Cumulative LDL cholesterol exposure and the risk of coronary artery lesion progression: a linear association

Numerous studies have confirmed that the cumulative exposure of low-density lipoprotein cholesterol (LDL-C) is closely related to the occurrence of adverse cardiovascular events. However, the effect of cumulative LDL-C exposure on substantial lesion progression (SLP) of coronary artery stenosis remains unclear. Patients admitted to the First Affiliated Hospital of Xinjiang Medical University between January 1, 2016, and July 30, 2024 were screened. Eligibility criteria included: (1) two coronary angiography (CAG) results with an interval of more than one year, (2) at least two LDL-C test results, (3) baseline CAG indicated mild to moderate lumen stenosis, and (4) no coronary intervention performed at any point between the initial and second CAG. Cumulative LDL-C exposure was calculated based on the results of 2–3 LDL-C tests. A patient was defined as having SLP if CAG indicated a > 20% diameter stenosis increases in any vessel. Logistic regression and restricted cubic spline analyses were performed to evaluate the relationship between cumulative LDL-C exposure and the risk of SLP. A total of 1705 participants were included, with an average age of 58.72 years. The incidences of SLP in the tertile 1, tertile 2, and tertile 3 groups of cumulative LDL-C were 23.2%, 26.1%, and 29.9%, respectively. Cumulative LDL-C was linearly and positively correlated with the risk of SLP. After adjusting for confounders such as age, gender, systolic blood pressure, body mass index, hypertension, diabetes, smoking, alcohol consumption, baseline LDL-C, and the use of lipid-lowering drugs (statins, ezetimibe, and PCSK9 inhibitors), the risk of SLP in the tertile 3 group of cumulative LDL-C was 41.1% higher than that in the tertile 1 group (OR 1.411, 95% CI 1.044–1.908). Cumulative LDL-C remained significantly and positively correlated with SLP in subgroups such as males, patients aged < 60 years, those with hypertension, smokers, alcohol drinkers, those with maximum stenosis ≥ 50% at first coronary angiography, and those with baseline lipoprotein a ≥ 300 mg/L. This study demonstrates a linear positive association between cumulative LDL-C exposure and the risk of SLP in patients with mild-to-moderate coronary artery stenosis. These findings support the consideration of more aggressive lipid-lowering strategies in this patient population to mitigate SLP risk.