Introduction The relationship between LDL cholesterol levels and atherosclerotic cardiovascular disease (ASCVD) is complex and non-linear. Recent studies suggest that achieving low LDL levels doesn’t guarantee protection against acute coronary syndromes (ACS), with some patients experiencing severe clinical outcomes.

Objectives To identify potential predictors of severe clinical presentation and severe coronary artery disease among ACS patients with good LDL levels.

Methods This single-centre retrospective cohort study comprised 280 ACS patients divided into good LDL control (n=69) and poor LDL control (n=211). Demographic characteristics and lipid profiles were collected. Outcomes looked into the clinical ACS severity using the GRACE score, and angiographic severity based on the Gensini score.

Results Despite achieving their LDL targets, patients with good LDL control had similar coronary artery disease severity to those with poor LDL control. The median Gensini scores were 23.5 (interquartile range 35) in the good LDL group and 24.0 (interquartile range 33) in the poor LDL group, with no significant difference (p=0.88). Furthermore, the clinical severity of ACS was worse in the good LDL group, as evidenced by a higher mean GRACE score (149.7 ± 41.1 vs. 137.1 ± 38.4, p=0.02). Among those with good LDC control, logistic regression analysis identified age (OR: 1.06, 95% CI: 1.01–1.11) and chronic kidney disease (OR: 9.14, 95% CI: 1.08–77.70) as potential predictors of severe ACS.

Discussion These findings suggest that low LDL cholesterol levels may not always correlate with reduced ASCVD risk, possibly due to underlying chronic diseases, increased inflammation, and the presence of highly atherogenic cholesterol particles. Crucially, however, the paradoxical association between good LDL control and poor clinical outcomes in ACS patients warrants further investigation.

Conclusion This study highlights the need for a deeper understanding of the mechanisms linking low LDL cholesterol to severe ACS. Furthermore, the findings raise concerns about the sufficiency of LDL as a sole target for ASCVD prevention, emphasizing the potential role of inflammation and other lipid parameters in patient risk stratification.