May 29, 2025

Episode 389: 400. CRP, Lipoprotein A, LDL for cardiac risk assessment

9 minutes

https://www.nejm.org/doi/full/10.1056/NEJMoa2405182?query=recirc_Semantic

Key Takeaways

Extended Predictive Value of Biomarkers:

High-sensitivity C-reactive protein (CRP), LDL cholesterol, and lipoprotein(a) levels were found to be predictive of cardiovascular events over a 30-year period.

These markers contribute independently to long-term cardiovascular risk beyond traditional 10-year risk estimates.

Study Design and Population:

The study enrolled 27,939 initially healthy U.S. women who were followed for 30 years.

The primary endpoint was the occurrence of a first major adverse cardiovascular event, including myocardial infarction, coronary revascularization, stroke, or death from cardiovascular causes.

Predictive Strength of Biomarkers:

Among the biomarkers, high-sensitivity CRP showed the strongest association with future cardiovascular events (hazard ratio for top quintile: 1.70).

LDL cholesterol and lipoprotein(a) also significantly predicted risk, albeit to a slightly lower degree (hazard ratios: 1.36 and 1.33, respectively). NOT STATIN WITH CRP

Implications for Clinical Practice:

Combining all three biomarkers may offer the best method for identifying high-risk individuals who might benefit from early intervention. YOU HAVE TO PROSPECTIVELY VALIDATE THIS

The study supports extending cardiovascular prevention strategies beyond traditional risk assessments.

Lifestyle and pharmacologic interventions should target multiple pathways, including lipid levels and inflammation.

Key Limitations

Study Population:

The study cohort predominantly consisted of female health professionals who are mostly White (94%), which may limit generalizability.

The results may not extend to males or more diverse populations without further studies.

Absence of Repeated Measures:

Biomarkers were measured only at baseline without repeated measures over time.

This limits the ability to observe changes in biomarker levels and their association with risk over time.

Statin Use Data:

Increasing use of statins over the study period was not thoroughly considered in initial analyses, and detailed data on adherence and duration are lacking.

Sensitivity analyses attempted to account for this by censoring data at the time of first statin prescription, but residual confounding may be present.

Concerns with Study Design

Cohort Composition:

The study's focus on health professionals might have led to better access to healthcare and healthier lifestyle choices, potentially skewing outcomes.

Non-White participants were underrepresented, raising concerns about the applicability of findings to more diverse groups.

Single Time Point Measurement:

Only baseline biomarker levels were used for long-term prediction, which may not account for variability and changes in risk factors over time.

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