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Find video protocols related to scientific articles indexed in Pubmed.
Optimal Number of Days for Home Blood Pressure Measurement.
Am. J. Hypertens.
PUBLISHED: 11-16-2014
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Current guidelines make no outcome-based recommendations on the optimal measurement schedule for home blood pressure (BP).
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Blood Pressure in Relation to Environmental Lead Exposure in the National Health and Nutrition Examination Survey 2003 to 2010.
Hypertension
PUBLISHED: 10-08-2014
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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 ?g/dL) and in women than in men (1.25 versus 1.80 ?g/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.
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Doppler Indexes of Left Ventricular Systolic and Diastolic Flow and Central Pulse Pressure in Relation to Renal Resistive Index.
Am. J. Hypertens.
PUBLISHED: 09-22-2014
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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.
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Age-specific differences between conventional and ambulatory daytime blood pressure values.
Hypertension
PUBLISHED: 09-02-2014
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Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional BP values, but data on this relation among younger individuals <50 years are scarce. Conventional and 24-hour ambulatory BP were measured in 9550 individuals not taking antihypertensive treatment from 13 population-based cohorts. We compared individual differences between daytime ambulatory and conventional BP according to 10-year age categories. Age-specific prevalences of white coat and masked hypertension were calculated. Among individuals aged 18 to 30, 30 to 40, and 40 to 50 years, mean daytime BP was significantly higher than the corresponding conventional BP (6.0, 5.2, and 4.7 mm Hg for systolic; 2.5, 2.7, and 1.7 mm Hg for diastolic BP; all P<0.0001). In individuals aged 60 to 70 and ?70 years, conventional BP was significantly higher than daytime ambulatory BP (5.0 and 13.0 mm Hg for systolic; 2.0 and 4.2 mm Hg for diastolic BP; all P<0.0001).The prevalence of white coat hypertension exponentially increased from 2.2% to 19.5% from those aged 18 to 30 years to those aged ?70 years, with little variation between men and women (8.0% versus 6.1%; P=0.0003). Masked hypertension was more prevalent among men (21.1% versus 11.4%; P<0.0001). The age-specific prevalences of masked hypertension were 18.2%, 27.3%, 27.8%, 20.1%, 13.6%, and 10.2% among men and 9.0%, 9.9%, 12.2%, 11.9%, 14.7%, and 12.1% among women. In conclusion, this large collaborative analysis showed that the relation between daytime ambulatory and conventional BP strongly varies by age. These findings may have implications for diagnosing hypertension and its subtypes in clinical practice.
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Blood pressure variability in risk stratification: What does it add?
Clin. Exp. Pharmacol. Physiol.
PUBLISHED: 08-19-2014
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1. In this minireview we address the predictive value of blood pressure variability, over and beyond level of pressure, in randomly selected population samples. All reviewed studies had sufficient power, long follow-up duration and a wide age range. 2. We assessed blood pressure variability derived from home visit, self-measured home pressure and 24 h ambulatory monitoring. The conclusions are based mainly on novel indices of blood pressure variability: variability independent of the mean, difference between maximum and minimum blood pressure and average real variability. 3. None of these variability indices or morning surge in blood pressure substantially refined risk profiling over and beyond the blood pressure level. 4. In risk stratification, clinicians should concentrate on blood pressure level, the predominant risk factor modifiable by lifestyle measures and antihypertensive drug treatment.
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Setting thresholds to varying blood pressure monitoring intervals differentially affects risk estimates associated with white-coat and masked hypertension in the population.
Hypertension
PUBLISHED: 08-18-2014
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Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using ?140/?90, ?130/?80, ?135/?85, and ?120/?70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascular event. In multivariable analyses with normotension during all intervals of the day as reference, hazard ratios associated with white-coat hypertension progressively weakened considering daytime only (1.38; P=0.033), nighttime only (1.43; P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24 hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime (1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension were all significant (P<0.0001), ranging from 1.76 to 2.03. In conclusion, identification of truly low-risk white-coat hypertension requires setting thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure. Although any time interval suffices to diagnose masked hypertension, as proposed in current guidelines, full 24-hour recordings remain standard in clinical practice.
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Left ventricular diastolic function associated with common genetic variation in ATP12A in a general population.
BMC Med. Genet.
PUBLISHED: 08-04-2014
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BackgroundLeft ventricular (LV) function depends on the activity of transmembrane electrolyte transporters. Failing human myocardium has lower Na+/K+ ATPase expression and higher intracellular sodium concentrations. The ATP12A gene encodes a catalytic subunit of an ATPase that can function as a Na+/K+ pump. We, therefore, investigated the association between LV function and common genetic variants in ATP12A.MethodsA random sample of 1166 participants (53.7% women; mean age 49.5 years, 44.8% hypertensive) was recruited in Belgium, Poland, Italy and Russia. We measured transmitral early and late diastolic velocities (E and A) by pulsed wave Doppler, and mitral annular velocities (e¿ and a¿) by tissue Doppler. Using principal component analysis, we summarized 7 Doppler indexes ¿ namely, E, A, e¿ and a¿ velocities, and their ratios (E/A, e¿/a¿, and E/e¿) ¿ into a single diastolic score. We genotyped 5 tag SNPs (rs963984, rs9553395, rs10507337, rs12872010, rs2071490) in ATP12A. In our analysis we focused on rs10507337 because it is located within a transcription factor binding site.ResultsIn the population-based analyses while adjusting for covariables and accounting for family clusters and country, rs10507337 C allele carriers had significantly higher E/A (P¿=¿0.003), e¿ (P¿=¿5.8x10¿5), e¿/a¿ (P¿=¿0.003) and diastolic score (P¿=¿0.0001) compared to TT homozygotes. Our findings were confirmed in the haplotype analysis and in the family-based analyses in 74 informative offspring.ConclusionsLV diastolic function as assessed by conventional and tissue Doppler indexes including a composite diastolic score was associated with genetic variation in ATP12A. Further experimental studies are necessary to clarify the role of ATP12A in myocardial relaxation.
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Hypertension. Age-specificity of blood-pressure-associated complications.
Nat Rev Cardiol
PUBLISHED: 07-29-2014
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In an analysis of electronic health records, 1.25 million patients aged ?30 years without diagnosed cardiovascular disease experienced 83,098 cardiovascular events during follow-up (median 5.2 years). Associations between incident cardiovascular disease and blood pressure differed for systolic and diastolic blood pressures and between the 12 cardiovascular end points examined.
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Heritability and other determinants of left ventricular diastolic function in the family-based population study.
J. Hypertens.
PUBLISHED: 07-09-2014
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Understanding to what extent genetic factors influence diastolic Doppler indexes is an important issue in view of the relation of left ventricular diastolic dysfunction with outcome. We, therefore, investigated the heritability of left ventricular diastolic traits and the composite diastolic score in nuclear families recruited from the general population.
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The urinary proteome as correlate and predictor of renal function in a population study.
Nephrol. Dial. Transplant.
PUBLISHED: 06-30-2014
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We investigate whether the urinary proteome refines the diagnosis of renal dysfunction, which affects over 10% of the adult population.
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Thresholds for conventional and home blood pressure by sex and age in 5018 participants from 5 populations.
