Low-density lipoprotein cholesterol and cardiovascular risk in the absence of calcifications on computed tomography: the Western Denmark Heart Registry

AIMS: Coronary atherosclerosis tends to be non-calcified at early stages, questioning the implications of a coronary artery calcification score of zero (CAC = 0) at younger ages. This study investigates whether elevated low-density lipoprotein cholesterol (LDL-C) is associated with the presence of non-calcified plaques and future cardiovascular events in individuals with CAC = 0 across different ages. METHODS AND RESULTS: This cohort study from the Western Denmark Heart Registry included symptomatic individuals undergoing coronary computed tomography angiography (CCTA) from 2008-2021, with a 7.1-year median follow-up time. Outcomes included adjusted odds ratios (aOR) for non-calcified plaque on CCTA and adjusted hazard ratios (aHR) for coronary heart disease (CHD).The study included 23 777 individuals with CAC = 0. Median age was 54 (Q1-Q3 47-61) years, and 61% were women. The prevalence of non-calcified plaques was 11%. Per 1 mmol/L higher LDL-C, the overall aOR for non-calcified plaques was 1.21 [95% confidence interval (CI) 1.16-1.27]; corresponding values were 1.39 (1.23-1.56) at age ≤45, 1.22 (1.14-1.31) at age 46-60, and 1.11 (1.02-1.21) at age >60. During follow-up, 299 (1%) had a CHD event. Per 1 mmol/L higher LDL-C, the overall aHR was 1.28 (1.13-1.46) for CHD; corresponding values were 1.37 (1.04-1.82) at age ≤45, 1.24 (1.04-1.49) at age 46-60, and 1.26 (1.00-1.60) at age >60. CONCLUSION: In symptomatic individuals with CAC = 0, elevated LDL-C is associated with higher risk of non-calcified plaque and with higher relative risk of future CHD events, most pronounced at age ≤45 years. This indicates that LDL-C control over a long-time horizon remains important in younger individuals despite CAC = 0.