Blood Biomarkers Associated with Atherosclerosis and Mortality
Researchers here present evidence for leukocyte telomere length and a few other less well explored blood biomarkers to correlate with the progression of atherosclerosis and vascular calcification and later mortality. Calcification of blood vessels and the development of fatty atherosclerotic lesions are two distinct processes, but they tend to progress together, most likely because they are both driven to a sizable degree by the presence of chronic inflammation, and related issues such as burden of senescent cells.
Increased oxidative stress, leukocyte telomere length (LTL) shortening, endothelial dysfunction, and lower insulin-like growth factor (IGF)-1 concentrations reflect key molecular mechanisms of aging. We hypothesized that biomarkers representing these pathways are associated with measures of subclinical atherosclerosis and all-cause mortality.
We evaluated 2,314 Framingham Offspring Study participants (mean age 61 years, 55% women) with available biomarkers of aging: LTL, circulating concentrations of IGF-1, asymmetrical dimethylarginine (ADMA), and urinary F2-Isoprostanes indexed to urinary creatinine. We evaluated the association of each biomarker with coronary artery calcium (CAC) and carotid intima-media thickness (IMT).
In multivariable-adjusted linear regression models, higher ADMA levels were associated with higher CAC values. Additionally, shorter LTL and lower IGF-1 values were associated with higher IMT values. During a median follow-up of 15.5 years, 593 subjects died. In multivariable-adjusted Cox regression models, LTL and IGF-1 values were inversely associated with all-cause mortality. F2-Isoprostanes and ADMA values were positively associated with all-cause mortality.
In conclusion, in our prospective community-based study, aging-related biomarkers were associated with measures of subclinical atherosclerosis cross-sectionally and with all-cause mortality prospectively, supporting the concept that these biomarkers may reflect the aging process in community-dwelling adults.