Hypertension
PUBLISHED: 06-30-2014
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Whether blood pressure thresholds for hypertension should differ according to sex or age remains debated. We did a subject-level meta-analysis of 5018 people untreated for hypertension and randomly recruited from 5 populations (women, 56.7%; ?60 years, 42.3%). We used multivariable-adjusted Cox regression and a bootstrap procedure to determine home blood pressure (HBP) levels yielding 10-year cardiovascular risks similar to those associated with established systolic/diastolic thresholds (140-160/80-100 mm Hg) for the conventional blood pressure (CBP). Conversely, we estimated CBP thresholds providing 10-year cardiovascular risks similar to those associated established HBP levels (125-135/80-85 mm Hg). All analyses were stratified for sex and age (<60 versus ?60 years). During 8.3 years (median), 414 participants experienced a cardiovascular event. The sex differences between HBP thresholds derived from CBP and between CBP thresholds derived from HBP were all nonsignificant (P?0.24), ranging from -4.6 to 3.6 mm Hg systolic and from -4.3 to 2.1 mm Hg diastolic. The age differences between HBP thresholds derived from CBP and between CBP thresholds derived from HBP ranged from -6.7 to 8.4 mm Hg systolic and from -1.9 to 1.7 mm Hg diastolic and were nonsignificant (P?0.08), except for HBP thresholds derived from CBP levels of 140 mm Hg systolic and 80 mm Hg diastolic (P?0.04). Sensitivity analyses based on cardiac or cerebrovascular complications were confirmatory. In conclusion, our findings based on outcome-driven criteria support contemporary guidelines that propose single blood pressure thresholds that can be indiscriminately applied in both sexes and across the age range.
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Estimation of Glomerular Filtration Rate Based on Serum Cystatin C versus Creatinine in a Uruguayan Population.
Int J Nephrol
PUBLISHED: 06-09-2014
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Background. Estimation of glomerular filtration rate (eGFR) from biomarkers has evolved and multiple equations are available to estimate renal function at bedside. Methods. In a random sample of 119 Uruguayans (54.5% women; 56.2 years (mean)), we used Bland and Altman's method and Cohen's kappa statistic to assess concordance on a continuous or categorical (eGFR < 60 versus ?60?mL/min/1.73?m(2)) scale between eGFRcys (reference) and eGFR derived from serum creatinine according to the Modification of Diet in Renal Disease (eGFRmdrd) or the Chronic Kidney Disease Epidemiology Collaboration equations (eGFRepi) or from both serum cystatin C and creatinine (eGFRmix). Results. In all participants, eGFRmdrd, eGFRepi, and eGFRmix were, respectively, 9.7, 11.5, and 5.6?mL/min/1.73?m(2) higher (P < 0.0001) than eGFRcys. The prevalence of eGFR <60?mL/min/1.73?m(2) was the highest for eGFRcys (21.8%), intermediate for eGFRmix (11.8%), and the lowest for eGFRmdrd (5.9%) and eGFRepi (3.4%). Using eGFRcys as reference, we found only fair agreement with the equations based on creatinine (Cohen's kappa statistic 0.15 to 0.23). Conclusion. Using different equations we reached clinically significant differences in the estimation of renal function. eGFRcys provides lower estimates, resulting in higher prevalence of eGFR <60?mL/min/1.73?m(2).
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Quality of blood pressure phenotype in the Nigerian Population Research on Environment Gene and Health.
Blood Press Monit
PUBLISHED: 06-04-2014
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In the ongoing Nigerian Population Research on Environment Gene and Health (NIPREGH), we are applying standardized epidemiologic methods to determine cardiovascular phenotypes including blood pressure (BP) among adult Black Africans of Nigerian origin. We present the quality control of the conventionally measured BP.
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European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring.
J. Hypertens.
PUBLISHED: 06-03-2014
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Given the increasing use of ambulatory blood pressure monitoring (ABPM) in both clinical practice and hypertension research, a group of scientists, participating in the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability, in year 2013 published a comprehensive position paper dealing with all aspects of the technique, based on the available scientific evidence for ABPM. The present work represents an updated schematic summary of the most important aspects related to the use of ABPM in daily practice, and is aimed at providing recommendations for proper use of this technique in a clinical setting by both specialists and practicing physicians. The present article details the requirements and the methodological issues to be addressed for using ABPM in clinical practice, The clinical indications for ABPM suggested by the available studies, among which white-coat phenomena, masked hypertension, and nocturnal hypertension, are outlined in detail, and the place of home measurement of blood pressure in relation to ABPM is discussed. The role of ABPM in pharmacological, epidemiological, and clinical research is also briefly mentioned. Finally, the implementation of ABPM in practice is considered in relation to the situation of different countries with regard to the reimbursement and the availability of ABPM in primary care practices, hospital clinics, and pharmacies.
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Prognostic value of left ventricular diastolic dysfunction in a general population.
J Am Heart Assoc
PUBLISHED: 05-01-2014
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New techniques of Tissue Doppler Imaging (TDI) enable the measurement of myocardial velocities and provide information about left ventricular (LV) diastolic function. Recent studies explored the prognostic role of TDI-derived indexes. However, these studies considered only total mortality and did not provide information on cardiovascular mortality and morbidity. Therefore, we investigated in continuous and categorical analyses whether Doppler diastolic indexes contained any prognostic information over and beyond traditional cardiovascular risk factors in a general population.
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Rationale and design of the Investigator-Steered Project on Intravascular Renal Denervation for Management of Drug-Resistant Hypertension (INSPiRED) trial.
Blood Press.
PUBLISHED: 04-17-2014
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The SYMPLICITY studies showed that renal denervation (RDN) is feasible as novel treatment for resistant hypertension. However, RDN is a costly and invasive procedure, the long-term efficacy and safety of which has not yet been proven. Therefore, we designed the INSPiRED trial to compare the blood pressure lowering efficacy and safety of RDN vs usual medical therapy. INSPiRED is a randomized controlled trial enrolling 240 treatment-resistant hypertensive patients at 16 expert hypertension centres in Belgium. Eligible patients, aged 20-69 years old, have a 24-h ambulatory blood pressure of 130 mmHg systolic or 80 mmHg diastolic or more, while taking at least three antihypertensive drugs. They are randomized to RDN (EnligHTN(TM), SJM system) plus usual care (intervention group) or usual care alone (control group) in a ratio of 1:1. The primary endpoints for efficacy and safety, measured after 6 months, are the baseline-adjusted between-group differences in 24h systolic blood pressure and in glomerular filtration rate as estimated by the Chronic Kidney Disease Epidemiology Collaboration equation. Follow-up will continue up to 36 months after randomization. INSPiRED is powered to demonstrate a 10-mmHg difference in systolic blood pressure between randomized groups with a two-sided p-value of 0.01 and 90% power. It will generate long-term efficacy and safety data, identify the subset of treatment-resistant hypertensive patients responsive to RDN, provide information on cost-effectiveness, and by doing so INSPiRED will inform guideline committees and health policy makers. Trial registration: ClinicalTrials.gov Identifier: NCT 01505010.
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Left ventricular diastolic function in relation to the urinary proteome: a proof-of-concept study in a general population.
Int. J. Cardiol.
PUBLISHED: 04-02-2014
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In previous studies, we identified two urinary proteomic classifiers, termed HF1 and HF2, which discriminated subclinical diastolic left ventricular (LV) dysfunction from normal. HF1 and HF2 combine information from 85 and 671 urinary peptides, mainly up- or down-regulated collagen fragments. We sought to validate these classifiers in a population study.
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Association of digital vascular function with cardiovascular risk factors: a population study.
BMJ Open
PUBLISHED: 03-26-2014
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Vasodilation of the peripheral arteries during reactive hyperaemia depends in part on release of nitric oxide from endothelial cells. Previous studies mainly employed a fingertip tonometric device to derive pulse wave amplitude (PWA) and PWA hyperaemic changes. An alternative approach is based on photoplethysmography (PPG). We sought to evaluate the correlates of digital PPG PWA hyperaemic responses as a measure of peripheral vascular function.
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Eligibility for renal denervation: experience at 11 European expert centers.
Hypertension
PUBLISHED: 03-24-2014
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Based on the SYMPLICITY studies and CE (Conformité Européenne) certification, renal denervation is currently applied as a novel treatment of resistant hypertension in Europe. However, information on the proportion of patients with resistant hypertension qualifying for renal denervation after a thorough work-up and treatment adjustment remains scarce. The aim of this study was to investigate the proportion of patients eligible for renal denervation and the reasons for noneligibility at 11 expert centers participating in the European Network COordinating Research on renal Denervation in treatment-resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure-lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according to the SYMPLICITY HTN-2 criteria and each center's criteria was 42.5% (95% confidence interval, 38.0%-47.0%) and 39.7% (36.2%-43.2%), respectively. The main reasons of noneligibility were normalization of blood pressure after treatment adjustment (46.9%), unsuitable renal arterial anatomy (17.0%), and previously undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ?40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Our findings highlight that hypertension centers with a record in clinical experience and research should remain the gatekeepers before renal denervation is considered.
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Reference frame for home pulse pressure based on cardiovascular risk in 6470 subjects from 5 populations.
Hypertens. Res.
PUBLISHED: 03-20-2014
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The absence of an outcome-driven reference frame for self-measured pulse pressure (PP) limits its clinical applicability. In an attempt to derive an operational threshold for self-measured PP, we analyzed 6470 participants (mean age 59.3 years; 56.9% women; 22.5% on antihypertensive treatment) from 5 general population cohorts included in the International Database on HOme blood pressure in relation to Cardiovascular Outcome. During 8.3 years of follow-up (median), 294 cardiovascular deaths, 393 strokes and 336 cardiac events occurred. In 3285 younger subjects (<60 years), home PP only predicted all-cause and cardiovascular mortality (P?0.036), whereas in 3185 older subjects (?60 years) PP predicted total and cardiovascular mortality (P?0.0067) and all cardiovascular and coronary events (P?0.044). However, PP did not substantially refine risk prediction based on classical risk factors including mean blood pressure (generalized R(2) statistic ?0.20%). In older subjects, the adjusted hazard ratios expressing the risk in the upper decile of home PP (?76?mm?Hg) versus the average risk in whole population were 1.41 (95% confidence interval, 1.09-1.81; P=0.0081) for all-cause mortality, 1.62 (1.11-2.35; P=0.012) for cardiovascular mortality and 1.31 (1.00-1.70; P=0.047) for all fatal and nonfatal cardiovascular end points combined. The low number of events precluded an analysis by tenths of the PP distribution in younger participants. In conclusion, a home PP of ?76?mm?Hg predicted cardiovascular outcomes in the elderly with the exception of stroke, whereas in younger subjects no threshold could be established.
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Heart 'omics' in AGEing (HOMAGE): design, research objectives and characteristics of the common database.
J Biomed Res
PUBLISHED: 03-08-2014
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Heart failure is common in older people and its prevalence is increasing. The Heart 'omics' in AGEing (HOMAGE) project aims to provide a biomarker approach that will improve the early diagnosis of heart failure. A large clinical database, based on (1) prospective population studies or (2) cross-sectional, prospective studies or randomized controlled trials (RCTs) of patients at risk for or with overt cardiovascular disease will be constructed to determine most promising 'omics'-based biomarkers to identify the risk of developing heart failure and/or comorbidities. Population studies, patient cohorts and RCTs are eligible for inclusion in the common database, if they received ethical approval to obtain and share data and have baseline information on cardiovascular risk factors. Currently, the HOMAGE database includes 43,065 subjects, from 20 studies in eight European countries, including healthy subjects from three population studies in France, Belgium and Italy (n ?=? 7,124), patients with heart failure (n ?=? 4,312) from four cohorts in the UK, Spain and Switzerland and patients at high risk for cardiovascular disease (n ?=? 31,629) in 13 cohorts. It is anticipated that more partners will join the consortium and enlarge the pooled data. This large merged database will be a useful resource with which to identify candidate biomarkers that play a role in the mechanism underlying the onset and progression of heart failure.
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Nigerian Population Research on Environment, Gene and Health (NIPREGH) - objectives and protocol.
J Biomed Res
PUBLISHED: 02-25-2014
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Sub-Saharan Africa is currently undergoing an epidemiological transition from a disease burden largely attributable to communicable diseases to that resulting from a combination of both communicable and chronic non-communicable diseases. Data on chronic disease incidence, lifestyle, environmental and genetic risk factors are sparse in this region. This report aimed at providing relevant information in respect to risk factors that increase blood pressure and lead to development of intermediate cardiovascular phenotypes. We presented the rationale, objectives and key methodological features of the Nigerian Population Research on Environment, Gene and Health (NIPREGH) study. The challenges encountered in carrying out population study in this part of the world and the approaches at surmounting them were also presented. The preliminary data as at 20 November 2013 showed that out of the 205 individuals invited starting from early April 2013, 160 (72 women) consented and were enrolled; giving a response rate of 78%. Participants' age ranged from 18 to 80 years, with a mean (SD) of 39.8 (12.4) years and they were of 34 different ethnic groups spread over 24 states out of the 36 states that constitute Nigeria. The mean (SD) of office and home blood pressures were 113.0 (15.2) mm Hg systolic, 73.5 (12.5) mm Hg diastolic and 117.3 (15.0) mm Hg systolic, and 76.0 (9.6) mm Hg diastolic, respectively. Forty-three (26.8%) participants were hypertensive and 8 (5.0%) were diabetic. In addition to having the unique potential of recruiting a cohort that is a true representative of the entire Nigerian population, NIPREGH is feasible and the objectives realisable.
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Blood pressure load does not add to ambulatory blood pressure level for cardiovascular risk stratification.
Hypertension
PUBLISHED: 02-17-2014
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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.
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Prognosis of white-coat and masked hypertension: International Database of HOme blood pressure in relation to Cardiovascular Outcome.
Hypertension
PUBLISHED: 01-13-2014
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Home blood pressure monitoring is useful in detecting white-coat and masked hypertension and is recommended for patients with suspected or treated hypertension. The prognostic significance of white-coat and masked hypertension detected by home measurement was investigated in 6458 participants from 5 populations enrolled in the International Database of HOme blood pressure in relation to Cardiovascular Outcomes. During a median follow-up of 8.3 years, 714 fatal plus nonfatal cardiovascular events occurred. Among untreated subjects (n=5007), cardiovascular risk was higher in those with white-coat hypertension (adjusted hazard ratio 1.42; 95% CI [1.06-1.91]; P=0.02), masked hypertension (1.55; 95% CI [1.12-2.14]; P<0.01) and sustained hypertension (2.13; 95% CI [1.66-2.73]; P<0.0001) compared with normotensive subjects. Among treated patients (n=1451), the cardiovascular risk did not differ between those with high office and low home blood pressure (white-coat) and treated controlled subjects (low office and home blood pressure; 1.16; 95% CI [0.79-1.72]; P=0.45). However, treated subjects with masked hypertension (low office and high home blood pressure; 1.76; 95% CI [1.23-2.53]; P=0.002) and uncontrolled hypertension (high office and home blood pressure; 1.40; 95% CI [1.02-1.94]; P=0.04) had higher cardiovascular risk than treated controlled patients. In conclusion, white-coat hypertension assessed by home measurements is a cardiovascular risk factor in untreated but not in treated subjects probably because the latter receive effective treatment on the basis of their elevated office blood pressure. In contrast, masked uncontrolled hypertension is associated with increased cardiovascular risk in both untreated and treated patients, who are probably undertreated because of their low office blood pressure.
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Does blood pressure variability contribute to risk stratification? Methodological issues and a review of outcome studies based on home blood pressure.
Hypertens. Res.
PUBLISHED: 01-09-2014
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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.Hypertension Research advance online publication, 16 October 2014; doi:10.1038/hr.2014.153.
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Beat-to-beat, reading-to-reading, and day-to-day blood pressure variability in relation to organ damage in untreated Chinese.
