Martorell, Reynaldo, Mathiesen, Ellisiv B., Matijasevich, Alicia, Matsha, Tandi E., Mbanya, Jean Claude N., Posso, Anselmo J. Mc Donald, McFarlane, Shelly R., McGarvey, Stephen T., McLachlan, Stela, McLean, Rachael M., McLean, Scott B., McNulty, Breige A., Mediene-Benchekor, Sounnia, Medzioniene, Jurate, Meirhaeghe, Aline, Meisinger, Christa, Menezes, Ana Maria B., Menon, Geetha R., Meshram, Indrapal I., Metspalu, Andres, Meyer, Haakon E., Mi, Jie, Mikkel, Kairit, Miller, Jody C., Minderico, Claudia S., Francisco, Juan, Jaime Miranda, J., Mirrakhimov, Erkin, Misigoj-Durakovic, Marjeta, Modesti, Pietro A., Mohamed, Mostafa K., Mohammad, Kazem, Mohammadifard, Noushin, Mohan, Viswanathan, Mohanna, Salim, Yusoff, Muhammad Fadhli Mohd, Mollehave, Line T., Moller, Niels C., Molnar, Denes, Momenan, Amirabbas, Mondo, Charles K., Monyeki, Kotsedi Daniel K., Moon, Jin Soo, Moreira, Leila B., Morejon, Alain, Moreno, Luis A., Morgan, Karen, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mota, Jorge, Motlagh, Mohammad Esmaeel, Motta, Jorge, Msyamboza, Kelias P., Mu, Thet Thet, Muiesan, Maria L., Mueller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Musil, Vera, Nabipour, Iraj, Nagel, Gabriele, Naidu, Balkish M., Nakamura, Harunobu, Namesna, Jana, Nang, Ei Ei K., Nangia, Vinay B., Narake, Sameer, Nauck, Matthias, Maria Navarrete-Munoz, Eva, Ndiaye, Ndeye Coumba, Neal, William A., Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T., Nguyen, D. Nguyen, Quang Ngoc Nguyen, Quang Ngoc Nguyen, Nguyen, Quang V., Nieto-Martinez, Ramfis E., Niiranen, Teemu J., Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A., Noorbala, Ahmad Ali, Norat, Teresa, Noto, Davide, Al Nsour, Mohannad, O'Reilly, Dermot, Oda, Eiji, Oehlers, Glenn, Oh, Kyungwon, Ohara, Kumiko, Olinto, Maria Teresa A., Oliveira, Isabel O., Azahadi, Mohd, Onat, Altan, Ong, Sok King, Ono, Lariane M., Ordunez, Pedro, Ornelas, Rui, Osmond, Clive, Ostojic, Sergej M., Ostovar, Afshin, Otero, Johanna A., Overvad, Kim, Owusu-Dabo, Ellis, Paccaud, Fred Michel, Padez, Cristina, Pahomova, Elena, Pajak, Andrzej, Palli, Domenico, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Panza, Francesco, Papandreou, Dimitrios, Park, Soon-Woo, Parnell, Winsome R., Parsaeian, Mahboubeh, Patel, Nikhil D., Pecin, Ivan, Pednekar, Mangesh S., Peer, Nasheeta, Peeters, Petra H., Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C., Peters, Annette, Petersmann, Astrid, Petkeviciene, Janina, Son Thai Pham, Son Thai Pham, Pigeot, Iris, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pitakaka, Freda, Piwonska, Aleksandra, Plans-Rubio, Pedro, Polasek, Ozren, Porta, Miquel, Portegies, Marileen L. P., Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Prashant, Mathur, Price, Jacqueline F., Puder, Jardena J., Puiu, Maria, Punab, Margus, Qasrawi, Radwan F., Qorbani, Mostafa, Tran Quoc Bao, Tran Quoc Bao, Radic, Ivana, Radisauskas, Ricardas, Rahman, Mahfuzar, Raitakari, Olli, Raj, Manu, Rao, Sudha Ramachandra, Ramachandran, Ambady, Ramos, Elisabete, Rampal, Lekhraj, Rampal, Sanjay, Reina, Daniel A. Rangel, Redon, Josep, Reganit, Paul Ferdinand M., Ribeiro, Robespierre, Riboli, Elio, Rigo, Fernando, de Wit, Tobias F. Rinke, Ritti-Dias, Raphael M., Robinson, Sian M., Robitaille, Cynthia, Rodriguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, Maria, Rodriguez-Villamizar, Laura