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Background: We investigate whether peripheral arterial disease (PAD) detected by ankle brachial index (ABI)

Objective: To develop scientific consensus recommendations for the optimal design and functions of different types of blood pressure (BP) measuring devices used in clinical practice for the detection, management, and long-term follow-up of hypertension., Methods: A scientific consensus meeting was performed by the European Society of Hypertension (ESH) Working Group on BP Monitoring and Cardiovascular Variability and STRIDE BP (Science and Technology for Regional Innovation and Development in Europe) during the 2022 Scientific Meeting of the ESH in Athens, Greece. Manufacturers were also invited to provide their feedback on BP device design and development. Thirty-one international experts in clinical hypertension and BP monitoring contributed to the development of consensus recommendations on the optimal design of BP devices., Statement: International consensus was reached on the requirements for the design and features of five types of BP monitors, including office (or clinic) BP monitors, ambulatory BP monitors, home BP monitors, home BP telemonitors, and kiosk BP monitors for public spaces. For each device type "essential" requirements (must have), and "optional" ones (may have) are presented, as well as additional comments on the optimal device design and features., Conclusions: These consensus recommendations aim at providing manufacturers of BP devices with the requirements that are considered mandatory, or optional, by clinical experts involved in the detection and management of hypertension. They are also directed to administrative healthcare personnel involved in the provision and purchase of BP devices so that they can recommend the most appropriate ones., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: We analyzed the mortality risk and its predictors in patients hospitalized for heart failure (HF)., Methods: Patients discharged from hospitalization for acute decompensation of HF in 2010-2020 and younger than 86 years were followed (n=4097). We assessed the incidence and trends of all-cause death, its main predictors, and the pharmacotherapy recommended at discharge from the hospital., Results: The 30 days all-cause mortality was in discharged patients 3.2%, while 1-year 20.4% and 5-years 55.4%. We observed a modest trend to decreased 1-year mortality risk over time. Any increase of year of hospitalization by one was associated with about 5% lower risk in the fully adjusted model. Regarding predictors of 1-year mortality risk, a positive association was found for age over 65, history of malignancy, and peak brain natriuretic peptide during hospitalization ≥10times higher than normal concentration. In contrast, as protective factors, we identified LDL ≥1.8 mmol/L, treatment with beta-blockers, renin-angiotensin axis blockers, statins, and implanted cardioverter in the same regression model. The ejection fraction category and primary etiology of HF (coronary artery disease vs. others) did not significantly affect the mortality risk in a fully adjusted model., Conclusions: Despite advances in cardiovascular disease management over the last two decades, the prognosis of patients hospitalized for heart failure remained highly unfavorable., Competing Interests: The authors report no conflicts of interest in this work.

Objective: Due to contradictory results of previous studies evaluating the association between ischemic stroke (IS) and thrombophilic polymorphisms, their routine screening in IS patients, particularly those older than 60 years, is not recommended. We evaluated the differences in the distribution of rs6025 and rs1799963 polymorphisms according to IS subtypes and their interaction with smoking., Methods: We conducted a case-control study of 423 hospital-based consecutive survivors of their first-ever IS and 614 population-based controls. Survivors (18-81 years) with IS documented by brain imagining were examined at a median of 16 months after the index event. The stroke subtype was categorized using the Causative Classification of Stroke System. Controls (50-75 years) were free of a history of stroke/TIA, coronary heart disease, and venous thromboembolism., Results: Age- and gender-adjusted prevalence of individuals carrying at least one copy of the rs1799963A minor allele was 5.3% among stroke survivors (by subtypes: 3.1% in large artery atherosclerosis, 2.0% in cardio-aortic embolism, 2.4% in small artery occlusion, and 10.3% in undetermined stroke) vs. 2.4% among controls. In multinomial multivariate adjusted analysis, rs1799963 was exclusively associated with undetermined stroke (OR: 3.67; 95% CI: 1.52-8.85; p = 0.004). There was strong evidence of rs1799963 × smoking synergistic interaction (OR: 5.14; 95% CI: 1.65-16.01; p = 0.005). There was no association of rs6025 with IS in general, or with any subtype., Conclusions: In our consecutive IS survivors, carriage of the rs1799963A allele is associated with undetermined stroke. This effect appears to be confined to smokers., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Although obesity is a risk factor for stroke and achieving normal weight is advocated to decrease stroke risk, the risk associated with obesity and weight loss after stroke has not been well established. The aim of this study was to assess the association of obesity at the time of stroke admission and weight loss after stroke with total mortality., Methods: We analyzed 736 consecutive patients (mean age, 66 ± 11 years; 58% men) hospitalized for their first ischemic stroke. Body weight at hospital admission and at the outpatient visit during follow-up was used in the analysis., Results: After multivariate adjustment, obesity at admission was associated with lower mortality risk as compared with normal weight (hazard ratio [HR], .50, P = .03). At the outpatient visit, with a median follow-up time of 16 months, 21% of patients had lost more than 3 kg of weight. Stroke severity, heart failure, transient ischemic attack, and depression after stroke were independently associated with significant weight loss. Weight loss of more than 3 kg was associated with increased mortality risk (HR, 5.87; P = .001) independently of other factors. Similar results were seen when weight loss was defined as losing more than 3% of baseline weight (HR, 4.97; P = .004). Weight gain of more than 5% of the baseline weight tended to be associated with better survival when compared with no weight change (log-rank test, P = .07)., Conclusions: Normal weight at hospital admission and weight loss after ischemic stroke are independently associated with increased mortality. Overweight and obesity at baseline do not decrease the risk associated with weight loss., (Copyright © 2015 National Stroke Association. All rights reserved.)

