Increased LDL-C encourages cholesterol buildup in artery walls, which results in the development of plaque and the advancement of subclinical atherosclerosis. Measured by CT, CAC is a common indicator of atherosclerotic load and a reliable predictor of cardiovascular events. But in the early stages, some people with high LDL-C levels have zero CAC scores, which raises significant concerns about their cardiovascular risk profile.
To improve risk assessment, directing treatment plans, and maximizing preventive actions in individuals who could otherwise be undervalued by imaging alone, it is crucial to comprehend how LDL-C and cardiovascular outcomes interact when calcifications are absent. This study examines whether high levels of LDL-C are linked to future cardiovascular events and the existence of non-calcified plaques in people with CAC = 0 at various ages.
Symptomatic patients receiving coronary computed tomography angiography (CCTA) between 2008 and 2021 were included in this Western Denmark Heart Registry cohort research, which had a median follow-up period of 7.1 years. The results included adjusted hazard ratios (aHR) for coronary heart disease (CHD) and adjusted odds ratios (aOR) for non-calcified plaque on CCTA.
There were 23,777 participants in the research with CAC = 0. With a median age of 54 (Q1-Q3 47-61) years, 61% of the population was female. Eleven percent of people had non-calcified plaques.
The overall aOR for non-calcified plaques was 1.21 [95% CI 1.16-1.27] for every 1 mmol/L increase in LDL-C; 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 were the equivalent values.
A CHD incident occurred in 299 (1%) during follow-up. The overall aHR for CHD was 1.28 (1.13-1.46) per 1 mmol/L higher LDL-C; the values that corresponded 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.
Overall, elevated LDL-C is linked to a greater risk of non-calcified plaque and a higher relative risk of future CHD events in symptomatic persons with CAC = 0, with the relationship being most noticeable at age ≤45. This suggests that even when CAC = 0, LDL-C control over an extended period of time is still significant in younger people.
Reference:
Andersen, M. H., Jensen, J. M., Kanstrup, H., Sand, N. P. R., Busk, M., Hansen, M. K., Thrane, P. G., Olesen, K. K. W., Nordestgaard, B. G., Blaha, M. J., Maeng, M., Nørgaard, B. L., & Mortensen, M. B. (2025). Low-density lipoprotein cholesterol and cardiovascular risk in the absence of calcifications on computed tomography: the Western Denmark Heart Registry. European Heart Journal. https://doi.org/10.1093/eurheartj/ehaf497
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