40 results on '"Johan Ärnlöv"'
Search Results
2. Targeted multiplex proteomics for prediction of all-cause mortality during long-term follow-up in outpatients with peripheral arterial disease
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Philippe Wagner, Emma Skau, Johan Ärnlöv, Jerzy Leppert, Pär Hedberg, and Egil Henriksen
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Male ,Proteomics ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Population ,030204 cardiovascular system & hematology ,Risk Assessment ,Peripheral Arterial Disease ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Outpatients ,medicine ,Humans ,education ,Aged ,education.field_of_study ,Framingham Risk Score ,Receiver operating characteristic ,business.industry ,Proportional hazards model ,Blood proteins ,Confidence interval ,030104 developmental biology ,Cohort ,Female ,GDF15 ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Follow-Up Studies - Abstract
Background and aims Patients with peripheral arterial disease (PAD) are at high risk for fatal events. We aimed to investigate the ability among several serum proteins to predict all-cause mortality in outpatients with PAD. Methods Consecutive outpatients with carotid and/or lower extremity PAD were included in the discovery cohort (n = 436), and subjects with PAD from a population-based sample in the validation cohort (n = 129). Blood samples were analyzed for 81 proteins by a proximity extension assay. The proteins best predicting incident all-cause mortality were identified using L1-regularized Cox regression. The added value of the identified proteins to clinical risk markers was evaluated by Cox regression models and presented by the area under the receiver operator characteristics curves (AUC). Results In the discovery cohort (mean age 70 years; 59% men), 195 died (4.8 events per 100 person-years) during a 10.3 years median follow-up. The clinical risk markers generated an AUC of 0.70 (95% confidence interval [95%CI] 0.65–0.76). The two serum protein biomarkers with best prediction of all-cause mortality were growth differentiation factor 15 and tumor necrosis factor-related apoptosis-inducing ligand receptor 2. Adding these proteins to the clinical risk markers significantly improved prediction (p Conclusions In a large-sample targeted proteomics assay, we identified two proteins that improved risk prediction beyond the COPART risk score. The use of high-throughput proteomics assays may identify potential biomarkers for improved risk prediction in patients with PAD.
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- 2020
3. The plasma protein profile and cardiovascular risk differ between intima-media thickness of the common carotid artery and the bulb: A meta-analysis and a longitudinal evaluation
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Gunnar Engström, Johan Ärnlöv, Fabrizio Veglia, Marju Orho-Melander, Lars Lind, Anders Mälarstig, Bruna Gigante, Johan Sundström, Elena Tremoli, Jan Nilsson, Anders Hamsten, Yan Borné, Erik Ingelsson, Olle Melander, and Damiano Baldassarre
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Male ,0301 basic medicine ,medicine.medical_specialty ,Carotid Artery, Common ,medicine.drug_class ,030204 cardiovascular system & hematology ,Carotid Intima-Media Thickness ,03 medical and health sciences ,0302 clinical medicine ,Osteoprotegerin ,Internal medicine ,medicine.artery ,medicine ,Natriuretic peptide ,Humans ,Longitudinal Studies ,cardiovascular diseases ,Common carotid artery ,Myocardial infarction ,Stroke ,Aged ,Sweden ,business.industry ,Incidence ,Blood Proteins ,Middle Aged ,musculoskeletal system ,medicine.disease ,Blood proteins ,030104 developmental biology ,Intima-media thickness ,Cardiovascular Diseases ,Meta-analysis ,cardiovascular system ,Cardiology ,Intercellular Signaling Peptides and Proteins ,Female ,Cardiology and Cardiovascular Medicine ,business ,tissues - Abstract
Genetic loci associated with CHD show different relationships with intima-media thickness in the common carotid artery (IMT-CCA) and in the bulb (IMT-bulb). We evaluated if IMT-CCA and IMT-bulb differ also with respect to circulating protein profiles and risk of incident atherosclerotic disease.In three Swedish cohorts (MDC, IMPROVE, PIVUS, total n 7000), IMT-CCA and IMT-bulb were assessed by ultrasound at baseline, and 86 cardiovascular-related proteins were analyzed. In the PIVUS study only, IMT-CCA and IMT-bulb were investigated in relation to incident atherosclerotic disease over 10 years of follow-up.In a meta-analysis of the analysis performed separately in the cohorts, three proteins, matrix metalloproteinase-12 (MMP-12), hepatocyte growth factor (HGF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), were associated with IMT-CCA when adjusted for traditional cardiovascular risk factors. Five proteins were associated with IMT-bulb (MMP-12, growth/differentiation factor 15 (GDF-15), osteoprotegerin, growth hormone and renin). Following adjustment for cardiovascular risk factors, IMT-bulb was significantly more closely related to incident stroke or myocardial infarction (total number of cases, 111) than IMT-CCA in the PIVUS study (HR 1.51 for 1 SD, 95%CI 1.21-1.87, p 0.001 vs HR 1.17, 95%CI 0.93-1.47, p = 0.16). MMP-12 levels were related to this combined end-point (HR 1.30, 95%CI 1.08-1.56, p = 0.0061).Elevated levels of MMP-12 were associated with both IMT-CCA and IMT-bulb, but other proteins were significantly related to IMT in only one of these locations. The finding that IMT-bulb was more closely related to incident atherosclerotic disease than IMT-CCA emphasizes a difference between these measurements of IMT.
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- 2020
4. Endostatin predicts mortality in patients with acute dyspnea – A cohort study of patients seeking care in emergency departments
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Rafid Tofik, Olle Melander, Johan Ärnlöv, Thoralph Ruge, Axel C. Carlsson, G Leijonberg, Torgny Wessman, and Anders Larsson
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Male ,030213 general clinical medicine ,medicine.medical_specialty ,Clinical Biochemistry ,Population ,macromolecular substances ,030204 cardiovascular system & hematology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Epidemiology ,medicine ,Humans ,Hospital Mortality ,education ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,General Medicine ,Emergency department ,Middle Aged ,Triage ,Endostatins ,Dyspnea ,Acute Disease ,Cohort ,cardiovascular system ,Female ,Endostatin ,Emergency Service, Hospital ,business ,Body mass index ,Biomarkers ,Cohort study - Abstract
Background: Increased levels of circulating endostatin predicts cardiovascular morbidity and impaired kidney function in the general population. The utility of endostatin as a risk marker for mortality in the emergency department (ED) has not been reported. Aim: Our main aim was to study the association between plasma endostatin and 90-day mortality in an unselected cohort of patients admitted to the ED for acute dyspnea. Design Circulating endostatin was analyzed in plasma from 1710 adults and related to 90-day mortality in Cox proportional hazard models adjusted for age, sex, body mass index, oxygen saturation, respiratory rate, body temperature, C-reactive protein, lactate, creatinine and medical priority according to the Medical Emergency Triage and Treatment System–Adult score (METTS-A). The predictive value of endostatin for mortality was evaluated with receiver operating characteristic (ROC) analysis and compared with the clinical triage scoring system and age. Results: Each one standard deviation increment of endostatin was associated with a HR of 2.12 (95% CI 1.31–3.44 p < 0.01) for 90-day mortality after full adjustment. Levels of endostatin were significantly increased in the group of patients with highest METTS-A (p < 0.001). When tested for the outcome 90-day mortality, the area under the ROC curve (AUC) was 0.616 for METTS-A, 0.701 for endostatin, 0.708 for METTS -A and age and 0.738 for METTS-A, age and levels of endostatin. Conclusions: In an unselected cohort of patients admitted to the ED with acute dyspnea, endostatin had a string association to 90-day mortality and improved prediction of 90-day mortality in the ED beyond the clinical triage scoring system and age with 3%. (Less)
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- 2020
5. Cathepsin B and S as markers for cardiovascular risk and all-cause mortality in patients with stable coronary heart disease during 10 years: a CLARICOR trial sub-study
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Jørgen Hilden, Jonas Wuopio, Johan Ärnlöv, Janus Christian Jakobsen, Hans Jørn Kolmos, Erik Kjøller, Anders Larsson, Ahmad Sajadieh, Jens Kastrup, Carl Bring, Axel C. Carlsson, Christian Gluud, Gorm B. Jensen, and Per Winkel
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Male ,0301 basic medicine ,medicine.medical_specialty ,Proteases ,Denmark ,Ischemic heart disease ,Cardiovascular biomarkers ,Myocardial Infarction ,Coronary Disease ,030204 cardiovascular system & hematology ,Gastroenterology ,Cathepsin B ,Cathepsin ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Clarithromycin ,Internal medicine ,medicine ,Humans ,In patient ,Angina, Unstable ,Registries ,Mortality ,Aged ,Proportional Hazards Models ,Peripheral Vascular Diseases ,business.industry ,Middle Aged ,Atherosclerosis ,Cardiovascular risk ,Cathepsins ,Cardiovascular biomarker ,Coronary heart disease ,Cerebrovascular Disorders ,Treatment Outcome ,030104 developmental biology ,Cardiovascular Diseases ,Female ,Lysosomes ,Cardiology and Cardiovascular Medicine ,business ,All cause mortality ,Follow-Up Studies ,Glomerular Filtration Rate - Abstract
Background and aims: The lysosomal cysteine proteases cathepsin B and S have been implicated in the atherosclerotic process. The present paper investigates the association between serum levels of cathepsin B and S and cardiovascular events and mortality in patients with stable coronary heart disease. Methods: The CLARICOR trial is a randomised, placebo-controlled trial investigating the effect of clarithromycin versus placebo in patients with stable coronary heart disease. The outcome was time to either a cardiovascular event or all-cause mortality. The placebo group was used as discovery sample and the clarithromycin group as replication sample: n = 1998, n = 1979; mean age (years) 65, 65; 31%, 30% women; follow-up for 10 years; number of composite outcomes n = 1204, n = 1220; respectively. We used a pre-defined multivariable Cox regression model adjusting for inflammation, established cardiovascular risk factors, kidney function, and use of cardiovascular drugs. Results: Cathepsin B was associated with an increased risk of the composite outcome in both samples after multivariable adjustment (discovery: multivariable ratio (HR) per standard deviation increase 1.12, 95% confidence interval (CI) 1.05–1.19, p < 0.001, replication; HR 1.14, 95% CI 1.07–1.21, p < 0.001). There was no significant association between cathepsin S and the composite outcome in either the discovery or replication sample after multivariable adjustment (p>0.45). Secondary analyses suggest that cathepsin B was predominantly associated with mortality rather than specific cardiovascular events. Conclusions: Cathepsin B, but not serum cathepsin S, was associated with an increased risk of cardiovascular events in patients with stable coronary heart disease. The clinical implications of our findings remain to be established.
