Association of Leukocyte Telomere Length With Circulating Biomarkers of the Renin-Angiotensin-Aldosterone System: The Framingham Heart Study

Abstract

Background— Leukocyte telomere length (LTL) chronicles the cumulative burden of oxidative stress and inflammation over a life course. Activation of the renin-angiotensin-aldosterone system is associated with increased oxidative stress and inflammation. Therefore, LTL may be related to circulating biomarkers of the renin-angiotensin-aldosterone system. Methods and Results— We evaluated the cross-sectional relations of LTL (dependent variable) to circulating renin and aldosterone concentrations and the renin-to-aldosterone ratio (all logarithmically transformed; independent variables) in 1203 Framingham Study participants (mean age, 59 years; 51% women). We used multivariable linear regression and adjusted for age, blood pressure, hypertension treatment, smoking, diabetes mellitus, body mass index, hormone replacement therapy, serum creatinine, and the urine sodium-to-creatinine ratio. Overall, multivariable-adjusted LTL was inversely related to renin (β coefficient per unit increase, −0.038; P=0.036), directly related to aldosterone (β=0.099; P=0.002), and inversely related to the renin-to-aldosterone ratio (β=−0.049; P=0.003). Relations of LTL to biomarkers were stronger in those with hypertension, although a formal test of interaction was not statistically significant (P=0.20). Individuals with hypertension displayed significant associations of LTL with renin (β=−0.060; P=0.005), aldosterone (β=0.134; P=0.002), and renin-to-aldosterone ratio (β=−0.072; P<0.001). Participants with hypertension who were in the top tertile of the renin-to-aldosterone ratio had LTL that was 182 base pairs shorter relative to those in the lowest tertile. Conclusions— In our community-based sample, LTL was shorter in individuals with a higher renin-to-aldosterone ratio, especially in participants with hypertension. Additional investigations are warranted to confirm our observations.