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Inflammation, Cholesterol, Lipoprotein(a), and 30-Year Cardiovascular Outcomes in Women
Paul M Ridker1, M Vinayaga Moorthy1, Nancy R Cook1
1From the Divisions of Preventive Medicine (P.M.R., M.V.M., N.R.C., I.-M.L., J.E.B.) and Cardiovascular Diseases (P.M.R.), Brigham and Women's Hospital, the Department of Epidemiology, Harvard T.H. Chan School of Public Health (P.M.R., N.R.C., I.-M.L., J.E.B.), and the Department of Laboratory Medicine, Boston Children's Hospital (N.R.) - all in Boston; and the Faculty of Medicine, University of Porto, Porto, Portugal (N.R.).
Insights
High-sensitivity C-reactive protein (CRP), LDL cholesterol, and lipoprotein(a) predict 30-year cardiovascular risk in women. Combining these biomarkers improves risk prediction for primary prevention strategies.
Area of Science:
- Cardiovascular disease research
- Biomarker analysis
- Preventive medicine
Background:
- Cardiovascular risk prediction traditionally relies on 5- and 10-year estimates.
- High-sensitivity C-reactive protein (CRP), LDL cholesterol, and lipoprotein(a) are key biomarkers for cardiovascular risk.
- Longer-term risk prediction in women is needed for effective early intervention.
Purpose of the Study:
- To evaluate the 30-year predictive value of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) for cardiovascular events in initially healthy U.S. women.
- To assess the combined predictive power of these biomarkers for long-term cardiovascular risk.
- To inform primary prevention strategies for atherosclerotic events.
Main Methods:
- Prospective cohort study of 27,939 initially healthy U.S. women followed for 30 years.
- Measurement of baseline high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) levels.
- Analysis of major adverse cardiovascular events (MACE) including myocardial infarction, coronary revascularization, stroke, or cardiovascular death.
- Calculation of hazard ratios and cumulative incidence curves adjusted for age and competing risks.
Main Results:
- Increasing levels of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) were independently associated with a higher 30-year risk of major adverse cardiovascular events.
- Hazard ratios for the highest versus lowest quintile were 1.70 for CRP, 1.36 for LDL cholesterol, and 1.33 for lipoprotein(a).
- A combined assessment of all three biomarkers provided the most comprehensive risk stratification.
Conclusions:
- Baseline levels of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) effectively predict incident cardiovascular events over a 30-year period in women.
- These findings support extending primary prevention strategies beyond traditional 10-year risk assessments.
- The study underscores the value of these biomarkers in identifying women at long-term risk for cardiovascular disease.
Background:
High-sensitivity C-reactive protein (CRP), low-density lipoprotein (LDL) cholesterol, and lipoprotein(a) levels contribute to 5-year and 10-year predictions of cardiovascular risk and represent distinct pathways for pharmacologic intervention. More information about the usefulness of these biomarkers for predicting cardiovascular risk over longer periods of time in women is needed because early-life intervention represents an important risk-reduction method.
Methods:
We measured high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) levels at baseline in 27,939 initially healthy U.S. women who were subsequently followed for 30 years. The primary end point was a first major adverse cardiovascular event, which was a composite of myocardial infarction, coronary revascularization, stroke, or death from cardiovascular causes. We calculated the adjusted hazard ratios and 95% confidence intervals across quintiles of each biomarker, along with 30-year cumulative incidence curves adjusted for age and competing risks.
Results:
The mean age of the participants at baseline was 54.7 years. During the 30-year follow-up, 3662 first major cardiovascular events occurred. Quintiles of increasing baseline levels of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) all predicted 30-year risks. Covariable-adjusted hazard ratios for the primary end point in a comparison of the top with the bottom quintile were 1.70 (95% confidence interval [CI], 1.52 to 1.90) for high-sensitivity CRP, 1.36 (95% CI, 1.23 to 1.52) for LDL cholesterol, and 1.33 (95% CI, 1.21 to 1.47) for lipoprotein(a). Findings for coronary heart disease and stroke appeared to be consistent with those for the primary end point. Each biomarker showed independent contributions to overall risk. The greatest spread for risk was obtained in models that incorporated all three biomarkers.
Conclusions:
A single combined measure of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) levels among initially healthy U.S. women was predictive of incident cardiovascular events during a 30-year period. These data support efforts to extend strategies for the primary prevention of atherosclerotic events beyond traditional 10-year estimates of risk. (Funded by the National Institutes of Health; Women's Health Study ClinicalTrials.gov number, NCT00000479.).
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