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Women’s Health Study: hs-CRP, LDL-C, Lp(a), and 30-Year CV Outcomes
Quick Takes
- Increasing baseline levels of hs-CRP, LDL-C, and Lp(a) were predictive of CVD outcomes at 30 years.
- The 30-year risk rose with each quintile increase for hs-CRP and LDL-C levels but was increased for Lp(a) predominantly at the highest quintile. These findings are consistent data using 5- to 10-year follow-up.
- Each biomarker provided additive information to the other two biomarkers, such that the combination of all three provided the greatest magnitude of spread for long-term risk stratification.
Study Questions:
How do high-sensitivity C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a) [Lp(a)] levels predict cardiovascular (CV) risk over decades of time in women?
Methods:
Data for this analysis are from the Women’s Health Study, a longitudinal cohort of 39,876 female health professionals residing in the US, enrolled between 1992 and 1995. Participants were healthy without apparent cardiovascular disease (CVD) at baseline. Follow-up continued through January 2023. hs-CRP, LDL-C, and Lp(a) levels in 27,939 initially healthy US women were measured at baseline. These participants were then followed for 30 years. The primary endpoint of interest was first major adverse CV event, which was a composite of myocardial infarction (MI), coronary revascularization, stroke, or death from CV causes. The authors calculated the adjusted hazard ratios and 95% confidence intervals (CIs) across quintiles of each biomarker, along with 30-year cumulative incidence curves adjusted for age and competing risks.
Results:
A total of 27,939 women were included in the present analysis; the mean age of the participants at baseline was 54.7 years. Of this sample, 25.0% had hypertension, 12.0% were current smokers, 2.5% had diabetes, 14.4% had a parental history of MI before 65 years of age, and 94.0% were White. The correlation between biomarkers was minimal; the Spearman correlation coefficient between hs-CRP and LDL-C was 0.08, between LDL-C and Lp(a) was 0.17, and between hs-CRP and Lp(a) was 0.01. During the 30-year follow-up, 3,662 first major CV events occurred. Quintiles of increasing baseline levels of hs-CRP, LDL-C, and Lp(a) all predicted 30-year risks. Adjusted hazard ratios for the primary endpoint (comparing the top to bottom quintiles) were 1.70 (95% CI, 1.52-1.90) for hs-CRP, 1.36 (95% CI, 1.23-1.52) for LDL-C, and 1.33 (95% CI, 1.21-1.47) for Lp(a). Outcomes of coronary heart disease and stroke demonstrated similar associations as observed for the primary endpoint.
Each biomarker showed independent contributions to overall risk; however, the greatest spread for risk was obtained in models that incorporated all three biomarkers. The covariable-adjusted hazard ratios for the primary endpoint were 1.0 (reference group) for participants with no biomarker levels in quintile 5, 1.27 (95% CI, 1.19-1.37) for participants with one biomarker level in quintile 5, 1.66 (95% CI, 1.51-1.83) for participants with two biomarker levels in quintile 5, and 2.63 (95% CI, 2.16-3.19) for participants with three biomarker levels in quintile 5.
Conclusions:
The authors conclude that a single combined measure of hs-CRP, LDL-C, and Lp(a) levels among initially healthy US women was predictive of incident CV events during a 30-year period. These data support efforts to extend strategies for the primary prevention of atherosclerotic events beyond traditional 10-year risk estimates.
Perspective:
These data support the use of biomarker assessment to assist in CVD risk prediction among women in the US. However, these results are recommended to be replicated in men and diverse cohorts prior to widespread implementation.
Clinical Topics: Dyslipidemia, Advanced Lipid Testing, Lipid Metabolism, Nonstatins, Prevention
Keywords: ESC24, ESC Congress, Cholesterol, LDL, C-Reactive Protein, Lipoprotein(a), Women
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