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IMPORTANCE: Blood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. OBJECTIVE: To evaluate the association of BP indexes with death and a composite CV event. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal population-based cohort study of 11 135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). EXPOSURES: Blood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). MAIN OUTCOMES AND MEASURES: Multivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). RESULTS: Among 11 135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P

ObjectiveData on the contribution of ambulatory blood pressure (ABP) components to the risk of developing atrial fibrillation (AF) are limited. We prospectively tested the hypothesis that ABP may represent a potentially modifiable risk factor for the development of AF in a European population study.MethodsWe recorded daytime blood pressure (BP) in 3956 subjects randomly recruited from the general population in five European countries. Of these participants, 2776 (70.2%) underwent complete 24-hour ABP monitoring. Median follow-up was 14 years. We defined daytime systolic BP load as the percentage BP readings above 135 mm Hg. The incidence of AF was assessed from ECGs obtained at baseline and follow-up and from records held by general practitioners and/or hospitals.ResultsOverall, during 58 810 person-years of follow-up, 143 participants experienced new-onset AF. In adjusted Cox models, each SD increase in baseline 24 hours, daytime and night-time systolic BP was associated with a 27% (P=0.0056), 22% (P=0.023) and 20% (P=0.029) increase in the risk for incident AF, respectively. Conventional systolic BP was borderline associated with the risk of AF (18%; P=0.06). As compared with the average population risk, participants in the lower quartile of daytime systolic BP load (38%), the risk was 46% higher (P=0.0094).ConclusionsSystolic ABP is a significant predictor of incident AF in a population-based cohort. We also observed that participants with a daytime systolic BP load >38% had significantly increased risk of incident AF.

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 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.

Aims Common carotid artery intima-media thickness (CCIMT) is widely used as a surrogate marker of atherosclerosis, given its predictive association with cardiovascular disease (CVD). The interpretation of CCIMT values has been hampered by the absence of reference values, however. We therefore aimed to establish reference intervals of CCIMT, obtained using the probably most accurate method at present (i.e. echotracking), to help interpretation of these measures. Methods and results We combined CCIMT data obtained by echotracking on 24 871 individuals (53% men; age range 15-101 years) from 24 research centres worldwide. Individuals without CVD, cardiovascular risk factors (CV-RFs), and BP-, lipid-, and/or glucose-lowering medication constituted a healthy sub-population (n 1/4 4234) used to establish sex-specific equations for percentiles of CCIMT across age. With these equations, we generated CCIMT Z-scores in different reference subpopulations, thereby allowing for a standardized comparison between observed and predicted ('normal') values from individuals of the same age and sex. In the sub-population without CVD and treatment (n 1/4 14 609), and in men and women, respectively, CCIMT Z-scores were independently associated with systolic blood pressure [standardized bs 0.19 (95% CI: 0.16-0.22) and 0.18 (0.15-0.21)], smoking [0.25 (0.19-0.31) and 0.11 (0.04-0.18)], diabetes [0.19 (0.05-0.33) and 0.19 (0.02-0.36)], total-to-HDL cholesterol ratio [0.07 (0.04-0.10) and 0.05 (0.02-0.09)], and body mass index [0.14 (0.12-0.17) and 0.07 (0.04-0.10)]. Conclusion We estimated age- and sex-specific percentiles of CCIMT in a healthy population and assessed the association of CVRFs with CCIMT Z-scores, which enables comparison of IMT values for (patient) groups with different cardiovascular risk profiles, helping interpretation of such measures obtained both in research and clinical settings. © 2012 The Author All rights reserved.

Carotid-femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population. We gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors. The present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.