A., Rojas-Martinez, Rosalba, Romaguera, Dora, Ronkainen, Kimmo, Rosengren, Annika, Roy, Joel G. R., Rubinstein, Adolfo, Sandra Ruiz-Betancourt, Blanca, Rutkowski, Marcin, Sabanayagam, Charumathi, Sachdev, Harshpal S., Saidi, Olfa, Sakarya, Sibel, Salanave, Benoit, Salazar Martinez, Eduardo, Salmeron, Diego, Salomaa, Veikko, Salonen, Jukka T., Salvetti, Massimo, Sanchez-Abanto, Jose, Sans, Susana, Santos, Diana A., Santos, Ina S., dos Santos, Renata Nunes, Santos, Rute, Saramies, Jouko L., Sardinha, Luis B., Sarganas, Giselle, Sarrafzadegan, Nizal, Saum, Kai-Uwe, Savva, Savvas, Scazufca, Marcia, Schargrodsky, Herman, Schipf, Sabine, Schmidt, Carsten O., Schoettker, Ben, Schultsz, Constance, Schutte, Aletta E., Sein, Aye Aye, Sen, Abhijit, Senbanjo, Idowu O., Sepanlou, Sadaf G., Sharma, Sanjib K., Shaw, Jonathan E., Shibuya, Kenji, Shin, Dong Wook, Shin, Youchan, Si-Ramlee, Khairil, Siantar, Rosalynn, Sibai, Abla M., Santos Silva, Diego Augusto, Simon, Mary, Simons, Judith, Simons, Leon A., Sjostrom, Michael, Skovbjerg, Sine, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, Smith, Margaret C., Snijder, Marieke B., So, Hung-Kwan, Sobngwi, Eugene, Soderberg, Stefan, Solfrizzi, Vincenzo, Sonestedt, Emily, Song, Yi, Sorensen, Thorkild I. A., Jerome, Charles Sossa, Soumare, Aicha, Staessen, Jan A., Stathopoulou, Maria G., Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D., Stergiou, George S., Stessman, Jochanan, Stieber, Jutta, Stoeckl, Doris, Stocks, Tanja, Stokwiszewski, Jakub, Stronks, Karien, Strufaldi, Maria Wany, Sun, Chien-An, Sung, Yn-Tz, Suriyawongpaisal, Paibul, Sy, Rody G., Tai, E. Shyong, Tammesoo, Mari-Liis, Tamosiunas, Abdonas, Tan, Eng Joo, Tang, Xun, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarqui-Mamani, Carolina B., Tautu, Oana-Florentina, Taylor, Anne, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thuesen, Betina H., Tjonneland, Anne, Tolonen, Hanna K., Tolstrup, Janne S., Topbas, Murat, Topor-Madry, Roman, Jose Tormo, Maria, Torrent, Maties, Traissac, Pierre, Trichopoulos, Dimitrios, Trichopoulou, Antonia, Trinh, Oanh T. H., Trivedi, Atul, Tshepo, Lechaba, Tulloch-Reid, Marshall K., Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L., Tynelius, Per, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice E., Ulmer, Hanno, Uusitalo, Hannu M. T., Valdivia, Gonzalo, Valvi, Damaskini, van der Schouw, Yvonne T., Van Herck, Koen, Hoang Van Minh, Hoang Van Minh, van Rossem, Lenie, Van Schoor, Natasja M., van Valkengoed, Irene G. M., Vanderschueren, Dirk, Vanuzzo, Diego, Vatten, Lars, Vega, Tomas, Velasquez-Melendez, Gustavo, Veronesi, Giovanni, Verschuren, W. M. Monique, Verstraeten, Roosmarijn, Victora, Cesar G., Viet, Lucie, Viikari-Juntura, Eira, Vineis, Paolo, Vioque, Jesus, Virtanen, Jyrki K., Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vlasoff, Tiina, Vollenweider, Peter, Voutilainen, Sari, Wade, Alisha N., Wagner, Aline, Walton, Janette, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, Wanderley, Rildo S., Jr., Wang, Ming-Dong, Wang, Qian, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S. Goya, Wareham, Nicholas, Wedderkopp, Niels, Weerasekera, Deepa, Whincup, Peter H., Widhalm, Kurt, Widyahening, Indah S., Wiecek, Andrzej, Wijga, Alet H., Wilks, Rainford J., Willeit, Johann, Willeit, Peter, Williams, Emmanuel A., Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A., Wong, Justin Y. Y., Wong, Tien Yin, Woo, Jean, Wu, Aleksander Giwercman, Wu, Frederick C., Wu, Shouling, Xu, Haiquan, Yan, Weili, Yang, Xiaoguang, Ye, Xingwang, Yiallouros, Panayiotis K., Yoshihara, Akihiro, Younger-Coleman, Novie O., Yusoff, Ahmad Faudzi, Zainuddin, Ahmad Ali, Zambon, Sabina, Zampelas, Antonis, Zdrojewski, Tomasz, Zeng, Yi, Zhao, Dong, Zhao, Wenhua, Zheng, Wei, Zheng, Yingfeng, Zhu, Dan, Zhussupov, Baurzhan, Zimmermann, Esther, and Cisneros, Julio Zuniga
