Effect of the HMG-CoA Reductase Inhibitors on Blood Pressure in Patients With Essential Hypertension and Primary Hypercholesterolemia

Abstract

Abstract-Certain hydroxymethylglutaryl coenzyme A reductase inhibitors, ie, statins, may cause vasodilation by restoring the endothelial dysfunction that frequently accompanies hypertension and hypercholesterolemia. Several studies have found that a blood pressure reduction is associated with the use of statins, but conclusive evidence from controlled trials is lacking. After an 8-week placebo and diet run-in period, 30 persons with moderate hypercholesterolemia and untreated hypertension (total cholesterol 6.29Ϯ0.52 mmol/L, systolic and diastolic blood pressure 149Ϯ6 and 97Ϯ2 mm Hg) were randomized in a double-blind manner to placebo or pravastatin (20 to 40 mg/d) in a crossover design. In 25 participants who completed the 32-week trial, pravastatin decreased total and LDL cholesterol (both Ϫ1.09 mmol/L, Pϭ0.001), systolic and diastolic blood pressure (Ϫ8 and Ϫ5 mm Hg, both Pϭ0.001), and pulse pressure (Ϫ3 mm Hg, Pϭ0.011) and blunted the blood pressure increase caused by the cold pressor test (Ϫ4 mm Hg, Pϭ0.005) compared with placebo. It also reduced the level of circulating endothelin-1 (Pϭ0.001). The blood pressure results were virtually unchanged in stratified analyses according to gender and age and in intention-to-treat analyses that included the 5 patients who dropped out of the study. When the participants were taking either placebo or pravastatin, blood pressure was not significantly correlated with total or LDL cholesterol or with circulating endothelin-1. Pravastatin decreases systolic, diastolic, and pulse pressures in persons with moderate hypercholesterolemia and hypertension. This antihypertensive effect may contribute to the documented health benefits of certain statins. (Hypertension. 1999;34:1281-1286.)Key Words: statins Ⅲ blood pressure Ⅲ cholesterol Ⅲ endothelin Ⅲ hypertension, essential Ⅲ hypercholesterolemia C ertain statins, or hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are clinically proven to prevent coronary and cerebrovascular events in persons with increased plasma cholesterol levels. 1 In a large primary prevention trial, 2 it has been observed that compared with placebo, pravastatin can decrease the risk of cardiovascular events early after randomization. These findings suggest that in addition to the long-term prevention of atherosclerosis, other more immediate mechanisms might account for the clinical benefits of statins. 3 Several short-term studies have shown that statins can improve endothelial function and the endothelium-dependent arterial vasodilation that are typically altered in persons with increased plasma cholesterol levels. 4 -7 Hypercholesterolemia, endothelial dysfunction, and hypertension are frequently coexisting conditions, even in the absence of documented atherosclerotic lesions. 8 -11 Moreover, recent animal data indicate that the effect of pravastatin on the endothelium might be due in part to nonlipid effects. 12 In theory, by improving endothelial dysfunction, cholesterol reduction with statins may decrease blood pressure in persons wi...

Long-term effects of statins on arterial pressure and stiffness of hypertensives

“…Previous studies have reported a BP-lowering effect of statins in hyperlipidaemic hypertensive patients who were not taking any antihypertensive drugs 6 and who had already received antihypertensive therapy. 7,8 However, the results of the present study clearly demonstrated that long-term use of pravastatin, simvastatin, fluvastatin, and nonstatin antihyperlipidaemic drug had no additional effect on BP but significantly decreased the serum TC levels in hypertensive patients with high serum TC levels and insufficiently controlled BP despite antihypertensive therapy.…”

“…Recent studies have shown that statins can be used to reduce BP in hypertensive patients with hypercholesterolaemia. [6][7][8] The mechanism of the reduction of BP by statins in hypertensive hyperlipidaemic patients involves the activation of endothelial nitric oxide synthase, 9 the downregulation of angiotensin II type 1 receptors, 10 and a reduction in the vascular production of reactive oxygen species. 11 In addition, the long-term administration of statins has been shown to inhibit the progression of aortic stenosis 12 and to reduce aortic stiffness, as assessed by PWV, in normotensive patients with hypercholesterolaemia.…”

Dyslipidemia and the Risk of Incident Hypertension in Men

“…12 In another study, there was no decrease in BP among normotensive subjects. 22 Glorioso et al 23 conducted a trial of pravastatin in 30 hypertensive, hypercholesterolemic subjects and demonstrated that, compared with placebo, treatment with pravastatin significantly decreased systolic, diastolic, and pulse pressures and blunted the BP increase induced by the cold pressor test.…”

Effects of atorvastatin on aortic pulse wave velocity in patients with hypertension and hypercholesterolaemia: a preliminary study

“…Because of the chronic use of antihypertensive agents, blood pressure was stable along the totality of the investigation and remained very close to normotensive values. Indeed, this situation did not allow the evaluation of whether statins might significantly reduce blood pressure, 23 but clearly showed that the PWV changes were roughly independent of blood pressure level, whether blood pressure was measured in the brachial or in the carotid arteries.…”