Genetics of Hypertension, Target-Organ Complications, and Response to Therapy

This issue of Circulation honors extraordinary achievements in cardiovascular disease research during the past half century and their impact on the prevention, evaluation, and treatment of cardiovascular disorders. One area of particularly noteworthy advancement has been that of hypertension, the most prevalent risk factor for diseases of the heart, brain, and kidneys and one of the most common indications for prescription medications. Because essential hypertension, defined by systolic blood pressure levels ≥140 mm Hg or diastolic blood pressure levels ≥90 mm Hg, was the subject of a comprehensive 2-part review recently published in Circulation ,1 2 this article will focus on 3 frontiers of hypertension research that are undergoing particularly rapid advancement and are poised to experience further profound developments with completion of the Human Genome Project.3 These areas include new understanding of the genetic causes of hypertension, the genetic susceptibility to target-organ complications, and the pharmacogenetics of antihypertensive therapy. In each of these areas, our objectives are to review present knowledge by highlighting salient findings and to suggest where future advancements are likely to improve the prevention, evaluation, and treatment of hypertension. Previous studies have yielded consistent and significant estimates of the genetic contribution to interindividual differences in both systolic and diastolic blood pressure levels. For example, in a sample of 1266 individuals in 278 non-Hispanic white pedigrees, the heritability of systolic blood pressure level (that is, the proportion of interindividual variation attributable to genetic differences among individuals) was estimated to be 0.37.4 Similar values have been reported for diastolic blood pressure level.5 Contemporary genetics research has advanced from the general recognition that “genes are involved” to identifying and characterizing specific contributing genes and gene variants. Blood pressure levels are controlled by a complex combination of processes that influence cardiac output and peripheral vascular resistance. …