Alterations in cholesterol homeostasis are associated with coronary heart disease in patients with aortic stenosis

Abstract

Objective: Hypercholesterolemia is a risk factor for aortic stenosis (AS) and for coronary artery disease (CAD). Serum cholesterol concentrations are determined by intestinal cholesterol absorption and endogenous cholesterol synthesis. Vascular effects of differences in cholesterol metabolism in patients with AS are so far unknown. Therefore, the aim of this study was to investigate differences in cholesterol metabolism in relation to vascular diseases in this subset of patients.

Methods: In addition to identifying conventional coronary risk factors, we determined plant sterols (indicators of cholesterol absorption) and lathosterol (indicator of cholesterol synthesis) levels in 40 consecutive men and women with AS. Coronary angiograms before the aortic valve replacement determined the extent of CAD.

Results: Patients with a positive history of cardiovascular disease exhibited an increased campesterol-to-lathosterol ratio in plasma (P<0.005) and in aortic valve cusps (P<0.05). The plasma campesterol-to-lathosterol ratio increased with CAD severity (zero, single, two, three-vessel disease; P<0.05). Coronary vessel score strongly correlated with the campesterol-to-lathosterol ratio in plasma (r = 0.52; P<0.001) and in aortic valve cusps (r = 0.33; P<0.03). Logistic regression analysis revealed that the ratio of campesterol-to-lathosterol was the sole predictor of CAD among coronary risk factors tested (P<0.01).

Conclusion: Enhanced absorption and reduced synthesis of cholesterol is related to a positive family history of cardiovascular diseases and the development of concomitant CAD in patients with AS.