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TOPLINE:

In symptomatic adults with a coronary artery calcification (CAC) score of zero, elevated levels of low-density lipoprotein (LDL) cholesterol were associated with increased risks for noncalcified plaques and future coronary heart disease events, especially in those younger than 45 years.

METHODOLOGY:

• Atherosclerosis is noncalcified in early stages, so a zero CAC score — especially in younger people — can obscure early disease and delay prevention.
• Researchers conducted a cohort study in Denmark to investigate whether high levels of LDL cholesterol could predict the presence of noncalcified plaques and the risk for future cardiovascular events.
• They included 23,777 adults (median age, 54 years; 61% women) who underwent coronary CT angiography between January 2008 and May 2021 due to symptoms suggestive of coronary artery disease; all had a CAC score of zero.
• Noncalcified plaques were identified on scan images; data on levels of LDL cholesterol were retrieved from a registry.
• Outcomes were the occurrence of myocardial infarction and coronary heart disease, assessed over a median follow-up duration of 7.1 years.

TAKEAWAY:

• Overall, 11% of participants had detectable noncalcified plaques. A CAC score of zero was most common among adults younger than 45 years.
• Each 1 mmol/L increase in levels of LDL cholesterol was associated with 21% increased odds of detecting noncalcified plaques (adjusted odds ratio [aOR], 1.21; 95% CI, 1.16-1.27).
• The association between elevated levels of LDL cholesterol and higher odds of noncalcified plaques persisted across all age groups but was most pronounced in adults younger than 45 years (aOR, 1.39; 95% CI, 1.23-1.56).
• Each 1 mmol/L increase in levels of LDL cholesterol predicted a 26% higher risk for myocardial infarction and a 28% higher risk for coronary heart disease, with greater risks in adults younger than 45 years.

IN PRACTICE:

“If CAC is used to guide treatment decisions — particularly in younger individuals — repeat CAC assessments and follow-up should be considered to help identify those who may transition to more advanced stages of atherosclerosis over time,” the researchers reported.

“[The study] findings are valuable for clinical practice, as they suggest that lowering LDL cholesterol in younger individuals with hypercholesterolemia should be considered independent of existing CAC or not to reduce atherosclerosis progression and lower long-term [coronary heart disease] risk,” they added.

SOURCE:

This study was led by Malene Højgaard Andersen, of Aarhus University in Aarhus, Denmark. It was published online on August 9, 2025, in the European Heart Journal.

LIMITATIONS:

Certain residual confounding factors may have remained despite adjustments, as this study was observational. The multicenter design may have introduced referral, selection, and reporting biases that may have affected the interpretation of results.

DISCLOSURES:

This study was supported by the Danish Cardiovascular Academy, which is funded by the Novo Nordisk Foundation and The Danish Heart Foundation. Several authors reported being minor shareholders; receiving lecture fees, research grants, and advisory board fees; and having other financial ties with multiple pharmaceutical and healthcare companies including Novo Nordisk.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.