Symptomatic individuals with no coronary artery calcium (CAC) but elevated LDL-C have a higher risk of noncalcified plaque and future coronary heart disease (CHD) events, especially among those aged ≤45 years, according to a large cohort study published Aug. 9 in EHJ.

Using data from the Western Denmark Heart Registry, Malene Højgaard Andersen, PhD, et al., analyzed data from 23,777 symptomatic individuals (median age, 54 years; 61% women) with CAC = 0 who underwent coronary CT angiography from 2008 to 2021.

Results showed that the proportion of individuals with a CAC = 0 was highest at 84% among those aged 18-45 years, followed by 56% of those aged 46-60 years and 28% for >60 years.

Additionally, researchers found an 11% prevalence of noncalcified plaques. The overall adjusted odds ratio (aOR) for noncalcified plaques was 1.21 for each 1 mmol/L increase in LDL-C, and for the three age groups this translated to an aOR of 1.39 for ≤45 years, 1.22 for 46-60 years and 1.11 for >60 years.

Over the 7.1-year median follow-up, 299 participants (1%) experienced a CHD event. The overall aHR per 1 mmol/L higher LDL-C was 1.28 for a CHD event. Across the age groups, the aHR was 1.37 for ≤45 years, 1.24 for 46-60 years and 1.26 for >60 years.

The study authors write that the results have important implications "for clinical practice and future guidelines aimed at atherosclerotic cardiovascular disease prevention as they advocate for lowering LDL-C in younger and middle-aged individuals, despite CAC = 0, to improve CHD prevention over a long-time horizon." Because the short-term absolute risk is low in those ≤45 years of age with no CAC, they suggest "LDL-C management may initially focus on lifestyle and dietary modifications rather than pharmacological intervention."