Published Online
on May 19, 2006

A more recent version of this article appeared on July 1, 2006

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Submitted on March 29, 2006
Revised on April 16, 2006

Valsartan, Blood Pressure Reduction, and C-Reactive Protein. Primary Report of the Val-MARC Trial

Paul M Ridker^*; Eleanor Danielson; Nader Rifai; Robert J. Glynn; for the Val-MARC Investigators

From the Center for Cardiovascular Disease Prevention, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

^* To whom correspondence should be addressed. E-mail: pridker{at}partners.org.

Abstract--Increased levels of high-sensitivity C-reactive protein (hsCRP) are associated with incident hypertension as well as cardiovascular events, and angiotensin II is a potent proinflammatory mediator. However, whether angiotensin receptor blockade lowers hsCRP is uncertain. We performed a randomized trial in which 1668 patients with stage 2 hypertension were treated with 160 mg valsartan or 160/12.5 mg valsartan/hydrochlorothiazide (HCTZ) once daily for 2 weeks with forced titration to 320 mg valsartan or 320/12.5 mg valsartan/HCTZ for an additional 4 weeks. After 6 weeks, systolic blood pressure (-25 versus -18 mm Hg; P<0.001) and diastolic blood pressure (-14 versus -9 mm Hg; P<0.001) were reduced to a greater degree among those allocated to valsartan/HCTZ than to valsartan monotherapy. The median change in hsCRP was -0.12 mg/L among those allocated to valsartan compared with +0.05 mg/L among those allocated to valsartan/HCTZ, a 13.3% difference (P<0.001); this difference between valsartan and valsartan/HCTZ was present in all subgroups evaluated despite the fact that blood pressure reduction was greater in the combined therapy group. No relationship was observed between hsCRP reduction and blood pressure; in all analyses, the proportion of variation in change in hsCRP with valsartan monotherapy explained by change in blood pressure was <2%. Thus, in this prospective trial, valsartan reduced hsCRP levels in a manner independent of degree of blood pressure reduction. These data raise the hypothesis that angiotensin receptor blockade may have anti-inflammatory effects in addition to blood pressure-lowering effects.

Key words: clinical trials • antihypertensive therapy • angiotensin antagonist

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