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 (beta coefficient per unit increase, -0.038; P=0.036), directly related to aldosterone (beta=0.099; P=0.002), and inversely related to the renin-to-aldosterone ratio (beta=-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 (beta=-0.060; P=0.005), aldosterone (beta=0.134; P=0.002), and renin-to-aldosterone ratio (beta=-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.

Figure 1

Least square means for adjusted leukocyte telomere length (LTL) according to tertile of the renin-aldosterone ratio in the entire sample (left panel), hypertensive individuals (middle panel) and nonhypertensive participants (right panel). P values indicate trend across tertiles of the ratio.

Appendix Figure

Illustration of an autoradiogram showing the terminal restriction fragments (LTLs) (A), the molecular weight ladders (B) and the superimposition of A and B The position of each band of the MW ladder (y) a was determined by y= a₀+a₁*exp^(-kb/a2). The mean LTL length was calculated as follows: LTL =ΣOD_i/Σ(OD_i/MW_i), where OD_i is optical density at a given position in the lane and MW_i is molecular weight at that position. This formula accounts for the fact that longer telomeres bind more labeled probe and consequently appear darker on the X-ray film.