Valsartan monotherapy reduces hs-CRP levels

Valsartan is associated with a reduction in the levels of high-sensitivity C-reactive protein (hs-CRP), the inflammatory marker that is highly predictive of adverse cardiovascular outcomes, independent of its blood pressure-lowering effect, said Paul M. Ridker, MD, MPH, lead investigator of a trial presented at the 21st annual meeting of ASH.

The trial, known as Val-MARC (Valsartan-Managing Blood Pressure Aggressively and Evaluating Reductions in hs-CRP), studied the effect of valsartan alone and in combination with hydrochlorothiazide on levels of hs-CRP in 1,688 patients with stage 2 hypertension. The patients were randomized to either valsartan, 160 mg/d, or valsartan plus hydrochlorothiazide, 12.5 mg/d. The valsartan dosage was then titrated to 320 mg/d at Week 2.

The primary blood pressure/hs-CRP end point was measured at Week 6. After Week 6, patients in the valsartan monotherapy group had hydrochlorothiazide 12.5 mg/d added to their regimen, while those in the combination arm had their dose of hydrochlorothiazide increased to 25 mg/d. Blood pressure and hs-CRP measurements were then repeated at Week 12.

The median hs-CRP level decreased from 2.17 g/L at baseline to 1.98 mg/L at 6 weeks in the group assigned to valsartan monotherapy, a reduction of 8.9%. In contrast, hs-CRP increased from 2.09 to 2.15 mg/L in the group assigned to valsartan/hydrochlorothiazide, an increase of 4.4%. The difference between groups in the median percentage change in hs-CRP was 13.3% (P<.001). The difference between valsartan and valsartan/hydrochlorothiazide on hs-CRP was present in all subgroups studied despite a greater blood pressure reduction in the group receiving combination therapy, said Dr Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital in Boston, Mass. Adding hydrochlorothiazide neutralized valsartan's effect on hs-CRP, he said.

"There was no relationship whatsoever between the extent of blood pressure reduction and the change in hs-CRP," Dr Ridker said. The same effect of valsartan on hs-CRP was observed in statin users and non-users and aspirin users and non-users, and hydrochlorothiazide may change levels of plasminogen activator inhibitor-1 and clotting parameters, "2 factors that track with hs-CRP levels," he said.

Valsartan is the first antihypertensive to demonstrate an ability to reduce hs-CRP levels. The same effect has not been demonstrated by ACE inhibitors, Dr Ridker said.