Objectives: There is no agreement on optimal blood pressure (BP) level during the acute phase of stroke, because studies on the relation between BP and stroke outcome have shown contradicting results. The aim of this study was to compare the relationship of admission, maximal, discharge BP and its components during hospitalization for the first-ever acute ischemic stroke with total mortality after stroke., Methods: In 532 consecutive patients (mean age 66 ± 10 years, 59% of men) hospitalized for their first-ever ischemic stroke, the association between BP and total mortality during a median follow-up of 66 weeks (interquartile range 33-119 weeks) was analyzed., Results: In multivariate analysis, both admission mean BP (MBP) and discharge SBP quartiles were independent predictors of mortality and outperformed other parameters of BP. After multivariate adjustments, patients with admission MBP below 100 mmHg had a higher risk of death than those with MBP between 100-110 and 110-121 mmHg, whereas the risk of mortality did not differ from the group with admission MBP above 122 mmHg. Similarly, patients with discharge SBP below 120 mmHg had an increased risk of death as compared to groups with SBP between 120-130 and 130-141 mmHg, whereas the risk of death was similar to that with discharge SBP above 141 mmHg., Conclusion: Among patients hospitalized for their first-ever ischemic stroke, the risk of all-cause death is significantly increased in those with admission MBP below 100 mmHg and discharge SBP below 120 mmHg, even after adjustments for other confounders.

Objective: Increased aortic stiffness may be one of the mechanisms by which obesity increases cardiovascular risk independently of traditional risk factors. While body mass index (BMI) is generally used to define excess adiposity, several studies have suggested that measures of central obesity may be better predictors of cardiovascular risk. However, data comparing the association between several measures of central and general obesity with aortic stiffness in the general population are inconclusive., Methods: In 1031 individuals (age 53 ± 13 years, 45% men) without manifest cardiovascular disease randomly selected from population, we tested the association between parameters of central obesity (waist circumference - WC, waist-to-hip-ratio - WHR, waist-to-height ratio - WHtR) and general obesity (BMI) with carotid-femoral pulse wave velocity (cfPWV)., Results: In univariate analysis, WC and WHtR were more strongly associated with cfPWV than BMI in both genders, while WHR showed a stronger association with cfPWV only in women. WHtR was more closely associated with cfPVW than WHR. This difference between obesity measures remained after multivariate adjustment. When the fully adjusted hierarchical regression was used, among central obesity measures, WHtR had the largest additive value on top of BMI, while there was no additive value of BMI on top of WHtR., Conclusion: Central obesity parameters are more closely associated with aortic stiffness than BMI. Of central adiposity measures, WHtR has the strongest association with aortic stiffness beyond body mass index and cardiovascular risk factors. Our results suggest that WHtR may be the best anthropometric measure of excess adiposity in the general population., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Guidelines propose classification of conventional blood pressure (CBP) into normotension (<120/<80 mm Hg), prehypertension (120-139/80-89 mm Hg), and hypertension (≥140/≥90 mm Hg)., Methods: To assess the potential differential contribution of ambulatory blood pressure (ABP) in predicting risk across CBP strata, we analyzed outcomes in 7,826 untreated people recruited from 11 populations., Results: During an 11.3-year period, 809 participants died (276 cardiovascular deaths) and 639, 383, and 225 experienced a cardiovascular, cardiac, or cerebrovascular event. Compared with normotension (n = 2,639), prehypertension (n = 3,076) carried higher risk (P ≤ 0.015) of cardiovascular (+41%) and cerebrovascular (+92%) endpoints; compared with hypertension (n = 2,111) prehypertension entailed lower risk (P ≤ 0.005) of total mortality (-14%) and cardiovascular mortality (-29%) and of cardiovascular (-34%), cardiac (-33%), or cerebrovascular (-47%) events. Multivariable-adjusted hazard ratios (HRs) for stroke associated with 24-hour and daytime diastolic ABP (+5 mm Hg) were higher (P ≤ 0.045) in normotension than in prehypertension and hypertension (1.98 vs.1.19 vs.1.28 and 1.73 vs.1.09 vs. 1.24, respectively) with similar trends (0.03 ≤ P ≤ 0.11) for systolic ABP (+10 mm Hg). However, HRs for fatal endpoints and cardiac events associated with ABP did not differ significantly (P ≥ 0.13) across CBP categories. Of normotensive and prehypertensive participants, 7.5% and 29.3% had masked hypertension (daytime ABP ≥135/≥85 mm Hg). Compared with true normotension (P ≤ 0.01), HRs for stroke were 3.02 in normotension and 2.97 in prehypertension associated with masked hypertension with no difference between the latter two conditions (P = 0.93)., Conclusion: ABP refines risk stratification in normotension and prehypertension mainly by enabling the diagnosis of masked hypertension., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Aortic stiffness is increased in lacunar stroke. The precise mechanism linking aortic stiffness to symptomatic lacunar stroke is not well understood. The aim of this study was to compare the effects of aortic stiffness, carotid stiffness, central blood pressure, and cerebrovascular resistance on carotid flow pulsatility according to stroke subtype., Methods: Two hundred and one consecutive patients were examined 13 months after hospitalization for their first-ever ischemic stroke. The stroke subtype was classified using the Causative Classification of Stroke System. Carotid-femoral pulse wave velocity (PWV) was used as a measure of aortic stiffness. Common carotid flow pulsatility was expressed as resistive index. Central blood pressure was measured using applanation tonometry., Results: Complete data were available for 174 patients (mean age… 67 ± 10 years, 64% men). In patients with lacunar stroke, aortic PWV was higher (13.11 ± 2.74 m/s) than in individuals with large artery atherosclerosis (9.98 ± 1.87 m/s, P <0.001), cardioembolic (11.31 ± 3.18 m/s, P = 0.04) or cryptogenic stroke (11.13 ± 3.2 m/s, P = 0.01). Similarly, central SBP and resistive index were higher in patients with lacunar stroke (145 ± 23 mmHg and 0.80 ± 0.04, respectively) than those with large artery atherosclerosis (128 ± 18 mmHg, P <0.01 and 0.74 ± 0.07, P <0.01, respectively) or cryptogenic stroke (132 ± 18 mmHg, P <0.01 and 0.76 ± 0.07, P <0.05, respectively). In multivariate analysis, aortic stiffness and central pulse pressure were the main determinants of resistive index independent of stroke subtype., Conclusion: Our results suggest that aortic stiffening, by reducing the buffering function of the aorta and thereby increasing the transmission of pressure and flow pulsatility into the cerebral arterioles, may contribute to the pathogenesis of lacunar stroke.

Experts proposed blood pressure (BP) load derived from 24-hour ambulatory BP recordings as a more accurate predictor of outcome than level, in particular in normotensive people. We analyzed 8711 subjects (mean age, 54.8 years; 47.0% women) randomly recruited from 10 populations. We expressed BP load as percentage (%) of systolic/diastolic readings ≥135/≥85 mm Hg and ≥120/≥70 mm Hg during day and night, respectively, or as the area under the BP curve (mm Hg×h) using the same ceiling values. During a period of 10.7 years (median), 1284 participants died and 1109 experienced a fatal or nonfatal cardiovascular end point. In multivariable-adjusted models, the risk of cardiovascular complications gradually increased across deciles of BP level and load (P<0.001), but BP load did not substantially refine risk prediction based on 24-hour systolic or diastolic BP level (generalized R(2) statistic ≤0.294%; net reclassification improvement ≤0.28%; integrated discrimination improvement ≤0.001%). Systolic/diastolic BP load of 40.0/42.3% or 91.8/73.6 mm Hg×h conferred a 10-year risk of a composite cardiovascular end point similar to a 24-hour systolic/diastolic BP of 130/80 mm Hg. In analyses dichotomized according to these thresholds, increased BP load did not refine risk prediction in the whole study population (R(2)≤0.051) or in untreated participants with 24-hour ambulatory normotension (R(2)≤0.034). In conclusion, BP load does not improve risk stratification based on 24-hour BP level. This also applies to subjects with normal 24-hour BP for whom BP load was proposed to be particularly useful in risk stratification.

Background: Central systolic blood pressure (cSBP) can be derived by the general transfer function of the radial pressure wave, as used in the SphygmoCor device, or by regression equation from directly measured late systolic shoulder of the radial pressure wave (pSBP2), as used in the Omron HEM-9000AI device. The aim of this study was to compare the SphygmoCor estimates of cSBP with 2 estimates of cSBP provided by the Omron HEM-9000AI (cSBP, pSBP2) in a large cohort of the white population., Methods: In 391 patients aged 52.3±13.5 years (46% men) from the Czech post-MONICA Study, cSBP was measured using the SphygmoCor and Omron HEM-9000AI devices in random order., Results: Omron cSBP and pSBP2 were perfectly correlated (r = 1.0; P < 0.0001). There was a strong correlation (r = 0.97; P < 0.0001) between Omron and SphygmoCor cSBP estimates, but Omron estimate was 13.1±4.7mm Hg higher than SphygmoCor cSBP. On the other hand, Omron pSBP2 strongly correlated with SphygmoCor cSBP (r = 0.97; P < 0.0001) and was 1.7±4.2mm Hg lower than SphygmoCor cSBP. In multivariable analysis, anthropometric and cardiovascular risk factors explained only 10% of the variance of the cSBP difference between devices while explaining 52% of the systolic blood pressure amplification variance., Conclusions: Estimation of cSBP based on the late systolic shoulder of the radial wave provides a comparable accuracy with the validated general transfer function. When comparing Omron HEM-9000AI and SphygmoCor estimates of cSBP, Omron pSBP2 should be used. The difference between both devices in cSBP may be explained by differences in calibration.

