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).


METHODS
Post-hoc analysis from a randomised trial.


METHODS
Val-MARC trial.


METHODS
1188 patients with stage 2 hypertension.


METHODS
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.


METHODS
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).


CONCLUSIONS
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.
Conen
D
D
Center for Cardiovascular Disease Prevention, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. conend@uhbs.ch
Everett
B M
BM
Glynn
R J
RJ
Ridker
P M
PM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000494:pharmacology*; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
D000959:Antihypertensive Agents; D013777:Tetrazoles; D019010:Vascular Cell Adhesion Molecule-1; D006852:Hydrochlorothiazide; D018799:Intercellular Adhesion Molecule-1; D000068756:Valsartan; D014633:Valine