Dataset Information

Cross-Sectional Associations of Flow Reversal, Vascular Function, and Arterial Stiffness in the Framingham Heart Study.

ABSTRACT:

Objective

Experimental studies link oscillatory flow accompanied by flow reversal to impaired endothelial cell function. The relation of flow reversal with vascular function and arterial stiffness remains incompletely defined.

Approach and results

We measured brachial diastolic flow patterns along with vasodilator function in addition to tonometry-based central and peripheral arterial stiffness in 5708 participants (age 47±13 years, 53% women) in the Framingham Heart Study Offspring and Third Generation cohorts. Brachial artery diastolic flow reversal was present in 35% of the participants. In multivariable regression models, the presence of flow reversal was associated with lower flow-mediated dilation (3.9±0.2 versus 5.0±0.2%; P<0.0001) and reactive hyperemic flow velocity (50±0.99 versus 57±0.93 cm/s; P<0.0001). The presence of flow reversal (compared with absence) was associated with higher central aortic stiffness (carotid-femoral pulse wave velocity 9.3±0.1 versus 8.9±0.1 m/s), lower muscular artery stiffness (carotid-radial pulse wave velocity 9.6±0.1 versus 9.8±0.1 m/s), and higher forearm vascular resistance (5.32±0.03 versus 4.66±0.02 log dyne/s/cm⁵; P<0.0001). The relations of diastolic flow velocity with flow-mediated dilation, aortic stiffness, and forearm vascular resistance were nonlinear, with a steeper decline in vascular function associated with increasing magnitude of flow reversal.

Conclusions

In our large, community-based sample, brachial artery flow reversal was common and associated with impaired vasodilator function and higher aortic stiffness. Our findings are consistent with the concept that flow reversal may contribute to vascular dysfunction.

SUBMITTER: Breton-Romero R

PROVIDER: S-EPMC5557404 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cross-Sectional Associations of Flow Reversal, Vascular Function, and Arterial Stiffness in the Framingham Heart Study.

Bretón-Romero Rosa R Wang Na N Palmisano Joseph J Larson Martin G MG Vasan Ramachandran S RS Mitchell Gary F GF Benjamin Emelia J EJ Vita Joseph A JA Hamburg Naomi M NM

Arteriosclerosis, thrombosis, and vascular biology 20161027 12

<h4>Objective</h4>Experimental studies link oscillatory flow accompanied by flow reversal to impaired endothelial cell function. The relation of flow reversal with vascular function and arterial stiffness remains incompletely defined.<h4>Approach and results</h4>We measured brachial diastolic flow patterns along with vasodilator function in addition to tonometry-based central and peripheral arterial stiffness in 5708 participants (age 47±13 years, 53% women) in the Framingham Heart Study Offspri ...[more]

PMID: 27789476

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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.

Project description:BackgroundArterial stiffness increases with age and is associated with an increased risk of adverse outcomes on short-term follow-up (typically <10 years). Data regarding associations of arterial stiffness with health outcomes on longer-term follow-up are lacking.MethodsWe evaluated 7283 Framingham Study participants (mean age 50 years, 53% women) who underwent assessment of carotid-femoral pulse wave velocity (a marker of arterial stiffness) via applanation tonometry at one or more routine examinations. We used time-dependent Cox proportional hazards regression models to relate carotid-femoral pulse wave velocity to the incidence of health outcomes (updating carotid-femoral pulse wave velocity and all covariates at serial examinations).ResultsOn long-term follow-up (median 15 years; minimum-maximum, 0-20), participants developed cardiometabolic disease (hypertension [1255 events]; diabetes [381 events]), chronic kidney disease (529 events), dementia (235 events), cardiovascular disease (684 events) and its components (coronary heart disease [314 events], heart failure [191 events], transient ischemic attacks or stroke [250 events]), and death (1086 events). In multivariable-adjusted models, each SD increment in carotid-femoral pulse wave velocity was associated with increased risk of hypertension (hazard ratio [HR], 1.32 [95% CI, 1.21-1.44]), diabetes (HR, 1.32 [95% CI, 1.11-1.58]), chronic kidney disease (1.19 [95% CI, 1.05-1.34]), dementia (HR 1.27 [95% CI, 1.06-1.53]), cardiovascular disease (HR, 1.20 [95% CI, 1.06-1.36]) and its components (coronary heart disease, HR 1.37 [95% CI, 1.13-1.65]; transient ischemic attack/stroke, HR, 1.24 [95% CI, 1.00-1.53]), and death (HR, 1.29 [95% CI, 1.17-1.43]). The association with heart failure was borderline nonsignificant (HR, 1.21 [95% CI, 0.98-1.51], P=0.08).ConclusionsOur prospective observations of a large community-based sample establish the long-term prognostic importance of arterial stiffness for multiple health outcomes.

Dataset Information

Cross-Sectional Associations of Flow Reversal, Vascular Function, and Arterial Stiffness in the Framingham Heart Study.

Objective

Approach and results

Conclusions

Publications

Cross-Sectional Associations of Flow Reversal, Vascular Function, and Arterial Stiffness in the Framingham Heart Study.

Similar Datasets

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