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The Effect of Valsartan Compared to Valsartan/Hydrochlorothiazide on Plasma Levels of Cellular Adhesion Molecules: The Val-MARC Trial
  1. David Conen (conend{at}uhbs.ch)
  1. Brigham and Women's Hospital, United States
    1. Brendan M Everett (beverett{at}partners.org)
    1. Brigham and Women's Hospital, United States
      1. Robert J Glynn (rglynn{at}rics.bwh.harvard.edu)
      1. Brigham and Women's Hospital, United States
        1. Paul M Ridker (pridker{at}partners.org)
        1. Brigham and Women's Hospital, United States

          Abstract

          Objective The Val-MARC trial showed that the angiotensin receptor blocker valsartan reduces high sensitivity C-reactive protein (hsCRP) levels, an effect that is blood pressure independent, and seems to be neutralized by the addition of hydrochlorothiazide. In the present study we evaluated whether valsartan influences soluble intercellular adhesion molecule 1 (sICAM-1) or vascular cell adhesion molecule 1 (sVCAM-1).

          Design Post-hoc analysis from a randomized trial

          Setting Val-MARC trial

          Patients 1188 patients with stage 2 hypertension

          Intervention Random allocation to either valsartan 320mg (n=607) or combination therapy with valsartan/hydrochlorothiazide 320mg/12.5mg (n=581) for 6 weeks

          Main outcome measure Change in sICAM-1 and sVCAM-1 from baseline to six weeks of follow-up

          Results Following treatment, median (interquartile range) sICAM-1 levels were reduced by both valsartan alone (-4 (-25, 16) ng/ml, p=0.005) and valsartan/hydrochlorothiazide (-4 (-22, 17) ng/ml, p=0.028), such that the between group difference was not statistically significant (p=0.7). The median percentage change from baseline was small in both groups (-1.6% and -1.3%). Median (interquartile range) sVCAM-1 levels were reduced by both valsartan alone (-13 (-70, 42) ng/ml, p=0.001) and valsartan/hydrochlorothiazide (-26 (-88, 38), p<0.0001); the between group difference was of borderline statistical significance (p=0.051). The median percentage change from baseline was small (-2.1% and -4.4%). The reduction of sICAM-1 and sVCAM-1 was independent of blood pressure reduction (r=0.03 and r=0.06 for the relationship of change in systolic blood pressure with change in sICAM-1 and sVCAM-1, respectively).

          Conclusion In contrast to hsCRP, both valsartan and valsartan/hydrochlorothiazide induced reductions of sICAM-1 and sVCAM-1 in the Val-MARC trial. These effects, while statistically significant, were small in magnitude and independent of changes in blood pressure.

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