Hypertension
PUBLISHED: 01-06-2014
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Whether target organ damage is associated with blood pressure (BP) variability independent of level remains debated. We assessed these associations from 10-minute beat-to-beat, 24-hour ambulatory, and 7-day home BP recordings in 256 untreated subjects referred to a hypertension clinic. BP variability indices were variability independent of the mean, maximum-minimum difference, and average real variability. Effect sizes (standardized ?) were computed using multivariable regression models. In beat-to-beat recordings, left ventricular mass index (n=128) was not (P?0.18) associated with systolic BP but increased with all 3 systolic variability indices (+2.97-3.53 g/m(2); P<0.04); the urinary albumin-to-creatinine ratio increased (P?0.03) with systolic BP (+1.14-1.17 mg/mmol) and maximum-minimum difference (+1.18 mg/mmol); and pulse wave velocity increased with systolic BP (+0.69 m/s; P<0.001). In 24-hour recordings, all 3 indices of organ damage increased (P<0.03) with systolic BP, whereas the associations with BP variability were nonsignificant (P?0.15) except for increases in pulse wave velocity (P<0.05) with variability independent of the mean (+0.16 m/s) and maximum-minimum difference (+0.17 m/s). In home recordings, the urinary albumin-to-creatinine ratio (+1.27-1.30 mg/mmol) and pulse wave velocity (+0.36-0.40 m/s) increased (P<0.05) with systolic BP, whereas all associations of target organ damage with the variability indices were nonsignificant (P?0.07). In conclusion, while accounting for BP level, associations of target organ damage with BP variability were readily detectable in beat-to-beat recordings, least noticeable in home recordings, with 24-hour ambulatory monitoring being informative only for pulse wave velocity.
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Randomised double-blind comparison of placebo and active drugs for effects on risks associated with blood pressure variability in the Systolic Hypertension in Europe trial.
PLoS ONE
PUBLISHED: 01-01-2014
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In the Systolic Hypertension in Europe trial (NCT02088450), we investigated whether systolic blood pressure variability determines prognosis over and beyond level.
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Heritability and clinical determinants of serum indoxyl sulfate and p-cresyl sulfate, candidate biomarkers of the human microbiome enterotype.
PLoS ONE
PUBLISHED: 01-01-2014
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Indoxyl sulfate and p-cresyl sulfate are unique microbial co-metabolites. Both co-metabolites have been involved in the pathogenesis of accelerated cardiovascular disease and renal disease progression. Available evidence suggests that indoxyl sulfate and p-cresyl sulfate may be considered candidate biomarkers of the human enterotype and may help to explain the link between diet and cardiovascular disease burden.
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Risk stratification by self-measured home blood pressure across categories of conventional blood pressure: a participant-level meta-analysis.
PLoS Med.
PUBLISHED: 01-01-2014
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The Global Burden of Diseases Study 2010 reported that hypertension is worldwide the leading risk factor for cardiovascular disease, causing 9.4 million deaths annually. We examined to what extent self-measurement of home blood pressure (HBP) refines risk stratification across increasing categories of conventional blood pressure (CBP).
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Tight Versus Standard Blood Pressure Control in Patients With Hypertension With and Without Cardiovascular Disease.
Hypertension
PUBLISHED: 12-16-2013
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An excessive blood pressure (BP) reduction might be dangerous in high-risk patients with cardiovascular disease. In the Studio Italiano Sugli Effetti CARDIOvascolari del Controllo della Pressione Arteriosa SIStolica (Cardio-Sis), 1111 nondiabetic patients with systolic BP ?150 mm Hg were randomly assigned to a systolic BP target <140 mm Hg (standard control) or <130 mm Hg (tight control). We stratified patients by absence (n=895) or presence (n=216) of established cardiovascular disease at entry. Antihypertensive treatment was open-label and tailored to each patients needs. After 2-year follow-up, the primary end point of the study, electrocardiographic left ventricular hypertrophy, occurred less frequently in the tight than in the standard control group in the patients without (10.8% versus 15.2%) and with (14.1% versus 23.5%) established cardiovascular disease (P for interaction=0.82). The main secondary end point, a composite of cardiovascular events and all-cause death, occurred less frequently in the tight than in the standard control group both in patients without (1.47 versus 3.68 patient-years; P=0.016) and with (7.87 versus 11.22 patient-years; P=0.049) previous cardiovascular disease. In a multivariable Cox model, allocation to tight BP control reduced the risk of cardiovascular events to a similar extent in patients with or without overt cardiovascular disease at randomization (P for interaction=0.43). In conclusion, an intensive treatment aimed to lower systolic BP<130 mm Hg reduced left ventricular hypertrophy and improved clinical outcomes to a similar extent in patients with hypertension and without established cardiovascular disease.
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Outcome-Driven Thresholds for Ambulatory Pulse Pressure in 9938 Participants Recruited From 11 Populations.
Hypertension
PUBLISHED: 12-09-2013
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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.
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Association of Target Organ Damage With 24-Hour Systolic and Diastolic Blood Pressure Levels and Hypertension Subtypes in Untreated Chinese.
Hypertension
PUBLISHED: 11-18-2013
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The association of target organ damage with 24-hour systolic and diastolic blood pressure levels and ambulatory hypertension subtypes has not yet been examined in untreated Chinese patients. We measured left ventricular mass index by echocardiography (n=619), the urinary albumin:creatinine ratio (n=1047), and aortic pulse wave velocity by tonometry (n=1013) in 1047 untreated subjects (mean age, 50.6 years; 48.9% women). Normotension was a 24-hour systolic/diastolic blood pressure <130/<80 mm Hg. Hypertension subtypes were isolated diastolic hypertension and mixed systolic plus diastolic hypertension. We assessed associations of interest by multivariable-adjusted linear models. Using normotension as reference, mixed hypertension was associated with higher (P?0.003) left ventricular mass index (+4.31 g/m(2)), urinary albumin:creatinine ratio (+1.63 mg/mmol), and pulse wave velocity (+0.76 m/s); and isolated diastolic hypertension was associated with similar left ventricular mass index and pulse wave velocity (P?0.39), but higher urinary albumin:creatinine ratio (+1.24 mg/mmol; P=0.002). In younger participants (<55 years), the mutually independent effect sizes associated with 1 SD increases in 24-hour systolic/diastolic blood pressure were +3.31/-0.36 g/m(2) (P=0.009/0.79) for left ventricular mass index, +1.15/+1.14 mg/mmol (P=0.02/0.04) for the urinary albumin:creatinine ratio, and +0.54/-0.05 m/s (P<0.001/0.54) for pulse wave velocity. In older participants, these estimates were +3.58/+0.30 g/m(2) (P=0.045/0.88), +1.23/+1.05 mg/mmol (P=0.002/0.54), and +0.76/-0.49 m/s (P<0.001/<0.001), respectively. In conclusion, 24-hour systolic blood pressure and mixed hypertension are major determinants of target organ damage irrespective of age and target organ, whereas 24-hour diastolic blood pressure and isolated diastolic hypertension only relate to the urinary albumin:creatinine ratio below middle age.
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Reference values and factors associated with renal resistive index in a family-based population study.
Hypertension
PUBLISHED: 10-14-2013
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Increased renal resistive index (RRI) has been recently associated with target organ damage and cardiovascular or renal outcomes in patients with hypertension and diabetes mellitus. However, reference values in the general population and information on familial aggregation are largely lacking. We determined the distribution of RRI, associated factors, and heritability in a population-based study. Families of European ancestry were randomly selected in 3 Swiss cities. Anthropometric parameters and cardiovascular risk factors were assessed. A renal Doppler ultrasound was performed, and RRI was measured in 3 segmental arteries of both kidneys. We used multilevel linear regression analysis to explore the factors associated with RRI, adjusting for center and family relationships. Sex-specific reference values for RRI were generated according to age. Heritability was estimated by variance components using the ASSOC program (SAGE software). Four hundred women (mean age±SD, 44.9±16.7 years) and 326 men (42.1±16.8 years) with normal renal ultrasound had mean RRI of 0.64±0.05 and 0.62±0.05, respectively (P<0.001). In multivariable analyses, RRI was positively associated with female sex, age, systolic blood pressure, and body mass index. We observed an inverse correlation with diastolic blood pressure and heart rate. Age had a nonlinear association with RRI. We found no independent association of RRI with diabetes mellitus, hypertension treatment, smoking, cholesterol levels, or estimated glomerular filtration rate. The adjusted heritability estimate was 42±8% (P<0.001). In a population-based sample with normal renal ultrasound, RRI normal values depend on sex, age, blood pressure, heart rate, and body mass index. The significant heritability of RRI suggests that genes influence this phenotype.
