@article {922, title = {Leukocyte telomere length and cardiovascular disease in the cardiovascular health study.}, journal = {Am J Epidemiol}, volume = {165}, year = {2007}, month = {2007 Jan 01}, pages = {14-21}, abstract = {

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.

}, keywords = {Aged, Cardiovascular Diseases, DNA, Female, Humans, Inflammation, Leukocytes, Male, Myocardial Infarction, Oxidative Stress, Pilot Projects, Polymorphism, Restriction Fragment Length, Risk, Risk Assessment, Risk Factors, Telomere}, issn = {0002-9262}, doi = {10.1093/aje/kwj346}, author = {Fitzpatrick, Annette L and Kronmal, Richard A and Gardner, Jeffrey P and Psaty, Bruce M and Jenny, Nancy S and Tracy, Russell P and Walston, Jeremy and Kimura, Masyuki and Aviv, Abraham} } @article {1265, title = {Leukocyte telomere length and mortality in the Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {66}, year = {2011}, month = {2011 Apr}, pages = {421-9}, abstract = {

BACKGROUND: Leukocyte telomere length (LTL) is related to diseases of aging, but studies of mortality have been inconsistent.

METHODS: We evaluated LTL in relation to total mortality and specific cause of death in 1,136 participants of the Cardiovascular Health Study who provided blood samples in 1992-1993 and survived through 1997-1998. LTL was measured by Southern blots of the terminal restriction fragments. Cause of death was classified by a committee of physicians reviewing death certificates, medical records, and informant interviews.

RESULTS: A total of 468 (41.2\%) deaths occurred over 6.1 years of follow-up in participants with mean age of 73.9 years (SD 4.7), 65.4\% female, and 14.8\% African American. Although increased age and male gender were associated with shorter LTLs, African Americans had significantly longer LTLs independent of age and sex (p < .001). Adjusted for age, sex, and race, persons with the shortest quartile of LTL were 60\% more likely to die during follow-up than those within the longest quartile (hazard ratio: 1.61, 95\% confidence interval: 1.22-2.12, p = .001). The association remained after adjustment for cardiovascular disease risk factors. Evaluations of cause of death found LTL to be related to deaths due to an infectious disease etiology (hazard ratio: 2.80, 95\% confidence interval: 1.32-5.94, p = .007), whereas a borderline association was found for cardiac deaths (hazard ratio: 1.82, 95\% confidence interval: 0.95-3.49, p = .07) in adjusted models. Risk estimates for deaths due to cancer, dementia, and ischemic stroke were not significant.

CONCLUSION: These data weakly corroborate prior findings of associations between LTL and mortality in the elderly.

}, keywords = {Aged, Aged, 80 and over, Aging, Body Mass Index, Cardiovascular Diseases, Cause of Death, Comorbidity, Coronary Disease, Diabetes Mellitus, Female, Humans, Hypertension, Leukocytes, Longitudinal Studies, Male, Prospective Studies, Smoking, Stroke, Telomere}, issn = {1758-535X}, doi = {10.1093/gerona/glq224}, author = {Fitzpatrick, Annette L and Kronmal, Richard A and Kimura, Masayuki and Gardner, Jeffrey P and Psaty, Bruce M and Jenny, Nancy S and Tracy, Russell P and Hardikar, Sheetal and Aviv, Abraham} } @article {1328, title = {Leukocyte telomere length is associated with noninvasively measured age-related disease: The Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {67}, year = {2012}, month = {2012 Apr}, pages = {409-16}, abstract = {

BACKGROUND: Most studies of leukocyte telomere length (LTL) focus on diagnosed disease in one system. A more encompassing depiction of health is disease burden, defined here as the sum of noninvasively measured markers of structure or function in different organ systems. We determined if (a) shorter LTL is associated with greater age-related disease burden and (b) shorter LTL is less strongly associated with disease in individual systems or diagnosed chronic conditions (cardiovascular disease, stroke, pulmonary disease, diabetes, kidney disease, arthritis, or depression).

