Clinical Correlates and Heritability of Flow-Mediated Dilation in the Community

Abstract

Background-Studies in selected samples have linked impaired endothelial function with cardiovascular disease and its risk factors. The clinical correlates and heritability of endothelial function in the community have not been described. Methods and Results-We examined a measure of endothelial function, brachial artery flow-mediated dilation (FMD), expressed as both percent (FMD%) and actual dilation by ultrasound with the occlusion cuff below the elbow in 2883 Framingham Study participants (52.9% women; mean age, 61 years). A subset of 1096 participants performed a 6-minute walk test before FMD determination. Mean FMD% was 3.3Ϯ3.0% in women and 2.4Ϯ2.4% in men. In stepwise multivariable linear regression models, FMD% was inversely related to age, systolic blood pressure, body mass index (BMI), lipid-lowering medication, and smoking, whereas it was positively related to female gender, heart rate, and prior walk test. The estimated heritability of FMD% was 0.14. FMD actual dilation findings were similar, except that female sex and BMI were not significantly associated. Conclusions-Increasing age, systolic blood pressure, BMI, and smoking were associated with lower FMD% in our community-based sample, whereas prior exercise and increasing heart rate were associated with higher FMD%. The estimated heritability of FMD was modest. Future research will permit more complete characterization of the genetic and environmental determinants of endothelial function and its prognostic value in the community. Key Words: endothelium Ⅲ epidemiology Ⅲ risk factors Ⅲ genetics B rachial artery flow-mediated dilation (FMD) serves as a measure of endothelial vasodilator function in humans. 1 Experimental and clinical studies suggest that development of endothelial dysfunction, including reduced NO bioavailability, contributes to the atherosclerosis and pathogenesis of cardiovascular disease (CVD) events. 2 Human studies demonstrate that endothelial dysfunction precedes the development of clinically apparent atherosclerosis in individuals with CVD risk factors such as smoking, 3 hypertension, 4 hyperlipidemia, 5 diabetes mellitus, 5 and obesity. 6 Furthermore, effective treatment of risk factors may reverse endothelial dysfunction. 7 Finally, studies in individuals with risk factors or prevalent CVD have demonstrated that endothelial dysfunction identifies patients at risk for future CVD events. 2,8 Previous investigations relating risk factors to endothelial dysfunction largely were limited to small, highly selected samples. Our objective was to assess the independent correlates of endothelial function in a large community-based sample. MethodsThe Framingham Offspring Study design has been described elsewhere. 9 Participants in the seventh examination (1998 to 2001) were eligible for the present investigation (nϭ3539). Exclusion criteria were residence in a nursing home (nϭ205), mastectomy (nϭ34), Raynaud disease (nϭ9), subject refusal (nϭ83), equipment malfunction/miscellaneous (nϭ15), predigital capture (nϭ177), or technically inade...

Drug Treatment of Hypertension: Focus on Vascular Health

“…These include brachial artery flow-mediated dilatation and venous occlusion plethysmography 1,23 . Severity of hypertension correlates with impairment of endothelial function and anti-hypertensive therapies that improve endothelial function in addition to lowering blood pressure may be associated with greater improvements in overall cardiovascular risk 1,24,25 .…”

Endothelial dysfunction and hypertension in aging

“…38,39 Measurement of flow-mediated vasodilation (FMD) in the brachial artery using ultrasound is noninvasive and reflects NO production very well. 40,41 It is accepted that measurement of forearm blood flow responses to vasoactive agents and reactive hyperemia is an index of resistance artery endothelial function and that measurement of FMD is an index of conduit artery endothelial function. Recently, finger plethysmography peripheral arterial tonometry has also been used.…”

Endothelial Function Assessed by Automatic Measurement of Enclosed Zone Flow‐Mediated Vasodilation Using an Oscillometric Method Is an Independent Predictor of Cardiovascular Events

“…Aging, smoking, obesity, hypertension, dyslipidemia, and diabetes mellitus are well‐known risk factors of endothelial dysfunction 1, 2, 3, 4, 7, 8, 9, 23, 24, 25. We previously showed that ezFMD was significantly correlated with cardiovascular risk factors and endothelial function assessed by FMD in relatively young participants 15.…”

“…It is clinically important to assess endothelial function for early detection of atherosclerosis. Several methods have been developed to evaluate endothelial function in humans 3, 4, 5, 6, 7, 8, 9. Measurement of flow‐mediated vasodilation (FMD) in the brachial artery is a noninvasive and broadly applicable method for assessing endothelial function 4, 5, 6, 7, 8, 9.…”

“…Several methods have been developed to evaluate endothelial function in humans 3, 4, 5, 6, 7, 8, 9. Measurement of flow‐mediated vasodilation (FMD) in the brachial artery is a noninvasive and broadly applicable method for assessing endothelial function 4, 5, 6, 7, 8, 9. It has been shown that endothelial dysfunction evaluated by FMD is an independent predictor of cardiovascular events 10, 11, 12, 13, 14…”