Clinical Evidence of Cross Talk between Dyslipidemia and RAS Activation

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O'Callaghan et al. [38] examined the effects of pravastatin in the setting of background antihypertensive therapy with ACE inhibitors and calcium antagonists. They treated 25 hypertensive hypercholesterolemic patients with 12 weeks of either pravastatin or placebo in this double-blind, placebo-controlled parallel group study. Placebo treatment did not alter plasma lipids, whereas 12 weeks of treatment with pravastatin reduced total cholesterol by 27% and LDL cholesterol by 35%. There was no change in systolic or diastolic blood pressure following 12 weeks of treatment or 3 weeks of withdrawal of pravastatin. Sposito et al. [39] demonstrated an additional effect of statins on blood pressure reduction by comparing patients receiving ACE inhibitors alone with those receiving these medications plus statins after 3 months of dietary intervention. Although blood pressure was similarly reduced at week 4, the statin-treated group had a greater reduction in blood pressure and total cholesterol levels at week 16, suggesting a synergistic effect between cholesterol-lowering with statins and ACE inhibitor treatment for hypertensive patients. Borghi et al. [40] compared the extent of blood pressure changes in 41 patients with hypertension and hypercholesterol-emia taking antihypertensive drugs and treated for 3 months with statins (pravastatin or simvastatin) with matched controls with high or normal serum cholesterol undergoing antihypertensive treatment combined with dietary treatment alone. After 3 months of follow-up, a greater reduction of systolic and dia-stolic blood pressure values was observed in the statin recipients. In the statin-treated patients, a slight linear relation was found between changes in diastolic blood pressure and those in plasma total cholesterol. This study demonstrated that the use of statins in combination with antihypertensive drugs can improve blood pressure control in patients with uncontrolled hypertension and high serum cholesterol levels. The additional blood pressure reduction observed in patients treated with statins is clinically relevant and only partially related to the lipid-lowering effect [40]. Several other small studies have also shown that lipid-lowering treatment with statins may have a blood pressure-lowering effect. Some of the important studies are summarized in table 2.

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