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. 2025 Dec 8;46(46):5062-5072.
doi: 10.1093/eurheartj/ehaf497.

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

Malene Højgaard Andersen  1 , Jesper Møller Jensen  1 , Helle Kanstrup  1 , Niels P Rønnow Sand  2 , Martin Busk  3 , Malene Kærslund Hansen  1 , Pernille Gro Thrane  1 , Kevin Kris Warnakula Olesen  1 , Børge G Nordestgaard  4   5 , Michael J Blaha  6 , Michael Maeng  1 , Bjarne Linde Nørgaard  1 , Martin Bødtker Mortensen  1   6
Affiliations

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

Malene Højgaard Andersen et al. Eur Heart J. .

Abstract

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.

Keywords: Coronary artery calcification score; atherosclerosis; coronary computed tomography angiography; coronary heart disease; low-density lipoprotein cholesterol; non-calcified plaque.

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