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- 2018
6. 'Concerns regarding the 'meta-analysis' by A. S. Bhagavathula and J. Rahmani'
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Christoph Nowak, Johan Ärnlöv, and Jonas Wuopio
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medicine.medical_specialty ,Nutrition and Dietetics ,Risk Factors ,business.industry ,Internal medicine ,Meta-analysis ,Atrial Fibrillation ,medicine ,Humans ,Critical Care and Intensive Care Medicine ,business - Published
- 2021
7. Association between Atherosclerotic Aortic Calcification-Associated Genetic Variation in HDAC9 with Mortality, Cardiovascular Disease and Kidney Disease
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Christoph Nowak, Douglas F. Dluzen, and Johan Ärnlöv
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medicine.medical_specialty ,business.industry ,medicine.disease ,Pulse pressure ,Blood pressure ,Diabetes mellitus ,Heart failure ,Internal medicine ,medicine ,Albuminuria ,Cardiology ,Myocardial infarction ,medicine.symptom ,business ,Stroke ,Kidney disease - Abstract
Importance: Histone deacetylase 9 (HDAC9) has recently been demonstrated as a key regulator of vascular smooth muscle cell (VSMC) phenotype and is associated with abdominal aortic calcification, myocardial infarction and ischemic stroke. It is uncertain whether HDAC9 is also implicated in other VSMC-driven diseases. Objective: To investigate associations between abdominal aortic calcification-associated genetic variation in HDAC9 and VSMC-associated phenotypes. Design: Prospective population study.Setting: UK Biobank.Participants: 335,146 European, non-related person aged 40-69 years (mean 57±8 years, 54% women). Main outcomes: Blood pressure, heart rate, hypertension, myocardial infarction, stroke, arterial aneurysm, heart failure, glomerular filtration rate, albuminuria, end-stage renal disease, all-cause and cardiovascular mortality, HbA1c, diabetes, serum lipids, body mass index, and smoking. Results: We used the aortic calcification-raising A-allele of rs57301765 in HDAC9 as a genetic instrumental variable to query the long-term effects of HDAC9 variation. At the Bonferroni significance level, rs57301765 was associated with systolic blood pressure (effect per added risk allele in standard deviation units, 0.022; 95% CI, 0.016-0.029, P=1.71×10-11), pulse pressure (0.035; 95% CI, 0.028-0.041, P=5.76×10-27), hypertension (odds ratio, OR, 1.04; 95% CI, 1.02-1.05, P=1.26×10-6), myocardial infarction (OR, 1.08; 95% CI, 1.04-1.12, P=1.72×10-5, driven by non-ST segment elevation myocardial infarction, OR, 1.11; 95% CI, 1.04-1.17, P=0.001), and ischemic stroke (OR, 1.14; 95% CI, 1.07-1.22, P=6.29×10-5). There was a suggestive protective association with kidney disease outcomes that, however, did not reach experiment-wise significance. Look-ups in public genome-wide association study results concur with our findings for cardiovascular outcomes. Conclusions and Relevance: The genetic results in our study lend further support for HDAC9 as a key determinant of VSMC-associated cardiovascular pathology and its potential as a therapeutic target for arterial stenotic and calcific disease.
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- 2020
8. Levels of soluble tumor necrosis factor receptor 1 and 2, gender, and risk of myocardial infarction in Northern Sweden
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Jan-Håkan Jansson, Toralph Ruge, Johan Ärnlöv, Anders Larsson, Axel C. Carlsson, and Stefan Söderberg
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Adult ,Male ,Myocardial Infarction ,Coronary Disease ,Inflammation ,030204 cardiovascular system & hematology ,medicine.disease_cause ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Risk Factors ,Odds Ratio ,medicine ,Humans ,Receptors, Tumor Necrosis Factor, Type II ,Prospective Studies ,030212 general & internal medicine ,Myocardial infarction ,Receptor ,Sweden ,Anthropometry ,business.industry ,Middle Aged ,medicine.disease ,Soluble Tumor Necrosis Factor Receptor ,C-Reactive Protein ,Receptors, Tumor Necrosis Factor, Type I ,Case-Control Studies ,Cancer research ,Female ,Tumor necrosis factor alpha ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,All cause mortality ,Oxidative stress - Abstract
Soluble receptors for tumor necrosis factor alpha (sTNFR1 and sTNFR2) have been associated with cardiovascular diseases, and some evidence points towards a difference in associated risk between men and women. We aimed to study the association between sTNFR1 and sTNFR2 and incident myocardial infarctions (MI) and to explore the influence of established cardiovascular risk factors in men and women.We conducted a nested case control study in three large Swedish cohorts, including 533 myocardial infarction cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated.An association between circulating sTNFR1 and sTNFR2 and an increased risk for MI was found when comparing cases and controls. The odds ratios were significant after adjustment for established cardiovascular risk factors and C-reactive protein in women (OR 1.44, 95% CI 1.08-1.93 for TNFR1, and 1.61, 95% CI 1.11-2.34 for TNFR2), but was abolished in men. Women with a combination of elevated CRP and values in the upper quartile of TNFR1 or TNFR2 had a 5-fold higher risk of myocardial infarction versus those with normal CRP and values in the lower three quartiles of TNFR1 or TNFR2.As the risk estimates for TNFR1 and TNFR2 were higher and remained significant after adjustments for established cardiovascular risk factors in women but not in men, a potential role for TNFR1 and TNFR2 in identifying women with a higher MI risk is possible. The future clinical role of TNFR1 and TNFR2 in combination with CRP to identify high risk patients for coronary heart disease has yet to be determined.
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- 2018
9. Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system
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Karin M. Henriksson, Alessandro Gasparini, Morgan E. Grams, Josef Coresh, Erik Nilsson, Juan Jesus Carrero, Hairong Xu, and Johan Ärnlöv
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Adult ,Male ,medicine.medical_specialty ,Hyperkalemia ,Renal function ,Hypokalemia ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Cumulative incidence ,030212 general & internal medicine ,Myocardial infarction ,Intensive care medicine ,Thiazide ,Aged ,Retrospective Studies ,Sweden ,Creatinine ,business.industry ,Incidence ,Incidence (epidemiology) ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,chemistry ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Delivery of Health Care ,medicine.drug - Abstract
Background Hypo- and hyperkalemia in clinical settings are insufficiently characterized and large-scale data from Europe lacking. We studied incidence and determinants of these abnormalities in a large Swedish healthcare system. Methods Observational study from the Stockholm CREAtinine Measurements project, including adult individuals from Stockholm accessing healthcare in 2009 (n=364,955). Over 3-years, we estimated the incidence of hypokalemia, defined as potassium 5mmol/L, and moderate/severe hyperkalemia, defined as potassium>5.5mmol/L. Kidney function was assessed by estimated glomerular filtration rate (eGFR). Results Of 364,955 participants, 69.4% had 1–2 potassium tests, 16.7% had 3–4 tests and the remaining 13.9% had >4potassiumtests/year. Hypokalemia occurred in 49,662 (13.6%) individuals, with 33% recurrence. Hyperkalemia occurred in 25,461 (7%) individuals, with 35.7% recurrence. Moderate/severe hyperkalemia occurred in 9059 (2.5%) with 28% recurrence. The frequency of potassium testing was an important determinant of dyskalemia risk. The incidence proportion of hyperkalemia was higher in the presence of diabetes, lower eGFR, myocardial infarction, heart failure (HF), or use of renin angiotensin-aldosterone system inhibitors (RAASi). In adjusted analyses, women and use of loop/thiazide diuretics were associated with lower hyperkalemia risk. Older age, lower eGFR, diabetes, HF and use of RAASi were associated with higher hyperkalemia risk. On the other hand, women, younger age, higher eGFR and baseline use of diuretics were associated with higher hypokalemia risk. Conclusion Hypo- and hyperkalemia are common in healthcare. Optimal RAASi and diuretics use and careful potassium monitoring in the presence of certain comorbidities, especially lower eGFR, is advocated.
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- 2017
10. Effects of cigarette smoking on cardiovascular-related protein profiles in two community-based cohort studies
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Per Svensson, Biying Huang, Erik Ingelsson, Johan Ärnlöv, Lars Lind, and Johan Sundström
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Male ,0301 basic medicine ,medicine.medical_specialty ,Longitudinal study ,Proteome ,030204 cardiovascular system & hematology ,Polymerase Chain Reaction ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Internal medicine ,Epidemiology ,Ethnicity ,medicine ,Humans ,Longitudinal Studies ,Prospective Studies ,Endothelial dysfunction ,Prospective cohort study ,Aged ,Sweden ,COPD ,biology ,business.industry ,Gene Expression Profiling ,Smoking ,C-reactive protein ,Blood Proteins ,Atherosclerosis ,medicine.disease ,Former Smoker ,030104 developmental biology ,Cardiovascular Diseases ,Immunology ,Linear Models ,biology.protein ,Female ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Cohort study - Abstract
Cardiovascular diseases account for the largest fraction of smoking-induced deaths. Studies of smoking in relation to cardiovascular-related protein markers can provide novel insights into the biological effects of smoking. We investigated the associations between cigarette smoking and 80 protein markers known to be related to cardiovascular diseases in two community-based cohorts, the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 969, 50% women, all aged 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 717, all men aged 77 years).Smoking status was self-reported and defined as current smoker, former smoker or never-smoker. Levels of the 80 proteins were measured using the proximity extension assay, a novel PCR-based proteomics technique.We found 30 proteins to be significantly associated with current cigarette smoking in PIVUS (FDR5%); and ten were replicated in ULSAM (p 0.05). Matrix metalloproteinase-12 (MMP-12), growth/differentiation factor 15 (GDF-15), urokinase plasminogen activator surface receptor (uPAR), TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), lectin-like oxidized LDL receptor 1 (LOX-1), hepatocyte growth factor (HGF), matrix metalloproteinase-10 (MMP-10) and matrix metalloproteinase-1 (MMP-1) were positively associated, while endothelial cell-specific molecule 1 (ESM-1) and interleukin-27 subunit alpha (IL27-A) showed inverse associations. All of them remained significant in a subset of individuals without manifest cardiovascular disease.The findings of the present study suggest that cigarette smoking may interfere with several essential parts of the atherosclerosis process, as evidenced by associations with protein markers representing endothelial dysfunction, inflammation, neointimal formation, foam cell formation and plaque instability.
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- 2016
11. Cystatin C and Cardiovascular Disease
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Heribert Schunkert, Wolfgang Koenig, Jessica van Setten, Meena Kumari, Johan Ärnlöv, J. Wouter Jukema, Vinicius Tragante, Alanna C. Morrison, Bradford B. Worrall, Brendan J. Keating, Alexander Teumer, Vilmantas Giedraitis, Tom Wilsgaard, Nilesh J. Samani, Barbara Thorand, Patricia B. Munroe, Rainer Malik, Melanie Waldenberger, Christopher P. Nelson, Sebastian E. Baumeister, Aroon D. Hingorani, Stéphanie Debette, Tove Fall, Patrik K. E. Magnusson, Nora Franceschini, Anders Larsson, Andrew P. Morris, Folkert W. Asselbergs, Maryam Kavousi, Oscar H. Franco, Jeanette Erdmann, Jonathan Marchini, Mika Kivimäki, Ivana Išgum, Fotios Drenos, N. Charlotte Onland-Moret, Bjørn Odvar Eriksen, Aicha Soumare, Christopher J. O'Donnell, Ingrid Toft, Paul I.W. de Bakker, Johannes Arpegård, Jacqueline de Graaf, Abbas Dehghan, Delilah Zabaneh, Michael V. Holmes, Yvonne T. van der Schouw, Alexander P. Reiner, André G. Uitterlinden, Christa Meisinger, Janine F. Felix, Erik Ingelsson, Lars Lind, Martin Dichgans, Marcus Dörr, Albert Hofman, Sanaz Sedaghat, Lambertus A. Kiemeney, Joshua C. Bis, Jens Baumert, Tessel E. Galesloot, Hester M. den Ruijter, Gerard Pasterkamp, Annette Peters, Naveed Sattar, Nancy L. Pedersen, Pim van der Harst, Stella Trompet, Per Svensson, Riyaz S. Patel, Philippe Amouyel, and Sander W. van der Laan
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Pathology ,Population ,Renal function ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Mendelian randomization ,medicine ,education ,education.field_of_study ,biology ,business.industry ,Confounding ,Mendelian Randomization Analysis ,3. Good health ,Minor allele frequency ,030104 developmental biology ,Cystatin C ,biology.protein ,Cystatin ,Cardiology and Cardiovascular Medicine ,business - Abstract
BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license.