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Hypertension control in community health centers across china: analysis of antihypertensive drug treatment patterns.
Am. J. Hypertens.
PUBLISHED: 10-09-2013
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Blood pressure (BP) control in China is generally poor. It is assumed that an important cause of this unsatisfactory situation is the present standard of care provided by primary care physicians.
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Heart rate variability on antihypertensive drugs in Black patients living in sub-Saharan Africa.
Blood Press.
PUBLISHED: 09-25-2013
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Background. Compared with Caucasians, African Americans have lower heart rate variability (HRV) in the high-frequency domain, but there are no studies in Blacks born and living in Africa. Methods. In the Newer versus Older Antihypertensive agents in African Hypertensive patients trial (NCT01030458), patients (30-69 years) with uncomplicated hypertension (140-179/90-109 mmHg) were randomized to single-pill combinations of bisoprolol/hydrochlorothiazide (R) or amlodipine/valsartan (E). 72 R and 84 E patients underwent 5-min ECG recordings at randomization and 8, 16 and 24 weeks. HRV was determined by fast Fourier transform and autoregressive modelling. Results. Heart rate decreased by 9.5 beats/min in R patients with no change in E patients (- 2.2 beats/min). R patients had reduced total (- 0.13 ms²; p = 0.0038) and low-frequency power (- 3.6 nu; p = 0.057), higher high-frequency (+ 3.3 nu; p = 0.050) and a reduced low- to high-frequency ratio (- 0.08; p = 0.040). With adjustment for heart rate, these differences disappeared, except for the reduced low-frequency power in the R group (- 4.67 nu; p = 0.02). Analyses confined to 39 R and 47 E patients with HRV measurements at all visits or based on autoregressive modelling were confirmatory. Conclusion. In native Black African patients, antihypertensive drugs modulate HRV, an index of autonomous nervous tone. However, these effects were mediated by changes in heart rate except for low-frequency variability, which was reduced on beta blockade independent of heart rate.
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Left ventricular radial function associated with genetic variation in the cGMP-dependent protein kinase.
Hypertension
PUBLISHED: 09-23-2013
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cGMP-dependent protein kinase type I is a major mediator of cGMP signaling in the cardiovascular system. Recent studies on cardiac-specific PRKG1 knockout mice demonstrated that cGMP-dependent protein kinase type I mediates the negative inotropic effect of cGMP in the myocardium. We therefore investigated the association between left ventricular (LV) function and common polymorphisms in the PRKG1 gene in a general population. In 609 randomly selected participants (51.2% women; mean age, 48.8 years; 36.6% hypertensive) who were free from overt cardiac disease, we performed echocardiography and genotyped intronic tag single-nucleotide polymorphisms (SNPs) rs1904694, rs7897633, and rs7905063 in PRKG1. On the basis of color Doppler myocardial motion data, we calculated end-systolic longitudinal and radial deformation (strain) of the LV inferolateral wall. In multivariable-adjusted analyses accounting for confounders and relatedness, systolic radial strain was significantly (P ? 0.005) higher in homozygotes for rs1904694 (GG), rs7897633 (AA), and rs7905063 (TT) compared with heterozygotes or noncarriers. Haplotype analysis confirmed that LV radial strain was significantly higher in GAT homozygotes than in noncarriers (62.3% versus 56.0%; P = 0.0005). Transmission of the PRKG1 GAT haplotype to informative offspring was associated with higher LV radial strain (effect size, 6.11%; P = 0.017). For other LV phenotypes, none of the phenotype-genotype associations reached statistical significance. In conclusion, LV systolic radial function was associated with common polymorphisms in PRKG1. If experimental studies and longitudinal follow-up of LV function confirm the causality of this association, interference with cGMP-dependent protein kinase type I function might be a target for pharmacological intervention.
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cGMP-dependent protein kinase 1 polymorphisms underlie renal sodium handling impairment.
Hypertension
PUBLISHED: 09-23-2013
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Defective pressure-natriuresis related to abnormalities in the natriuretic response has been associated with hypertension development. A major signaling pathway mediating pressure natriuresis involves the cGMP-dependent protein kinase 1 (PRKG1) that, once activated by Src kinase, inhibits renal Na(+) reabsorption via a direct action on basolateral Na-K ATPase and luminal Na-H exchanger type 3, as shown in renal tubuli of animals. Because a clear implication of PRKG1 in humans is still lacking, here we addressed whether PRKG1 polymorphisms affect pressure-natriuresis in patients. Naive hypertensive patients (n = 574), genotyped for PRKG1 rs1904694, rs7897633, and rs7905063 single nucleotide polymorphisms (SNPs), underwent an acute Na(+) loading, and the slope of the pressure-natriuresis relationship between blood pressure and Na(+) excretion was calculated. The underlying molecular mechanism was investigated by immunoblotting protein quantifications in human kidneys. The results demonstrate that the PRKG1 risk haplotype GAT (rs1904694, rs7897633, rs7905063, respectively) associates with a rightward shift of the pressure-natriuresis curve (0.017 ± 0.004 ?Eq/mm Hg per minute) compared with the ACC (0.0013 ± 0.003 ?Eq/mm Hg per minute; P = 0.001). In human kidneys, a positive correlation of protein expression levels between PRKG1 and Src (r = 0.83; P<0.001) or ?1 Na-K ATPase (r = 0.557; P<0.01) and between ?1 Na-K ATPase and Na-H exchanger type 3 (r = 0.584; P<0.01) or Src (r = 0.691; P<0.001) was observed in patients carrying PRKG1 risk GAT (n = 23) but not ACC (n = 14) variants. A functional signaling complex among PRKG1, ?1 Na-K ATPase, and Src was shown by immunoprecipitation from human renal caveolae. These findings indicate that PRKG1 risk alleles associate with salt-sensitivity related to a loss of the inhibitory control of renal Na(+) reabsorption, suggestive of a blunt pressure-natriuresis response.
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European society of hypertension position paper on ambulatory blood pressure monitoring.
J. Hypertens.
PUBLISHED: 09-14-2013
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Ambulatory blood pressure monitoring (ABPM) is being used increasingly in both clinical practice and hypertension research. Although there are many guidelines that emphasize the indications for ABPM, there is no comprehensive guideline dealing with all aspects of the technique. It was agreed at a consensus meeting on ABPM in Milan in 2011 that the 34 attendees should prepare a comprehensive position paper on the scientific evidence for ABPM.This position paper considers the historical background, the advantages and limitations of ABPM, the threshold levels for practice, and the cost-effectiveness of the technique. It examines the need for selecting an appropriate device, the accuracy of devices, the additional information and indices that ABPM devices may provide, and the software requirements.At a practical level, the paper details the requirements for using ABPM in clinical practice, editing considerations, the number of measurements required, and the circumstances, such as obesity and arrhythmias, when particular care needs to be taken when using ABPM.The clinical indications for ABPM, among which white-coat phenomena, masked hypertension, and nocturnal hypertension appear to be prominent, are outlined in detail along with special considerations that apply in certain clinical circumstances, such as childhood, the elderly and pregnancy, and in cardiovascular illness, examples being stroke and chronic renal disease, and the place of home measurement of blood pressure in relation to ABPM is appraised.The role of ABPM in research circumstances, such as pharmacological trials and in the prediction of outcome in epidemiological studies is examined and finally the implementation of ABPM in practice is considered in relation to the issue of reimbursement in different countries, the provision of the technique by primary care practices, hospital clinics and pharmacies, and the growing role of registries of ABPM in many countries.
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Target sequencing, cell experiments, and a population study establish endothelial nitric oxide synthase (eNOS) gene as hypertension susceptibility gene.
Hypertension
PUBLISHED: 09-09-2013
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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.
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Renal denervation in the management of resistant hypertension: current evidence and perspectives.
Curr. Opin. Nephrol. Hypertens.
PUBLISHED: 07-30-2013
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Catheter-based renal denervation has emerged as a novel treatment modality for resistant hypertension. This review summarizes the current evidence on this procedure in treatment of resistant hypertension, limitations of available evidence and questions to be answered.