Evidence-based thresholds for risk stratification based on pulse pressure (PP) are currently unavailable. To derive outcome-driven thresholds for the 24-hour ambulatory PP, we analyzed 9938 participants randomly recruited from 11 populations (47.3% women). After age stratification (<60 versus ≥60 years) and using average risk as reference, we computed multivariable-adjusted hazard ratios (HRs) to assess risk by tenths of the PP distribution or risk associated with stepwise increasing (+1 mm Hg) PP levels. All adjustments included mean arterial pressure. Among 6028 younger participants (68 853 person-years), the risk of cardiovascular (HR, 1.58; P=0.011) or cardiac (HR, 1.52; P=0.056) events increased only in the top PP tenth (mean, 60.6 mm Hg). Using stepwise increasing PP levels, the lower boundary of the 95% confidence interval of the successive thresholds did not cross unity. Among 3910 older participants (39 923 person-years), risk increased (P≤0.028) in the top PP tenth (mean, 76.1 mm Hg). HRs were 1.30 and 1.62 for total and cardiovascular mortality, and 1.52, 1.69, and 1.40 for all cardiovascular, cardiac, and cerebrovascular events. The lower boundary of the 95% confidence interval of the HRs associated with stepwise increasing PP levels crossed unity at 64 mm Hg. While accounting for all covariables, the top tenth of PP contributed less than 0.3% (generalized R(2) statistic) to the overall risk among the elderly. Thus, in randomly recruited people, ambulatory PP does not add to risk stratification below age 60; in the elderly, PP is a weak risk factor with levels below 64 mm Hg probably being innocuous.

Background: Average real variability (ARV) is a recently proposed index for short-term blood pressure (BP) variability. We aimed to determine the minimum number of BP readings required to compute ARV without loss of prognostic information., Methods: ARV was calculated from a discovery dataset that included 24-hour ambulatory BP measurements for 1,254 residents (mean age = 56.6 years; 43.5% women) of Copenhagen, Denmark. Concordance between ARV from full (≥80 BP readings) and randomly reduced 24-hour BP recordings was examined, as was prognostic accuracy. A test dataset that included 5,353 subjects (mean age = 54.0 years; 45.6% women) with at least 48 BP measurements from 11 randomly recruited population cohorts was used to validate the results., Results: In the discovery dataset, a minimum of 48 BP readings allowed an accurate assessment of the association between cardiovascular risk and ARV. In the test dataset, over 10.2 years (median), 806 participants died (335 cardiovascular deaths, 206 cardiac deaths) and 696 experienced a major fatal or nonfatal cardiovascular event. Standardized multivariable-adjusted hazard ratios (HRs) were computed for associations between outcome and BP variability. Higher diastolic ARV in 24-hour ambulatory BP recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular (HR = 1.19), and cardiac (HR = 1.19) mortality and fatal combined with nonfatal cerebrovascular events (HR = 1.16). Higher systolic ARV in 24-hour ambulatory BP recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular (HR = 1.17), and cardiac (HR = 1.24) mortality., Conclusions: Forty-eight BP readings over 24 hours were observed to be adequate to compute ARV without meaningful loss of prognostic information.

A case-control study revealed association between hypertension and rs3918226 in the endothelial nitric oxide synthase (eNOS) gene promoter (minor/major allele, T/C allele). We aimed at substantiating these preliminary findings by target sequencing, cell experiments, and a population study. We sequenced the 140-kb genomic area encompassing the eNOS gene. In HeLa and HEK293T cells transfected with the eNOS promoter carrying either the T or the C allele, we quantified transcription by luciferase assay. In 2722 randomly recruited Europeans (53.0% women; mean age 40.1 years), we studied blood pressure change and incidence of hypertension in relation to rs3918226, using multivariable-adjusted models. Sequencing confirmed rs3918226, a binding site of E-twenty six transcription factors, as the single nucleotide polymorphism most closely associated with hypertension. In T compared with C transfected cells, eNOS promoter activity was from 20% to 40% (P<0.01) lower. In the population, systolic/diastolic blood pressure increased over 7.6 years (median) by 9.7/6.8 mm Hg in 28 TT homozygotes and by 3.8/1.9 mm Hg in 2694 C allele carriers (P≤0.0004). The blood pressure rise was 5.9 mm Hg systolic (confidence interval [CI], 0.6-11.1; P=0.028) and 4.8 mm Hg diastolic (CI, 1.5-8.2; P=0.0046) greater in TT homozygotes, with no differences between the CT and CC genotypes (P≥0.90). Among 2013 participants normotensive at baseline, 692 (34.4%) developed hypertension. The hazard ratio and attributable risk associated with TT homozygosity were 2.04 (CI, 1.24-3.37; P=0.0054) and 51.0%, respectively. In conclusion, rs3918226 in the eNOS promoter tags a hypertension susceptibility locus, TT homozygosity being associated with lesser transcription and higher risk of hypertension.

