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No previous population study assessed sublingual capillary density (CD) or perfused boundary region (PBR). Lower PBR indicates greater glycocalyx width. In 252 Han and 220 She Chinese and 254 Flemish people (mean age, 51.1 years; 54.7% women), representing random population samples, we measured total and perfused CD and PBR in the sublingual capillary bed, using oblique profiled epi-illumination, and cardiovascular risk factors. In multivariable analyses, we modeled ethnicity as random effect. Significance level was α ≤ 0.05. Compared with Chinese, Flemish had lower total (577 versus 546 n°/mm(2)) and perfused (338 versus 320 n°/mm(2)) CD, but similar perfused-to-total CD ratio (mean, 0.59). Perfused-to-total CD ratio increased with age (effect size per 1-SD increase, +0.015 per year), body mass index (+0.008 per kg/m(2)), total cholesterol (+0.012 per mmol/L), and Framingham risk score (+0.018 per point) with no ethnic differences in these associations. For age and Framingham risk score, associations with perfused-to-total CD ratio were driven by positive relationships with perfused CD, whereas associations with total CD were nonsignificant. Chinese when compared with Flemish had higher hematocrit (43.0 versus 41.1%), PBR (2010 versus 1876 nm), and pulse rate (72.6 versus 63.3 bpm). PBR standardized for hematocrit, perfused CD, and pulse rate decreased with body mass index (-26.7 nm/kg/m2), mean arterial pressure (-30.6 nm/mm Hg), and diastolic pressure (-28.5 nm/mm Hg) with no ethnic differences in these associations. In conclusion, a higher cardiovascular risk profile is associated with functional recruitment of capillaries with preserved glycocalyx that protects the endothelial lining., (© 2015 American Heart Association, Inc.)

Background: The cardio-renal interaction occurs via hemodynamic and humoral factors. Noninvasive assessment of renal hemodynamics is currently possible by assessment of renal resistive index (RRI) derived from intrarenal Doppler arterial waveforms as ((peak systolic velocity - end-diastolic velocity)/peak systolic velocity). Limited information is available regarding the relationship between RRI and cardiac hemodynamics. We investigated these associations in randomly recruited subjects from a general population., Methods: In 171 participants (48.5% women; mean age, 52.2 years), using pulsed wave Doppler, we measured RRI (mean, 0.60) and left ventricular outflow tract (LVOT) and transmitral (E and A) blood flow peak velocities and its velocity time integrals (VTI). Using carotid applanation tonometry, we measured central pulse pressure and arterial stiffness indexes such as augmentation pressure and carotid-femoral pulse wave velocity., Results: In stepwise regression analysis, RRI independently and significantly increased with female sex, age, body weight, brachial pulse pressure, and use of β-blockers, whereas it decreased with body height and mean arterial pressure. In multivariable-adjusted models with central pulse pressure and arterial stiffness indexes as the explanatory variables, we observed a significant and positive correlation of RRI only with central pulse pressure (P < 0.0001). Among the Doppler indexes of left ventricular blood flow, RRI was significantly and positively associated with LVOT and E peak velocities (P ≤ 0.012) and VTIs (P ≤ 0.010)., Conclusions: We demonstrated that in unselected subjects RRI was significantly associated with central pulse pressure and left ventricular systolic and diastolic Doppler blood flow indexes. Our findings imply that in addition to the anthropometric characteristics, cardiac hemodynamic factors influence the intrarenal arterial Doppler waveform patterns., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Platelet endothelial aggregation receptor 1 (PEAR1) is a membrane protein involved in platelet contact-induced activation and sustained platelet aggregation. Experimental studies identified PEAR1, as a candidate gene that may be linked to the blood-pressure driven kidney injury in salt-sensitive Dahl rats., Aim: In a family-based European population study (mean age 39.7 years; 52.2% women), we searched for association of changes in blood pressure or incidence of hypertension with genetic variation in PEAR1., Methods: Among 1973 randomly recruited people, genotyped for PEAR1, we measured blood pressure at baseline and follow-up., Results: Median follow-up was 10.0 years. While accounting for family clusters and blood pressure at baseline and with adjustments applied for sex, age, body mass index, smoking and drinking, total cholesterol, and antihypertensive drug treatment, all associations of systolic and diastolic blood pressure changes with nine single nucleotide polymorphisms (SNPs) in PEAR1 were all non-significant (p ≥ 0.059). With similar adjustments, the incidence of hypertension (397 cases among 1532 participants were normotensive at baseline [25.9%]) was not related to the SNPs in PEAR1 (hazard ratios ≤ 1.09; p ≥ 0.09)., Conclusion: Our study suggests that PEAR1 is not a hypertension susceptibility gene in humans.

