Arterial calcification in the prediction of atherosclerotic cardiovascular disease among women and men
Authors: Van Der Toorn J.E , Bos D , Arshi B , Ikram M.K , Vernooij M.W , Ikram M.A , Kavousi M 
Published: November 2020

Abstract

Background
The Coronary Artery Calcium (CAC) Score has emerged as a valuable tool in atherosclerotic cardiovascular disease (ASCVD) risk stratification. However, data on the relevance of arterial calcification in different vascular territories for ASCVD risk prediction is lacking.

Purpose
First, to assess the sex-specific distribution of arterial calcification in different vessel beds across ASCVD risk categories. Second, to determine the added value of arterial calcification in different vascular territories for ASCVD risk prediction.

Methods
From a large population-based study, 2,139 participants (mean age 69 years, 55% women) underwent non-contrast computed tomography to quantify CAC, aortic arch calcification (AAC), extracranial- (ECAC) and intracranial carotid artery calcification (ICAC), and vertebrobasilar artery calcification (VBAC). The outcome measure, incident ASCVD, composed of fatal and nonfatal myocardial infarction (MI), other coronary heart disease (CHD) mortality, and stroke. We fitted sex-specific prediction models according to the Pooled Cohort Equations (PCE), and categorized participants into low- (&lt;5%), borderline- (5% to 7.5%), intermediate- (7.5% to 20%), and high ASCVD risk (≥20%), based on the American College of Cardiology (ACC) and American Heart Association (AHA) guideline. Subsequently, we determined the distribution of calcifications in different vascular territories across the risk categories. Next, we extended the PCE prediction model with calcification volumes and calculated the c-statistic and the net reclassification improvement for events (NRIe) and non-events (NRIne).

Results
The median follow-up for ASCVD was 9.3 years. Among women, 38% was classified as low-risk, 19% as borderline risk, 31% as intermediate risk, and 12% as high risk. Among men, 2% was classified as low-risk, 10% as borderline risk, 60% as intermediate risk, and 28% as high risk. With increasing risk of ASCVD, a larger burden of calcification was observed. In women, simultaneously adding calcification volumes in all vessel beds led to the largest increase in c statistic (from 0.71 to 0.75) for the prediction of ASCVD and the most beneficial reclassification (NRIe: 11%, NRIne: 2%). Among men, the addition of CAC alone most substantially improved the prediction of ASCVD (c statistic improved from 0.65 to 0.68, NRIe and NRIne were 4% and 14%, respectively).

Conclusions
Our findings suggest a potential role for comprehensive assessment of calcification in different vessel beds for ASCVD risk stratification in particular among women.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): The Rotterdam Study is supported by Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; European Commission; and the Municipality of Rotterdam. Dr. Kavousi is supported by the VENI grant (91616079) from ZonMw. Dr. Bos was supported by a fellowship of the BrightFocus Foundation (A2017424F). Oscar L. Rueda-Ochoa receives a scholarship from COLCIENCIAS-Colombia and support from Universidad Industrial de Santander,UIS-Colombia. None of the funders had any role in study design; study conduct; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the article.