Background: Recently, an expert group advised to measure carotid-femoral (cf) pulse wave velocity (PWV) on the right side of the body, and to use a sliding caliper when tape measure distance cannot be obtained in a straight line. The present study investigates the evidence for this advice by comparing the real travelled cf path lengths (RTPLs) at both body sides and comparing the straight distance (as can be obtained with a sliding caliper) with the tape measure distance., Methods: RTPLs were measured with MRI in 98 individuals (49 men, age 21-76 years). Path lengths from the aortic arch to the carotid (AA-CA) and femoral (AA-FA) sites were determined. RTPL was calculated as (AA-FA) - (AA-CA) and compared between both sides. RTPLs were compared with 80% of the direct cf distance using a tape measure and the straight cf distance obtained from MRI images., Results: RTPL was slightly longer [11 mm (12), P < 0.001] at the right side. The 80%-rule overestimated RTPLs with 0.5% at the right and 2.7% at the left side. Straight MRI distance tended (P = 0.09) to perform slightly better than tape measure distance., Conclusion: The travelled cf path is slightly longer at the right than at the left body side and the straight MRI distance tends to perform better than tape measure distance. The present study supports the advice of the expert consensus group to measure cf-PWV at the right body side using a sliding caliper when tape measure distance cannot be obtained in a straight line.

Background: The double product (DP), consisting of the systolic blood pressure (SBP) multiplied by the pulse rate (PR), is an index of myocardial oxygen consumption, but its prognostic value in the general population remains unknown., Methods: We recorded health outcomes in 9,937 subjects (median age, 53.2 years; 47.3% women) randomly recruited from 11 populations and enrolled in the International Database on Ambulatory blood pressure in relation to Cardiovascular Outcomes (IDACO) study. We obtained the SBP, PR, and DP for these subjects as determined through 24-hour ambulatory monitoring., Results: Over a median period of 11.0 years, 1,388 of the 9,937 study subjects died, of whom 536 and 794, respectively, died of cardiovascular (CV) and non-CV causes, and a further 1,161, 658, 494, and 465 subjects, respectively, experienced a CV, cardiac, coronary, or cerebrovascular event. In multivariate-adjusted Cox models, not including SBP and PR, DP predicted total, CV, and non-CV mortality (standardized hazard ratio [HR], ≥ 1.10; P ≤ 0.02), and all CV, cardiac, coronary, and stroke events (HR, ≥ 1.21; P < 0.0001). For CV mortality (HR, 1.34 vs. 1.30; P = 0.71) and coronary events (1.28 vs. 1.21; P = 0.26), SBP and the DP were equally predictive. As compared with DP, SBP was a stronger predictor of all CV events (1.39 vs. 1.27; P = 0.002) and stroke (1.61 vs. 1.36; P < 0.0001), and a slightly stronger predictor of cardiac events (1.32 vs. 1.22; P = 0.06). In fully adjusted models, including both SBP and PR, the predictive value of DP disappeared for fatal endpoints (P ≥ 0.07), coronary events (P = 0.06), and stroke (P = 0.12), or DP was even inversely associated with the risk of all CV and cardiac events (both P ≤ 0.01)., Conclusion: In the general population, we did not observe DP to add to risk stratification over and beyond SBP and PR.

Although distinguishing features of masked hypertension in diabetics are well known, the significance of antihypertensive treatment on clinical practice decisions has not been fully explored. We analyzed 9691 subjects from the population-based 11-country International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes. Prevalence of masked hypertension in untreated normotensive participants was higher (P<0.0001) among 229 diabetics (29.3%, n=67) than among 5486 nondiabetics (18.8%, n=1031). Over a median of 11.0 years of follow-up, the adjusted risk for a composite cardiovascular end point in untreated diabetic-masked hypertensives tended to be higher than in normotensives (hazard rate [HR], 1.96; 95% confidence interval [CI], 0.97-3.97; P=0.059), similar to untreated stage 1 hypertensives (HR, 1.07; CI, 0.58-1.98; P=0.82), but less than stage 2 hypertensives (HR, 0.53; CI, 0.29-0.99; P=0.048). In contrast, cardiovascular risk was not significantly different in antihypertensive-treated diabetic-masked hypertensives, as compared with the normotensive comparator group (HR, 1.13; CI, 0.54-2.35; P=0.75), stage 1 hypertensives (HR, 0.91; CI, 0.49-1.69; P=0.76), and stage 2 hypertensives (HR, 0.65; CI, 0.35-1.20; P=0.17). In the untreated diabetic-masked hypertensive population, mean conventional systolic/diastolic blood pressure was 129.2 ± 8.0/76.0 ± 7.3 mm Hg, and mean daytime systolic/diastolic blood pressure 141.5 ± 9.1/83.7 ± 6.5 mm Hg. In conclusion, masked hypertension occurred in 29% of untreated diabetics, had comparable cardiovascular risk as stage 1 hypertension, and would require considerable reduction in conventional blood pressure to reach daytime ambulatory treatment goal. Importantly, many hypertensive diabetics when receiving antihypertensive therapy can present with normalized conventional and elevated ambulatory blood pressure that mimics masked hypertension.