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- 2016
12. Excess protein intake relative to fiber and cardiovascular events in elderly men with chronic kidney disease
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Gloria Lissete Sencion, Tommy Cederholm, Per Sjögren, Bengt Lindholm, Megan Rossi, Johan Ärnlöv, Katrina L. Campbell, Hong Xu, Ulf Risérus, and Juan Jesus Carrero
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Dietary Fiber ,Male ,Time Factors ,Endocrinology, Diabetes and Metabolism ,030232 urology & nephrology ,Medicine (miscellaneous) ,Recommended Dietary Allowances ,Gastroenterology ,0302 clinical medicine ,Risk Factors ,Longitudinal Studies ,Prospective Studies ,030212 general & internal medicine ,Prospective cohort study ,education.field_of_study ,Nutrition and Dietetics ,biology ,Incidence ,Incidence (epidemiology) ,Hazard ratio ,CVD ,Diet Records ,protein-fiber intake ratio ,C-Reactive Protein ,Cardiovascular Diseases ,Dietary Proteins ,Cardiology and Cardiovascular Medicine ,medicine.medical_specialty ,Population ,Nutritional Status ,Risk Assessment ,03 medical and health sciences ,Internal medicine ,CKD ,medicine ,Humans ,Renal Insufficiency, Chronic ,Risk factor ,education ,Geriatric Assessment ,Aged ,Proportional Hazards Models ,Sweden ,Proportional hazards model ,business.industry ,C-reactive protein ,Feeding Behavior ,fiber intake ,Protective Factors ,medicine.disease ,protein intake ,Nutrition Assessment ,Endocrinology ,biology.protein ,business ,Biomarkers ,Kidney disease - Abstract
Background and Aims The elevated cardiovascular (CVD) risk observed in chronic kidney disease (CKD) may be partially alleviated through diet. While protein intake may link to CVD events in this patient population, dietary fiber has shown cardioprotective associations. Nutrients are not consumed in isolation; we hypothesize that CVD events in CKD may be associated with dietary patterns aligned with an excess of dietary protein relative to fiber. Methods and Results Prospective cohort study from the Uppsala Longitudinal Study of Adult Men. Included were 390 elderly men aged 70–71 years with CKD and without clinical history of CVD. Protein and fiber intake, as well as its ratio, were calculated from 7-day dietary records. Cardiovascular events were registered prospectively during a median follow-up of 9.1 (inter-quartile range, 4.5-10.7) years. The median dietary intake of protein and fiber was 66.7 (60.7-71.1) and 16.6 (14.5-19.1) grams/day respectively and the protein-to-fiber intake ratio was 4.0 (3.5-4.7). Protein-to-fiber intake ratio was directly associated with serum C-reactive protein levels. During follow-up, 164 first-time CVD events occurred (incidence rate 54.5/1,000 per year). Protein-fiber intake ratio was an independent risk factor for CVD events [adjusted hazard ratio, HR per standard deviation increase (95% confidence interval, CI) 1.33 (1.08, 1.64)]. Although in opposing directions, dietary protein [1.18 (0.97, 1.44)], dietary fiber alone [0.81 (0.64, 1.02)], were not significantly associated with CVD events. Conclusions An excess of dietary protein relative to fiber intake was associated with the incidence of cardiovascular events in a homogeneous population of older men with CKD.
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- 2016
13. A Multi-Cohort Metabolomics Analysis Discloses Sphingomyelin (32:1) Levels to be Inversely Related to Incident Ischemic Stroke
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Jessica E. Prenni, Johan Ärnlöv, Patrik K. E. Magnusson, Nancy L. Pedersen, Agneta Siegbahn, Corey D. Broeckling, Samira Salihovic, Andrea Ganna, Tove Fall, Lars Lind, Erik Ingelsson, and Johan Sundström
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Male ,Oncology ,medicine.medical_specialty ,Longitudinal study ,Time Factors ,medicine.medical_treatment ,Population ,Brain Ischemia ,03 medical and health sciences ,0302 clinical medicine ,Tandem Mass Spectrometry ,Internal medicine ,Epidemiology ,Fibrinolysis ,medicine ,Humans ,Metabolomics ,Risk factor ,education ,Stroke ,Aged ,Subclinical infection ,Sweden ,education.field_of_study ,business.industry ,Incidence ,Rehabilitation ,Middle Aged ,Prognosis ,medicine.disease ,Sphingomyelins ,Cohort ,Female ,Surgery ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,030217 neurology & neurosurgery ,Chromatography, Liquid - Abstract
To search for novel pathophysiological pathways related to ischemic stroke using a metabolomics approach.We identified 204 metabolites in plasma by liquid chromatography mass spectrometry in 3 independent population-based samples (TwinGene, Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) and Uppsala Longitudinal Study of Adult Men). TwinGene was used for discovery and the other 2 samples were meta-analyzed as replication. In PIVUS, traditional cardiovascular (CV) risk factors, multiple markers of subclinical CV disease, markers of coagulation/fibrinolysis were measured and analyzed in relation to top metabolites.In TwinGene (177 incident cases, median follow-up 4.3 years), levels of 28 metabolites were associated with incident ischemic stroke at a false discover rate (FDR) of 5%. In the replication (together 194 incident cases, follow-up 10 and 12 years, respectively), only sphingomyelin (32:1) was significantly associated (HR .69 per SD change, 95% CI .57-0.83, P value = .00014; FDR5%) when adjusted for systolic blood pressure, diabetes, smoking, low density lipoportein (LDL)- and high density lipoprotein (HDL), body mass index (BMI) and atrial fibrillation. In PIVUS, sphingomyelin (32:1) levels were significantly related to both LDL- and HDL-cholesterol in a positive fashion, and to serum triglycerides, BMI and diabetes in a negative fashion. Furthermore, sphingomyelin (32:1) levels were related to vasodilation in the forearm resistance vessels, and inversely to leukocyte count (P.0069 and .0026, respectively).An inverse relationship between sphingomyelin (32:1) and incident ischemic stroke was identified, replicated, and characterized. A possible protective role for sphingomyelins in stroke development has to be further investigated in additional experimental and clinical studies.
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- 2020
14. Urinary KIM-1, but not urinary cystatin C, should be corrected for urinary creatinine
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Johanna Helmersson-Karlqvist, Axel C. Carlsson, Lars Lind, Johan Ärnlöv, and Anders Larsson
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Male ,medicine.medical_specialty ,Urinary system ,Clinical Biochemistry ,Population ,030232 urology & nephrology ,Urology ,Renal function ,Urine ,030204 cardiovascular system & hematology ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Humans ,Medicine ,Hepatitis A Virus Cellular Receptor 1 ,Cystatin C ,education ,Aged ,education.field_of_study ,Creatinine ,biology ,business.industry ,Confounding ,Acute kidney injury ,General Medicine ,medicine.disease ,chemistry ,biology.protein ,Female ,business - Abstract
The interest for tubular damage markers such as urinary cystatin C (U-CystC) and kidney injury molecule-1 (U-KIM-1) grows, especially for the diagnosis of acute kidney injury. The trend to measure proteins in spot urine samples instead of 24-h urine collections calls for adjustment of urine dilution with urinary creatinine (UCr). However, it is not known whether UCr adjustment provides a more true value of basal U-CystC and U-KIM-1 levels than absolute values.This study examines the rationale for UCr correction for U-CystC and U-KIM-1 by exploring the linear relations between U-CystC and U-KIM-1 and UCr, respectively, and the biological day to day variation of absolute concentrations and UCr adjusted values of the two biomarkers.Both U-CystC and U-KIM-1 concentrations correlated positively with UCr (R=0.37, P0.001 and R=0.62, P0.001, respectively) in 378 participants in a community cohort, which indicated a rationale for adjustment with UCr. However, U-CystC/Cr ratio associated negatively with UCr (R=- 0.31, P0.001), which could indicate a certain amount of 'over-adjustment'. Morning urine collected for 10 consecutive days from 13 healthy volunteers showed a biological day to day variation of 82% for U-CystC, 75% for U-cystC/Cr ratio, 70% for U-KIM-1 and 46% for U-KIM-1/Cr ratio.This study supports the use of U-KIM-1/Cr ratio in clinical population studies. Data supporting the use of U-CysC/U-Cr ratio were less convincing and the possible confounding of UCr has to be acknowledged in clinical settings.
- Published
- 2016
15. Use of a proximity extension assay proteomics chip to discover new biomarkers for human atherosclerosis
- Author
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Johan Ärnlöv, Bertil Lindahl, Lars Lind, Johan Sundström, Agneta Siegbahn, and Erik Ingelsson
- Subjects
Carotid Artery Diseases ,Male ,Proteomics ,Oncology ,medicine.medical_specialty ,Pathology ,Population ,Protein Array Analysis ,Carotid Intima-Media Thickness ,chemistry.chemical_compound ,High-density lipoprotein ,Osteoprotegerin ,Predictive Value of Tests ,Risk Factors ,medicine.artery ,Internal medicine ,Odds Ratio ,Prevalence ,medicine ,Humans ,Prospective Studies ,Common carotid artery ,education ,Prospective cohort study ,Aged ,Sweden ,education.field_of_study ,business.industry ,Blood Proteins ,Odds ratio ,Plaque, Atherosclerotic ,Carotid Arteries ,Logistic Models ,chemistry ,Linear Models ,Female ,GDF15 ,Internal carotid artery ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers - Abstract
Background and aims We used a proteomics array to simultaneously measure multiple proteins that have been suggested to be associated with atherosclerosis and related them to plaque prevalence in carotid arteries in a human population-based study. Methods In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS; n = 931, 50% women, all aged 70 years), the number of carotid arteries with plaques was recorded by ultrasound. Levels of 82 proteins were assessed in plasma by a proximity extension assay (Proseek Multiplex CVD, Olink Bioscience, Uppsala, Sweden) and related to carotid measures in a regression framework. Results Following adjustment for multiple testing with Bonferroni correction, seven of the proteins were significantly related to the number of carotid arteries affected by plaques in sex-adjusted models (osteoprotegrin, T-cell immunoglobulin and mucin domain (TIM)-1, growth/differentiation factor 15 (GDF-15), matrix metalloprotease-12 (MMP-12), renin, tumor necrosis factor ligand superfamily member 14 (TNFSF14) and growth hormone). Of these, renin (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.13–1.49 per standard deviation increase), growth hormone (OR, 1.24; 95% CI, 1.08–1.43), osteoprotegerin (OR, 1.22; 95% CI, 1.05–1.43) and TNFSF14 (OR, 1.17; 95% CI, 1.01–1.35) were related to plaque prevalence independently of each other and traditional cardiovascular risk factors. Conclusion A novel targeted proteomics approach using the proximity extension technique discovered several new associations of candidate proteins with carotid artery plaque prevalence in a large human sample.
- Published
- 2015
16. A Proinflammatory Diet Is Associated with Systemic Inflammation and Reduced Kidney Function in Elderly Adults
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Tanushree Banerjee, Per Sjögren, Hong Xu, Lars Lind, Ulf Risérus, Juan Jesus Carrero, Johan Ärnlöv, Tommy Cederholm, and Bengt Lindholm
- Subjects
Male ,medicine.medical_specialty ,Medicine (miscellaneous) ,Renal function ,Inflammation ,Systemic inflammation ,White People ,Proinflammatory cytokine ,chemistry.chemical_compound ,Risk Factors ,Internal medicine ,medicine ,Humans ,Longitudinal Studies ,Prospective Studies ,Cystatin C ,Aged ,Sweden ,Creatinine ,Kidney ,Nutrition and Dietetics ,biology ,urogenital system ,business.industry ,C-reactive protein ,food and beverages ,Diet ,C-Reactive Protein ,Cross-Sectional Studies ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Multivariate Analysis ,Linear Models ,biology.protein ,Female ,Kidney Diseases ,medicine.symptom ,business ,Glomerular Filtration Rate - Abstract
Diet can affect kidney health through its effects on inflammation.We tested whether the Adapted Dietary Inflammatory Index (ADII) is associated with kidney function and whether effects of diet on chronic low-grade inflammation explain this association.This was an observational analysis in 1942 elderly community-dwelling participants aged 70-71 y from 2 independent cohorts: the Uppsala Longitudinal Study of Adult Men (n = 1097 men) and the Prospective Investigation of Vasculature in Uppsala Seniors (n = 845 men and women). The ADII was calculated from 7-d food records, combining putatively proinflammatory and anti-inflammatory effects of nutrients, vitamins, and trace elements. The ADII was validated against serum C-reactive protein (CRP) concentrations. The estimated glomerular filtration rate (eGFR) was assessed from serum cystatin C (cys) and creatinine (crea). Associations between the ADII and eGFR were investigated, and CRP was considered to be a mediator.In adjusted analysis, a 1-SD higher ADII was associated with higher CRP (β: 6%; 95% CI: 1%, 10%; P = 0.01) and lower eGFR [Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)cys: -2.1%; 95% CI: -3.2%, -1.1%; CKD-EPIcys+crea: -1.8%; 95% CI: -2.7%, -0.9%; both P0.001]. CRP was also inversely associated with eGFR. Mediation analyses showed that of the total effect of the ADII on kidney function, 15% and 17% (for CKD-EPIcys+crea and CKD-EPIcys equations, respectively) were explained/mediated by serum CRP. Findings were similar when each cohort was analyzed separately.A proinflammatory diet was associated with systemic inflammation as well as with reduced kidney function in a combined analysis of 2 community-based cohorts of elderly individuals. Our results also suggest systemic inflammation to be one potential pathway through which this dietary pattern is linked to kidney function.
