ETIOLOGY, PATHOPHYSIOLOGY, AND TREATMENT OF LEFT-VENTRICULAR HYPERTROPHY - FOCUS ON SEVERE HYPERTENSION

Left ventricular hypertrophy (LVH), a common finding in hypertensive p atients, has emerged as one of the most potent risk factors for future cardiovascular mortality in patients with hypertension. LVH is associ ated with multiple physiologic abnormalities, which may account for th e increased risk. These include coronary perfusion abnormalities such as reduced coronary flow reserve, altered coronary flow autoregulation , subendocardial hypoperfusion, and abnormal left ventricular (LV) dia stolic function. Although abnormalities of LV diastolic function are m ore common in LVH, they may occur early in the course of the disease. There may be a threshold of average awake ambulatory blood pressure (B P), 130/85 mm Hg, below which neither diastolic abnormalities nor LVH is detected. The reasons for reduced reserve coronary flow reserve are complex and include structural and functional abnormalities of myocar dial blood vessels such as reduced capillary density, reduced luminal diameter of intramyocardial small arteries, and increased vascular ton e, possibly as a result of factors such as abnormal endothelium-depend ent relaxation. Preliminary data suggest that regression of LVH is ass ociated with improved survival. Severe hypertensive patients would be expected to achieve the greatest benefit, because, if left untreated, this group has nearly 20% mortality within 2 years. To evaluate the ef fect of nifedipine gastrointestinal therapeutic system (GITS) on LV ma ss, 16 patients with initial diastolic BP > 120 mm Hg were treated for 1 year with either monotherapy or in combination with a thiazide diur etic. Because it has not been unequivocally shown that changes in LV m ass have physiologic benefit, associated alterations in LV systolic fu nction, LV filling, plasma renin activity, atrial natriuretic peptide, and catecholamines were also evaluated. LV mass regressed over the co urse of 6 months, and this was sustained at 1 year. Treatment with nif edipine GITS did not adversely affect intrinsic LV contractility. LV f illing appeared to improve over the course of the year. There was a tr end toward a relationship between LV mass regression and an improvemen t in diastolic function. Atrial natriuretic peptide was markedly reduc ed at 2 months, and this effect was sustained at 1 year. Over the peri od of 1 year, there was no detectable activation of either the catecho lamine or renin systems.