Dataset Information

Genetic Association of Finger Photoplethysmography-Derived Arterial Stiffness Index With Blood Pressure and Coronary Artery Disease.

ABSTRACT: Objective- Arterial stiffness index (ASI) is independently associated with blood pressure (BP) and coronary artery disease (CAD) epidemiologically. However, it is unknown whether these associations represent causal relationships. Here, we assess whether genetic predisposition to increased ASI is associated with elevated BP and CAD risk. Approach and Results- We first performed a large-scale epidemiological association of finger photoplethysmography-derived ASI in the UK Biobank, finding significant associations with systolic BP (?=0.55 mm?Hg; [95% CI, 0.45-0.65]; P=5.77×10-24; N=137?858), diastolic BP (?=1.05 mm?Hg; [95% CI, 0.99-1.11]; P=7.27×10-272; N=137?862), and incident CAD (hazard ratio, 1.08; [95% CI, 1.04-1.11]; P=1.5×10-6; N=3692 cases, 126?615 controls) in multivariable models. We then performed an ASI genome-wide association study analysis in 131?686 participants from the UK Biobank. Across participants not in the ASI genome-wide association study, a 6-variant ASI polygenic risk score was calculated. Each SD increase in genetic ASI was associated with systolic BP (?=4.63 mm?Hg; [95% CI, 2.1-7.2]; P=3.37×10-4; N=208?897), and diastolic BP (?=2.61 mm?Hg; [95% CI, 1.2-4.0]; P=2.85×10-4; N=208?897); however, no association was observed with incident CAD (hazard ratio, 1.12; [95% CI, 0.55-2.3]; P=0.75; N=223?061; 7534 cases). The lack of CAD association observed was replicated among 184?305 participants (60?810 cases) from the CARDIOGRAMplusC4D (Coronary Artery Disease Genetics Consortium; odds ratio, 0.56; [95% CI, 0.26-1.24]; P=0.15). Conclusions- Our data support the conclusion that finger photoplethysmography-derived ASI is an independent, genetically causal risk factor for BP, but do not support the notion that ASI is a suitable surrogate for CAD risk.

SUBMITTER: Zekavat SM

PROVIDER: S-EPMC6531323 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Genetic Association of Finger Photoplethysmography-Derived Arterial Stiffness Index With Blood Pressure and Coronary Artery Disease.

Zekavat Seyedeh M SM Aragam Krishna K Emdin Connor C Khera Amit V AV Klarin Derek D Zhao Hongyu H Natarajan Pradeep P

Arteriosclerosis, thrombosis, and vascular biology 20190601 6

Objective- Arterial stiffness index (ASI) is independently associated with blood pressure (BP) and coronary artery disease (CAD) epidemiologically. However, it is unknown whether these associations represent causal relationships. Here, we assess whether genetic predisposition to increased ASI is associated with elevated BP and CAD risk. Approach and Results- We first performed a large-scale epidemiological association of finger photoplethysmography-derived ASI in the UK Biobank, finding signific ...[more]

PMID: 31070453

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Project description:Background Arterial stiffness predicts the risk of cardiovascular events and all-cause mortality and is associated with age and hypertension. However, the magnitude of the relationship between blood pressure (BP) and progression of arterial stiffness is unclear, limiting our understanding of how arterial stiffness mediates clinical effects of hypertension and planning of clinical trials. Methods and Results Medline and EMBASE were searched for prospective studies reporting linear models between baseline BP and progression of arterial stiffness, with and without adjustment for demographic characteristics and baseline stiffness. Standardized and unstandardized β coefficients for pulse wave velocity were combined by fixed and random effects meta-analysis, weighted by the inverse variance. Of 566 fully reviewed articles from 30, 524 titles, 22 populations from 21 reports were included. In 9 cohorts, there were consistent, adjusted associations between baseline systolic BP and progression of arterial stiffness (11 781 patients; standardized β=0.041; 95% CI, 0.026-0.055; P<0.001; P value for heterogeneity=0.70), equivalent to a 1.14-m/s increase in standard carotid-femoral pulse wave velocity per decade per 20-mm Hg systolic BP, independent of age. Unstandardized, adjusted associations were similar (1762 patients; β=0.0047; 95% CI, 0.004-0.006; P<0.001; P value for heterogeneity=0.64), equivalent to a 0.94-m/s increase per decade per 20-mm Hg systolic BP. In limited studies, standardized associations between mean BP and arterial stiffness progression were not significant and heterogeneous (913 patients; β=0.039; 95% CI, -0.008 to 0.086; P=0.11; P value for heterogeneity=0.03). Conclusions Baseline systolic BP was associated with a clinically important progression of arterial stiffness, independent of age, providing a reference for the potential effect of arterial stiffness in mediating changes in clinical outcomes associated with hypertension and providing a reference value to aid clinical trial design.

Project description:About one quarter of adults are hypertensive and high blood pressure carries increased risk for heart disease, stroke, kidney disease and death. Increased arterial stiffness is a key factor in the pathogenesis of systolic hypertension and cardiovascular disease. Substantial heritability of blood-pressure (BP) and arterial-stiffness suggests important genetic contributions.In Framingham Heart Study families, we analyzed genome-wide SNP (Affymetrix 100K GeneChip) associations with systolic (SBP) and diastolic (DBP) BP at a single examination in 1971-1975 (n = 1260), at a recent examination in 1998-2001 (n = 1233), and long-term averaged SBP and DBP from 1971-2001 (n = 1327, mean age 52 years, 54% women) and with arterial stiffness measured by arterial tonometry (carotid-femoral and carotid-brachial pulse wave velocity, forward and reflected pressure wave amplitude, and mean arterial pressure; 1998-2001, n = 644). In primary analyses we used generalized estimating equations in models for an additive genetic effect to test associations between SNPs and phenotypes of interest using multivariable-adjusted residuals. A total of 70,987 autosomal SNPs with minor allele frequency > or = 0.10, genotype call rate > or = 0.80, and Hardy-Weinberg equilibrium p > or = 0.001 were analyzed. We also tested for association of 69 SNPs in six renin-angiotensin-aldosterone pathway genes with BP and arterial stiffness phenotypes as part of a candidate gene search.In the primary analyses, none of the associations attained genome-wide significance. For the six BP phenotypes, seven SNPs yielded p values < 10(-5). The lowest p-values for SBP and DBP respectively were rs10493340 (p = 1.7 x 10(-6)) and rs1963982 (p = 3.3 x 10(-6)). For the five tonometry phenotypes, five SNPs had p values < 10(-5); lowest p-values were for reflected wave (rs6063312, p = 2.1 x 10(-6)) and carotid-brachial pulse wave velocity (rs770189, p = 2.5 x 10(-6)) in MEF2C, a regulator of cardiac morphogenesis. We found only weak association of SNPs in the renin-angiotensin-aldosterone pathway with BP or arterial stiffness.These results of genome-wide association testing for blood pressure and arterial stiffness phenotypes in an unselected community-based sample of adults may aid in the identification of the genetic basis of hypertension and arterial disease, help identify high risk individuals, and guide novel therapies for hypertension. Additional studies are needed to replicate any associations identified in these analyses.

Dataset Information

Genetic Association of Finger Photoplethysmography-Derived Arterial Stiffness Index With Blood Pressure and Coronary Artery Disease.

Publications

Genetic Association of Finger Photoplethysmography-Derived Arterial Stiffness Index With Blood Pressure and Coronary Artery Disease.

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