Six plasma biomarkers including BNP and proadrenomedullin predicted cardiovascular death for at least 15 years in 7,745 patients with chronic coronary heart disease, with associations sustained well beyond initial measurement.
15+ years predictiveAll six biomarkers including the peptides BNP and proadrenomedullin maintained statistically significant prediction of cardiovascular death for at least 15 years after measurement (p<0.001)
What the researchers found
All 6 biomarkers — BNP, troponin I, cystatin-C, CRP, D-dimer, and midregional proadrenomedullin — were significantly associated with cardiovascular death (n=1,903) both during the randomized trial period and for 10 additional years after trial completion (each p<0.001). Associations were sustained for at least 15 years total.
Why it matters
Most biomarker studies only assess short-term prediction. Finding that peptide biomarkers like BNP and proadrenomedullin remain predictive for 15+ years suggests they capture deep, stable aspects of cardiovascular disease that don't fluctuate quickly. This has implications for long-term risk stratification and treatment decisions in coronary heart disease patients.
The numbers in context
7,745 patients from the LIPID trial. Biomarkers measured: BNP, troponin I, cystatin-C, and C-reactive protein.
How the study worked
Cohort study of 7,745 patients from the LIPID trial (Long-Term Intervention with Pravastatin in Ischemic Disease). Biomarkers measured at baseline and 1 year. Landmark analyses from 1 year evaluated discrimination for cardiovascular death during the next 5 years of the trial and 10 additional years of follow-up.
Who was studied
Patients with chronic coronary heart disease from the LIPID trial
What this study cannot tell us
The LIPID trial enrolled patients in the 1990s, and cardiovascular management has evolved significantly since then. Biomarker associations may differ with modern treatments. The study didn't assess whether serial measurements improve prediction over single measurements. Observational analysis from a statin trial — cannot establish whether biomarker-guided treatment improves outcomes.
How to read the evidence
Strong evidence from a large, well-characterized clinical trial cohort (LIPID) with exceptionally long follow-up. Published in JAHA, a major cardiovascular journal.
When this study was published
Published in 2024, analyzing data from the LIPID trial (patients enrolled in the 1990s) with extended follow-up through the 2010s.
The bigger picture
This study demonstrates that a single set of biomarker measurements can inform cardiovascular risk for over a decade. The peptide biomarkers BNP and proadrenomedullin are particularly interesting because they reflect cardiac and vascular stress that may drive long-term disease progression. This supports the concept of multi-biomarker risk panels for personalized cardiovascular medicine.
Questions still open
- Would biomarker-guided intensification of therapy in high-risk patients improve long-term cardiovascular outcomes?
- Do BNP and proadrenomedullin levels change with contemporary cardiovascular treatments in ways that affect their long-term predictive value?
Common questions
What is BNP and why does it predict heart problems?
Should I ask my doctor for these biomarker tests?
Read the original research
Plasma Protein Biomarkers and Long-Term Cardiovascular Mortality Risk in Patients With Chronic Coronary Heart Disease.
Journal of the American Heart Association, 13(21), e034367
Citation
Stewart, Ralph A H; Robledo, Kristy P; Tonkin, Andrew M; Keech, Anthony; Kritharides, Leonard; Marschner, Ian; Janus, Edward; Thompson, Peter L; Watts, Gerald F; Zeller, Tanja; White, Harvey D; Simes, John. (2024). Plasma Protein Biomarkers and Long-Term Cardiovascular Mortality Risk in Patients With Chronic Coronary Heart Disease.. Journal of the American Heart Association, 13(21), e034367. https://doi.org/10.1161/JAHA.123.034367