Familial Aggregation of Low-Renin Hypertension

Low-renin hypertension, representing roughly one quarter of all essential hypertension, is widely recognized by distinct physiological features, including salt-sensitivity, diuretic- responsiveness, and a favorable natural history. Although certain demographic features including age, ethnicity, and diabetes mellitus predispose to low-renin hypertension, these factors account for only a minority of cases. We examined familial concordance for renin status in 119 families with 257 hypertensive members. Low-renin was defined rigorously by plasma renin activity ≤0.69 ng angiotensin I/L per second, drawn when subjects had achieved balance after 5 to 7 days on a 10 mmol sodium diet and had stood upright for at least 1 hour. Given the prevalence of low-renin hypertension in our general population, low-renin hypertension was significantly more concordant among siblings than expected by chance (P =0.01). There were twice as many low-renin families as expected (10.9% versus 5.5%), in sharp contrast to the normal-renin state, in which the observed and expected were similar (61.0% versus 58.6%). These results were independent of age, race, and gender. Variance in renin status attributable to family membership was 35%. Association studies were performed on 8 polymorphisms in 5 candidate genes, and significant association was confirmed with the G460W polymorphism of the adducin gene. Familial determinants, which are probably but not definitely genetic, contribute to the low-renin hypertension state.