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Validity of Vascular Calcification as a Screening Tool and as a Surrogate End Point in Clinical Research.

On a world scale, in 2013, there have been >17 million cardiovascular deaths, one half of which attributable to ischemic heart disease.1 More than 50% of cases of ischemic heart disease deaths presenting as sudden cardiac death have no history of symptoms heralding the critical event,2 and most myocardial infarctions occur in low or moderate risk subjects (ie, in the largest segment of the general population). On a life-time scale, the risk of myocardial infarction at the age of 40 years is 1 in 2 men and 1 in 3 in women.3 These figures underline the potential relevance of timely screening and treatment of individuals at risk of cardiovascular disease.

The Framingham Risk Score or the recently developed risk calculator, which informs the American College of Cardiology/American Heart Association cholesterol guideline,4 the HeartScore,5 or the QRISK calculator,6 are center pieces of current policies for cardiovascular risk assessment and for lipid-lowering treatment. Because in these calculators age is the most informative risk factor for the prediction of cardiovascular events,7 these instruments have limited precision for the prediction of coronary atherosclerosis at individual level particularly in young subjects who have a low absolute risk for cardiovascular disease events.8 Novel biomarkers measurable in plasma or serum have been intensively investigated to refine risk prediction in individuals at low or moderate risk, but the gain in prediction power by these biomarkers is just of modest degree.9

Imaging biomarkers provide an estimate of the atherosclerotic burden in critical areas of the arterial system like the coronary circulation and may provide an integrated measure of life time exposure to risk factors. Among imaging markers of atherosclerosis assessment of vascular calcification, in particular of coronary calcification, is considered as the most valuable one because it outperforms other imaging …