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Renal denervation in treatment-resistant hypertension: the need for restraint and more and better evidence.
Expert Rev Cardiovasc Ther
PUBLISHED: 06-12-2013
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The Symplicity studies suggest that intravascular renal sympathetic nervous denervation improves blood pressure in patients with resistant hypertension, thus potentially opening a market for devices to be used when conventional drug therapy fails to restore blood pressure control. However, the size and durability of the antihypertensive, renal and sympatholytic effects of renal denervation, the long-term safety, improvement of quality of life, the possibility to relax antihypertensive drug treatment, the cost-effectiveness, and long-term hard cardiovascular-renal outcomes still remain to be firmly established. Most ongoing studies are small, industry-driven and purely observational with objectives to test new catheters and source of energy for renal nerve ablation or to search for ancillary benefits and new indications of the technique. The most urgent need, that is adequately powered randomized clinical trials testing renal denervation versus usual medical therapy delivered according to the state-of-the-art are under-represented and seldom funded by industry. The authors make a plea for a coordinated research effort in Europe. With this objective, they established collaboration with leading European experts and started the European Network for Coordinating Research on Renal Denervation. In the meantime, renal denervation should remain the ultima ratio in adherent and truly resistant patients with severe hypertension, confirmed by ambulatory monitoring, in whom secondary hypertension has been excluded and in whom all other efforts to reduce blood pressure have failed.
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Sexual dimorphism in the transition from masked to sustained hypertension in healthy youths.
Hypertension
PUBLISHED: 06-03-2013
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The risk and factors related to the development of hypertension among healthy youths with elevated ambulatory and normal conventional blood pressure, masked hypertension, have not been established. We performed a long-term follow-up study assessing how hypertension develops over time in healthy, masked hypertensive youths. The potential sex dimorphism in the incidence and timing of the development of hypertension has been analyzed. In a long-term follow-up study (median follow-up, 36 months), we enrolled 272 healthy conventional normotensive youths (aged 6-18 years; 55.8% girls) of whom 39 had masked hypertension at baseline. Development of sustained hypertension (hypertension in both conventional and ambulatory measurement) was recorded. The daytime systolic blood pressure increased from baseline to last available follow-up in boys (3.5 mm Hg; P<0.001) but not in girls (0.7 mm Hg; P=0.23), leading to a significant between-sex difference (P=0.0022). The incidence of sustained hypertension was 7.0/100 subjects/y (n=12) in masked hypertensives and 0.6/100 subjects/y (n=4) in normotensives. Masked hypertensive boys more frequently proceeded to sustained hypertension as compared with masked hypertensive girls (50.0% versus 17.4%; P=0.041). Masked hypertension at baseline (hazard ratio, 15.6; 95% confidence interval, 4.91-49.7; P<0.0001) and male sex (hazard ratio, 3.25; 95% confidence interval, 1.12-9.39; P=0.0295) were independent factors associated with the incidence of sustained hypertension during the follow-up. In youth, masked hypertension is a precursor of sustained hypertension. The risk of developing sustained hypertension is higher in boys than it is for girls. The fact that masked hypertension is not prognostically innocent increases the importance of the diagnosis at an early age.
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Predictive power of home blood pressure and clinic blood pressure in hypertensive patients with impaired glucose metabolism and diabetes.
J. Hypertens.
PUBLISHED: 05-16-2013
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We evaluated the predictive power of home blood pressure and clinic blood pressure based on the long-term cardiovascular outcome in hypertensive patients with and without impaired glucose metabolism (IGM).
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Masked hypertension in diabetes mellitus: treatment implications for clinical practice.
Hypertension
PUBLISHED: 03-11-2013
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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.
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Sodium and potassium and the pathogenesis of hypertension.
Curr. Hypertens. Rep.
PUBLISHED: 02-12-2013
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The evidence relating blood pressure to salt intake in humans originates from population studies and randomized clinical trials of interventions on dietary salt intake. Estimates from meta-analyses of trials in normotensive subjects generally are similar to estimates derived from prospective population studies (+1.7-mm Hg increase in systolic blood pressure per 100 mmol increment in 24-hour urinary sodium). This estimate, however, does not translate into an increased risk of incident hypertension in subjects consuming a high-salt diet. The meta-analyses of intervention trials have consistently shown that potassium supplementation is associated with lowering of blood pressure. However, prospective studies relating health outcomes to 24-hour urinary sodium and/or potassium excretion produced inconsistent results. Taken together, available evidence does not support the current recommendations of a generalized and indiscriminate reduction of salt intake at the population level, although the blood-pressure lowering effect of dietary sodium restriction might be of value in hypertensive patients. Potassium supplementation in hypertensive patients or healthy persons is not recommended by the current guidelines, but importance of adhering to healthy diet rich in vegetables and fruits is emphasized.
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Central systolic augmentation indexes and urinary sodium in a white population.
Am. J. Hypertens.
PUBLISHED: 02-06-2013
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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.
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Associations of urinary cadmium with age and urinary proteins: further evidence of physiological variations unrelated to metal accumulation and toxicity.
Environ. Health Perspect.
PUBLISHED: 02-04-2013
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The current risk assessment for environmental cadmium (Cd) largely relies on the assumption that urinary Cd (U-Cd) is a reliable biomarker of the Cd body burden. Recent studies have questioned the validity of this assumption.
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Meta-analysis of randomised trials with a continuous outcome according to baseline imbalance and availability of individual participant data.
Stat Med
PUBLISHED: 01-10-2013
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We describe methods for meta-analysis of randomised trials where a continuous outcome is of interest, such as blood pressure, recorded at both baseline (pre treatment) and follow-up (post treatment). We used four examples for illustration, covering situations with and without individual participant data (IPD) and with and without baseline imbalance between treatment groups in each trial. Given IPD, meta-analysts can choose to synthesise treatment effect estimates derived using analysis of covariance (ANCOVA), a regression of just final scores, or a regression of the change scores. When there is baseline balance in each trial, treatment effect estimates derived using ANCOVA are more precise and thus preferred. However, we show that meta-analysis results for the summary treatment effect are similar regardless of the approach taken. Thus, without IPD, if trials are balanced, reviewers can happily utilise treatment effect estimates derived from any of the approaches. However, when some trials have baseline imbalance, meta-analysts should use treatment effect estimates derived from ANCOVA, as this adjusts for imbalance and accounts for the correlation between baseline and follow-up; we show that the other approaches can give substantially different meta-analysis results. Without IPD and with unavailable ANCOVA estimates, reviewers should limit meta-analyses to those trials with baseline balance. Trowmans method to adjust for baseline imbalance without IPD performs poorly in our examples and so is not recommended. Finally, we extend the ANCOVA model to estimate the interaction between treatment effect and baseline values and compare options for estimating this interaction given only aggregate data.
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Heritability of the retinal microcirculation in Flemish families.
Am. J. Hypertens.
PUBLISHED: 01-07-2013
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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.
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Genomewide association study using a high-density single nucleotide polymorphism array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of endothelial NO synthase.
Hypertension
PUBLISHED: 12-19-2011
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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.
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Blood flow pattern in the middle cerebral artery in relation to indices of arterial stiffness in the systemic circulation.
Am. J. Hypertens.
PUBLISHED: 11-24-2011
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The brain is perfused at high-volume flow throughout systole and diastole. We explored the association of blood flow in the middle cerebral artery (MCA) with the pulsatile components of blood pressure in the systemic circulation and indices of arterial stiffness.
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Determinants of arterial properties in Chinese type-2 diabetic patients compared with population-based controls.
Acta Cardiol
PUBLISHED: 10-29-2011
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To our knowledge, few studies compared the association of brachial-ankle pulse wave velocity (baPWV) with cardiovascular risk factors among Chinese with type-2 diabetes mellitus and non-diabetic controls. This study addresses this issue.
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Short-term blood pressure variability in relation to outcome in the International Database of Ambulatory blood pressure in relation to Cardiovascular Outcome (IDACO).