Subjects: hypertension, Blood pressure, global health, sense organs, population health, non-communicable disease
Abstract: Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probit-transformed) prevalence of raised blood pressure and age-group-and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the high-income Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups.
Published: 2018

48. Worldwide trends in blood pressure from 1975 to 2015 : a pooled analysis of 1479 population-based measurement studies with 19.1 million participants

Author: Zhou, Bin, Bentham, James, Di Cesare, Mariachiara, Bixby, Honor, Danaei, Goodarz, Cowan, Melanie J, Paciorek, Christopher J, Singh, Gitanjali, Hajifathalian, Kaveh, Bennett, James E, Taddei, Cristina, Bilano, Ver, Carrillo-Larco, Rodrigo M, Djalalinia, Shirin, Khatibzadeh, Shahab, Lugero, Charles, Peykari, Niloofar, Zhang, Wan Zhu, Lu, Yuan, Stevens, Gretchen A, Riley, Leanne M, Bovet, Pascal, Elliott, Paul, Gu, Dongfeng, Ikeda, Nayu, Jackson, Rod T, Joffres, Michel, Kengne, Andre Pascal, Laatikainen, Tiina, Lam, Tai Hing, Laxmaiah, Avula, Liu, Jing, Miranda, J Jaime, Mondo, Charles K, Neuhauser, Hannelore K, Sundstrom, Johan, Smeeth, Liam, Soric, Maroje, Woodward, Mark, Ezzati, Majid, Abarca-Gomez, Leandra, Abdeen, Ziad A, Rahim, Hanan Abdul, Abu-Rmeileh, Niveen M, Acosta-Cazares, Benjamin, Adams, Robert, Aekplakorn, Wichai, Afsana, Kaosar, Aguilar-Salinas, Carlos A, Agyemang, Charles, Ahmadvand, Alireza, Ahrens, Wolfgang, Al Raddadi, Rajaa, Al Woyatan, Rihab, Ali, Mohamed M, Alkerwi, Ala'a, Aly, Eman, Amouyel, Philippe, Amuzu, Antoinette, Andersen, Lars Bo, Anderssen, Sigmund A, Angquist, Lars, Anjana, Ranjit Mohan, Ansong, Daniel, Aounallah-Skhiri, Hajer, Araujo, Joana, Ariansen, Inger, Aris, Tahir, Arlappa, Nimmathota, Aryal, Krishna, Arveiler, Dominique, Assah, Felix K, Assuncao, Maria Cecilia F, Avdicova, Maria, Azevedo, Ana, Azizi, Fereidoun, Babu, Bontha V, Bahijri, Suhad, Balakrishna, Nagalla, Bandosz, Piotr, Banegas, Jose R, Barbagallo, Carlo M, Barcelo, Alberto, Barkat, Amina, Barros, Aluisio JD, Barros, Mauro V, Bata, Iqbal, Batieha, Anwar M, Baur, Louise A, Beaglehole, Robert, Ben Romdhane, Habiba, Benet, Mikhail, Benson, Lowell S, Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloisa, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K, Bi, Yufang, Bikbov, Mukharram, Bjerregaard, Peter, Bjertness, Espen, Bjokelund, Cecilia, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boeing, Heiner, Boggia, Jose G, Boissonnet, Carlos P, Bongard, 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Sarrafzadegan, Nizal, Saum, Kai-Uwe, Savva, Savvas C, Scazufca, Marcia, Schargrodsky, Herman, Schneider, Ione J, Schultsz, Constance, Schutte, Aletta E, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sharma, Sanjib K, Shaw, Jonathan E, Shibuya, Kenji, Shin, Dong