Blood pressure (BP) in the high-normal range is now considered a prehypertensive state/borderline hypertension, and its importance as a risk factor for the development of cardiovascular (CV) disease has been consistently demonstrated across various populations. Longitudinal data from the Framingham Heart Study have recently indicated that men and women with an initial high-normal BP had a higher rate of CV (Generic Adalat Treating certain kinds of angina) events on follow-up than those with normal BP. One possible explanation for the higher CV event rates is that such high-normal BP, even before hypertension becomes clinically apparent, may contribute to morphological changes of the heart characterized by elevated left ventricular mass (LVM). Alternatively, the clustering of high-normal BP with other risk factors may also parallel an increased LVM and promote the premature development of atherosclerotic morbid events. Because increased LVM, i.e., LV hypertrophy (LVH), is a major risk factor for overall and CV (Isoptin drug is used for treating high blood pressure) mortality, early identification of factors that lead to its development is of paramount importance for early intervention or prevention of clinical complications. Unfortunately, BP (Accupril medication is used for lowering high blood pressure and managing heart failure) alone only accounts for a fraction (20-30%) of the variability in LVM and risk of LVH, particularly in the early stage of development of hypertension. In contrast, there is increasing evidence that inherited factors may play an important role. Studies of families and twins have suggested that cardiac growth may be substantially modulated by genetic factors that act either independently or synergistically with elevated BP and environmental factors, such as dietary salt and obesity.
The reactive nitrogen species, nitric oxide (NO), synthesized from L-arginine by endothelial NO synthase (eNOS) enzyme, is a potent vasodilator with antihypertrophic properties. Because NO modulates the growth of the myocardium, genetic variations in the regulation of NO synthesis could thus influence the structure of the left ventricle. Three polymorphisms in the gene that encodes vascular eNOS have received considerable attention because of their substantial association to BP (Canadian Norvasc used to control high blood pressure or angina) elevation and early development of CV disease. Among them, the 894T allele of a single base substitution polymorphism (G894T) in exon 7 (Glu298Asp) of the eNOS gene has recently been implicated in the development of hypertension in some but not all studies. However, the extent to which this variant of the eNOS gene may interact with environmental stimuli to alter LVM in individuals with high-normal BP has not been addressed. Because high-normal BP confers an increased risk for the development of hypertension and other CV (Generic Cordarone Treating life-threatening recurrent heart rhythm disturbances) disorders, including LVH, we postulated that the allelic varia tion (894T) in the eNOS gene would directly correlate with alterations in LVM in individuals with high-normal BP. We, therefore, sought to study the association between the G894T eNOS polymorphism and alterations in LVM in a well-characterized population sample of healthy African Americans with high-normal BP.