This review addresses methodological issues in the assessment of blood pressure variability and the predictive value of blood pressure variability derived from blood pressure readings obtained in the relaxed home environment. Preference should be given to indexes of blood pressure variability that are independent of the mean because we should evaluate the impact of blood pressure variability by eliminating the effect of blood pressure levels. Beat-to-beat blood pressure recordings outperform home blood pressure measurement in the assessment of blood pressure variability in longitudinal Belgian and Japanese population studies, whereas blood pressure variability did not incrementally predict outcome beyond blood pressure level and other cardiovascular risk factors. In conclusion, clinicians should focus on blood pressure level, given that it is the predominant risk factor and is manageable by lifestyle modifications and adequate antihypertensive drug treatment. Blood pressure variability remains a research tool that requires further prospective studies with hard end points to define its potential application, as it may be potentially useful in daily clinical practice.

In view of the declining environmental lead exposure in the United States, we analyzed the National Health and Nutrition Examination Survey (2003-2010) for association of blood pressure and hypertension with blood lead. The 12 725 participants included 21.1% blacks, 20.5% Hispanics, 58.4% whites, and 48.7% women. Blacks compared with non-Blacks had higher systolic and diastolic pressures (126.5 versus 123.9 and 71.9 versus 69.6 mm Hg) and higher hypertension prevalence (44.7 versus 36.8%). Blood lead was lower in whites than in non-whites (1.46 versus 1.57 μg/dL) and in women than in men (1.25 versus 1.80 μg/dL). In multivariable analyses of all participants, blood lead doubling was associated with higher (P≤0.0007) systolic and diastolic pressure (+0.76 mm Hg; 95% confidence interval, 0.38-1.13 and +0.43 mm Hg; 0.18-0.68), but not with the odds of hypertension (0.95; 0.90-1.01; P=0.11). Associations with blood lead were nonsignificant (P≥0.09) for systolic pressure in women and for diastolic pressure in non-whites. Among men, systolic pressure increased with blood lead (P≤0.060) with effect sizes associated with blood lead doubling ranging from +0.65 mm Hg in whites to +1.61 mm Hg in blacks. For systolic pressure, interactions of ethnicity and sex with blood lead were all significant (P≤0.019). In conclusion, small and inconsistent effect sizes in the associations of blood pressure with blood lead likely exclude current environmental lead exposure as a major hypertension cause in the United States., (© 2014 American Heart Association, Inc.)

Background: Data on risk associated with 24-hour ambulatory diastolic (DBP24) versus systolic (SBP24) blood pressure are scarce., Methods and Results: We recorded 24-hour blood pressure and health outcomes in 8341 untreated people (mean age, 50.8 years; 46.6% women) randomly recruited from 12 populations. We computed hazard ratios (HRs) using multivariable-adjusted Cox regression. Over 11.2 years (median), 927 (11.1%) participants died, 356 (4.3%) from cardiovascular causes, and 744 (8.9%) experienced a fatal or nonfatal cardiovascular event. Isolated diastolic hypertension (DBP24≥80 mm Hg) did not increase the risk of total mortality, cardiovascular mortality, or stroke (HRs≤1.54; P≥0.18), but was associated with a higher risk of fatal combined with nonfatal cardiovascular, cardiac, or coronary events (HRs≥1.75; P≤0.0054). Isolated systolic hypertension (SBP24≥130 mm Hg) and mixed diastolic plus systolic hypertension were associated with increased risks of all aforementioned end points (P≤0.0012). Below age 50, DBP24 was the main driver of risk, reaching significance for total (HR for 1-SD increase, 2.05; P=0.0039) and cardiovascular mortality (HR, 4.07; P=0.0032) and for all cardiovascular end points combined (HR, 1.74; P=0.039) with a nonsignificant contribution of SBP24 (HR≤0.92; P≥0.068); above age 50, SBP24 predicted all end points (HR≥1.19; P≤0.0002) with a nonsignificant contribution of DBP24 (0.96≤HR≤1.14; P≥0.10). The interactions of age with SBP24 and DBP24 were significant for all cardiovascular and coronary events (P≤0.043)., Conclusions: The risks conferred by DBP24 and SBP24 are age dependent. DBP24 and isolated diastolic hypertension drive coronary complications below age 50, whereas above age 50 SBP24 and isolated systolic and mixed hypertension are the predominant risk factors., (© 2014 American Heart Association, Inc.)

