Prospective Cohort: Combined CRP, LDL Cholesterol, and Lipoprotein(a) Levels Predict 30-Year Cardiovascular Risk in Women
8 Dec, 2024 | 20:58h | UTCBackground: Current 10-year risk models do not fully capture lifetime cardiovascular disease (CVD) risk. Inflammation, low-density lipoprotein (LDL) cholesterol, and lipoprotein(a) are distinct pathways associated with atherosclerosis. While their value in predicting 5- to 10-year cardiovascular risk is established, data on their combined long-term predictive utility, particularly over three decades in women, are limited.
Objective: To determine whether a single baseline measurement of high-sensitivity C-reactive protein (CRP), LDL cholesterol, and lipoprotein(a) provides additive and independent predictive value for 30-year cardiovascular outcomes in initially healthy women.
Methods: This prospective cohort study included 27,939 initially healthy U.S. women (mean age, 54.7 years) from the Women’s Health Study, enrolled between 1992 and 1995. Baseline levels of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) were measured. Participants were followed for 30 years for a first major adverse cardiovascular event (myocardial infarction, coronary revascularization, stroke, or cardiovascular death). Adjusted hazard ratios (HRs) for each biomarker’s quintiles were estimated, as well as combined models including all three biomarkers simultaneously.
Results: Over 30 years, 3,662 first major cardiovascular events occurred. Higher baseline quintiles of CRP, LDL cholesterol, and lipoprotein(a) were each associated with elevated 30-year risk. Compared to the lowest quintile, adjusted HRs for the top quintile were 1.70 (95% CI, 1.52–1.90) for CRP, 1.36 (95% CI, 1.23–1.52) for LDL cholesterol, and 1.33 (95% CI, 1.21–1.47) for lipoprotein(a). Each marker contributed independently, and models incorporating all three showed the greatest risk discrimination. Participants with all three biomarkers in the highest quintile had a HR of 2.63 (95% CI, 2.16–3.19) for the primary endpoint.
Conclusions: A single combined baseline assessment of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) strongly predicted CVD events over 30 years. These findings suggest extending beyond traditional 10-year estimates to identify long-term risk, reinforcing the need for early prevention strategies addressing multiple biological pathways.
Implications for Practice: Measuring these three biomarkers early may inform more personalized, prolonged preventive efforts. While lowering LDL cholesterol remains foundational, addressing inflammation and lipoprotein(a) could further optimize long-term CVD prevention. Nonetheless, caution is advised before embracing new interventions lacking robust long-term data.
Study Strengths and Limitations: Strengths include the extended 30-year follow-up, a large, well-characterized cohort, and standardized biomarker assessments. Limitations include a predominantly White, female population, limiting generalizability. Single-time-point biomarker measurements and evolving statin use over time add complexity. Despite these constraints, the study underscores the multifactorial nature of long-term CVD risk.
Future Research: Further investigations should evaluate targeted interventions on inflammation and lipoprotein(a), potentially through long-term clinical trials and more diverse populations. Such research could clarify the benefits of a multimodal risk-reduction strategy.