Acta Cardiol
PUBLISHED: 10-17-2011
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Ambulatory blood pressure monitoring not only provides information on the blood pressure level, but on the diurnal changes in blood pressure as well. The present review summarizes the main findings of the International Database on Ambulatory blood pressure in relation to Cardiovascular Outcome (IDACO) with regard to risk stratification based on short-term blood pressure variability. An exaggerated morning surge, exceeding the 90th percentile of the population, is an independent risk factor for mortality and cardiovascular and cardiac events. Conversely, a sleep-through or pre-awakening morning surge less than 20 mm Hg in systolic blood pressure is probably not associated with an increased risk of death or cardiovascular events. Blood pressure variability represented by the average of the daytime and nighttime SD weighted for the duration of the daytime and nighttime interval (SDdn) and by average real variability (ARV24) predicted outcome, but only improved the prediction of the composite cardiovascular events by 0.1%. Overall, results of analyses using the IDACO support the concept that short-term blood pressure variability adds to risk stratification, but 24-hour ambulatory blood pressure level is the most valuable predictor for use in clinical practice.
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Prognostic significance of home arterial stiffness index derived from self-measurement of blood pressure: the Ohasama Study.
Am. J. Hypertens.
PUBLISHED: 09-29-2011
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Arterial stiffness is a stroke risk factor. The home arterial stiffness index (HASI) can be calculated from self-measured blood pressure using the same formula as the calculation of ambulatory arterial stiffness index (AASI).
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Age dependency of peripheral and central systolic blood pressures: cross-sectional and longitudinal observations in a Chinese population.
Hypertens. Res.
PUBLISHED: 09-15-2011
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Few studies have described the age-related changes in both peripheral and central systolic blood pressures (SBPs) in populations. We addressed this issue in 1066 women and 978 men, all untreated (mean age, 45.1 years; 27.2% hypertensive) and randomly selected from a Chinese population, of whom 369 and 330 underwent a repeat examination after 3.6 years (median). In cross-sectional analyses, central SBP increased more with age than peripheral SBP in women below age 50 (1.21 vs. 1.01 mm Hg per year; P<0.001) and in men below age 60 (0.73 vs. 0.48 mm Hg per year; P<0.001), whereas in older women (0.64 vs. 0.58 mm Hg per year; P=0.27) and older men (0.45 vs. 0.44 mm Hg per year; P=0.79), the slopes of central and peripheral SBPs on age were similar. Compared with men, women had steeper (P<0.001) age-related increases in peripheral and central SBPs. Systolic augmentation pressure increased with age, but this increase was substantially smaller (P<0.0001) for peripheral than central augmentation (women, 0.086 vs. 0.45 mm Hg per year; men, 0.083 vs. 0.39 mm Hg per year). In multivariable-adjusted regression, age contributed ?89.7% of the explained variance in peripheral and central SBPs. In longitudinal analyses, the annual percentage increases from baseline to follow-up in peripheral and central SBP were similar (P?0.76) in both women (2.14% vs. 2.16 % per year) and men (1.33% vs. 1.34 % per year; P-values for sex difference ?0.044). In conclusion, in younger subjects assessed cross-sectionally, the age-related increase was larger for central than peripheral SBP, whereas the corresponding cross-sectional estimates in older subjects and the longitudinal estimates in all subjects showed similar age-related increases in central and peripheral SBP.
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Are retinal microvascular phenotypes associated with the 1675G/A polymorphism in the angiotensin II type-2 receptor gene?
Am. J. Hypertens.
PUBLISHED: 08-18-2011
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The 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.
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Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
, Georg B Ehret, Patricia B Munroe, Kenneth M Rice, Murielle Bochud, Andrew D Johnson, Daniel I Chasman, Albert V Smith, Martin D Tobin, Germaine C Verwoert, Shih-Jen Hwang, Vasyl Pihur, Peter Vollenweider, Paul F O'Reilly, Najaf Amin, Jennifer L Bragg-Gresham, Alexander Teumer, Nicole L Glazer, Lenore Launer, Jing Hua Zhao, Yurii Aulchenko, Simon Heath, Siim Sõber, Afshin Parsa, Jian'an Luan, Pankaj Arora, Abbas Dehghan, Feng Zhang, Gavin Lucas, Andrew A Hicks, Anne U Jackson, John F Peden, Toshiko Tanaka, Sarah H Wild, Igor Rudan, Wilmar Igl, Yuri Milaneschi, Alex N Parker, Cristiano Fava, John C Chambers, Ervin R Fox, Meena Kumari, Min Jin Go, Pim van der Harst, Wen Hong Linda Kao, Marketa Sjögren, D G Vinay, Myriam Alexander, Yasuharu Tabara, Sue Shaw-Hawkins, Peter H Whincup, Yongmei Liu, Gang Shi, Johanna Kuusisto, Bamidele Tayo, Mark Seielstad, Xueling Sim, Khanh-Dung Hoang Nguyen, Terho Lehtimäki, Giuseppe Matullo, Ying Wu, Tom R Gaunt, N Charlotte Onland-Moret, Matthew N Cooper, Carl G P Platou, Elin Org, Rebecca Hardy, Santosh Dahgam, Jutta Palmen, Veronique Vitart, Peter S Braund, Tatiana Kuznetsova, Cuno S P M Uiterwaal, Adebowale Adeyemo, Walter Palmas, Harry Campbell, Barbara Ludwig, Maciej Tomaszewski, Ioanna Tzoulaki, Nicholette D Palmer, Thor Aspelund, Melissa Garcia, Yen-Pei C Chang, Jeffrey R O'Connell, Nanette I Steinle, Diederick E Grobbee, Dan E Arking, Sharon L Kardia, Alanna C Morrison, Dena Hernandez, Samer Najjar, Wendy L McArdle, David Hadley, Morris J Brown, John M Connell, Aroon D Hingorani, Ian N M Day, Debbie A Lawlor, John P Beilby, Robert W Lawrence, Robert Clarke, Jemma C Hopewell, Halit Ongen, Albert W Dreisbach, Yali Li, J Hunter Young, Joshua C Bis, Mika Kähönen, Jorma Viikari, Linda S Adair, Nanette R Lee, Ming-Huei Chen, Matthias Olden, Cristian Pattaro, Judith A Hoffman Bolton, Anna Köttgen, Sven Bergmann, Vincent Mooser, Nish Chaturvedi, Timothy M Frayling, Muhammad Islam, Tazeen H Jafar, Jeanette Erdmann, Smita R Kulkarni, Stefan R Bornstein, Jürgen Gräßler, Leif Groop, Benjamin F Voight, Johannes Kettunen, Philip Howard, Andrew Taylor, Simonetta Guarrera, Fulvio Ricceri, Valur Emilsson, Andrew Plump, Inês Barroso, Kay-Tee Khaw, Alan B Weder, Steven C Hunt, Yan V Sun, Richard N Bergman, Francis S Collins, Lori L Bonnycastle, Laura J Scott, Heather M Stringham, Leena Peltonen, Markus Perola, Erkki Vartiainen, Stefan-Martin Brand, Jan A Staessen, Thomas J Wang, Paul R Burton, María Soler Artigas, Yanbin Dong, Harold Snieder, Xiaoling Wang, Haidong Zhu, Kurt K Lohman, Megan E Rudock, Susan R Heckbert, Nicholas L Smith, Kerri L Wiggins, Ayo Doumatey, Daniel Shriner, Gudrun Veldre, Margus Viigimaa, Sanjay Kinra, Dorairaj Prabhakaran, Vikal Tripathy, Carl D Langefeld, Annika Rosengren, Dag S Thelle, Anna Maria Corsi, Andrew Singleton, Terrence Forrester, Gina Hilton, Colin A McKenzie, Tunde