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on February 11, 2008

Circulation. 2008
Published online before print February 11, 2008, doi: 10.1161/CIRCULATIONAHA.107.731794
A more recent version of this article appeared on March 4, 2008
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Submitted on August 2, 2007
Accepted on November 30, 2007

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

Ramachandran S. Vasan MD*, Serkalem Demissie PhD, Masayuki Kimura MD, PhD, L. Adrienne Cupples PhD, Nader Rifai PhD, Charles White MPH, Thomas J. Wang MD, Jeffrey P. Gardner PhD, Xiaogian Cao BS, Emelia J. Benjamin MD, ScM, Daniel Levy MD, and Abraham Aviv MD

From the Framingham Heart Study of the National Heart, Lung, and Blood Institute, Framingham, Mass (R.S.V., S.D., L.A.C., E.J.B.); Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass (R.S.V., E.J.B.); Department of Biostatistics (S.D., L.A.C., C.W.) and Department of Epidemiology (L.A.C., E.J.B.), Boston University School of Public Health, Boston, Mass; Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (N.R.); Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (T.J.W.); National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md (D.L.); and Center of Human Development and Aging, University of Medicine and Dentistry of New Jersey, Newark (M.K., J.P.G., X.C., A.A.).

* To whom correspondence should be addressed. E-mail: vasan{at}bu.edu.

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.


Key words: aldosterone • epidemiology • hypertension • oxidative stress • renin • telomere


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Clinical Summaries
Circulation 2008 117: 1121-1123. [Full Text]