American Journal of Epidemiology Advance Access originally published online on October 16, 2006
American Journal of Epidemiology 2007 165(1):14-21; doi:10.1093/aje/kwj346
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ORIGINAL CONTRIBUTIONS |
Leukocyte Telomere Length and Cardiovascular Disease in the Cardiovascular Health Study
1 Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA
2 Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, WA
3 Center of Human Development and Aging, University of Medicine and Dentistry of New Jersey, Newark, NJ
4 Department of Medicine, School of Medicine, University of Washington, Seattle, WA
5 Department of Pathology, College of Medicine, University of Vermont, Burlington, VT
6 Department of Biochemistry, College of Medicine, University of Vermont, Burlington, VT
7 Center on Aging and Health, Schools of Public Health and Medicine, Johns Hopkins University, Baltimore, MD
Correspondence to Dr. Annette L. Fitzpatrick, Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Collaborative Health Studies Coordinating Center, Building 29, Suite 310, 6200 NE 74th Street, Seattle, WA 98115 (e-mail: fitzpal{at}u.washington.edu).
The telomere length of replicating somatic cells is inversely correlated with age and has been reported to be associated cross-sectionally with cardiovascular disease (CVD). Leukocyte telomere length, as expressed by mean terminal restriction fragment (TRF) length, was measured in 419 randomly selected participants from the Cardiovascular Health Study, comprising a community-dwelling cohort recruited in four US communities. The authors investigated associations between TRF length and selected measures of subclinical CVD/risk factors for CVD (data were collected at the 1992/1993 clinic visit) and incident CVD (ascertained through June 2002). In these participants (average age = 74.2 years (standard deviation, 5.2)), mean TRF length was 6.3 kilobase pairs (standard deviation, 0.62). Significant or borderline inverse associations were found between TRF length and diabetes, glucose, insulin, diastolic blood pressure, carotid intima-media thickness, and interleukin-6. Associations with body size and C-reactive protein were modified by gender and age, occurring only in men and in participants aged 73 years or younger. In younger (but not older) participants, each shortened kilobase pair of TRF corresponded with a threefold increased risk of myocardial infarction (hazard ratio = 3.08, 95% confidence interval: 1.22, 7.73) and stroke (hazard ratio = 3.22, 95% confidence interval: 1.29, 8.02). These results support the hypotheses that telomere attrition may be related to diseases of aging through mechanisms involving oxidative stress, inflammation, and progression to CVD.
cardiovascular diseases; inflammation; mortality; myocardial infarction; telomere
Abbreviations: CHS, Cardiovascular Health Study; CI, confidence interval; HR, hazard ratio; kb, kilobase pairs; SSC, sodium chloride/sodium citrate; TRF, terminal restriction fragment
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