Non-HDL cholesterol and residual risk of myocardial infarction and death in statin-treated patients with and without diabetes

Abstract

Abstract Background Patients with coronary artery disease continue to be at risk of myocardial infarction despite lipid-lowering treatment with statins. However, it is uncertain whether non-high-density lipoprotein (non-HDL) cholesterol identifies increased residual risk in patients with and without diabetes. Purpose To test the hypothesis that non-HDL cholesterol identifies residual risk of myocardial infarction and death in statin-treated patients with and without diabetes. Methods Contemporary cohort study of consecutive patients undergoing coronary angiography (CAG) for evaluation of coronary artery disease between 2011 and 2020. Analyses were performed in the semi-national Western Denmark Heart Registry. Non-HDL cholesterol was calculated within one year after CAG as total cholesterol minus HDL cholesterol and divided into four groups according to percentile level (<25th, 25th-74th, 75th-94th, and ≥95th percentile). Outcomes were diagnosis of myocardial infarction and all-cause death occurring between one year after CAG and end of follow-up (July 31, 2022). Risk according to non-HDL-C percentile group was estimated as adjusted hazard ratio (95% confidence interval). Results A total of 105,804 patients underwent CAG. We included 54,037 statin-treated patients with median duration of follow-up 4.6 years. Among 11,400 patients with diabetes, we observed 587 myocardial infarctions and 2,654 patients died. In 42,637 patients without diabetes, we observed 1,548 myocardial infarctions and 5,842 patients died. The risk of myocardial infarction was similarly increased in patients with and without diabetes. Compared to non-HDL cholesterol <25th percentile, the adjusted hazard ratios were in patients with diabetes 1.2 (95% CI: 0.9-1.5) for 25th-74th percentile, 1.3 (95% CI: 0.9-1.9) for 75th-94th percentile, and 2.2 (95% CI: 1.3-4.0) for ≥95th percentile, and in patients without diabetes 1.0 (95% CI: 0.9-1.2), 1.3 (95% CI: 1.0-1.6), and 2.0 (95% CI: 1.4-3.0). Non-HDL cholesterol was associated with increased risk of death in patients without diabetes with adjusted hazard ratios of 1.0 (95% CI: 0.9-1.1), 1.3 (95% CI: 1.2-1.5), and 2.1 (95% CI: 1.6-2.6), however this association was attenuated in patients with diabetes (0.9 (95% CI: 0.8-1.0), 1.0 (95% CI: 0.9-1.2), and 1.2 (95% CI: 0.9-1.7)). Results were similar when stratifying on presence of obstructive coronary artery disease in both patients with and without diabetes. Conclusion In statin-treated patients with and without diabetes, non-HDL cholesterol identified residual risk of myocardial infarction. Further, elevated non-HDL cholesterol was associated with increased risk of all-cause death in patients without diabetes.Figure 1.Figure 2.