Wook, Shin, Youchan, Siantar, Rosalynn, Sibai, Abla M, Santos Silva, Diego Augusto, Simon, Mary, Simons, Judith, Simons, Leon A, Sjotrom, Michael, Skovbjerg, Sine, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smith, Margaret C, Snijder, Marieke B, So, Hung-Kwan, Sobngwi, Eugene, Soderberg, Stefan, Solfrizzi, Vincenzo, Sonestedt, Emily, Song, Yi, Sorensen, Thorkild IA, Jerome, Charles Sossa, Soumare, Aicha, Staessen, Jan A, Starc, Gregor, Stathopoulou, Maria G, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stieber, Jutta, Stoeckl, Doris, Stocks, Tanja, Stokwiszewski, Jakub, Stronks, Karien, Strufaldi, Maria Wany, Sun, Chien-An, Sung, Yn-Tz, Suriyawongpaisal, Paibul, Sy, Rody G, Tai, E Shyong, Tammesoo, Mari-Liis, Tamosiunas, Abdonas, Tang, Line, Tang, Xun, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarqui-Mamani, Carolina B, Taylor, Anne, Theobald, Holger, Thijs, Lutgarde, Thuesen, Betina H, Tjonneland, Anne, Tolonen, Hanna K, Topbas, Murat, Topor-Madry, Roman, Jose Tormo, Maria, Torrent, Maties, Traissac, Pierre, Trichopoulos, Dimitrios, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tulloch-Reid, Marshall K, Tuomainen, Tomi-Pekka, Turley, Maria L, Tynelius, Per, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ulmer, Hanno, Uusitalo, Hannu MT, Valdivia, Gonzalo, Valvi, Damaskini, van der Schouw, Yvonne T, Van Herck, Koen, van Rossem, Lenie, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Vatten, Lars, Vega, Tomas, Velasquez-Melendez, Gustavo, Veronesi, Giovanni, Verschuren, WM Monique, Verstraeten, Roosmarijn, Victora, Cesar G, Viet, Lucie, Viikari-Juntura, Eira, Vineis, Paolo, Vioque, Jesus, Virtanen, Jyrki K, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vollenweider, Peter, Vrdoljak, Ana, Vrijheid, Martine, Wade, Alisha N, Wagner, Aline, Walton, Janette, Mohamud, Wan Nazaimoon Wan, Wang, Ming-Dong, Wang, Qian, Wang, Ya Xing, Wannamethee, S Goya, Wareham, Nicholas, Wederkopp, Niels, Weerasekera, Deepa, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wijga, Alet H, Wilks, Rainford J, Willeit, Peter, Williams, Emmanuel A., Wilsgaard, Tom, Wojtyniak, Bogdan, Wong, Tien Yin, Wong-McClure, Roy A, Woo, Jean, Wu, Aleksander Giwercman, Wu, Frederick C, Wu, Shou Ling, Xu, Haiquan, Yan, Weili, Yang, Xiaoguang, Ye, Xingwang, Yiallouros, Panayiotis K, Yoshihara, Akihiro, Younger-Coleman, Novie O, Yusoff, Ahmad F, Zambon, Sabina, Zdrojewski, Tomasz, Zeng, Yi, Zhao, Dong, Zhao, Wenhua, Zheng, Yingffeng, Zhu, Dan, Zimmermann, Esther, and Zuniga Cisneros, Julio
Subjects: GENDER-DIFFERENCES, Kardiologi, HYPERTENSION, HEALTH EXAMINATION SURVEYS, Omvårdnad, General Practice, UNITED-STATES, Nursing, GLOBAL BURDEN, PREVALENCE, SECULAR TRENDS, Allmänmedicin, MONICA PROJECT, Medicine and Health Sciences, CARDIOVASCULAR RISK-FACTORS, SYSTEMATIC ANALYSIS, Cardiac and Cardiovascular Systems, INCOME COUNTRIES
Abstract: Background Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher. Methods For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure. Findings We pooled 1479 studies that had measured the blood pressures of 19.1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127.0 mm Hg (95% credible interval 125.7-128.3) in men and 122.3 mm Hg (121.0-123.6) in women; age-standardised mean diastolic blood pressure was 78.7 mm Hg (77.9-79.5) for men and 76.7 mm Hg (75.9-77.6) for women. Global age-standardised prevalence of raised blood pressure was 24.1% (21.4-27.1) in men and 20.1% (17.8-22.5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1.13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence. Interpretation During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe. Funding Wellcome Trust.