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.)

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.

Depending on the populations studied and the definitions applied, the prevalence of treatment-resistant hypertension varies from 10% to 15%, but is higher in conditions associated with increased sympathetic drive, such as obesity, obstructive sleep apnoea, diabetes or renal dysfunction. The Symplicity studies recently demonstrated that reducing sympathetic tone by intravascular renal denervation is feasible in treatment-resistant hypertension, but failed to provide conclusive evidence on the size and durability of the antihypertensive, renal and sympatholytic effects, long-term safety, quality of life, the possibility to relax antihypertensive drug treatment, cost-effectiveness, and long-term hard cardiovascular-renal outcomes. Renal denervation should therefore only be offered within a clinical research context at highly skilled tertiary referral centres that participate in international registries constructed independent of the manufacturers.

Background. The level at which low-level lead exposure produces subclinical adverse health effects in adults remains to be established. Methods. The Study for Promotion of Health in Recycling Lead (SPHERL) will enroll 500 newly hired workers, whose blood lead during 2 years of follow-up is expected to increase from levels less than 2 μg/dl, as currently observed in the US population, to 20-30 μg/dl. The main outcome variables to be studied are (i) blood pressure (BP) analyzed as a continuous or categorical variable, both cross-sectionally and longitudinally, and using conventional and ambulatory BP measurement; (ii) indexes of glomerular and tubular renal function, (iii) heart rate variability analyzed in the frequency domain as measure of autonomous sympathetic modulation, (iv) peripheral nerve conductivity velocity, (v) neurocognitive performance, and (vi) quality of life. Expected outcomes. Assuming a 10-fold increase in blood lead, SPHERL will have sufficient statistical power to detect over 2 years a steepening of the age-related rise in systolic BP from 1 to 5 mmHg and a doubling of the age-related decline in the estimated glomerular filtration rate from 3.5 to 7.0 ml/min/1.73 m2. The longitudinal design of our study complies with the temporality principle of the Bradford-Hill criteria for assessing possible causality between outcomes and exposure. SPHERL will attempt to resolve the apparent contradiction between general population studies showing associations between adverse health effects and low lead exposure with blood lead levels below 5 μg/dl and studies conducted in occupational cohorts indicating that adverse effects of lead exposure occur at much higher blood lead levels. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND Few population studies have described the heritability and intrafamilial concordance of the retinal microvessels, or the genetic or environmental correlations of the phenotypes of these vessels. METHODS We randomly selected 413 participants from 70 families (mean age, 51.5 years; 50.1% women) from a Flemish population. We postprocessed retinal images using IVAN software to generate the central retinal arteriole equivalent (CRAE), central retinal venule equivalent (CRVE), and arteriole-to-venule-ratio (AVR) from these images. We used SAGE version 6.2 and SAS version 9.2 to compute multivariate-adjusted estimates of heritability and intrafamilial correlations of the CRAE, CRVE, and AVR of the retinal microvessels in the images. RESULTS Sex, age, mean arterial pressure, and smoking explained up to 12.7% of the variance of the phenotypes of the retinal microvessels of the study participants. With adjustments applied for these covariates, the heritability estimates of CRAE, CRVE, and AVR were 0.213 (P = 0.044), 0.339 (P = 0.010), and 0.272 (P = 0.004), respectively. The parent–offspring correlations for CRAE, CRVE, and AVR were 0.118 (NS), 0.225 (P < 0.01), and 0.215 (P < 0.05), respectively. The corresponding values were 0.222 (P < 0.05), 0.213 (P < 0.05), and 0.390 (P < 0.001) for sib–sib correlations, respectively. The genetic and environmental correlations between CRAE and CRVE were 0.360 and 0.545 (P < 0.001 for both). CONCLUSION Our study showed moderate heritability for CRAE, CRVE, and AVR, and a significant genetic correlation of CRAE with CRVE in the Flemish population of our study. These findings suggest that genetic factors influence the diameter of the retinal microvessels, and that CRAE and CRVE share some genetic determinants. [ABSTRACT FROM PUBLISHER]

