The 'valvulo-metabolic' risk in calcific aortic valve disease

Abstract

Calcific aortic stenosis (AS) has been considered a degenerative and unmodifiable process resulting from aging and 'wear and tear' of the aortic valve. Over the past decade, studies in the field of epidemiology, molecular biology and lipid metabolism have highlighted similarities between vascular atherosclerosis and calcific AS. In particular, work from the Quebec Heart Institute and from that of others has documented evidence of valvular infiltration by oxidized low-density lipoproteins and the presence of inflammatory cells, along with important tissue remodelling in valves explanted from patients with AS. Recent studies have also emphasized the role of visceral obesity in the development and progression of AS. In addition, visceral obesity, with its attendant metabolic complications, commonly referred to as the metabolic syndrome, has been associated with degenerative changes in bioprosthetic heart valves. The purpose of the present review is to introduce the concept of 'valvulo-metabolic risk' and to provide an update on the recent and important discoveries regarding the pathogenesis of heart valve diseases in relation to obesity, and to discuss how these novel mechanisms might translate into clinical practice.

Figures

Figure 1)

Macroscopic appearance of explanted leaflets from calcific aortic stenosis showing the presence of yellowish material indicating lipids (arrows) infiltrating the aortic side (A); hematoxylin and eosin staining at low magnification showing the presence of a calcific nodule within the aortic valve (B), which is surrounded by oxidized low-density lipoproteins (immunohistochemistry with high magnification) (C)

Figure 2)

Kaplan-Meier analysis of event-free survival (absence of death or aortic valve replacement) in patients with or without the metabolic syndrome (MS). Reproduced from Briand et al (9) with permission

Figure 3)

Rate of progression of aortic valve area (AVA) decrease among groups of patients according to the Framingham score (dichotomized at the median value) and the presence or absence of the metabolic syndrome (MS). †Significant difference versus group 2 (P<0.05). Reproduced from Briand et al (9) with permission

Figure 4)

Patients with visceral obesity have low high-density lipoprotein (HDL) levels with an increased proportion of circulating small and dense low-density lipoprotein (LDL). The small and dense LDLs have a greater ability to infiltrate the aortic valve and are transformed rapidly to oxidized LDL owing to low HDL levels with a decreased anti-inflammatory activity. Inflammatory cells are attracted within the aortic valve and macrophages are stimulated by oxidized LDL to produce cytokines such as tumour necrosis factor (TNF)alpha, which promotes calcification of valve fibroblasts

Figure 5)

Rate of progression of mean gradient (MG) among groups of patients according to the presence of diabetes and the metabolic syndrome (MS). P†group 2. Reproduced from Briand et al (10) with permission