- Published
- 2015
17. Parathyroid hormone and calcium are independently associated with subclinical vascular disease in a community-based cohort
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Håkan Melhus, Anders Larsson, Johan Ärnlöv, Tommy Ahlström, Emil Hagström, Per Hellman, and Lars Lind
- Subjects
Male ,medicine.medical_specialty ,Population ,Parathyroid hormone ,Vascular Stiffness ,Risk Factors ,Internal medicine ,medicine ,Humans ,Arterial Pressure ,Prospective Studies ,Vascular Diseases ,education ,Aged ,Sweden ,education.field_of_study ,business.industry ,Vascular disease ,Age Factors ,Stroke volume ,medicine.disease ,Pulse pressure ,Endocrinology ,Blood pressure ,Parathyroid Hormone ,Asymptomatic Diseases ,Multivariate Analysis ,Linear Models ,Arterial stiffness ,Cardiology ,Calcium ,Female ,Secondary hyperparathyroidism ,Endothelium, Vascular ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers - Abstract
Diseases with abnormal levels of parathyroid hormone (PTH) and calcium, such as primary and secondary hyperparathyroidism, are associated with an increased risk of cardiovascular morbidity and mortality. However, there is paucity on the association between calcium, PTH and abnormalities in the vascular system in the general population.In the PIVUS study (Prospective Investigation of the Vasculature in Uppsala Seniors), a community based cohort of 70-year old men and women (n = 1016), the associations between s-calcium, p-PTH and endothelial function, arterial stiffness and blood pressures were investigated, adjusting for cardiovascular risk factors and mineral metabolism.In multivariable linear regression models 1 SD increase in calcium was associated with 1.1 units decrease in the stroke volume/pulse pressure ratio and 0.06 decrease in common carotid artery distensibility (p 0.001) indicative of increased arterial stiffness. Further, calcium was associated with increasing calculated central pulse pressure with 1.3 mmHg elevation per 1 SD increase in calcium (p 0.05). 1 SD increase in PTH was associated with 1.9 and 1.0 mmHg increase in intra-arterially measured brachial artery systolic and diastolic blood pressures, respectively (p 0.01), as well as 1.6 and 0.9 mmHg increase in calculated central systolic and diastolic blood pressures (p 0.05). PTH was not associated with arterial stiffness, endothelial function or pulse pressure.In a large community-based sample of elderly, calcium was independently associated with increased arterial stiffness, and PTH independently to intra-arterial peripheral and calculated central blood pressures. The findings indicate a possible link between the vasculature and mineral metabolism.
- Published
- 2015
18. Estimated Dietary Acid Load Is Not Associated with Blood Pressure or Hypertension Incidence in Men Who Are Approximately 70 Years Old
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Xiaoyan Huang, Per Sjögren, Ulf Risérus, Bengt Lindholm, Desiree Luis, Juan Jesus Carrero, Johan Ärnlöv, and Tommy Cederholm
- Subjects
Male ,medicine.medical_specialty ,Ambulatory blood pressure ,Diastole ,Medicine (miscellaneous) ,Renal function ,Blood Pressure ,Kidney ,Internal medicine ,Humans ,Medicine ,Longitudinal Studies ,Micronutrients ,Renal Insufficiency, Chronic ,Aged ,Sweden ,Nutrition and Dietetics ,business.industry ,Incidence ,Incidence (epidemiology) ,Metabolic acidosis ,Blood Pressure Monitoring, Ambulatory ,medicine.disease ,Diet ,Cross-Sectional Studies ,Nutrition Assessment ,Blood pressure ,Endocrinology ,medicine.anatomical_structure ,Hypertension ,Multivariate Analysis ,Linear Models ,Cardiology ,Acidosis ,Energy Intake ,business ,Acids ,Kidney disease - Abstract
Background: Dietary acid load affects acid-base homeostasis, which may be associated with blood pressure (BP). Previous research on dietary acid load and BP in the community has provided conflicting results, which may be confounded by underlying kidney function with inability to eliminate acid excess. Objective: The objective of this study was to determine whether dietary acid load is associated with blood pressure or the incidence of hypertension in older men taking into account each individual's kidney function. Methods: We included 673 men aged 70-71 y and not receiving antihypertensive medication from the Uppsala Longitudinal Study of Adult Men. Of those, 378 men were re-examined after 7 y. Dietary acid load was estimated at baseline by potential renal acid load (PRAL) and net endogenous acid production (NEAP), based on nutrient intake assessed by 7-d food records at baseline. Ambulatory blood pressure monitoring (ABPM) was performed at both visits. Cystatin C-estimated kidney function allowed identification of underlying chronic kidney disease. Results: Median estimated PRAL and NEAP were 3.3 and 40.7 mEq/d, respectively. In cross-section, PRAL was in general not associated with ABPM measurements (all P > 0.05, except for the 24-h diastolic BP). During follow-up, PRAL did not predict ABPM changes (all P > 0.05). When individuals with baseline hypertension (ABPM >= 130/80 mm Hg) or nondippers (with nighttime-to-daytime systolic BP ratio > 0.9) were excluded, PRAL was not a predictor of incident cases (P > 0.30). Kidney function did not modify these null relations. Similar findings were obtained with the use of NEAP as the exposure. Conclusion: Our analyses linking estimated dietary acid load with BP outcome measurements both cross-sectionally and after 7 y in community-based older Swedish men of similar age did not reveal an association between dietary acid load and BP.
- Published
- 2015
19. Relation between Cardiovascular Disease Risk Markers and Brain Infarcts Detected by Magnetic Resonance Imaging in an Elderly Population
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Per Venge, Lars Johansson, Lars Berglund, Lars Lind, Håkan Ahlström, Johan Ärnlöv, Ruta Nylander, Bertil Lindahl, Elna-Marie Larsson, Johan Wikström, and Anders Larsson
- Subjects
Brain Infarction ,Male ,medicine.medical_specialty ,Pathology ,medicine.drug_class ,Population ,Blood Pressure ,Risk Factors ,Internal medicine ,Troponin I ,medicine ,Natriuretic peptide ,Humans ,cardiovascular diseases ,education ,Stroke ,Aged ,education.field_of_study ,medicine.diagnostic_test ,biology ,business.industry ,Rehabilitation ,Brain ,Magnetic resonance imaging ,Odds ratio ,medicine.disease ,Magnetic Resonance Imaging ,Confidence interval ,Cystatin C ,Cardiovascular Diseases ,Cardiology ,biology.protein ,Female ,Surgery ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers - Abstract
Background: Established cardiovascular risk markers, such as hypertension, are associated with increased risk of brain infarcts. The newer markers N-terminal pro-brain natriuretic peptide, troponin I, C-reactive protein, and cystatin C may affect the risk of cardiovascular events and potentially, thereby, also stroke. We investigated the association between established and new risk markers for cardiovascular disease and brain infarcts detected by magnetic resonance imaging (MRI) at age 75. Methods: Four hundred six randomly selected subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors study were examined with MRI of the brain at age 75. Blood samples, measurements, and dedicated questionnairesatage70wereusedforanalysisofriskmarkers.Ahistoryofdiseaseshadbeen obtained at age 70 and 75. MRI was evaluated regarding lacunar and cortical infarcts. Univariate associations between outcomes and risk markers were assessed with logistic regression models. Results: One or more infarcts were seen in 23% of the subjects (20% had only lacunar infarcts, 1% had only cortical infarcts, and 2% had both). Hypertension (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.4, 4.7) and obesity (OR 1.3; CI 1.0, 1.8) were significantly associated with increased risk of brain infarction. The newer risk markers were not significantly associated with the brain infarcts. Conclusions: The new markers were not associated with the predominantly lacunar infarcts in our 75-year-old population, why troponin I and NT-proBNP may be associated mainly with cardioembolic infarcts as shown
- Published
- 2015
20. Validation of insulin sensitivity surrogate indices and prediction of clinical outcomes in individuals with and without impaired renal function
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Abdul Rashid Qureshi, Johan Ärnlöv, Juan Jesus Carrero, Peter Stenvinkel, Ting Jia, Hong Xu, Tommy Cederholm, Bengt Lindholm, Xiaoyan Huang, and Ulf Risérus
- Subjects
medicine.medical_specialty ,Glucose tolerance test ,endocrine system diseases ,medicine.diagnostic_test ,business.industry ,nutritional and metabolic diseases ,Insulin sensitivity ,Renal function ,Glucose clamp technique ,medicine.disease ,humanities ,Impaired renal function ,Insulin resistance ,Endocrinology ,Nephrology ,Internal medicine ,medicine ,Cardiology ,business ,hormones, hormone substitutes, and hormone antagonists ,Kidney disease ,Cardiovascular mortality - Abstract
As chronic kidney disease (CKD) progresses with abnormalities in glucose and insulin metabolism, commonly used insulin sensitivity indices (ISIs) may not be applicable in individuals with CKD. Here we sought to validate surrogate ISIs against the glucose disposal rate by the gold-standard hyperinsulinemic euglycemic glucose clamp (HEGC) technique in 1074 elderly men of similar age (70 years) of whom 495 had and 579 did not have CKD (estimated glomerular filtration rate (eGFR) under 60ml/min per 1.73m 2 (median eGFR of 46ml/min per 1.73m 2 )). All ISIs provided satisfactory (weighted κ over 0.6) estimates of the glucose disposal rate in patients with CKD. ISIs derived from oral glucose tolerance tests (OGTTs) agreed better with HEGC than those from fasting samples (higher predictive accuracy). Regardless of CKD strata, all ISIs allowed satisfactory clinical discrimination between the presence and absence of insulin resistance (glucose disposal rate under 4mg/kg/min). We also assessed the ability of both HEGC and ISIs to predict all-cause and cardiovascular mortality during a 10-year follow-up. Neither HEGC nor ISIs independently predicted mortality. Adjustment for renal function did not materially change these associations. Thus, ISIs can be applied in individuals with moderately impaired renal function for diagnostic purposes. For research matters, OGTT-derived ISIs may be preferred. Our data do not support the hypothesis of kidney function mediating insulin sensitivity (IS)–associated outcomes nor a role for IS as a predictor of mortality.