Published: 2017

49. Migraine And Risk Of Ischaemic Stroke: A Case-Control Study

Author: Tzourio, Christophe, Iglesias, Serge, Hubert, Jean-Baptiste, Visy, Jean-Marc, Alpérovitch, Annick, Tehindrazanarivelo, Alain, Biousse, Valérie, Woimant, France, and Bousser, Marie-Germaine
Published: 1993

50. Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection

Author: Debette, Stéphanie, Kamatani, Yoichiro, Wolf, Christiane, Agabiti Rosei, Enrico, Lanfranconi, Silvia, Ferrarese, Carlo, Susani, Emanuela, Bicocca, Milano, Giacalone, Giacomo, Paolucci, Stefano, Palmirotta, Raffaele, Paciaroni, Maurizio, Ballabio, Elena, Dittrich, Ralf, Parati, Eugenio A, Ciusani, Emilio, Fluri, Felix, Hatz, Florian, Gisler, Dominique, Amort, Margareth, Bevan, Steve, James, Tom, Olsson, Sandra, Holmegaard, Lukas, Touzé, Emmanuel, Altintas, Ayse, Martin, Juan José, Kittner, Steven, MItchell, Braxton, Stine, Colin, O'Connell, Jeff, Dueker, Nicole, Koudstaal, Peter J, de Lau, Lonneke M L, Hofman, Albert, Southerland, Andrew M, Verhaaren, Benjamin F, Uitterlinden, Andre G, Montaner, Joan, Mendioroz, Maite, Yadav, Sunaina, Khan, Muhammad Saleem, Wilder, Michael, van Dijk, Ewoud, Maaijwee, Noortje, Rutten-Jacobs, Loes, Samson, Yves, Kramer, Jamie, Malik, Shaneela, Brott, Thomas G, Brown, Robert D, Singleton, Andrew, Hardy, John, Rich, Stephen S, Tanislav, Christian, Jungehülsing, Jan, Abboud, Shérine, Béjot, Yannick, Caso, Valeria, Bersano, Anna, Gschwendtner, Andreas, Metso, Tiina M, Sessa, Maria, Cole, John, Lamy, Chantal, Medeiros, Elisabeth, Beretta, Simone, Bonati, Leo H, Grau, Armin J, Michel, Patrik, Majersik, Jennifer J, Sharma, Pankaj, Kloss, Manja, Kalashnikova, Ludmila, Nazarova, Maria, Dobrynina, Larisa, Bartels, Eva, Guillon, Benoit, van den Herik, Evita G, Fernandez-Cadenas, Israel, Jood, Katarina, Nalls, Michael A, De Leeuw, Frank-Erik, Chauhan, Ganesh, Jern, Christina, Cheng, Yu-Ching, Werner, Inge, Metso, Antti J, Lichy, Christoph, Lyrer, Philippe A, Brandt, Tobias, Boncoraglio, Giorgio B, Wichmann, Heinz-Erich, Gieger, Christian, Engelter, Stefan T, Johnson, Andrew D, Böttcher, Thomas, Castellano, Maurizio, Arveiler, Dominique, Ikram, M Arfan, Breteler, Monique M B, Padovani, Alessandro, Meschia, James F, Kuhlenbäumer, Gregor, Rolfs, Arndt, Pezzini, Alessandro, Worrall, Bradford B, Consortium, International Stroke Genetics, Ringelstein, Erich-Bernd, Zelenika, Diana, Tatlisumak, Turgut, Lathrop, Mark, Leys, Didier, Amouyel, Philippe, Dallongeville, Jean, Group, CADISP, Thijs, Vincent, Lemmens, Robin, Pandolfo, Massimo, Bodenant, Marie, Louillet, Fabien, Mas, Jean-Louis, Deltour, Sandrine, Leder, Sara, Léger, Anne, Canaple, Sandrine, Godefroy, Olivier, Markus, Hugh S, Giroud, Maurice, Jacquin, Agnès, Moulin, Thierry, Vullier, Fabrice, Tzourio, Christophe, Dos Santos, Michael, Malik, Rainer, Hausser, Ingrid, Thomas-Feles, Constanze, Weber, Ralf, Dichgans, Martin, Grond-Ginsbach, Caspar, Hacke, Werner, Giossi, Alessia, Volonghi, Irene, Costa, Paolo, del Zotto, Elisabetta, Morotti, Andrea, Poli, Loris, Lorenza