Sex Differences in Trajectories of LDL Cholesterol Control in Chronic Coronary Syndromes

Sex differences in the longitudinal evolution of low-density lipoprotein cholesterol (LDL-C) management among patients with chronic coronary syndromes (CCS) are not well known.

In the international CLARIFY registry, which included patients with CCS, LDL-C levels were monitored annually over the 5-year follow-up period. The analysis included patients with available LDL-C measurement at baseline. Target LDL-C was set at 100 mg/dL, in line with prevailing recommendations at enrolment. Sex-specific differences in LDL-C were adjusted for age and geographical region. Impact of longitudinal LDL-C was assessed using mean LDL-C up to the primary outcome of interest or last follow-up defined as cardiovascular (CV) death or MI during 5-year follow-up, evaluated using multivariable analysis.

Of 32,376 patients in the initial cohort, women were less likely to have LDL-C measurement available at baseline (aOR 1.12, 95%CI 1.06-1.18, p<0.001). Of the 21,925 patients with LDL-C measurement at baseline, 21.6% were women. At inclusion, women were less likely to receive statins (82.7% vs. 85.4%, p<0.001) and more likely to fail reaching the LDL-C target (45.6% vs. 37.4%; aOR 1.47, 95%CI 1.38-1.58, p<0.001). This disparity persisted across the 5-year follow-up (p<0.001 for every year). Overall, women were more likely than men to never reach the target LDL-C during follow-up (20.7% vs. 15.8%; aOR 1.44, 95% CI 1.32-1.56, p<0.001). Higher mean LDL-C during follow-up was associated with an increased risk of the primary outcome (aHR 1.06 per 10 mg/dL increase, 95% CI 1.04-1.07, p<0.001).

Women with CCS were less likely to have LDL-C measurement available at baseline, to receive lipid-lowering drugs and consistently exhibited poorer LDL-C control than men over the 5-year follow-up. Given the association of LDL-C and adverse CV outcomes, targeted interventions to close the sex gap in secondary prevention are needed.