The influence of endothelin-1, hs-CRP, coronary artery plaque burden and plaque morphology on calcific aortic valve disease

Abstract

Background: Calcific aortic valve disease (CAVD) affects 1 in 4 of the population >65 years. Subsequent progression to severe aortic valve stenosis has a high morbidity and mortality. The pathophysiology of CAVD is poorly understood. Understanding the processes involved are important if successful non-surgical treatments are to be developed. Both systemic levels of inflammation and coronary atherosclerotic artery disease (CAD) - itself an inflammatory process - are predictors of CAVD. However, whether their effects are independent of each other are unknown. Furthermore, the specific influences of plaque burden, differing coronary plaque morphology and systemic levels of the inflammatory mediator endothelin-1 (ET-1), on CAVD are unknown. Purpose: To investigate the inter-relationships between coronary artery plaque burden, plaque morphology and markers of inflammation (hs-CRP and ET-1), with aortic valve calcification (AVC). Methods: Patients undergoing CT coronary angiography (CTCA) for investigation of chest pain were recruited. Those with significant CAD (>50% luminal stenosis) and significant valvular dysfunction were excluded (aortic valve velocity ≥2.0m/s). Coronary artery plaque burden, plaque morphology, and AVC were assessedwith CTCA. Inflammatory markers were obtained from venous sampling. Results: 183 patients, 53% male, mean age 59.8 (±9.6) years were recruited. AVC was present in 111 (61%) patients and atherosclerotic plaque also in 111 (61%) patients. Multivariable linear regression modeling including demographic data, AVC, total plaque length (TPL) (mm), inflammatory markers (hs- CRP mg/L and ET-1 pg/mL) and different plaque morphologies (completely calcified/ predominantly calcified/predominantly non-calcified/completely non-calcified, calcium score and positive remodeling) demonstrated the following. Increasing TPL (β= +0.02, 95% CI: +0.01, +0.03 p=<0.001), hs-CRP (β=+0.07, 95% CI: +0.01, +0.14, p=0.02), ET-1 (β=+0.66, 95% CI: +0.07,+1.24, p=0.028), male sex (β=+0.73, 95% CI: +0.08, +1.38, p=0.028), age (β=+0.04, 95% CI: +0.01,+0.07, p=0.026), calcified plaque (β=-0.31, 95% CI: +0.57, -0.04, p=0.027), total cholesterol (β=+1.80, 95% CI: +0.98, +2.62, p=<0.001), and decreasing LDL (β=-2.12, 95% CI: -2.97, -1.26, p=<0.001), were all independent predictors of increasing AVC. This model explained 45% of the variance in AVC. Conclusions: This study has shown that coronary artery plaque burden, calcified coronary plaque morphology and the markers of inflammation, hs-CRP and ET-1, are all independent predictors of CAVD.<br />