A positive family history of premature coronary artery disease is associated with impaired endothelium-dependent coronary blood flow regulation

Background-The aim of the study was to determine whether a positive family history of coronary artery disease is related to impaired coronary blood fl ow regulation. Methods ana Results-In 150 patients with angiographically normal or minimal ly diseased coronary vessels, risk factors for coronary artery disease, the extent of atherosclerosis and endothelium-dependent vasomotor responses to acetylcholine, and endothelium-independent blood flow regulation by papave rine or adenosine were assessed. Coronary blood flow responses to acetylcho line were reduced in a dose-dependent manner in patients with a positive fa mily history (P=0.030). By multivariate analysis, hypercholesterolemia (P=0 .001), age (P=0.002), and a positive family history (P=0.008) remained pred ictors of coronary blood flow increase to acetylcholine. The extent of athe rosclerotic coronary artery disease was, by multivariate analysis, an addit ional independent predictor of acetylcholine-induced blood flow (P=0.014), but also of endothelium-independent blood flow regulation (P=0.001). A posi tive family history had additive effects in addition to the other risk fact ors, such as hypercholesterolemia or increased age. Angiotensin-converting- enzyme genotype polymorphism had no influence either on endothelium-depende nt or endothelium-independent coronary blood flow responses. However, in a subset of 28 patients, homocysteine (which is, in part, genetically determi ned) was inversely related to maximal acetylcholine-induced blood flow regu lation (r=-0.47, P=0.012). Conclusions-The results of this study demonstrate, for the first time, that a positive family history of coronary artery disease is an important predi ctor of impaired endothelium-dependent coronary blood flow regulation in hu mans. The influence of a positive family history is independent of Ether we ll known risk factors but instead aggravates endothelial vasodilator dysfun ction associated with hypercholesterolemia and increased age, suggesting im portant interacting effects between genetic and environmental risk factors.