Mitral Annular Calcification and Cardiovascular Diseases: Does Correlation Imply Causation?

Abstract

Mitral annular calcification (MAC) is a chronic degenerative process characterized by calcification and lipid deposition in the surrounding fibrous support of the mitral valve involving mainly the posterior annulus. It is frequently seen in females with advanced age. Mitral annular calcification has been associated with several cardiovascular diseases including coronary artery disease (CAD), myocardial infarction (MI), impaired coronary microvascular function, peripheral arterial disease, atrial fibrillation, and aortic atheromatous disease. A correlation has also been demonstrated between serum high-sensitivity C-reactive protein levels and MAC as a reflection of systemic inflammation. In a prospective cohort study, MAC was a strong and independent predictor of cardiovascular events, especially MI and vascular death (stroke, MI, heart failure, and cardiac arrhythmia). Mitral annular calcification has also been associated with a high prevalence of risk factors for the development of atherosclerosis. In contrast, Nair et al did not find any correlation between MAC and CAD in patients younger than 60 years of age. However, their findings were based solely on clinical data rather than objective methods such as coronary angiography. More recently, in contrast to previous studies, Bhatt et al found that MAC was not significantly associated with a history of CAD, and cardiovascular risk factors such as hypertension, diabetes mellitus, and worsening renal function. In addition, the coronary lesion characteristics and Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery score were not independently associated with MAC. These authors suggested that MAC should not be considered as a marker of CAD in isolation from cardiovascular risk factors and that it is probably a benign marker of age-related degenerative changes in the heart independent of the severity and complexity of coronary disease. The main limitations of this study are the lack of data on aortic valve calcification (AVC) and severity of MAC. In a subgroup analysis of the Framingham Heart Study, risks of incident cardiovascular disease, cardiovascular death, and all-cause death was found to increase by approximately 10% per 1-mm increase in MAC thickness. In the Northern Manhattan Study, the increased cardiovascular event risk was directly related to MAC severity rather than its presence. In another study, not trivial but advanced MAC was significantly associated with CAD. In their retrospective study, Bhatt et al mentioned that AVC should be looked at separately from MAC. However, it has been previously shown that in patients with mild to moderate aortic stenosis, there is more extensive MAC and AVC in patients with tricuspid aortic valves compared with bicuspid aortic valves independent of age and systemic blood pressure. In another study, the combined presence of AVC and MAC was highly associated with the presence, extent, and vulnerable characteristics of coronary plaque identified by 64-multidetector computed tomography. Additionally, Acarturk et al showed that the absence of MAC and AVC was a stronger predictor for absence of CAD than all conventional risk factors, except diabetes mellitus. The MAC is frequently associated with calcific deposits in other cardiac structures, such as the aortic root, the tips of the papillary muscles, and the chordae tendineae. An autopsy review of 200 patients older than the age of 65 reported that of the patients with MAC, 69% had AVC. Therefore, specific information about both AVC and severity of MAC would appear useful for consolidating, assessing, and evaluating the results and value of various studies. Likewise, MAC and AVC may be a result of a primary degenerative process that increases with age or the outcome of increased valvular stress other than an expression of generalized atherosclerosis as suggested by Bhatt et al. There is no standard definition of MAC. All of the abovementioned studies have used 2-dimensional or M-mode echocardiography for the definition or presence of MAC. However, 2-dimensional echocardiography may be insufficient for imaging the anterior mitral annulus. Currently, there is no evidence-based treatment modality that reduces the progression of MAC or prevents its occurrence. It is also unknown whether drugs that are commonly used in cardiovascular patients such as aspirin, statins, b-blockers, and renin–angiotensin system blockers have a