Disproportionate atherosclerotic burden in the left anterior descending coronary artery in participants without standard modifiable cardiovascular risk factors: The multi-ethnic study of atherosclerosis (MESA)

BACKGROUND: Standard modifiable cardiovascular risk factors (SMuRF) have been identified for coronary artery disease (CAD) and targeted in primary prevention efforts, resulting in significantly improved outcomes. However, an increasing proportion of individuals present with ST elevation myocardial infarction (STEMI) in the absence of conventionally elevated levels of modifiable risk factors ("SMuRFless"), with significantly worse short-term outcomes. Culprit lesions of the left anterior descending artery (LAD) are more frequently implicated in SMuRFless STEMI patients than those with at least one risk factor. Differences in segmental-level coronary disease burden outside the acute setting in SMuRFless individuals are largely unknown. OBJECTIVES: To characterise vessel-level coronary calcification, comparing SMuRFless to SMuRF≥1 participants. METHODS: Secondary analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) was completed. Coronary artery calcium score (CACS) was measured at baseline and follow-up (median 6.3 years). RESULTS: 6792 participants were included, with 20.6 ​% classified as SMuRFless. Among participants with detectable coronary calcification at baseline, SMuRFless participants had a significantly higher proportion of their total coronary calcium localised to the LAD, compared to SMuRF≥1 participants (74.2 ​% vs. 58.9 ​%, p ​< ​0.0001). This difference was most pronounced in individuals with higher baseline total CACS (CACS 100-400 Agatston units [AU] and CACS 401+), but attenuated after multivariable adjustment and was not statistically significant in best-subsets modelling. LAD CACS progressed in both groups during follow-up; however, annualised progression rates were similar between SMuRFless and SMuRF≥1 participants after adjustment for total coronary calcium progression and follow-up duration. CONCLUSION: SMuRFless MESA participants had a higher unadjusted proportion of coronary calcification in the LAD compared SMuRF≥1 participants; however, this associated attenuated after multivariable adjustment. Further research is warranted to better understand the development of atherosclerotic CAD in SMuRFless individuals, and biological relevance and potentially different susceptibility at the epicardial segment level.