No previous study addressed whether in the general population estimated glomerular filtration rate (eGFR [Chronic Kidney Disease Epidemiology Collaboration formula]) adds to the prediction of cardiovascular outcome over and beyond ambulatory blood pressure. We recorded health outcomes in 5322 subjects (median age, 51.8 years; 43.1% women) randomly recruited from 11 populations, who had baseline measurements of 24-hour ambulatory blood pressure (ABP(24)) and eGFR. We computed hazard ratios using multivariable-adjusted Cox regression. Median follow-up was 9.3 years. In fully adjusted models, which included both ABP(24) and eGFR, ABP(24) predicted (P≤0.008) both total (513 deaths) and cardiovascular (206) mortality; eGFR only predicted cardiovascular mortality (P=0.012). Furthermore, ABP(24) predicted (P≤0.0056) fatal combined with nonfatal events as a result of all cardiovascular causes (555 events), cardiac disease (335 events), or stroke (218 events), whereas eGFR only predicted the composite cardiovascular end point and stroke (P≤0.035). The interaction terms between ABP(24) and eGFR were all nonsignificant (P≥0.082). For cardiovascular mortality, the composite cardiovascular end point, and stroke, ABP(24) added 0.35%, 1.17%, and 1.00% to the risk already explained by cohort, sex, age, body mass index, smoking and drinking, previous cardiovascular disease, diabetes mellitus, and antihypertensive drug treatment. Adding eGFR explained an additional 0.13%, 0.09%, and 0.14%, respectively. Sensitivity analyses stratified for ethnicity, sex, and the presence of hypertension or chronic kidney disease (eGFR <60 mL/min per 1.73 m(2)) were confirmatory. In conclusion, in the general population, eGFR predicts fewer end points than ABP(24). Relative to ABP(24), eGFR is as an additive, not a multiplicative, risk factor and refines risk stratification 2- to 14-fold less.

Stiffness of elastic arteries like the aorta predicts cardiovascular risk. By directly reflecting arterial stiffness, having the best predictive value for cardiovascular outcome and the ease of its measurement, carotid-femoral pulse wave velocity is now considered the gold standard for arterial stiffness assessment in daily practice. Many different measurement procedures have been proposed. Therefore, standardization of its measurement is urgently needed, particularly regarding the distance measurement. This consensus document advises on the measurement procedures in general and provides arguments for the use of 80% of the direct carotid-femoral distance as the most accurate distance estimate. It also advises the use of 10 m/s as new cut-off value for carotid-femoral pulse wave velocity.

Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1865 cases and 1750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1385 cases and 1246 controls that were genotyped with a custom array of 14 055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial NO synthase gene (odds ratio: 1.54 [95% CI: 1.37-1.73]; combined P=2.58 · 10(-13)). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25-1.44; P=1.032 · 10(-14)). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16-3.66) for systolic and 1.40 (95% CI: 0.25-2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to rs3918226, suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus.

Background: Ankle brachial index (ABI) has been increasingly used in general practice to identify individuals with low ABI at high cardiovascular risk. However, there has been no consensus on the clinical significance of high ABI. The aim of our study was to compare aortic stiffness as a marker of cardiovascular risk in individuals with low (<1.0), normal (1.0-1.4), and high ABI (>1.4)., Methods: A total of 911 individuals from the Czech post-MONICA study (a randomly selected 1% representative population sample, aged 54 ± 13.5 years, 47% of men) were examined. ABI was measured using a handheld Doppler and aortic pulse wave velocity (aPWV) using the Sphygmocor device., Results: Of the 911 individuals, 28 (3.1%) had low ABI and 23 (2.5%) high ABI. There was a U-shaped association between aPWV and ABI. aPWV was significantly higher in individuals with low and high ABI compared with the normal ABI group (11.1 ± 2.8, 8.3 ± 2.3, p < 0.001; 10.8 ± 2.5, 8.3 ± 2.3 m/s, p < 0.001, respectively). In a model adjusted for age, sex, systolic, diastolic, mean blood pressure and examiner, aPWV remained increased in both extreme ABI groups compared with the normal ABI group. In logistic regression analysis, aPWV together with glucose level, male sex, and a history of deep venous thrombosis were independent predictors of high ABI, while cholesterol was not., Conclusion: This is the first study showing increased aortic stiffness in individuals with high ABI, presumably responsible for increased left ventricular mass described previously in this group. These findings suggest increased cardiovascular risk of high ABI individuals.

Aim: Residual thrombotic occlusion (RTO) after deep vein thrombosis (DVT) is considered as a risk factor of recurrent venous thromboembolism (VTE). We searched for risk factors associated with RTO after proximal DVT at the lower extremities., Methods: Using compression ultrasound, we evaluated the presence of RTO at 6 months after DVT (RTO defined as a residual thrombus occupying, at maximum compressibility, >/=20% of the vein lumen before compression)., Results: We examined 126 Czech patients: mean age 57.5 years; 50.0% women, 68.3% femoral location of DVT (otherwise popliteal), RTO found in 45.2%. While accounting for covariates, in the whole population, RTO was significantly associated with following factors: (OR; 95% confidence limit; p value): male sex (2.01; 1.27-3.19; P=0.003), femoral location (2.76; 1.59-4.78; P=0.0003). In women, but not in men, an association was demonstrated for: concurrent pulmonary embolism (PE) (18.51; 1.85-185.7; P=0.0131), diabetes mellitus (4.62; 1.38-15.51; P=0.0133) and statin use (0.11; 0.02-0.62; P=0.0125). In contrast, in men RTO was associated with an unprovoked DVT (2.6; 1.26-5.34; P=0.0094)., Conclusion: In the whole study population, male sex and femoral location of DVT were positively associated with RTO. In women, concurrent PE and diabetes mellitus were risk factors for RTO, while the use of statins was a protective factor. There was a positive association between RTO and unprovoked DVT in men. These findings deserve further evaluation in a larger study.

