Interaction between serum cholesterol levels and the renin–angiotensin system on the new onset of arterial hypertension in subjects with high-normal blood pressure

Abstract

To investigate the possible interactions between serum cholesterol levels and the renin-angiotensin system on the development of stable hypertension in subjects with high-normal blood pressure (BP). Hypercholesterolemia increases angiotensin-II type 1 (AT1) receptor density and pressor responsiveness to angiotensin II, and has been reported to contribute to the development of hypertension. The effects of elevated serum cholesterol levels on BP control might be exaggerated by concomitant activation of the renin-angiotensin system, and their combination might contribute to the development of stable hypertension. We investigated the relationship between serum cholesterol levels, plasma renin activity (PRA) and the long-term development of hypertension in 66 young (age < 45 years) patients with high-normal BP and elevated (> 200 mg/dl, n = 46: HC) or normal (</=200 mg/dl, n = 20: NC) serum cholesterol levels and in 20 normotensive, normocholesterolemic controls (C). The main outcome measure was the prospective evaluation of the 15-year incidence of stable hypertension in the different populations. New-onset hypertension was higher in patients with high-normal BP and HC when compared to NC patients [relative risk (RR) = 1.9; 95% confidence interval (CI), 1.1-4.3, P < 0.001] and control subjects (RR = 3.1; 95% CI = 1.4-5.3, P < 0.001). High PRA increased the overall rate of hypertension in both HC and NC. The interaction between HC and PRA was more evident in patients with borderline high cholesterol levels (200-240 mg/dl) where the adjusted relative risk of new onset of hypertension was 2.17 (95% CI 1.2-3.74; P < 0.05) in high PRA subjects and 1.17 (95% CI 0.67-2.23; P = 0.87) in subjects with normal PRA. We support the hypothesis that the presence of hypercholesterolemia can promote the development of stable hypertension through its interaction with the circulating renin-angiotensin system in patients with high-normal blood pressure.