Cholesterol and risk of ST-segment elevation versus non-ST-segment elevation myocardial infarction: a population-based cohort study

Abstract Background Statins decrease cholesterol levels and reduce the risk of myocardial infarction (MI). Hence, international guidelines recommend specific secondary prevention treatment goals for low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) to reduce MI risk. However, MI includes the two clinically different entities ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI), with STEMI being associated with higher early mortality than NSTEMI. No studies have assessed how cholesterol levels affect the risk of STEMI and NSTEMI separately. Purpose To examine whether LDL-C and non-HDL-C levels were more strongly associated with risk of STEMI than NSTEMI in statin-treated patients. Methods We conducted a population-based cohort study leveraging unique registry data from a tax-funded Danish healthcare system. Statin-treated patients with ischemic heart disease determined by coronary angiography (CAG) were included from the Western Denmark Heart Registry between 2011-2020. LDL-C and non-HDL-C levels were measured within 1 year after CAG. The risk of STEMI and NSTEMI was estimated as adjusted hazard ratios (aHR). The comparison of STEMI versus NSTEMI and 30-day mortality after STEMI versus NSTEMI was estimated as adjusted odds ratios (aOR). Results The study included 36,739 statin-treated patients. Of these, 26,178 (71%) were men, the median age was 66 years (Q1-Q3: 58-74), and 11,247 (31%) reached the guideline-recommended LDL-C goal ≤1.4 mmol/L within 1 year after CAG. During a median follow-up of 4.9 years (Q1-Q3: 3.0-7.0), 531 STEMI and 1,614 NSTEMI events occurred. A STEMI event was associated with higher 30-day mortality than NSTEMI: aOR 1.62 (95% CI: 1.02-2.57). Per 1 mmol/L higher LDL-C, the aHRs of STEMI and NSTEMI were 1.43 (95% CI: 1.30-1.57) and 1.23 (95% CI: 1.16-1.31) corresponding to 18% higher odds of STEMI versus NSTEMI: aOR 1.18 (95% CI: 1.04-1.32) (Figure 1). Patients who achieved the LDL-C goal ≤1.4 mmol/L versus 2.2 mmol/L had a lower risk of STEMI and NSTEMI separately, and importantly, patients at goal had 22% lower odds of STEMI than NSTEMI (Figure 2). All results were similar for non-HDL-C. Conclusion In statin-treated patients with ischemic heart disease, STEMI events were associated with higher 30-day mortality than NSTEMI events and cholesterol levels were more strongly associated with the risk of STEMI than NSTEMI. Importantly, low LDL-C and non-HDL-C levels seem to reduce the risk of STEMI to a greater extent than observed for NSTEMI. These novel findings are of paramount importance to clinicians and patients in preventive care aiming to reduce cardiovascular mortality.Figure 1 Figure 2