- Published
- 2014
21. Increased urinary cystatin C indicated higher risk of cardiovascular death in a community cohort
- Author
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Johanna Helmersson-Karlqvist, Johan Härmä, Johan Ärnlöv, Axel C. Carlsson, and Anders Larsson
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,Urinary system ,Risk Assessment ,Gastroenterology ,Cohort Studies ,chemistry.chemical_compound ,Residence Characteristics ,Risk Factors ,Internal medicine ,Epidemiology ,medicine ,Humans ,Cystatin C ,Aged ,Creatinine ,biology ,urogenital system ,business.industry ,Hazard ratio ,Klinisk medicin ,medicine.disease ,Endocrinology ,chemistry ,Cardiovascular Diseases ,Cohort ,biology.protein ,Biomarker (medicine) ,Clinical Medicine ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Follow-Up Studies ,Kidney disease - Abstract
OBJECTIVES: Urinary cystatin C (u-CysC) is a new biomarker for acute tubular kidney dysfunction and may also indicate chronic tubular dysfunction. Chronic kidney disease is an important cardiovascular risk factor, however it is not known if u-CysC is a risk marker for cardiovascular death. METHODS: The association between u-CysC and cardiovascular mortality was investigated in a Swedish community-based cohort of 604 men aged 78 years. During follow-up (mean 6.7 years), 203 participants died, of which 90 due to cardiovascular causes. RESULTS: High u-CysC (>0.029 mg/mmol Cr) was associated with a more than 2-fold risk of cardiovascular death (multivariable hazard ratio for quintile 5 vs. 1: 2.5, 95% CI 1.2-5.2, P 0.029 mg/mmol Cr) combined had a significantly higher cardiovascular mortality risk compared to participants with one or two of these biomarkers normal (hazard ratio 15, 95% CI: 6.7-36, P
- Published
- 2014
22. Intake and serum concentrations of α-tocopherol in relation to fractures in elderly women and men: 2 cohort studies
- Author
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Karl Michaëlsson, Håkan Melhus, Liisa Byberg, Alicja Wolk, and Johan Ärnlöv
- Subjects
Adult ,Male ,medicine.medical_specialty ,Longitudinal study ,medicine.medical_treatment ,alpha-Tocopherol ,Medicine (miscellaneous) ,Diet Surveys ,Bone and Bones ,White People ,Fractures, Bone ,Sex Factors ,Vitamins, Minerals, and Phytochemicals ,Risk Factors ,Surveys and Questionnaires ,Internal medicine ,medicine ,Humans ,Vitamin E Deficiency ,Longitudinal Studies ,Tocopherol ,Muscle, Skeletal ,Wasting ,Aged ,Proportional Hazards Models ,Sweden ,Hip fracture ,Nutrition and Dietetics ,business.industry ,Proportional hazards model ,Vitamin E ,Middle Aged ,medicine.disease ,Surgery ,Dietary Supplements ,Multivariate Analysis ,Cohort ,Female ,medicine.symptom ,business ,Follow-Up Studies ,Cohort study - Abstract
Background: A reduction in the formation of free radicals and oxidative stress might reduce the rate of bone loss and muscle wasting. Objective: The objective was to determine whether a-tocopherol intake or serum concentrations are associated with fracture risk in older women and men. Design: Two cohort studies, the Swedish Mammography Cohort (SMC; n = 61,433 women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 1138 men), were used. Results: During 19 y of follow-up, 14,738 women in the SMC experienced a first fracture at any site (3871 hip fractures). A higher hip fracture rate was observed with lower intakes of a-tocopherol. Compared with the highest quintile of intake, the lowest quintile had a multivariable-adjusted HR of 1.86 (95% CI: 1.67, 2.06). The HR of any fracture was 1.20 (95% CI: 1.14, 1.28). a-Tocopherol‐ containing supplement use was associated with a reduced rate of hip fracture (HR: 0.78; 95% CI: 0.65, 0.93) and any fracture (HR: 0.86; 95% CI: 0.78, 0.94). Compared with the highest quintile of a-tocopherol intake in ULSAM (follow-up: 12 y), lower intakes (quintiles 1‐4) were associated with a higher rate of hip fracture (HR: 3.33; 95% CI: 1.43, 7.76) and any fracture (HR: 1.84; 95% CI: 1.18, 2.88). The HR for hip fracture in men for each 1-SD decrease in serum a-tocopherol was 1.58 (95% CI: 1.13, 2.22) and for any fracture was 1.23 (95% CI: 1.02, 1.48). Conclusion: Low intakes and low serum concentrations of a-tocopherol are associated with an increased rate of fracture in elderly women and men. Am J Clin Nutr 2014;99:107‐14.
- Published
- 2014
23. Plasma vitamin D and mortality in older men: a community-based prospective cohort study
- Author
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Håkan Melhus, Liisa Byberg, Lars Berglund, Rune Blomhoff, Johan Sundström, Greta Snellman, Karl Michaëlsson, Johan Ärnlöv, Hans Garmo, Per Hellman, Lars Holmberg, Rolf Gedeborg, John A. Baron, and Alicja Wolk
- Subjects
Male ,medicine.medical_specialty ,Medicine (miscellaneous) ,Blood Pressure ,macromolecular substances ,Affect (psychology) ,Cohort Studies ,Leisure Activities ,Internal medicine ,Vitamin D and neurology ,Humans ,Medicine ,Mortality ,Vitamin D ,Prospective cohort study ,Life Style ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Sweden ,Community based ,Nutrition and Dietetics ,Proportional hazards model ,business.industry ,Cancer ,medicine.disease ,Cholesterol ,Blood pressure ,Endocrinology ,Cardiovascular Diseases ,Calcium ,Energy Metabolism ,business ,Cohort study - Abstract
Vitamin D status is known to be important for bone health but may also affect the development of several chronic diseases, including cancer and cardiovascular diseases, which are 2 major causes of death.We aimed to examine how vitamin D status relates to overall and cause-specific mortality.The Uppsala Longitudinal Study of Adult Men, a community-based cohort of elderly men (mean age at baseline: 71 y; n = 1194), was used to investigate the association between plasma 25-hydroxyvitamin D [25(OH)D] and mortality. Total plasma 25(OH)D was determined with HPLC atmospheric pressure chemical ionization mass spectrometry. Proportional hazards regression was used to compute hazard ratios (HRs).During follow-up (median: 12.7 y), 584 (49%) participants died. There was a U-shaped association between vitamin D concentrations and total mortality. An approximately 50% higher total mortality rate was observed among men in the lowest 10% (46 nmol/L) and the highest 5% (98 nmol/L) of plasma 25(OH)D concentrations compared with intermediate concentrations. Cancer mortality was also higher at low plasma concentrations (multivariable-adjusted HR: 2.20; 95% CI: 1.44, 3.38) and at high concentrations (HR: 2.64; 95% CI: 1.46, 4.78). For cardiovascular death, only low (HR: 1.89; 95% CI: 1.21, 2.96) but not high (HR: 1.33; 95% CI: 0.69, 2.54) concentrations indicated higher risk.Both high and low concentrations of plasma 25(OH)D are associated with elevated risks of overall and cancer mortality. Low concentrations are associated with cardiovascular mortality.
- Published
- 2010
24. Serum fatty acid composition and insulin resistance are independently associated with liver fat markers in elderly men
- Author
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Helena Petersson, Björn Zethelius, Johan Ärnlöv, and Ulf Risérus
- Subjects
Male ,Aging ,medicine.medical_specialty ,Linolenic acid ,Endocrinology, Diabetes and Metabolism ,Linoleic acid ,medicine.medical_treatment ,Fluoroimmunoassay ,Blood lipids ,Body Mass Index ,chemistry.chemical_compound ,Endocrinology ,Insulin resistance ,Internal medicine ,Internal Medicine ,Humans ,Medicine ,Life Style ,Aged ,Sweden ,chemistry.chemical_classification ,business.industry ,Insulin ,Fatty Acids ,Fatty acid ,General Medicine ,medicine.disease ,Dietary Fats ,Fatty Liver ,chemistry ,Obesity, Abdominal ,Lipogenesis ,Regression Analysis ,Liver function ,Insulin Resistance ,business ,Stearoyl-CoA Desaturase - Abstract
To investigate the relationships of serum fatty acid (FA) composition and estimated desaturase activities with the liver fat marker alanine aminotransferase (ALT).546 Swedish elderly men of a population-based cohort participated in this cross-sectional study. FA composition was assessed in serum cholesterol esters to determine dietary fat quality (e.g. linoleic) and desaturation products (e.g. dihomo-gamma-linolenic acid). Desaturase indices, including stearoyl coenzymeA desaturase-1 (SCD-1), were calculated by FA product-to-precursor ratios.In linear regression analyses adjusting for lifestyle, abdominal obesity and insulin sensitivity, the dietary biomarker linoleic acid (n-6), but not n-3 FAs, was inversely related to ALT. Desaturation products including palmitoleic, oleic, gamma-linolenic and dihomo-gamma-linolenic acids, and Delta6-desaturase and SCD-1 indices were directly related to ALT (all p0.05). After further adjustment for factors previously linked to fatty liver (i.e. serum lipids, adiponectin concentrations), SCD-1 index (p=0.004) and insulin resistance (p0.0001) were independent determinants of ALT activity, whereas waist circumference, triglycerides, non-esterified FA and adiponectin were not.A low dietary intake of linoleic acid and elevated SCD-1 index may contribute to higher ALT activity in elderly men, even independently of obesity and insulin resistance.
- Published
- 2010
25. Circulating retinol-binding protein 4, cardiovascular risk factors and prevalent cardiovascular disease in elderly
- Author
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Lars Lind, Rune Blomhoff, Christian Berne, Ramachandran S. Vasan, Karl Michaëlsson, Erik Ingelsson, Håkan Melhus, Johan Sundström, Johan Ärnlöv, and Ulf Risérus
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Blood lipids ,Body Mass Index ,Insulin resistance ,Risk Factors ,Internal medicine ,Humans ,Insulin ,Medicine ,Risk factor ,Triglycerides ,Aged ,Aged, 80 and over ,Metabolic Syndrome ,Retinol binding protein 4 ,biology ,business.industry ,Atherosclerosis ,medicine.disease ,Obesity ,Endocrinology ,Blood pressure ,Cardiovascular Diseases ,biology.protein ,Female ,Waist Circumference ,Metabolic syndrome ,Cardiology and Cardiovascular Medicine ,business ,Retinol-Binding Proteins, Plasma ,Body mass index - Abstract
Our aim was to examine relations of serum retinol-binding protein 4 (RBP4) to cardiovascular risk factors, and prevalent metabolic syndrome (MetS) and cardiovascular disease (CVD) in a large community-based sample of elderly.We evaluated cross-sectional relations of serum RBP4 to cardiovascular risk factors including anthropometrical measures, blood pressure, lipid measures, fasting glucose and insulin, body fat distribution including truncal fat by dual-energy x-ray absorptiometry (DXA), homeostasis model assessment insulin resistance (HOMA-IR) and prevalent MetS in one thousand eight 70-year old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), and in five hundred seven 82-year old men from Uppsala Longitudinal Study of Adult Men (ULSAM). In ULSAM, we also examined associations with prevalent CVD.RBP4 concentrations were positively correlated with serum triglycerides (r=0.30; P0.0001 in both samples), whereas correlations with body mass index (BMI), waist circumference, sagittal abdominal diameter, total and truncal fat mass, total cholesterol, fasting glucose and HOMA-IR were weak. In multivariable-adjusted models, RBP-4 was associated with MetS (odds ratio (OR), 1.16 and 1.33; 95% confidence interval (CI), 0.99-1.37 and 1.05-1.67 per 1-standard deviation (SD) increase in PIVUS and ULSAM, respectively), and prior cerebrovascular disease (OR, 1.37; 95% CI, 1.00-1.88 per 1-SD increase in ULSAM), but not with prior myocardial infarction.In elderly, RBP4 concentrations were associated with MetS and its components in both sexes, and prior cerebrovascular disease in men. These findings are consistent with the hypothesis that circulating RBP4 could be a marker of metabolic complications and possibly also atherosclerosis and overt CVD.