The objective of our study was to evaluate the significance of extended antiphospholipid profile in patients with venous thromboembolism without any systemic autoimmune disease. In 140 patients (age 18-69 years; 47.1% men) with venous thromboembolism and 136 control participants we tested anticardiolipin antibodies, anti-beta 2 glycoprotein I (anti-beta2-GPI) and also non-criteria antiphospholipid antibodies: antiphosphatidic acid, antiphosphatidylethanolamine, antiphosphatidylglycerol, antiphosphatidylinositol, antiphosphatidylserine. Commercial and in-house enzyme-linked immunosorbent assays were used. The antibodies with significantly higher prevalence in patients (compared to controls) were: immunoglobulin (Ig) M-anticardiolipin antibodies (12.9%; P = 0.035), IgG-anti-beta2-GPI (16.4%; P = 0.0032), IgM-antiphosphatidylethanolamine (14.3%; P = 0.014). In most cases, these three antibodies did not overlap. In conclusion, of non-criteria antiphospholipid antibodies, only antiphosphatidylethanolamine were significantly more prevalent in patients with venous thromboembolism, with only minor overlapping with the criteria antiphospholipid antibodies. Our results suggest the possible utility of searching for antiphosphatidylethanolamine in the clinical suspicion of antiphospholipid syndrome and the absence of criteria antiphospholipid antibodies.

Objective: To assess, in a population-based approach, sympathetic nervous system activity by the use of power spectral analysis of heart rate variability, in normotension, white-coat hypertension, masked hypertension and sustained hypertension., Methods: The electrocardiographic RR interval was registered in the supine and standing positions and the low-frequency and high-frequency components of its variability were quantified. Cut-off values of 140/90 mmHg for conventional blood pressure and 135/85 mmHg for daytime ambulatory blood pressure were used to define the four blood pressure groups., Results: After exclusion of patients with diabetes, myocardial infarction or treated hypertension, 1485 subjects with complete data remained for the analysis in the supine position. Age averaged 39 +/- 14 years; 54% were women. Conventional and ambulatory blood pressure averaged, respectively, 122 +/- 16/79 +/- 11 mmHg and 124 +/- 12/77 +/- 8 mmHg. After adjusting for demographic, anthropometric and lifestyle characteristics, the low-frequency to high-frequency ratio (geometric mean) averaged 0.81 in normotension and was significantly higher in white-coat hypertension (1.11; P < 0.001), based on a higher low-frequency component and a lower high-frequency component (P < 0.01). This ratio was not significantly different between normotension, masked hypertension (0.97) and sustained hypertension (0.93). The adjusted standing-to-supine ratio of the high-frequency component (geometric mean) was significantly higher in sustained hypertension (0.50) than in normotension (0.39; P < 0.01), but not in white-coat (0.40) and masked hypertension (0.45)., Conclusion: The findings at rest are compatible with increased sympathetic activity and decreased parasympathetic modulation in white-coat hypertension, with normal autonomic cardiac regulation in masked and sustained hypertension. In addition, sustained hypertension is characterized by a blunted decrease of the high-frequency component on standing.

Objectives: The International Database on Ambulatory Blood Pressure Monitoring (1993-1994) lacked a prospective dimension. We are constructing a new resource of longitudinal population studies to investigate with great precision to what extent the ambulatory blood pressure improves risk stratification., Methods: The acronym IDACO refers to the new International Database of Ambulatory blood pressure in relation to Cardiovascular Outcome. Eligible studies are population based, have fatal as well as nonfatal outcomes available for analysis, comply with ethical standards, and have been previously published in peer-reviewed journals. In a meta-analysis based on individual patient data, composite and cause-specific cardiovascular events will be related to various indexes derived by ambulatory blood pressure monitoring. The analyses will be stratified by cohort and adjusted for the conventional blood pressure and other cardiovascular risk factors., Results: To date, the international database includes 7609 patients from four cohorts recruited in Copenhagen, Denmark (n=2311), Noorderkempen, Belgium (n=2542), Ohasama, Japan (n=1535), and Uppsala, Sweden (n=1221). In these four cohorts, during a total of 69,295 person-years of follow-up (median 9.3 years), 1026 patients died and 929 participants experienced a fatal or nonfatal cardiovascular event. Follow-up in five other eligible cohorts, involving a total of 4027 participants, is still in progress. We expect that this follow-up will be completed by the end of 2007., Conclusion: The international database of ambulatory blood pressure in relation to cardiovascular outcome will provide a shared resource to investigate risk stratification by ambulatory blood pressure monitoring to an extent not possible in any earlier individual study.

