Cardiovascular disease (CVD) remains the leading cause of mortality and major cause of morbidity worldwide, with underlying atherosclerosis as one of the key elements. In more than 90% of cases, the cause of myocardial ischemia is atherosclerotic plaque progression and rupture which leads to thrombus formation and obstruction of blood flow in the coronary arteries.
More than 50% of patients die without clinical symptoms . To identify asymptomatic individuals at highest risk, attempts have been made on developing tools to risk-stratify individuals with sub-clinical atherosclerosis.
Many risk factors of atherosclerosis have been identified, of which the most widely accepted are elevated total and low-density lipoprotein (LDL) cholesterol, reduced high-density lipoprotein (HDL) cholesterol, hypertension, obesity, diabetes, and cigarette smoking [2–4]. In the face of these well-recognized risk factors, it is still debated whether postprandial serum triglyceride levels are an independent predictor of cardiovascular risk. Some studies have indicated that non-fasting triglyceride levels are associated with incident of cardiovascular events independent of the traditional risk factors whereas fasting triglyceride levels have displayed little independent relationship [5, 6]. In contrast, we have demonstrated that fasting triglyceride levels in combination with specific distributions of adiposity are strong predictors of accelerated atherosclerosis [7–9]. These and other discrepancies highlight the need for additional understanding of risk factors of CVD.
Non-invasive diagnostic tools, such as imaging techniques, for identification of advanced atherosclerotic plaques prior to manifestation of clinical symptoms, or even death, would be clinically useful. Calcification of coronary arteries has been shown to be directly related to the severity and the extent of underlying coronary plaque burden [10, 11], and to be associated with increased risk of coronary heart disease (CHD) [12–14].
A variety of imaging techniques for examining vascular calcifications have emerged with increasing attention being focused on the assessment of abdominal aortic calcifications from simple X-rays. Lumbar abdominal X-ray for investigation of lumbar aortic calcification has been shown to correlate with the extent of calcified plaques in the coronary arteries [15–17]. These calcifications may be important risk factors of congestive heart failure (CHF) independent of CHD and other risk factors.
X-rays are traditionally analysed according to the categorical Framingham score system. We have recently demonstrated [18, 19] that additional information could be harvested from these x-rays by including measures of the number, length, width, and morphology of the calcified plaques. Assessment of risk of CVD death using this novel quantification system Morphological Atherosclerotic Calcification Distribution (MACD) quantification system resulted in an odds ratio of 20 compared with 4.5 using the Framingham scoring systems . Interestingly, the MACD was associated with CVD death independently of traditional risk factors including BMI, hypertension, obesity etc, suggesting that the MACD index contained additional critically useful information.
The aim of the current study was to further investigate the biological basis for the predictability of the MACD index. In post-menopausal women as previously described [18, 19], we correlated traditional risk factors with MACD scores in a cross-sectional and a longitudinal study, and compared these correlations to the gold standard, the AC24 index developed on the basis of the Framingham Heart Study cohorts.