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Hemodynamic correlates of blood pressure across the adult age spectrum: noninvasive evaluation in the Framingham Heart Study.

ABSTRACT: BACKGROUND:Systolic blood pressure and pulse pressure are substantially higher in older adults. The relative contributions of increased forward versus reflected pressure wave amplitude or earlier arrival of the reflected wave to elevated pulse pressure remain controversial. METHODS AND RESULTS:We measured proximal aortic pressure and flow, forward pressure wave amplitude, global wave reflection, reflected wave timing, and pulse wave velocity noninvasively in 6417 (age range, 19 to 90 years; 53 women) Framingham Heart Study Third Generation and Offspring participants. Variation in forward wave amplitude paralleled pulse pressure throughout adulthood. In contrast, wave reflection and pulse pressure were divergent across adulthood: In younger participants, pulse pressure was lower and wave reflection was higher with advancing age, whereas in older participants, pulse pressure was higher and wave reflection was lower with age. Reflected wave timing differed modestly across age groups despite considerable differences in pulse wave velocity. Forward wave amplitude explained 80 (central) and 66 (peripheral) of the variance in pulse pressure in younger participants (<50 years) and 90 and 84 in the older participants (? 50 years; all P<0.0001). In a stepwise model that evaluated age-pulse pressure relations in the full sample, the late accelerated increases in central and peripheral pulse pressure were markedly attenuated when variation in forward wave amplitude was considered. CONCLUSIONS:Higher pulse pressure at any age and higher pulse pressure with advancing age is associated predominantly with a larger forward pressure wave. The influence of wave reflection on age-related differences in pulse pressure was minor.

SUBMITTER: Mitchell GF

PROVIDER: S-EPMC2981604 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Hemodynamic correlates of blood pressure across the adult age spectrum: noninvasive evaluation in the Framingham Heart Study.

Mitchell Gary F GF Wang Na N Palmisano Joseph N JN Larson Martin G MG Hamburg Naomi M NM Vita Joseph A JA Levy Daniel D Benjamin Emelia J EJ Vasan Ramachandran S RS

Circulation 20100920 14

<h4>Background</h4>Systolic blood pressure and pulse pressure are substantially higher in older adults. The relative contributions of increased forward versus reflected pressure wave amplitude or earlier arrival of the reflected wave to elevated pulse pressure remain controversial.<h4>Methods and results</h4>We measured proximal aortic pressure and flow, forward pressure wave amplitude, global wave reflection, reflected wave timing, and pulse wave velocity noninvasively in 6417 (age range, 19 to ...[more]

PMID: 20855656

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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.

Dataset Information

Hemodynamic correlates of blood pressure across the adult age spectrum: noninvasive evaluation in the Framingham Heart Study.

Publications

Hemodynamic correlates of blood pressure across the adult age spectrum: noninvasive evaluation in the Framingham Heart Study.

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