The effect of angiotensin-converting enzyme inhibitors and statins on the progression of aortic sclerosis and mortality.
OBJECTIVE
Although aortic sclerosis has been associated with an increase in adverse cardiovascular outcomes, no proven therapy has been shown to slow its progression to overt aortic stenosis (AS). Thus, the hypothesis was assessed that treatment with angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs) or statins may be associated with an improvement in the clinical outcome of these patients.


METHODS
A total of 4,105 patients with evidence of aortic sclerosis seen on transthoracic echocardiography (defined as thickening or calcification with a mean valve gradient < or = 15 mmHg) was identified. Patients with a sclerotic valve who were treated with ACE-Is/ARBs or statins were followed for a mean period of 1,078 +/- 615 days. After adjustment for the propensity to receive ACE-Is/ARBs or statins, mortality, hemodynamic progression to AS, hospitalization for ischemic heart disease (IHD), and congestive heart failure (CHF) were assessed and related to the medical treatment.


RESULTS
At baseline, patients with aortic sclerosis who were treated with an ACE-I/ARB or a statin suffered significantly more from comorbidities such as IHD, CHF, hypertension, diabetes, and peripheral arterial disease, when compared to subjects with sclerotic valves not treated with these drugs. After adjustment for confounding factors, treatment with statins was associated with a significant reduction in mortality (odds ratio [OR] 0.73, 95% CI 0.56-0.98, p = 0.001), admission for IHD (OR 0.81, 95% CI 0.66-0.99, p = 0.03), admission for CHF (OR 0.68, 95% CI 0.55-0.85, p = 0.01) and progression to AS (OR 0.64, 95% CI 0.42-0.97, p = 0.03). While ACE-I treatment resulted in a significant reduction in admission for IHD (OR 0.80, 95% CI 0.65-0.98, p = 0.03) and CHF (OR 0.76, 95% CI 0.62-0.94, p = 0.01), the beneficial trend towards reduced mortality and delayed progression to AS was not significant.


CONCLUSIONS
Treatment of this patient population with statins led to a significant reduction in mortality and also slowed the progression to AS--an effect that was not statistically significant with ACE-I treatment.
Division of Cardiology, University of California Los Angeles, Los Angeles, CA 90095-1760, USA. rardehali@mednet.ucla.edu
Reza
R
Ardehali
Nicholas J
NJ
Leeper
Andrew M
AM
Wilson
Paul A
PA
Heidenreich
D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001018:Aortic Diseases / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D001024:Aortic Valve Stenosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D002908:Chronic Disease; D015897:Comorbidity; D018450:Disease Progression; D004452:Echocardiography / Q000379:methods; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D019057:Quality-Adjusted Life Years; D055502:Secondary Prevention / Q000379:methods; D012720:Severity of Illness Index; D016896:Treatment Outcome
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors