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

Key Takeaways

1. 
   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.
   
   
   
   


2. 
   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.
   
   
   
   


3. 
   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
   
   
   
   


4. 
   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

1. 
   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.
   
   
   
   


2. 
   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.
   
   
   
   


3. 
   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

1. 
   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.
   
   
   
   


2. 
   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.