- Published
- 2009
26. A polymorphism in the cyclooxygenase 1 gene is associated with decreased inflammatory prostaglandin F2α formation and lower risk of cardiovascular disease
- Author
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Samar Basu, Tomas Axelsson, Johanna Helmersson, and Johan Ärnlöv
- Subjects
Male ,medicine.medical_specialty ,Clinical Biochemistry ,Alpha (ethology) ,Prostaglandin ,Single-nucleotide polymorphism ,Biology ,Dinoprost ,Lower risk ,Linkage Disequilibrium ,chemistry.chemical_compound ,Risk Factors ,Polymorphism (computer science) ,Internal medicine ,Genotype ,medicine ,Humans ,Allele ,Aged ,Sweden ,Polymorphism, Genetic ,Cell Biology ,Phenotype ,Endocrinology ,Haplotypes ,chemistry ,Cardiovascular Diseases ,Cyclooxygenase 1 ,Gene polymorphism - Abstract
This study investigates the impact of genetic variation in the cyclooxygenase-1 (COX-1) gene on formation of the vasoconstrictive, pro-inflammatory prostaglandin F(2)(alpha) (PGF(2)(alpha)) and development of cardiovascular disease (CVD). We determined COX-1 genotypes, PGF(2)(alpha) formation and CVD prevalence in a Swedish cohort of 809 men at age 77 years. Of these, 237 had a history of CVD according to the registry data. Four of nine COX-1 single nucleotide polymorphisms were associated with altered formation of PGF(2)(alpha) (P
- Published
- 2009
27. Socioeconomic Factors as Predictors of Incident Heart Failure
- Author
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Lars Lind, Johan Sundström, Johan Ärnlöv, and Erik Ingelsson
- Subjects
Employment ,Male ,medicine.medical_specialty ,Left ventricular hypertrophy ,Cohort Studies ,Risk Factors ,Internal medicine ,Epidemiology ,Humans ,Medicine ,Myocardial infarction ,Proportional Hazards Models ,Heart Failure ,Marital Status ,business.industry ,Proportional hazards model ,Hazard ratio ,Middle Aged ,Prognosis ,medicine.disease ,Confidence interval ,Socioeconomic Factors ,Heart failure ,Cohort ,Physical therapy ,Cardiology ,Educational Status ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Studies of socioeconomic factors as predictors of heart failure (HF) are few and have given opposing results. Further, it is unknown if these factors predict incident HF independently of myocardial infarction and other established risk factors for HF. Methods and Results In a community-based cohort of 2314 middle-age men free from HF, valvular disease, and previous myocardial infarction at baseline, socioeconomic factors were examined as predictors for HF using Cox proportional hazards analyses. In multivariable Cox proportional hazards models adjusted for established risk factors for HF (hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, serum cholesterol, and interim myocardial infarction), low occupational classification (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.03–2.35 for low vs. high occupational classification), low education level (HR 1.98, 95% CI 1.07–3.68 for elementary school vs. college exam) and being unmarried (HR 1.44, 95% CI 0.99–2.10 for being unmarried vs. being married) increased the risk of HF. Conclusion High occupational classification and high education level decreased, and being unmarried increased, the risk of subsequent HF in middle-age men, via mechanisms largely independent of established risk factors for HF, including an interim myocardial infarction. Further studies are needed to understand the mechanisms behind these associations.
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- 2006
28. Insulin resistance, dietary fat intake and blood pressure predict left ventricular diastolic function 20 years later
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Bengt Vessby, Lars Lind, Johan Ärnlöv, Bertil Andrén, Hans Lithell, and Johan Sundström
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Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Blood Pressure ,Cohort Studies ,Ventricular Dysfunction, Left ,Insulin resistance ,Heart Rate ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Diastolic function ,Longitudinal Studies ,Dietary fat ,Aged ,Sweden ,Nutrition and Dietetics ,business.industry ,Fatty Acids ,Heart ,Middle Aged ,medicine.disease ,Dietary Fats ,Health Surveys ,Diet Records ,Cross-Sectional Studies ,Endocrinology ,Blood pressure ,Dietary fat intake ,Echocardiography ,Glucose Clamp Technique ,Cardiology ,Cholesterol Esters ,Insulin Resistance ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Our knowledge on the development of left ventricular diastolic dysfunction is scarce. Thus, we aimed to investigate the relationship between left ventricular diastolic function and a wide variety of cardiovascular risk factors, including dietary factors using both cross-sectional and longitudinal data with 20 years follow-up.A population-based cohort of 505 50-year-old men was examined with determinations of blood pressure, insulin, glucose and fatty acid composition of serum cholesterol esters. A reinvestigation 20 years later also included hyperinsulinaemic euglycaemic clamp, 7-day diet record and Doppler echocardiography with determination of left ventricular diastolic function (early (E) and late (A) peak mitral velocities and left atrial diameter). Blood pressure both at age 50 and 70 was negatively correlated to the E/A ratio (r=-0.15, p0.001 and r=-0.23, p0.001) at age 70. Insulin resistance at age 50 and 70 were negatively correlated to the A-wave and left atrial diameter at follow-up. A fatty acid profile indicating a diet high in saturated fats at age 50 was correlated to an increased left atrial diameter 20 years later and the dietary intake of fat was negatively correlated to the E/A ratio (r=-0.09, p0.05) at age 70. All findings were independent of myocardial infarction and cardiovascular medication.Apart from blood pressure, insulin resistance and dietary fat intake predicted left ventricular diastolic function after 20 years. These findings suggest that both hemodynamic and metabolic factors may play a role for left ventricular diastolic function and disclose new possibilities for prevention of left ventricular diastolic dysfunction.
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- 2005
29. Inflammation, as Measured by the Erythrocyte Sedimentation Rate, Is an Independent Predictor for the Development of Heart Failure
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Johan Ärnlöv, Johan Sundström, Lars Lind, and Erik Ingelsson
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Male ,medicine.medical_specialty ,Heart disease ,Population ,Blood Sedimentation ,Left ventricular hypertrophy ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Myocardial infarction ,education ,Heart Failure ,Inflammation ,Sweden ,education.field_of_study ,medicine.diagnostic_test ,Proportional hazards model ,business.industry ,Incidence ,Hazard ratio ,Middle Aged ,medicine.disease ,Endocrinology ,Erythrocyte sedimentation rate ,Heart failure ,Cardiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
OBJECTIVES: Our objective was to explore inflammation, measured as erythrocyte sedimentation rate (ESR), as a predictor for the development of heart failure (HF). BACKGROUND: In recent years, evidence of the importance of inflammation in the pathophysiology of HF has emerged, and various inflammatory markers have been found to predict future HF. Erythrocyte sedimentation rate is an inexpensive and easily accessible marker of systemic inflammation, but to this date it is unknown whether ESR predicts subsequent HF. METHODS: In a community-based prospective study of 2,314 middle-aged men free from HF, myocardial infarction, and valvular disease at baseline, ESR was analyzed in multivariable models together with established risk factors for HF (hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, obesity, and serum cholesterol) and hematocrit. RESULTS: A total of 282 men developed HF during a median follow-up time of 30 years. In Cox proportional hazards analyses, ESR was an independent predictor of HF (hazard ratio 1.46 for highest quartile vs. the lowest, 95% confidence interval 1.04 to 2.06). This observation remained significant when also adjusting for interim myocardial infarction during follow-up. CONCLUSIONS: Erythrocyte sedimentation rate was a significant predictor of HF, independent of established risk factors for HF, and interim myocardial infarction after three decades of follow-up in a population-based sample of middle-aged men. Our findings indicate that inflammation occurs early in the process leading to HF and that ESR could be used to evaluate this process.
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- 2005
30. Neurohormonal Activation in Populations Susceptible to Heart Failure
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Johan Ärnlöv and Ramachandran S. Vasan
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medicine.hormone ,Cardiotonic Agents ,Treatment outcome ,Myocardial Infarction ,Physiology ,Renin-Angiotensin System ,Endothelins ,Ventricular Dysfunction, Left ,Catecholamines ,Humans ,Medicine ,Natriuretic Peptides ,Heart Failure ,Neurotransmitter Agents ,business.industry ,Mechanism (biology) ,General Medicine ,medicine.disease ,Treatment Outcome ,Cardiovascular Diseases ,Heart failure ,Hypertension ,Potassium excretion ,Hypertrophy, Left Ventricular ,Cardiology and Cardiovascular Medicine ,business ,Sodium retention ,Homeostasis - Abstract
During the course of evolution, life forms moved from an aquatic to a terrestrial environment and a need for salt conservation arose. The neurohormonal defense systems that evolved to ensure salt and circulatory homeostasis have been essential for survival. For instance, the renin–angiotensin–aldosterone system (RAAS) played a fundamental role in promoting water and sodium retention, and in facilitating potassium excretion in prehistoric humans, hunter-gatherers who consumed a diet high in potassium and who were prone to death from hemorrhage or diarrhea [1]. As our living conditions have changed over millions of years, however, the need for salt conservation has diminished and the neurohormonal systems essential to survival in prehistoric times may become maladaptive under select circumstances. Consequently, the term neurohormonal activation often has a negative connotation, despite it being a mechanism essential for species preservation under some conditions. This article focuses on the adverse effects of neurohormonal activation, acknowledging that it is
- Published
- 2005
31. Day-to-day variation of urinary NGAL and rational for creatinine correction
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Johan Ärnlöv, Anders Larsson, and Johanna Helmersson-Karlqvist
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Adult ,Male ,medicine.medical_specialty ,Urinary system ,Clinical Biochemistry ,Urology ,Urine ,Lipocalin ,chemistry.chemical_compound ,Lipocalin-2 ,Proto-Oncogene Proteins ,Internal medicine ,Urologi och njurmedicin ,medicine ,Humans ,Urology and Nephrology ,Aged ,Creatinine ,integumentary system ,Chemistry ,General Medicine ,Lipocalins ,Neutrophil gelatinase-associated lipocalin ,Kidney Tubules ,Endocrinology ,Biomarker (medicine) ,Female ,Kidney Diseases ,Day to day ,Creatinine urine ,Biomarkers ,Acute-Phase Proteins - Abstract
OBJECTIVES: Clinical studies evaluating the new tubular biomarker urinary neutrophil gelatinase-associated lipocalin (U-NGAL) in urine increase and there is no consensus whether absolute U-NGAL concentrations or urinary NGAL/creatinine (U-NGAL/Cr) ratios should be used when chronic tubular dysfunction is studied. The aim was to study the biological variation of U-NGAL in healthy subjects and the rational for urinary Creatinine (U-Cr) correction in two different study samples. DESIGN AND METHODS: To study biological variation of U-NGAL and U-NGAL/Cr ratio and the association between U-NGAL and U-Cr in healthy subjects 13 young males and females (median age 29years) collected morning urine in 10 consecutive days. Additionally, a random subsample of 400 males from a population-based cohort (aged 78years) collecting 24-hour urine during one day was studied. RESULTS: The calculated biological variation for absolute U-NGAL was 27% and for U-NGAL/Cr ratio 101%. Absolute U-NGAL increased linearly with U-Cr concentration (the theoretical basis for creatinine adjustment) in the older males (R=0.19, P
- Published
- 2013
32. Effects of cis-9,trans-11 conjugated linoleic acid supplementation on insulin sensitivity, lipid peroxidation, and proinflammatory markers in obese men
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Bengt Vessby, Samar Basu, Johan Ärnlöv, and Ulf Risérus
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Adult ,Male ,medicine.medical_specialty ,Linoleic acid ,medicine.medical_treatment ,Conjugated linoleic acid ,Administration, Oral ,Medicine (miscellaneous) ,Blood lipids ,Biology ,Dinoprost ,Lipid peroxidation ,chemistry.chemical_compound ,Insulin resistance ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,Linoleic Acids, Conjugated ,Obesity ,Aged ,Nutrition and Dietetics ,Cholesterol ,Insulin ,food and beverages ,Stereoisomerism ,Lipid metabolism ,Middle Aged ,medicine.disease ,Oxidative Stress ,Glucose ,Endocrinology ,chemistry ,Body Composition ,lipids (amino acids, peptides, and proteins) ,Lipid Peroxidation ,Insulin Resistance - Abstract
BACKGROUND We recently showed that trans-10,cis-12 (t10,c12) conjugated linoleic acid (CLA) causes insulin resistance in obese men. However, metabolic effects of the c9,t11 CLA isomer are still unknown in obese men. Because c9,t11 CLA is the predominant CLA isomer in foods and is included in dietary weight-loss products, it is important to conduct randomized controlled studies that use c9,t11 CLA preparations. OBJECTIVE We investigated the effects of c9,t11 CLA supplementation on insulin sensitivity, body composition, and lipid peroxidation in a group at high risk for cardiovascular disease. DESIGN In a randomized, double-blind, placebo-controlled study, 25 abdominally obese men received 3 g c9,t11 CLA/d or placebo (olive oil). Before and after 3 mo of supplementation, we assessed insulin sensitivity (hyperinsulinemic euglycemic clamp), lipid metabolism, body composition, and urinary 8-iso-prostaglandin F(2alpha) (a major F(2)-isoprostane) and 15-keto-dihydro-prostaglandin F(2alpha), markers of in vivo oxidative stress and inflammation, respectively. RESULTS All subjects completed the study. Compared with placebo, c9,t11 CLA decreased insulin sensitivity by 15% (P < 0.05) and increased 8-iso-prostaglandin F(2alpha) and 15-keto-dihydro-prostaglandin F(2alpha) excretion by 50% (P < 0.01) and 15% (P < 0.05), respectively. The decreased insulin sensitivity was independent of changes in serum lipids, glycemia, body mass index, and body fat but was abolished after adjustment for changes in 8-iso-prostaglandin F(2alpha) concentrations. There were no differences between groups in body composition. CONCLUSIONS A CLA preparation containing the purified c9,t11 CLA isomer increased insulin resistance and lipid peroxidation compared with placebo in obese men. Because c9,t11 CLA occurs in commercial supplements as well as in the diet, the present results should be confirmed in larger studies that also include women.
