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Which biomarkers are predictive specifically for cardiovascular or for non-cardiovascular mortality in men? Evidence
Christopher C Patterson1, Stefan Blankenberg2, Yoav Ben-Shlomo3
1Centre for Public Health, Queen's University Belfast, Belfast, UK.
Insights
Cardiac necrosis biomarkers like troponin strongly predict cardiovascular disease (CVD) mortality. Inflammatory markers, however, predict non-CVD mortality, highlighting distinct biomarker roles in population health.
Area of Science:
- Biomarker discovery and cardiovascular epidemiology.
- Clinical biochemistry and risk stratification.
- Population health and mortality prediction.
Background:
- Cardiovascular disease (CVD) remains a leading cause of mortality.
- Identifying reliable biomarkers for CVD and non-CVD mortality is crucial for risk assessment.
- Previous studies have explored various biomarkers, but a comprehensive analysis in a population-based cohort is needed.
Purpose of the Study:
- To evaluate 28 biomarkers for their predictive power regarding CVD and non-CVD mortality.
- To analyze these associations in a population-based cohort of middle-aged men.
- To differentiate the predictive roles of biomarkers for specific mortality outcomes.
Main Methods:
- A cohort of 2171 middle-aged men from Caerphilly was re-examined between 1989-1993.
- Fasting blood samples were analyzed for routine biochemistry, lipids, fibrinogen, viscosity, white cell count (WCC), and novel biomarkers.
- Competing risk Cox regression models were used to assess biomarker associations with CVD and non-CVD mortality after covariate adjustment.
Main Results:
- Troponin and B-natriuretic peptide (BNP) showed strong associations with CVD mortality, but not non-CVD mortality.
- White cell count (WCC) and fibrinogen demonstrated weaker associations with CVD mortality.
- Growth differentiation factor 15 (GDF-15), interleukin-6 (IL-6), and plasma viscosity were associated with both CVD and non-CVD mortality, while total cholesterol showed opposing associations.
Conclusions:
- Biomarkers indicative of cardiac necrosis, such as troponin, are potent and specific predictors of CVD mortality.
- Several inflammatory markers were found to be equally predictive of non-CVD mortality.
- These findings underscore the distinct prognostic value of different biomarker classes for specific mortality outcomes.
Objective:
To examine a panel of 28 biomarkers for prediction of cardiovascular disease (CVD) and non-CVD mortality in a population-based cohort of men.
Methods:
Starting in 1979, middle-aged men in Caerphilly underwent detailed medical examination. Subsequently 2171 men were re-examined during 1989-1993, and fasting blood samples obtained from 1911 men (88%). Fibrinogen, viscosity and white cell count (WCC), routine biochemistry tests and lipids were analysed using fresh samples. Stored aliquots were later analysed for novel biomarkers. Statistical analysis of CVD and non-CVD mortality follow-up used competing risk Cox regression models with biomarkers in thirds tested at the 1% significance level after covariate adjustment.
Results:
During an average of 15.4 years follow-up, troponin (subhazard ratio per third 1.71, 95% CI 1.46-1.99) and B-natriuretic peptide (BNP) (subhazard ratio per third 1.54, 95% CI 1.34-1.78) showed strong trends with CVD death but not with non-CVD death. WCC and fibrinogen showed similar weaker findings. Plasma viscosity, growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6) were associated positively with both CVD death and non-CVD death while total cholesterol was associated positively with CVD death but negatively with non-CVD death. C-reactive protein (C-RP), alkaline phosphatase, gamma-glutamyltransferase (GGT), retinol binding protein 4 (RBP-4) and vitamin B6 were significantly associated only with non-CVD death, the last two negatively. Troponin, BNP and IL-6 showed evidence of diminishing associations with CVD mortality through follow-up.
Conclusion:
Biomarkers for cardiac necrosis were strong, specific predictors of CVD mortality while many inflammatory markers were equally predictive of non-CVD mortality.