Effect of valsartan compared with valsartan/hydrochlorothiazide on plasma levels of cellular adhesion molecules: the Val-MARC trial

Background: The Val-MARC trial showed that the angiotensin receptor blocker valsartan reduces high-sensitivity C reactive protein (hsCRP) levels, an effect that is independent of blood pressure, and seems to be neutralised by the addition of hydrochlorothiazide. Objective: To evaluate whether valsartan influences soluble intercellular adhesion molecule 1 (sICAM-1) or vascular cell adhesion molecule 1 (sVCAM-1). Design: Post-hoc analysis from a randomised trial. Setting: Val-MARC trial. Patients: 1188 patients with stage 2 hypertension. Intervention: Random allocation to either valsartan 320 mg (n = 607) or combination therapy with valsartan/hydrochlorothiazide 320 mg/12.5 mg (n = 581) for 6 weeks. Main outcome measure: Change in sICAM-1 and sVCAM-1 from baseline to 6 weeks of follow-up Results: After treatment, median (interquartile range) sICAM-1 levels were reduced by both valsartan alone (−4 (−25 to 16) ng/ml, p = 0.005) and valsartan/hydrochlorothiazide (−4 (−22 to 17) ng/ml, p = 0.028), such that the between-group difference was not 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 to 42) ng/ml, p = 0.001) and valsartan/hydrochlorothiazide (−26 (−88 to 38), p<0.001); the between-group difference was of borderline 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 (rs = 0.03 and rs = 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, although statistically significant, were small and independent of changes in blood pressure.

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