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- 2004
33. Impaired insulin sensitivity is an independent predictor of common carotid intima-media thickness in a population sample of elderly men
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Lars Lind, Johan Sundström, Martin Wohlin, Björn Zethelius, Bertil Andrén, and Johan Ärnlöv
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Blood Glucose ,Carotid Artery Diseases ,Male ,medicine.medical_specialty ,Carotid Artery, Common ,Systole ,medicine.medical_treatment ,Statistics as Topic ,Population ,Blood Pressure ,Body Mass Index ,Insulin resistance ,Diastole ,Heart Rate ,Predictive Value of Tests ,Internal medicine ,medicine.artery ,parasitic diseases ,Humans ,Insulin ,Medicine ,cardiovascular diseases ,Common carotid artery ,education ,Aged ,Sweden ,education.field_of_study ,business.industry ,Cholesterol, HDL ,Smoking ,Cholesterol, LDL ,medicine.disease ,Circadian Rhythm ,Endocrinology ,Clamp ,Blood pressure ,Intima-media thickness ,cardiovascular system ,Tunica Intima ,Cardiology and Cardiovascular Medicine ,business ,Body mass index ,Biomarkers - Abstract
Most previous studies of associations between insulin sensitivity and common carotid artery (CCA) atherosclerosis have been conducted in small samples, have not used direct measurement of insulin sensitivity, and have yielded inconclusive results. We investigated associations of CCA intima-media thickness (IMT) and diameter (CCA-D) measured by B-mode ultrasound and insulin sensitivity measured by the euglycemic hyperinsulinemic clamp test together with risk factors of the insulin resistance syndrome in a community-based sample of 493 elderly men. The clamp glucose disposal rate was an independent predictor of CCA-IMT in multivariate models adjusting for blood pressure, smoking, serum cholesterol, and body mass index (1% decrease in CCA-IMT for a 1 unit increase in glucose disposal rate, P=0.009). Glucose disposal rate was significantly related to CCA-D in univariate (r=-0.11, P=0.02) but not in multivariate models. In conclusion, this study is the first to establish impaired insulin sensitivity, measured by the euglycemic hyperinsulinemic clamp test, as an independent predictor of CCA-IMT in a population-based sample of elderly men.
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- 2003
34. OUTCOME AFTER MYOCARDIAL INFARCTION IN A COHORT STUDY OF CROSS COUNTRY SKIERS IN SWEDEN
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Bo Lagerqvist, Karl Michaëlsson, Johan Lindbäck, Stefan James, Johan Ärnlöv, and Ulf Hållmarker
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medicine.medical_specialty ,Cross country ,business.industry ,Emergency medicine ,Medicine ,Myocardial infarction ,business ,medicine.disease ,Cardiology and Cardiovascular Medicine ,Outcome (game theory) ,Cohort study - Published
- 2014
- Full Text
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35. Several factors associated with the insulin resistance syndrome are predictors of left ventricular systolic dysfunction in a male population after 20 years of follow-up
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Lars Lind, Hans Lithell, Bengt Vessby, C. Nicholas Hales, Johan Ärnlöv, Björn Zethelius, and Bertil Andrén
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Blood Glucose ,Male ,medicine.medical_specialty ,Ambulatory blood pressure ,Heart disease ,Cohort Studies ,Ventricular Dysfunction, Left ,Insulin resistance ,Heart Rate ,Risk Factors ,Diabetes mellitus ,Internal medicine ,Humans ,Medicine ,Myocardial infarction ,Aged ,Metabolic Syndrome ,Sweden ,Ejection fraction ,business.industry ,Age Factors ,Middle Aged ,medicine.disease ,Surgery ,Glucose ,Blood pressure ,Echocardiography ,Case-Control Studies ,Heart failure ,Cardiology ,Insulin Resistance ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies ,Proinsulin - Abstract
The epidemiologic data on heart failure are scarce. This study aimed at identifying predictors of left ventricular systolic dysfunction in a cohort of middle-aged men with a 20-year follow-up.A population-based cohort of 431 50-year-old men was examined with blood pressure and anthropometric measurements together with lipid, glucose, and insulin determinations. A reinvestigation 20 years later also included echocardiography, ambulatory blood pressure monitoring, hyperinsulinemic euglycemic clamp, and oral glucose tolerance test. Sixteen subjects were found to have left ventricular systolic dysfunction at age 70 years, defined as an ejection fraction/=0.40. A control group of 48 subjects matched on myocardial infarction, hypertension, diabetes, and use of cardiovascular medication, but with an ejection fraction0.40, was used in a nested case-control analysis.At age 50 years, heart rate (P.01), plasma proinsulin (P.05), and the proportion of dihomogammalinolenic acid in serum cholesterol esters (P.05) were increased and serum phosphate decreased (P.01) in the subjects identified with left ventricular systolic dysfunction at age 70 years compared with controls. No major metabolic abnormalities were associated with left ventricular systolic dysfunction at age 70 years compared with controls.Factors associated with insulin resistance precede left ventricular systolic dysfunction independently of ischemic heart disease and hypertension after 20 years of follow-up.
- Published
- 2001
36. Cardiac Arrest in a Long-Distance Ski Race (Vasaloppet) in Sweden
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Ulf Hållmarker, Karl Michaëlsson, Stefan James, and Johan Ärnlöv
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medicine.medical_specialty ,education.field_of_study ,business.industry ,Mortality rate ,Population ,Atrial fibrillation ,medicine.disease ,Sudden death ,Race (biology) ,Epidemiology ,cardiovascular system ,medicine ,Physical therapy ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,education ,business ,human activities ,Socioeconomic status ,Stroke ,Demography - Abstract
The overall aim of this thesis was to study the influence of physical activity on health. Risks and benefits of physical activity is of particular interest since there is a global trend of less physical activity among youths and adults.In order to investigate this aim we used a database from a large cross country ski race, Vasaloppet, with participants with a wide age range, and with both elite athletes and ordinary people who exercise and promote their health. The most serious risk of strenuous exercise is sudden death and it is challenging to identify preventive effects of major endemic diseases.Using epidemiological methodology we studied 200 000 Vasaloppet skiers and compared them with the general population. Based on personal identification numbers we added data from Swedish national personal and health registers, clinical registers as the cancer register, Swedeheart, or Swedish stroke register, and socioeconomic information from Statistics Sweden. In the Vasaloppet database we collected data on age, gender, finish time and number of races during the period 1989 to 2010.We evaluated risk of death during the race in two papers (I,II). During 90 years of annual races, cardiac arrest occurred in 20 skiers, of which five survived. The death rate is in average two per 100 000 skiers.We also studied the association with cancer incidence (paper III). The overall reduction of cancer was modest among skiers compared with the general population, but for cancers related to lifestyle the risks were markedly lower.We investigated the risk for recurrent myocardial infarction and found a 30% reduction among skiers (paper IV). In paper V we showed that skiers with a first stroke have a lower incidence of all-cause death. The skiers had a higher frequency of atrial fibrillation but had less severe stroke and no increased risk of recurrent stroke. Thus our data suggest that a lifestyle with a high level of physical activity may work as a protection after a cardiovascular event.Summary: The short excess mortality in endurance physical activity is by far outweighed by the long term protective effect of exercise in cardiovascular diseases and cancer.