Muiesan, Maria, Salvetti, Massimo, Epidémiologie des maladies chroniques: impact des intéractions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Epidemiologie-Biostatistique [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Helsinki University Central Hospital [Finland] (HUCH), Heidelberg University Hospital [Heidelberg], University Hospital Basel [Basel], Università degli Studi di Brescia = University of Brescia (UniBs), University Hospitals Leuven [Leuven], Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), University of Cambridge [UK] (CAM), Institute for Stroke and Dementia Research (ISD), Klinikum der Universität [München]-Ludwig Maximilian University [Munich] (LMU), Ludwig-Maximilians-Universität München (LMU), University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), University of Virginia, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Neurochirurgie Expérimentale [Brussels] (ULB 257), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Università degli Studi di Perugia = University of Perugia (UNIPG), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Ospedale San Raffaele, University of Maryland School of Medicine, University of Maryland System, Service de neurologie [Amiens], CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Klinikum Ludwigshafen [Germany], Service of Neurology [CHUV, Lausanne, Switzerland], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Utah School of Medicine [Salt Lake City], Institute of Cardiovascular Research (ICR2UL), Royal Holloway [University of London] (RHUL), Ashford and St Peter's hospitals NHS foundation trust, Russian Academy of Sciences [Moscow] (RAS), Centre for Cognition and Decision Making [HSE, Moscow], Institut of Cognitive Neuroscience [HSE, Moscow] (ICN), Vysšaja škola èkonomiki = National Research University Higher School of Economics [Moscow] (HSE)-Vysšaja škola èkonomiki = National Research University Higher School of Economics [Moscow] (HSE), Zentrum für neurologische Gefäßdiagnostik - Center for Neurological Vascular Diagnostics [Munich, Germany], Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Department of Neurology [Erasmus MC, Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hospital Universitario Mutua de Terrassa, Vall d'Hebron University Hospital [Barcelona], Insitute of Neuroscience and Physiology, University of Gothenburg (GU), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], Schmieder Klinik [Heidelberg, Germany], Helmholtz Zentrum München = German Research Center for Environmental Health, Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University Hospital Rostock, Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie, Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Institut Régional du Cancer-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Brescia, Mayo Clinic [Jacksonville], Institute of Experimental Medicine - Institut für Experimentelle Medizin [Kiel, Germany] (IEM), Christian-Albrechts-Universität zu Kiel (CAU), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Centre d'Etude du Polymorphisme Humain (CEPH), Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, McGill University and Genome Quebec Innovation Centre, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Pharmacologie de la mort neuronale et de la plasticité cérébrale, IFR114-Université de Lille, Droit et Santé, Réseau