Isolated systolic hypertension is predominantly observed in the elderly because of increased arterial stiffness. Aggressive treatment leads to excessive lowering of diastolic blood pressure and favors the presence of a J-shaped curve association with mortality. We investigated whether, in the elderly, this pattern of association is a simple epiphenomenon of increased arterial stiffness and impaired cardiac function. In a cohort of 331 hospitalized subjects >70 years old (mean age+/-SD: 85+/-7 years), aortic pulse wave velocity and pressure wave reflections, by pulse wave analysis, and cardiac function, by ultrasound, were assessed. During a 2-year follow-up period, 110 subjects died. No association of prognosis with systolic pressure, pulse pressure, or pulse wave velocity was observed. A J-shaped association between diastolic pressure and overall and cardiovascular mortality was observed. Unadjusted Cox regression analysis showed that patients in the first tertile of diastolic pressure (< or =60 mm Hg) had higher mortality. In Cox regression analysis, diastolic pressure < or =60 mm Hg was a predictor of mortality independently from cardiac-vascular properties, cardiovascular risk factors, and drug treatment. Multivariate regression analysis showed that increased age and low total peripheral resistance, but not left ventricular function, were the cardinal determinants of low diastolic pressure. An "optimal" diastolic pressure of 70 mm Hg in subjects with isolated systolic hypertension was found. We showed that, in the frail elderly, a value of diastolic blood pressure < or =60 mm Hg is associated with reduced survival, independent from large artery stiffness and left ventricular function, suggesting that more rational antihypertensive therapy, not only based on systolic pressure level, is needed.

Objectives: In the European Project on Genes in Hypertension (EPOGH) standardized epidemiological methods were used to determine complex phenotypes consisting of blood pressure (BP) in combination with other traits. In this report, we present the quality control of one of the BP phenotypes., Methods: In seven European countries eight different research groups recruited random samples of nuclear families. Trained observers measured the BP five times consecutively with the participants in the seated position at each of two separate home visits, 1 to 3 weeks apart, according to the guidelines of the British Hypertension Society. Quality assurance and quality control of this BP phenotype were implemented according to detailed instructions defined in the protocol of the EPOGH study., Results: On 31 August 2001, BP measurements of 2476 subjects were available for analysis. Fewer BP readings than the five planned per visit occurred in one of the eight centres, but only in 0.4% of the home visits. Across centres the relative frequency of identical consecutive readings for systolic or diastolic blood pressure varied from 0 to 6%. The occurrence of odd readings ranged from 0 to 0.1%. Of the 49,488 systolic and diastolic BP readings, 24.0% ended on a zero (expected 20%). In most EPOGH centres there was a progressive decline in the BP from the first to the second home visit. Overall, these decreases averaged 2.36 mmHg [95% confidence interval (CI): 1.98-2.74, P < 0.001] for systolic BP and 1.74 mmHg (95% CI: 1.46-2.02, P < 0.001) for diastolic BP., Conclusions: Quality assurance and control should be planned at the design stage of a project involving BP measurement and implemented from its very beginnings until the end. The procedures of quality assurance set up in the EPOGH study for the BP measurements resulted in a well-defined BP phenotype, which was consistent across centres., (Copyright 2002 Lippincott Williams & Wilkins)

It is well known that mean blood pressure (BP) is higher in obese subjects. However, the nature of the relationships between hypertension and obesity is not fully understood; this concerns especially the role of carbohydrate metabolism and sympathetic activity. The aim of this study is to compare hypertensive (systolic BP > or = 160 mmHg) to normotensive men at different levels of body mass index (BMI). We analyzed data from the Paris Prospective Study I concerning 6,424 men aged 40-53 years at entry, who were not treated for hypertension, diabetes and had no sign of heart disease. The biological parameters were glucose and insulin levels, both assessed fasting (G0, I0) and two hours after a 75-g oral glucose load (G2, I2), free fatty acids and cortisol levels. Hypertensive subjects had significantly higher G0 and G2 levels in all BMI tertiles (p < 0.001). On the contrary, I0 was significantly higher only in the third BMI tertile, and the difference in I2 level between hypertensive and normotensive subjects increased with BMI. Free fatty acids level was significantly higher in hypertensives in all BMI tertiles, however, it showed a significant negative trend with BMI (p < 0.0001) which was not present in normotensives. Morning cortisol level showed the same tendency as well and the mean difference between hypertensive and normotensive men decreased with increasing BMI. In conclusion, (1) relative hyperglycemia is present in subjects with systolic hypertension at all BMI levels, while hyperinsulinemia is found only in the more corpulent ones, and (2) free fatty acids and cortisol levels are particularly elevated in lean hypertensive men.

Alcohol consumption in the week prior to examination was assessed in 352 men (average age 52.5 years) selected randomly from a cohort of employees of an industrial plant. Men drinking more than 350 g ethanol per week, largely in the form of a local beer, did not differ in respect of BP but they smoked more cigarettes and had lower serum magnesium levels and immunoreactive insulin levels than the rest of the sample. In a multiple linear (step-wise) regression analysis, body mass index, age, immunoreactive insulin two hours after glucose load and serum total cholesterol contributed directly to the BP value but the weekly ethanol intake did not. Smoking contributed negatively to the BP value after an a priori exclusion of total cholesterol, HDL cholesterol, magnesium and results of glucose tolerance tests. Only immunoreactive insulin and age were related significantly to ethanol consumption. No significant association of alcohol consumption with BP was found.