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- 2012
37. SERUM CALCIUM LEVELS BUT NOT SERUM PHOSPHATE PREDICT ISCHEMIC STROKE IN THE COMMUNITY
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Johan Ärnlöv, Bernice Wiberg, Emil Hagström, and Lars Lind
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medicine.medical_specialty ,Endocrinology ,chemistry ,business.industry ,Internal medicine ,Ischemic stroke ,medicine ,chemistry.chemical_element ,Serum phosphate ,Calcium ,Cardiology and Cardiovascular Medicine ,business - Published
- 2011
38. Inflammation, as Measured by the Erythrocyte Sedimentation Rate (ESR), Is an Independent Predictor for the Development of Heart Failure
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Johan Ärnlöv, Johan Sundström, Lars Lind, and Erik Ingelsson
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Erythrocyte sedimentation rate ,Heart failure ,Internal medicine ,medicine ,Cardiology ,Cardiology and Cardiovascular Medicine ,Independent predictor ,medicine.disease ,business ,General Nursing - Published
- 2005
39. HUNC-93B1, a novel gene mainly expressed in the heart, is related to left ventricular diastolic function in elderly men
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Vladimir I. Kashuba, Lars Lind, Johan Ärnlöv, Maria Andersson, Lars Berglund, Johan Sundström, Alexei Protopopov, Richard Reneland, Eugene R. Zabarovsky, Hans Lithell, and Bertil Andrén
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Novel gene ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Cardiology ,Diastolic function ,Cardiology and Cardiovascular Medicine ,business - Published
- 2003
40. Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016
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Abajobir, Amanuel Alemu, Abate, Kalkidan Hassen, Abbafati, Cristiana, Abbas, Kaja M, Abd-Allah, Foad, Abdulkader, Rizwan Suliankatchi, Abdulle, Abdishakur M, Abebo, Teshome Abuka, Abera, Semaw Ferede, Aboyans, Victor, Abu-Raddad, Laith J, Ackerman, Ilana N, Adedeji, Isaac A, Adetokunboh, Olatunji, Afshin, Ashkan, Aggarwal, Rakesh, Agrawal, Sutapa, Agrawal, Anurag, Ahmed, Muktar Beshir, Aichour, Miloud Taki Eddine, Aichour, Amani Nidhal, Aichour, Ibtihel, Aiyar, Sneha, Akinyemiju, Tomi F, Akseer, Nadia, Al Lami, Faris Hasan, Alahdab, Fares, Al-Aly, Ziyad, Alam, Khurshid, Alam, Noore, Alam, Tahiya, Alasfoor, Deena, Alene, Kefyalew Addis, Ali, Raghib, Alizadeh-Navaei, Reza, Alkaabi, Juma M, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Allen, Christine, Al-Maskari, Fatma, AlMazroa, Mohammad AbdulAziz, Al-Raddadi, Rajaa, Alsharif, Ubai, Alsowaidi, Shirina, Althouse, Benjamin M, Altirkawi, Khalid A, Alvis-Guzman, Nelson, Amare, Azmeraw T, Amini, Erfan, Ammar, Walid, Amoako, Yaw Ampem, Ansha, Mustafa Geleto, Antonio, Carl Abelardo T, Anwari, Palwasha, Ärnlöv, Johan, Arora, Megha, Artaman, Al, Aryal, Krishna Kumar, Asgedom, Solomon W, Atey, Tesfay Mehari, Atnafu, Niguse Tadele, Avila-Burgos, Leticia, Avokpaho, Euripide Frinel G Arthur, Awasthi, Ashish, Awasthi, Shally, Azarpazhooh, Mahmoud Reza, Azzopardi, Peter, Babalola, Tesleem Kayode, Bacha, Umar, Badawi, Alaa, Balakrishnan, Kalpana, Bannick, Marlena S, Barac, Aleksandra, Barker-Collo, Suzanne L, Bärnighausen, Till, Barquera, Simon, Barrero, Lope H, Basu, Sanjay, Battista, Robert, Battle, Katherine E, Baune, Bernhard T, Bazargan-Hejazi, Shahrzad, Beardsley, Justin, Bedi, Neeraj, Béjot, Yannick, Bekele, Bayu Begashaw, Bell, Michelle L, Bennett, Derrick A, Bennett, James R, Bensenor, Isabela M, Benson, Jennifer, Berhane, Adugnaw, Berhe, Derbew Fikadu, Bernabé, Eduardo, Betsu, Balem Demtsu, Beuran, Mircea, Beyene, Addisu Shunu, Bhansali, Anil, Bhatt, Samir, Bhutta, Zulfiqar A, Biadgilign, Sibhatu, Bicer, Burcu Kucuk, Bienhoff, Kelly, Bikbov, Boris, Birungi, Charles, Biryukov, Stan, Bisanzio, Donal, Bizuayehu, Habtamu Mellie, Blyth, Fiona M, Boneya, Dube Jara, Bose, Dipan, Bou-Orm, Ibrahim R, Bourne, Rupert R A, Brainin, Michael, Brayne, Carol, Brazinova, Alexandra, Breitborde, Nicholas J K, Briant, Paul S, Britton, Gabrielle, Brugha, Traolach S, Buchbinder, Rachelle, Bulto, Lemma Negesa Bulto, Bumgarner, Blair R, Butt, Zahid A, Cahuana-Hurtado, Lucero, Cameron, Ewan, Campos-Nonato, Ismael Ricardo, Carabin, Hélène, Cárdenas, Rosario, Carpenter, David O, Carrero, Juan Jesus, Carter, Austin, Carvalho, Felix, Casey, Daniel, Castañeda-Orjuela, Carlos A, Castle, Chris D, Catalá-López, Ferrán, Chang, Jung-Chen, Charlson, Fiona J, Chaturvedi, Pankaj, Chen, Honglei, Chibalabala, Mirriam, Chibueze, Chioma Ezinne, Chisumpa, Vesper Hichilombwe, Chitheer, Abdulaal A, Chowdhury, Rajiv, Christopher, Devasahayam Jesudas, Ciobanu, Liliana G, Cirillo, Massimo, Colombara, Danny, Cooper, Leslie Trumbull, Cooper, Cyrus, Cortesi, Paolo Angelo, Cortinovis, Monica, Criqui, Michael H, Cromwell, Elizabeth A, Cross, Marita, Crump, John A, Dadi, Abel Fekadu, Dalal, Koustuv, Damasceno, Albertino, Dandona, Lalit, Dandona, Rakhi, das Neves, José, Davitoiu, Dragos V, Davletov, Kairat, de Courten, Barbora, De Leo, Diego, De Steur, Hans, Defo, Barthelemy Kuate, Degenhardt, Louisa, Deiparine, Selina, Dellavalle, Robert P, Deribe, Kebede, Deribew, Amare, Des Jarlais, Don C, Dey, Subhojit, Dharmaratne, Samath D, Dhillon, Preet K, Dicker, Daniel, Djalainia, Shirin, Do, Huyen Phuc, Dokova, Klara, Doku, David Teye, Dorsey, E Ray, dos Santos, Kadine Priscila Bender, Driscoll, Tim R, Dubey, Manisha, Duncan, Bruce Bartholow, Ebel, Beth E, Echko, Michelle, El-Khatib, Ziad Ziad, Enayati, Ahmadali, Endries, Aman Yesuf, Ermakov, Sergey Petrovich, Erskine, Holly E, Eshetie, Setegn, Eshrati, Babak, Esteghamati, Alireza, Estep, Kara, Fanuel, Fanuel Belayneh Bekele, Farag, Tamer, Farinha, Carla Sofia e Sa, Faro, André, Farzadfar, Farshad, Fazeli, Mir Sohail, Feigin, Valery L, Feigl, Andrea B, Fereshtehnejad, Seyed-Mohammad, Fernandes, João C, Ferrari, Alize J, Feyissa, Tesfaye Regassa, Filip, Irina, Fischer, Florian, Fitzmaurice, Christina, Flaxman, Abraham D, Foigt, Nataliya, Foreman, Kyle J, Franklin, Richard C, Frostad, Joseph J, Fullman, Nancy, Fürst, Thomas, Furtado, Joao M, Futran, Neal D, Gakidou, Emmanuela, Garcia-Basteiro, Alberto L, Gebre, Teshome, Gebregergs, Gebremedhin Berhe, Gebrehiwot, Tsegaye Tewelde, Geleijnse, Johanna M, Geleto, Ayele, Gemechu, Bikila Lencha, Gesesew, Hailay Abrha, Gething, Peter W, Ghajar, Alireza, Gibney, Katherine B, Gillum, Richard F, Ginawi, Ibrahim Abdelmageem Mohamed, Gishu, Melkamu Dedefo, Giussani, Giorgia, Godwin, William W, Goel, Kashish, Goenka, Shifalika, Goldberg, Ellen M, Gona, Philimon N, Goodridge, Amador, Gopalani, Sameer Vali, Gosselin, Richard A, Gotay, Carolyn C, Goto, Atsushi, Goulart, Alessandra Carvalho, Graetz, Nicholas, Gugnani, Harish Chander, Gupta, Prakash C, Gupta, Rajeev, Gupta, Tanush, Gupta, Vipin, Gupta, Rahul, Gutiérrez, Reyna A, Hachinski, Vladimir, Hafezi-Nejad, Nima, Hailu, Alemayehu Desalegne, Hailu, Gessessew Bugssa, Hamadeh, Randah Ribhi, Hamidi, Samer, Hammami, Mouhanad, Handal, Alexis J, Hankey, Graeme J, Hao, Yuantao, Harb, Hilda L, Hareri, Habtamu Abera, Haro, Josep Maria, Harun, Kimani M, Harvey, James, Hassanvand, Mohammad Sadegh, Havmoeller, Rasmus, Hay, Simon I, Hay, Roderick J, Hedayati, Mohammad T, Hendrie, Delia, Henry, Nathaniel J, Heredia-Pi, Ileana Beatriz, Heydarpour, Pouria, Hoek, Hans W, Hoffman, Howard J, Horino, Masako, Horita, Nobuyuki, Hosgood, H Dean, Hostiuc, Sorin, Hotez, Peter J, Hoy, Damian G, Htet, Aung Soe, Hu, Guoqing, Huang, John J, Huynh, Chantal, Iburg, Kim Moesgaard, Igumbor, Ehimario Uche, Ikeda, Chad, Irvine, Caleb Mackay Salpeter, Islam, Sheikh Mohammed Shariful, Jacobsen, Kathryn H, Jahanmehr, Nader, Jakovljevic, Mihajlo B, James, Peter, Jassal, Simerjot K, 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Rahimi, K, Rahimi-Movaghar, A, Rahimi-Movaghar, V, Rahman, M, Rai, R, Rajsic, S, Ram, U, Ranabhat, C, Rangaswamy, T, Rankin, Z, Rao, P, Rawaf, S, Ray, S, Reiner, R, Reinig, N, Reitsma, M, Remuzzi, G, Renzaho, A, Resnikoff, S, Rezaei, S, Ribeiro, A, Rivas, J, Roba, H, Robinson, S, Rojas-Rueda, D, Rokni, M, Ronfani, L, Roshandel, G, Roth, G, Rothenbacher, D, Roy, A, Rubagotti, E, Ruhago, G, Saadat, S, Safdarian, M, Safiri, S, Sagar, R, Sahathevan, R, Sahraian, M, Salama, J, Saleh, M, Salomon, J, Salvi, S, Samy, A, Sanabria, J, Sanchez-Niño, M, Santomauro, D, Santos, J, Santos, I, Santric Milicevic, M, Sartorius, B, Satpathy, M, Sawhney, M, Saxena, S, Schelonka, K, Schmidt, M, Schneider, I, Schöttker, B, Schutte, A, Schwebel, D, Schwendicke, F, Seedat, S, Sepanlou, S, Servan-Mori, E, Shaheen, A, Shaikh, M, Shamsipour, M, Sharma, R, Sharma, J, She, J, Shi, P, Shibuya, K, Shields, C, Shifa, G, Shiferaw, M, Shigematsu, M, Shiri, R, Shirkoohi, R, Shirude, S, Shishani, K, Shoman, H, Siabani, 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Male ,Dánarmein ,AUSTRALIA ,GBD, disability-adjusted life-years (DALYs) ,Heilsufar ,Lífslíkur ,Epidemiology ,Life expectancy ,Diseases ,Global Health ,THERAPY ,Global Burden of Disease ,Residence Characteristics ,Fullorðnir ,Cause of Death ,Medicine and Health Sciences ,Psychology ,Konur ,Aged, 80 and over ,Tölfræði ,PLASMODIUM-FALCIPARUM ,Aldraðir ,Sjúkdómar ,Medicine (all) ,Fatlaðir ,Men ,Þjóðir ,11 Medical And Health Sciences ,ASSOCIATION ,Middle Aged ,Health policy ,PREVALENCE ,Sálfræði ,disability-adjusted life-years (DALYs) ,Female ,Lýðheilsa ,Quality-Adjusted Life Years ,Life Sciences & Biomedicine ,Global Health Metrics ,Adult ,AFRICA ,Quality of life ,People with disabilities ,GBD ,WEIGHTS ,Social ecology ,Lífsgæði ,Communicable Diseases ,World health/statistics ,Age Distribution ,Life Expectancy ,Medicine, General & Internal ,SDG 3 - Good Health and Well-being ,General & Internal Medicine ,Heilbrigðisstefna ,Humans ,Adults ,Disabled Persons ,Women ,Sex Distribution ,Mortality ,Noncommunicable Diseases ,Aged ,Science & Technology ,Faraldsfræði ,MORTALITY ,Wounds and injuries ,EPIDEMIOLOGIC TRANSITION ,HIV ,Áverkar ,Karlar ,Wounds and Injuries ,Félagshagfræði ,Older people - Abstract
Correction in: LANCET Volume: 390 Issue: 10106 Pages: E38-E38 Published: OCT 28 2017, Background Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. Findings The highest globally observed HALE at birth for both women and men was in Singapore, at 75.2 years (95% uncertainty interval 71.9-78.6) for females and 72.0 years (68.8-75.1) for males. The lowest for females was in the Central African Republic (45.6 years [42.0-49.5]) and for males was in Lesotho (41.5 years [39.0-44.0]). From 1990 to 2016, global HALE increased by an average of 6.24 years (5.97-6.48) for both sexes combined. Global HALE increased by 6.04 years (5.74-6.27) for males and 6.49 years (6.08-6.77) for females, whereas HALE at age 65 years increased by 1.78 years (1.61-1.93) for males and 1.96 years (1.69-2.13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2.3% [-5.9 to 0.9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16.1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. Interpretation At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support., Bill & Melinda Gates Foundation
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- 2017
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