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Consciousness of Blood Pressure Is Rising as Details About Possible Remedies Continue to Evolve: Statins Have Small but Statistically Significant Blood Pressure-Lowering Effect


Statins Have Small but Statistically Significant Blood Pressure-Lowering Effect

Statins have been linked to benefits in hypertension as a result of pleiotropic effects on endothelial function, their interactions with the renin-angiotensin system, and their influence on large artery compliance. In contrast, differing effects of statins on blood pressure have been shown in large-scale trials that have recruited patients with significant atherosclerosis or large numbers of risk factors, as well as in small-scale studies in primary prevention. Now a recently published meta-analysis of clinical trials has concluded that statin therapy has a "relatively small, but statistically significant and clinically meaningful effect on blood pressure." The study, which was a collaboration between researchers in Naples, Italy, and London and Coventry, United Kingdom, is published in the April issue of Hypertension.[15] The results were first presented at the 2006 European Meeting of Hypertension in Madrid, Spain (see Related Links).[16]

Lead researcher Pasquale Strazzullo, MD (Federico II University Medical School, Naples) and colleagues identified 18 randomized controlled trials of statins, reported as original articles in peer-reviewed English-language scientific journals from online databases (PUBMED, EMBASE, and HTA -- the database of the International Network of Agencies for Health Technology Assessment) and other database sources. All of the trials compared a statin with a placebo or another hypolipidemic drug, and concomitant antihypertensive treatment was kept constant for the duration of each trial. Two of the trials had 2 pairs of control and treatment groups and were each regarded as 2 trials each, making the final total 20 trials.

The studies involved a total of 828 patients, of whom 291 patients were given statins, 272 were given a placebo, and 265 were on crossover trials. Some of the studies recruited only hypertensive patients, some only normotensive patients, and some either normotensive or hypertensive patients in "reasonably good control." Most of the studies included hypercholesterolemic patients (serum total cholesterol ≥ 5.2 mmol/L [201 mg/dL]). In all but 7 studies the participants received drugs different from statins or control medications.

The researchers calculated that that overall, statins produced reduction of 1.9 mm Hg in systolic blood pressure (SBP) and 0.9 mm Hg in diastolic blood pressure (DBP). The effect was even more pronounced in patients with high baseline blood pressure. Statin therapy in patients with baseline SBP > 130 mm Hg showed an average reduction in 4.0 mm Hg, and those with DBP > 80 mm Hg a 1.2-mm Hg reduction. In patients with SBP ≤ 130 mm Hg and/or DBP ≤ 80 mm Hg, the average effect of statin therapy on blood pressure was negligible.

Meta-regression analysis indicated that the effect of statins on blood pressure was independent of response to statin therapy, age, length of trial, baseline serum cholesterol, change in total serum cholesterol, or low-density lipoprotein cholesterol, whether the patient had diabetes or not, or whether patients were taking antihypertensive medication or not.

Two other studies involving a total of 64 patients could not be included in the meta-analysis because of insufficient blood pressure data, but showed mean blood pressure reductions of 4.0 mm Hg and 2.0 mm Hg, respectively.

Prof. Strazzullo and colleagues note that the studies selected for their meta-analysis did not include any of the well-known large-scale outcomes trials that demonstrated the value of statins in primary and secondary prevention, because of insufficient reporting of blood pressure values and/or antihypertensive treatment in the patients with hypertension. However, their results are consistent with an analysis of data from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)[17] and the University of California San Diego (UCSD) Statin Study,[18] both of which showed lower blood pressures in patients on statins compared with patients taking placebo (see Related Links).

They suggest several mechanisms for the effect of statins on blood pressure, including increasing endothelial production of nitric oxide (NO), with corresponding upregulation of NO synthase expression, leading to increased NO availability, and downregulation of endothelin-1. These effects on endothelial function appear early after statin administration and are therefore probably unrelated to the effects of statins on cholesterol, Prof. Strazullo and his coauthors suggest. Statins have also been shown to reduce large artery stiffness and improve systemic arterial compliance and to reduce expression of the angiotensin II type-1 receptor, which is overexpressed in hypercholesterolemic patients. "Whatever the mechanism(s), our meta-analysis provided evidence of a favorable effect of statins on blood pressure, particularly SBP, and indicated that the effect was larger in individuals with elevated blood pressure," the authors conclude.

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