International des Instituts Pasteur (RIIP), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, The CADISP study has been supported by INSERM, Lille 2 University, Institut Pasteur de Lille and Lille University Hospital and received funding from the European Regional Development Fund (FEDER funds) and Région Nord-Pas-de-Calais in the framework of Contrat de Projets Etat-Region 2007–2013 Région Nord-Pas-de-Calais (grant 09120030), Centre National de Génotypage, the Emil Aaltonen Foundation, the Paavo Ilmari Ahvenainen Foundation, the Helsinki University Central Hospital Research Fund, the Helsinki University Medical Foundation, the Päivikki and Sakari Sohlberg Foundation, the Aarne Koskelo Foundation, the Maire Taponen Foundation, the Aarne and Aili Turunen Foundation, the Lilly Foundation, the Alfred Kordelin Foundation, the Finnish Medical Foundation, the Orion Farmos Research Foundation, the Maud Kuistila Foundation, the Finnish Brain Foundation, the Biomedicum Helsinki Foundation, Projet Hospitalier de Recherche Clinique Régional, Fondation de France, Génopôle de Lille, Adrinord, the Basel Stroke Funds, the Käthe-Zingg-Schwichtenberg-Fonds of the Swiss Academy of Medical Sciences and the Swiss Heart Foundation.L.H.B., S.T.E. and P.A.L. were supported, in part, by a grant from the Swiss National Science Foundation (33CM30-124119). S.D. is supported by a Chair of Excellence from the French National Research Agency (ANR). S.D. and M.D. are supported by a grant from the Leducq Foundation. M.D. is supported by the Vascular Dementia Research Foundation. I.F.-C. is supported by the Miguel Servet programme (CP12/03298) from the Spanish Ministry of Health (Instituto de Salud Carlos III). G.K. is a member of the Deutsche Forschungsgemeinschaft Cluster of Excellence 'Inflammation at Interfaces'. P.S. is supported by a Department of Health (UK) senior fellowship. A.M.S. is supported by the American Heart Association/American Stroke Association National Clinical Research Program (AHA 3CRP14140001). V.T. is supported by Fonds Wetenschappelijk Onderzoek Flanders., CADISP Group, RIKEN Center for Integrative Medical Science, Università degli Studi di Brescia [Brescia], University of Virginia [Charlottesville], Service des Urgences Cérébro-Vasculaires [CHU Pitié-Salpêtrière]], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Laboratoire de Neurologie Expérimentale [ULB, Brussels, Belgium] (ULB 257), Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Università degli Studi di Perugia (UNIPG), Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), National Research University Higher School of Economics [Moscow] (HSE)-National Research University Higher School of Economics [Moscow] (HSE), Radboud university [Nijmegen], Helmholtz-Zentrum München (HZM), Westfälische Wilhelms-Universität Münster (WWU), The authors thank the staff and participants of all CADISP centers for their important contributions., Service des Urgences Cérébro-Vasculaires [CHU Pitié-Salpétriêre], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fondation Jean Dausset-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Erasmus MC