Salako, Naoharu Iwai, Yoshikuni Kita, Toshio Ogihara, Takayoshi Ohkubo, Tomonori Okamura, Hirotsugu Ueshima, Satoshi Umemura, Susana Eyheramendy, Thomas Meitinger, H-Erich Wichmann, Yoon Shin Cho, Hyung-Lae Kim, Jong-Young Lee, James Scott, Joban S Sehmi, Weihua Zhang, Bo Hedblad, Peter Nilsson, George Davey Smith, Andrew Wong, Narisu Narisu, Alena Stančáková, Leslie J Raffel, Jie Yao, Sekar Kathiresan, Christopher J O'Donnell, Stephen M Schwartz, M Arfan Ikram, W T Longstreth, Thomas H Mosley, Sudha Seshadri, Nick R G Shrine, Louise V Wain, Mario A Morken, Amy J Swift, Jaana Laitinen, Inga Prokopenko, Paavo Zitting, Jackie A Cooper, Steve E Humphries, John Danesh, Asif Rasheed, Anuj Goel, Anders Hamsten, Hugh Watkins, Stephan J L Bakker, Wiek H van Gilst, Charles S Janipalli, K Radha Mani, Chittaranjan S Yajnik, Albert Hofman, Francesco U S Mattace-Raso, Ben A Oostra, Ayse Demirkan, Aaron Isaacs, Fernando Rivadeneira, Edward G Lakatta, Marco Orrù, Angelo Scuteri, Mika Ala-Korpela, Antti J Kangas, Leo-Pekka Lyytikäinen, Pasi Soininen, Taru Tukiainen, Peter Würtz, Rick Twee-Hee Ong, Marcus Dörr, Heyo K Kroemer, Uwe Völker, Henry Völzke, Pilar Galán, Serge Hercberg, Mark Lathrop, Diana Zelenika, Panos Deloukas, Massimo Mangino, Tim D Spector, Guangju Zhai, James F Meschia, Michael A Nalls, Pankaj Sharma, Janos Terzic, M V Kranthi Kumar, Matthew Denniff, Ewa Zukowska-Szczechowska, Lynne E Wagenknecht, F Gerald R Fowkes, Fadi J Charchar, Peter E H Schwarz, Caroline Hayward, Xiuqing Guo, Charles Rotimi, Michiel L Bots, Eva Brand, Nilesh J Samani, Ozren Polašek, Philippa J Talmud, Fredrik Nyberg, Diana Kuh, Maris Laan, Kristian Hveem, Lyle J Palmer, Yvonne T van der Schouw, Juan P Casas, Karen L Mohlke, Paolo Vineis, Olli Raitakari, Santhi K Ganesh, Tien Y Wong, E Shyong Tai, Richard S Cooper, Markku Laakso, Dabeeru C Rao, Tamara B Harris, Richard W Morris, Anna F Dominiczak, Mika Kivimäki, Michael G Marmot, Tetsuro Miki, Danish Saleheen, Giriraj R Chandak, Josef Coresh, Gerjan Navis, Veikko Salomaa, Bok-Ghee Han, Xiaofeng Zhu, Jaspal S Kooner, Olle Melander, Paul M Ridker, Stefania Bandinelli, Ulf B Gyllensten, Alan F Wright, James F Wilson, Luigi Ferrucci, Martin Farrall, Jaakko Tuomilehto, Peter P Pramstaller, Roberto Elosua, Nicole Soranzo, Eric J G Sijbrands, David Altshuler, Ruth J F Loos, Alan R Shuldiner, Christian Gieger, Pierre Meneton, André G Uitterlinden, Nicholas J Wareham, Vilmundur Gudnason, Jerome I Rotter, Rainer Rettig, Manuela Uda, David P Strachan, Jacqueline C M Witteman, Anna-Liisa Hartikainen, Jacques S Beckmann, Eric Boerwinkle, Ramachandran S Vasan, Michael Boehnke, Martin G Larson, Marjo-Riitta Järvelin, Bruce M Psaty, Gonçalo R Abecasis, Aravinda Chakravarti, Paul Elliott, Cornelia M van Duijn, Christopher Newton-Cheh, Daniel Levy, Mark J Caulfield, Toby Johnson.
Nature
PUBLISHED: 07-28-2011
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Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (?140?mm?Hg systolic blood pressure or? ?90?mm?Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
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Age dependency of central and peripheral systolic blood pressures: cross-sectional and longitudinal observations in European populations.
Blood Press.
PUBLISHED: 07-07-2011
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As arteries become stiffer with ageing, reflected waves move faster and augment late systolic pressure. We investigated the age dependency of peripheral and central systolic pressure, pressure amplification (peripheral systolic blood pressure - central systolic blood pressure), and peripheral and central systolic augmentation (maximal systolic pressure minus the first peak of the pressure wave).
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Blood pressure loci identified with a gene-centric array.
Toby Johnson, Tom R Gaunt, Stephen J Newhouse, Sandosh Padmanabhan, Maciej Tomaszewski, Meena Kumari, Richard W Morris, Ioanna Tzoulaki, Eoin T O'Brien, Neil R Poulter, Peter Sever, Denis C Shields, Simon Thom, Sasiwarang G Wannamethee, Peter H Whincup, Morris J Brown, John M Connell, Richard J Dobson, Philip J Howard, Charles A Mein, Abiodun Onipinla, Sue Shaw-Hawkins, Yun Zhang, George Davey Smith, Ian N M Day, Debbie A Lawlor, Alison H Goodall, , F Gerald Fowkes, Gonçalo R Abecasis, Paul Elliott, Vesela Gateva, Peter S Braund, Paul R Burton, Christopher P Nelson, Martin D Tobin, Pim van der Harst, Nicola Glorioso, Hani Neuvrith, Erika Salvi, Jan A Staessen, Andrea Stucchi, Nabila Devos, Xavier Jeunemaitre, Pierre-Francois Plouin, Jean Tichet, Peeter Juhanson, Elin Org, Margus Putku, Siim Sõber, Gudrun Veldre, Margus Viigimaa, Anna Levinsson, Annika Rosengren, Dag S Thelle, Claire E Hastie, Thomas Hedner, Wai K Lee, Olle Melander, Björn Wahlstrand, Rebecca Hardy, Andrew Wong, Jackie A Cooper, Jutta Palmen, Li Chen, Alexandre F R Stewart, George A Wells, Harm-Jan Westra, Marcel G M Wolfs, Robert Clarke, Maria Grazia Franzosi, Anuj Goel, Anders Hamsten, Mark Lathrop, John F Peden, Udo Seedorf, Hugh Watkins, Willem H Ouwehand, Jennifer Sambrook, Jonathan Stephens, Juan-Pablo Casas, Fotios Drenos, Michael V Holmes, Mika Kivimäki, Sonia Shah, Tina Shah, Philippa J Talmud, John Whittaker, Chris Wallace, Christian Delles, Maris Laan, Diana Kuh, Steve E Humphries, Fredrik Nyberg, Daniele Cusi, Robert Roberts, Christopher Newton-Cheh, Lude Franke, Alice V Stanton, Anna F Dominiczak, Martin Farrall, Aroon D Hingorani, Nilesh J Samani, Mark J Caulfield, Patricia B Munroe.
Am. J. Hum. Genet.
PUBLISHED: 06-15-2011
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Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
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Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion.
JAMA
PUBLISHED: 05-05-2011
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Extrapolations from observational studies and short-term intervention trials suggest that population-wide moderation of salt intake might reduce cardiovascular events.
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Rationale and design of the Newer Versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial.
Blood Press.
PUBLISHED: 04-15-2011
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Sub-Saharan Africa experiences an epidemic surge in hypertension. Studies in African Americans led to the recommendation to initiate antihypertensive treatment in Blacks with a diuretic or a low-dose fixed combination including a diuretic. We mounted the Newer versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial to compare in native African patients a fixed combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic.
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Heritability of left ventricular structure and function in Caucasian families.
Eur J Echocardiogr
PUBLISHED: 03-11-2011
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The aim of this study was to investigate the heritability as well as genetic and environmental correlations of left ventricular (LV) structural and functional traits in complex pedigrees of a Caucasian population.
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