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Association of a Blood-Based Aging Biomarker Index With Death and Chronic Disease: Cardiovascular Health Study
Xiao Zhang1,2, Jason L Sanders3, Robert M Boudreau1
1Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Insights
A new biomarker index (BI) strongly predicts mortality and chronic diseases in older adults. This index may help identify aging phenotypes and guide interventions to slow aging processes.
Area of Science:
- Gerontology and aging research
- Biomarker discovery and validation
- Chronic disease epidemiology
Background:
- Gerontology aims to identify aging phenotypes distinct from disease.
- Biomarkers associated with mortality are potential indicators of biological aging.
- The relationship between mortality biomarkers and multiple chronic conditions requires further investigation.
Purpose of the Study:
- To construct and validate a biomarker index (BI) associated with mortality and chronic diseases.
- To explore the BI's potential as an intermediate phenotype for aging.
- To assess the BI's ability to attenuate the effect of chronological age on health outcomes.
Main Methods:
- A biomarker index (BI) was developed using data from the Cardiovascular Health Study (N=3,197, mean age 74).
- The BI incorporated circulating levels of insulin-like growth factor-1, interleukin-6, amino-terminal pro-B-type natriuretic peptide, cystatin-C, C-reactive protein, tumor necrosis factor-alpha soluble receptor 1, fasting insulin, and fasting glucose.
- Cox proportional hazards models were used to predict a composite outcome of death and chronic diseases (cardiovascular disease, dementia, cancer) over 6 years.
Main Results:
- The BI was significantly associated with the composite outcome of death or chronic disease in both women and men.
- The hazard ratio for the composite outcome increased with each category of the BI and with age.
- The BI attenuated the effect of age on the composite outcome by 16.7% in women and 22.0% in men.
Conclusions:
- The developed biomarker index is significantly and independently associated with mortality and chronic disease.
- The BI may serve as a practical intermediate phenotype for interventions targeting aging.
- Plasma biomarkers can potentially be used to modify the aging process.
Background:
A goal of gerontology is to discover phenotypes that reflect biological aging distinct from disease pathogenesis. Biomarkers that are strongly associated with mortality could be used to define such a phenotype. However, the relation of such an index with multiple chronic conditions warrants further exploration.
Methods:
A biomarker index (BI) was constructed in the Cardiovascular Health Study (N = 3 197), with a mean age of 74 years. The BI incorporated circulating levels of new biomarkers, including insulin-like growth factor-1, interleukin-6, amino-terminal pro-B-type natriuretic peptide, cystatin-C, C-reactive protein, tumor necrosis factor-alpha soluble receptor 1, fasting insulin, and fasting glucose, and was built based on their relationships with mortality. Cox proportional hazards models predicting a composite of death and chronic disease involving cardiovascular disease, dementia, and cancer were calculated with 6 years of follow-up.
Results:
The hazard ratio (HR, 95% CI) for the composite outcome of death or chronic disease per category of BI was 1.65 (1.52, 1.80) and 1.75 (1.58, 1.94) in women and men, respectively. The HR (95% CI) per 5 years of age was 1.57 (1.48, 1.67) and 1.55 (1.44, 1.67) in women and men, respectively. Moreover, BI could attenuate the effect of age on the composite outcome by 16.7% and 22.0% in women and men, respectively.
Conclusions:
Biomarker index was significantly and independently associated with a composite outcome of death and chronic disease, and attenuated the effect of age. The BI that is composed of plasma biomarkers may be a practical intermediate phenotype for interventions aiming to modify the course of aging.
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