BACKGROUND The association between cardiovascular health and salt intake remains controversial. The objective of our study was to assess the association between arterial stiffness and urinary sodium, both cross-sectionally and prospectively. METHODS In 630 participants (mean age 40.6 years; 51% women), randomly recruited from a Flemish population, we measured sodium and creatinine in 24-hour urine samples at baseline and follow-up (median, 9.7 years) and the carotid and aortic augmentation indexes (AIs) standardized to heart rate at follow-up only. RESULTS From baseline to follow-up, the urinary sodium concentration decreased (117.1 vs. 105.2 mmol/L; P < 0.0001), whereas 24-hour urinary sodium did not change significantly (166.5 vs. 171.5 mmol/L; P = 0.12). In multivariable-adjusted longitudinal analyses, a 40 mmol/L (~1 SD) increase in the urinary sodium concentration was independently and inversely associated with the carotid AI (effect size, –1.38±0.66%; P = 0.04) and aortic AI (–1.54±0.72%; P = 0.02). In cross-sectional analyses of follow-up data, these estimates were –1.26±0.70% (P = 0.07) and –1.52±0.76% (P = 0.04), respectively. In the longitudinal and cross-sectional analyses, the carotid and aortic AIs were unrelated to the 24-hour urinary excretion of sodium. CONCLUSIONS Our study showed an inverse association between the central arterial AIs and the urinary sodium concentration. Further research is required to consolidate our findings, to unravel the underlying mechanism, and to establish the role of renal vasodilatation in the maintenance of sodium balance. [ABSTRACT FROM PUBLISHER]

BackgroundThe X-linked angiotensin II type-2 receptor (AT2R) gene 1675G/A polymorphism is located in the short intron 1 of the AT2R gene within a sequence motif conforming to a splice branch site. AT2R is expressed in the human retina, but no previous study examined the association between retinal microvascular phenotypes and the AT2R 1675G/A polymorphism.MethodsIn 340 subjects randomly selected from a Flemish population (mean age, 51.9 years; 51.5% women), we post-processed retinal images using IVAN software to generate the retinal arteriole and venule equivalents (central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE)) and the arteriole-to-venule ratio (AVR). DNA fragments including the AT2R 1675G/A polymorphism were amplified by PCR. We applied a mixed model to assess phenotype-genotype associations while accounting for relatedness and covariables.ResultsCRAE, CRVE, and AVR averaged 151.9 µm, 215.2 µm, and 0.710, respectively. CRAE was 5.5 µm greater in women than men and decreased with age (P < 0.05). In multivariable-adjusted analyses, CRAE was higher in hemizygous and homozygous carriers of the AT2R A allele than in their G allele counterparts in both sexes combined (+4.49 µm; P = 0.014) and in men (+4.91 µm; P = 0.032) with a similar trend in women (+3.41 µm; P = 0.14). AVR was increased in the presence of the AT2R A allele compared with AT2R G hemizygotes and homozygotes (+0.024; P = 0.0082). The associations of CRAE and CRVE with other polymorphisms were not significant.ConclusionsPending confirmation in experimental and epidemiological studies, our findings suggest that diameter of the retinal arterioles might be associated with the AT2R 1675G/A polymorphism.American Journal of Hypertension (2011). doi:10.1038/ajh.2011.151 [ABSTRACT FROM AUTHOR]