other, Epidemiology, Debette, S, Kamatani, Y, Metso, T, Kloss, M, Chauhan, G, Engelter, S, Pezzini, A, Thijs, V, Markus, H, Dichgans, M, Wolf, C, Dittrich, R, Touzé, E, Southerland, A, Samson, Y, Abboud, S, Béjot, Y, Caso, V, Bersano, A, Gschwendtner, A, Sessa, M, Cole, J, Lamy, C, Medeiros, E, Beretta, S, Bonati, L, Grau, A, Michel, P, Majersik, J, Sharma, P, Kalashnikova, L, Nazarova, M, Dobrynina, L, Bartels, E, Guillon, B, Van Den Herik, E, Fernandez Cadenas, I, Jood, K, Nalls, M, De Leeuw, F, Jern, C, Cheng, Y, Werner, I, Metso, A, Lichy, C, Lyrer, P, Brandt, T, Boncoraglio, G, Wichmann, H, Gieger, C, Johnson, A, Böttcher, T, Castellano, M, Arveiler, D, Ikram, M, Breteler, M, Padovani, A, Meschia, J, Kuhlenbäumer, G, Rolfs, A, Worrall, B, Ringelstein, E, Zelenika, D, Tatlisumak, T, Lathrop, M, Leys, D, Amouyel, P, Dallongeville, J, Lemmens R, P, and Ferrarese, C
Subjects: Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Myocardial Infarction, Genome-wide association study, Carotid Artery, Internal, Dissection, Gastroenterology, epidemiology [Carotid Artery, Internal, Dissection], Brain Ischemia, 0302 clinical medicine, Migraine Disorder, Odds Ratio, Finland, Vertebral Artery Dissection, 0303 health sciences, education.field_of_study, epidemiology [Hypercholesterolemia], MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, Phactr-1 protein, human, MESH: Brain Ischemia, MESH: Follow-Up Studies, 3. Good health, MESH: Myocardial Infarction, Human, medicine.medical_specialty, Migraine Disorders, Hypercholesterolemia, MESH: Vertebral Artery Dissection, Lower risk, genetics [Brain Ischemia], Article, Follow-Up Studie, MESH: Carotid Artery, Internal, Dissection, 03 medical and health sciences, Genetic, SDG 3 - Good Health and Well-being, genetics [Carotid Artery, Internal, Dissection], Genetics, Genetic predisposition, epidemiology [Brain Ischemia], Humans, epidemiology [Vertebral Artery Dissection], Polymorphism, education, Alleles, MESH: Humans, genetics [Vertebral Artery Dissection], MESH: Adult, Odds ratio, Microfilament Protein, medicine.disease, Adult, Female, Follow-Up Studies, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Hypertension, Microfilament Proteins, Middle Aged, Obesity, Risk Factors, Polymorphism, Single Nucleotide, MESH: Genome-Wide Association Study, Carotid Artery, MESH: Female, 030217 neurology & neurosurgery, epidemiology [Finland], Cervical Artery, Vertebral artery dissection, epidemiology [Hypertension], MESH: Hypertension, MESH: Risk Factors, MESH: Obesity, Stroke, Allele, Dissection, MESH: Finland, MESH: Genetic Predisposition to Disease, MESH: Hypercholesterolemia, Single Nucleotide, MESH: Migraine Disorders, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], epidemiology [Myocardial Infarction], [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Population, MESH: Genetic Pleiotropy, physiology [Microfilament Proteins], Biology, MESH: Microfilament Proteins, Internal medicine, ddc:570, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, 030304 developmental biology, epidemiology [Obesity], Risk Factor, MESH: Alleles, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Internal, MESH: Odds Ratio, MESH: Male, epidemiology [Migraine Disorders], genetics [Microfilament Proteins]
Abstract: Item does not contain fulltext Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 x 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 x 10(-3); combined P = 1.00 x 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.
Published: 2015

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