Frequency of low-density-lipoprotein-cholesterol measurement and risk of major adverse cardiovascular outcomes: a 5-million-person nationwide cohort study

Cardiovascular disease (CVD) is a leading cause of mortality globally and in the UK, with significant efforts focused on early risk identification and prevention. Elevated low-density lipoprotein cholesterol (LDL-C) is a key modifiable risk factor for cardiovascular disease (CVD), yet the impact of LDL-C monitoring frequency on major adverse cardiovascular events (MACE) remains unclear. This study evaluated the relationship between LDL-C measurement frequency and the risk of MACE in a large, nationwide cohort. A retrospective cohort study using anonymised electronic health records from the Clinical Practice Research Datalink (CPRD) Aurum, linked to hospitalisation, social deprivation, and mortality data. The cohort included individuals registered for at least one year with at least one recorded low-density LDL-C measurement between 1 January 2000 and 31 December 2022. The primary outcome was MACE, defined as a composite of non-fatal coronary heart disease, non-fatal stroke, or cardiovascular death. Multivariable Cox proportional hazards models and Kaplan-Meier survival plot were used to estimate the incidence and hazard ratios (HRs) by LDL-C monitoring frequency. The study cohort comprised 5,133,574 individuals, with 2,733,144 (53.2%) being women. The median follow-up duration was 3.31 years (IQR: 7.39-12.11). Among the 5,133,574 individuals, the incidence of MACE declined with more frequent LDL-C monitoring, from 1937.0 (95% CI: 1928.2-1945.8) events per 100,000 person-years (one measurement) to 1615.4 (95% CI: 1605.8-1625.0), 1484.6 (95% CI: 1473.7-1495.6), and 1204.9 (95% CI: 1200.1-1209.6) for those with two, three, and four or more measurements, respectively. Compared to individuals with one LDL-C measurement, the adjusted HRs for MACE were 0.703 (95% CI: 0.698-0.709), for two measurements, 0.570 (95% CI: 0.565-0.575) for three, and 0.312 (95% CI: 0.310-0.314) for four or more. The Kaplan-Meier curve demonstrated improved event-free survival with increased LDL-C monitoring (log-rank p<0.0001). More frequent LDL-C monitoring was associated with a lower risk of MACE. These findings highlight the potential benefits of regular LDL-C monitoring as a potentially impactful strategy for CVD prevention and long-term risk management.