16 May 2008 -Results from a randomized, double blind, placebo-controlled clinical trial have confirmed earlier observations that statins lower blood pressure. The modest reduction was observed in a largely normotensive patient population and occurred in patients taking relatively low doses of statins, report investigators.

Lead investigator Beatrice Golomb, MD (University of California, San Diego [UCSD]) told that the study provides confirmation that the effects of statins extend to reductions in a second primary cardiovascular risk factor. "The observed reduction in blood pressure, about 2.2 mm Hg, is modest but at the population level can contribute to significant reductions in the risk of stroke," she said.

The study, known as the University of California San Diego (UCSD) Statin Study, is published on Archives of Internal Medicine of April 15. A recent meta-analysis of 20 statin trials suggested that, as well as lowering lipids, the drugs produce a small but clinically meaningful reduction in blood pressure, noted Golomb, but the largest study had a sample size of only 100 patients, raising concerns about publication bias. Other reviews and meta-analyses had similar shortcomings.

In the UCSD study, Golomb and colleagues randomized 973 individuals who did not have diabetes or cardiovascular disease to statin therapy or placebo for six months. Of these participants, 322 were assigned to simvastatin 20 mg, 323 to pravastatin 40 mg, and 328 to placebo. Blood pressure was measured at the beginning of the study, at one and six months during treatment, and two months after treatment ended. Patients were included in the trial based on their LDL-cholesterol levels (between 115 mg/dL and 190 mg/dL) and not selected by baseline blood pressure. Mean systolic and diastolic blood pressures at baseline were 126 mm Hg and 75 mm Hg, respectively, across the three treatment groups.

Blood-pressure (BP) reductions in the statin arms vs placebo

In the intention-to-treat analysis, significant, although modest, reductions in blood pressure were observed in the combined statin group compared with placebo. The reductions, however, were slightly larger when investigators excluded those with high blood pressure at baseline. Those without high blood pressure and those not taking blood-pressure-lowering medications also had their blood pressure lowered on statin therapy. After drug therapy was stopped, the effect on blood pressure was lost.
Golomb said the results help explain the reduction in cardiovascular events with statins that occur early, those within the first six months. It is too early at that stage for statins to have an effect on plaque accumulation in arteries, so the benefit is a reduction in stroke risk, she said. She noted that reductions in blood pressure occurred with both the hydrophilic and lipophilic statins.
In terms of mechanism, the investigators suggest that statins might lower blood pressure through upregulation and/or activation of endothelial nitric-oxide synthase as well as through improvements in endothelial function and flow-mediated vasodilation. The antioxidant effects of the lipid-lowering medications are believed to bring about the latter two improvements, write Golomb and colleagues.