Date Published: November 29, 2016
Publisher: Public Library of Science
Author(s): David H. Rehkopf, Belinda L. Needham, Jue Lin, Elizabeth H. Blackburn, Ami R. Zota, Janet M. Wojcicki, Elissa S. Epel, Kazem Rahimi
Abstract: BackgroundLeukocyte telomere length (LTL) is a putative biological marker of immune system age, and there are demonstrated associations between LTL and cardiovascular disease. This may be due in part to the relationship of LTL with other biomarkers associated with cardiovascular disease risk. However, the strength of associations between LTL and adiposity, metabolic, proinflammatory, and cardiovascular biomarkers has not been systematically evaluated in a United States nationally representative population.Methods and FindingsWe examined associations between LTL and 17 cardiovascular biomarkers, including lipoproteins, blood sugar, circulatory pressure, proinflammatory markers, kidney function, and adiposity measures, in adults ages 20 to 84 from the cross-sectional US nationally representative 1999–2002 National Health and Nutrition Examination Survey (NHANES) (n = 7,252), statistically adjusting for immune cell type distributions. We also examine whether these associations differed systematically by age, race/ethnicity, gender, education, and income. We found that a one unit difference in the following biomarkers were associated with kilobase pair differences in LTL: BMI -0.00478 (95% CI -0.00749–-0.00206), waist circumference -0.00211 (95% CI -0.00325–-0.000969), percentage of body fat -0.00516 (95% CI -0.00761–-0.0027), high density lipoprotein (HDL) cholesterol 0.00179 (95% CI 0.000571–0.00301), triglycerides -0.000285 (95% CI -0.000555–-0.0000158), pulse rate -0.00194 (95% CI -0.00317–-0.000705), C-reactive protein -0.0363 (95% CI 0.0601–-0.0124), cystatin C -0.0391 (95% CI -0.0772–-0.00107). When using clinical cut-points we additionally found associations between LTL and insulin resistance -0.0412 (95% CI -0.0685–-0.0139), systolic blood pressure 0.0455 (95% CI 0.00137–0.0897), and diastolic blood pressure -0.0674 (95% CI -0.126–-0.00889). These associations were 10%–15% greater without controlling for leukocyte cell types. There were very few differences in the associations by age, race/ethnicity, gender, education, or income. Our findings are relevant to the relationships between these cardiovascular biomarkers in the general population but not to cardiovascular disease as a clinical outcome.ConclusionsLTL is most strongly associated with adiposity, but is also associated with biomarkers across several physiological systems. LTL may thus be a predictor of cardiovascular disease through its association with multiple risk factors that are physiologically correlated with risk for development of cardiovascular disease. Our results are consistent with LTL being a biomarker of cardiovascular aging through established physiological mechanisms.
Partial Text: Shorter leukocyte telomere length (LTL) is significantly associated with increased risk of cardiovascular disease, irrespective of adjustment for conventional risk factors . A meta-analysis of 24 studies with 43,725 participants and 8,400 patients with cardiovascular disease estimated a relative risk of 1.54 (95% CI 1.30–1.83), comparing those with the longest to shortest third of LTL . Although these finding are consistent with a role for LTL in cardiovascular disease etiology, the critical details of how LTL is related to known metabolic pro-inflammatory markers and cardiovascular risk factors in the pathway to cardiovascular disease are unclear . It is thought that telomere length shortens in relationship to multiple types of biochemical stressors and thus may represent a cumulative index of known risk factors. Our study will contribute to answering this question using a large US nationally representative sample with a comprehensive number of biomarkers measured along with LTL. Examining the relationship of telomere length with multiple biomarkers concurrently will inform us of whether LTL might be a marker for one primary risk factor, such as inflammation, or of multiple risk factors. This analysis will thus help to better understand whether LTL represents a unique biomarker that is independent from other known risk factors for cardiovascular disease.
The purpose of our study was to examine whether LTL is independent of other known biological risk markers of cardiovascular disease. This is an important question given associations of LTL with cardiovascular disease mortality. The significance of this question is whether across the life course LTL is independent of already well-documented biological mechanisms of cardiovascular disease risk. Our findings suggest that, among a nationally representative US population, there are moderate correlations between LTL and important cardiovascular risk factors, even after accounting for age, social and demographic factors, health behaviors, and white blood cell types. We found that controlling for cell type reduced magnitudes of association by between 10% and 20%.