METHODS: LTL was measured by Southern blots of terminal restriction fragment length. Age-related disease was measured noninvasively and included carotid intima-media thickness, lung vital capacity, white matter grade, cystatin-C, and fasting glucose; each graded 0 (best tertile), 1 (middle tertile), or 2 (worst tertile) and summed (0 to 10) to estimate disease burden. Of 419 participants randomly selected for LTL measurement, 236 had disease burden assessed (mean [SD] age 74.2 [4.9] years, 42.4\% male, 86.8\% white, and 13.2\% black).

RESULTS: Mean (SD) LTL was 6,312 (615) bp, and disease score was 4.7 (2.1) points. An SD higher disease score (β [SE] = -132 [47] bp, p < .01), age (β [SE] = -107 [46], p = .02) or carotid thickness (β [SE] = -95 [40] bp, p = .02) was associated with shorter LTL, but diagnosed conditions or number of conditions were not associated with LTL. Disease score attenuated the effect of age on LTL by 35\%.

CONCLUSION: LTL was associated with a characterization of age-related disease burden across multiple physiologic systems, which was comparable to, but independent of, its association with age.

}, keywords = {African Americans, Aged, Aged, 80 and over, Cardiovascular Diseases, Carotid Intima-Media Thickness, Chronic Disease, Cystatin C, European Continental Ancestry Group, Female, Humans, Leukocytes, Lung, Male, Middle Aged, Telomere Homeostasis}, issn = {1758-535X}, doi = {10.1093/gerona/glr173}, author = {Sanders, Jason L and Fitzpatrick, Annette L and Boudreau, Robert M and Arnold, Alice M and Aviv, Abraham and Kimura, Masayuki and Fried, Linda F and Harris, Tamara B and Newman, Anne B} } @article {6293, title = {Leukocyte telomere length and age at menopause.}, journal = {Epidemiology}, volume = {25}, year = {2014}, month = {2014 Jan}, pages = {139-46}, abstract = {

BACKGROUND: Telomere length is a marker of cellular aging that varies with the individual, is inherited, and is highly correlated across somatic cell types within persons. Interindividual variability of telomere length may partly explain differences in reproductive aging rates. We examined whether leukocyte telomere length was associated with menopausal age.

METHODS: We evaluated the relationship between leukocyte telomere length and age at natural menopause in 486 white women >=65 years of age. We fit linear regression models adjusted for age, income, education, body mass index, physical activity, smoking, and alcohol intake. We repeated the analysis in women with surgical menopause. We also performed sensitivity analyses excluding women (1) with unilateral oophorectomy, (2) who were nulliparous, or (3) reporting menopausal age <40 years, among other exclusions.

RESULTS: For every 1-kb increase in leukocyte telomere length, average age at natural menopause increased by 10.2 months (95\% confidence interval = 1.3 to 19.0). There was no association among 179 women reporting surgical menopause. In all but one sensitivity analysis, the association between leukocyte telomere length and age at menopause became stronger. However, when excluding women with menopausal age <40 years, the association decreased to 7.5 months (-0.4 to 15.5).

CONCLUSIONS: Women with the longest leukocyte telomere length underwent menopause 3 years later than those with the shortest leukocyte telomere length. If an artifact, an association would likely also have been observed in women with surgical menopause. If these results are replicated, leukocyte telomere length may prove to be a useful predictor of age at menopause.

}, keywords = {Adult, Age of Onset, Aged, Aging, Alcohol Drinking, Body Mass Index, Educational Status, European Continental Ancestry Group, Female, Humans, Leukocytes, Linear Models, Menopause, Middle Aged, Motor Activity, Smoking, Telomere}, issn = {1531-5487}, doi = {10.1097/EDE.0000000000000017}, author = {Gray, Kristen E and Schiff, Melissa A and Fitzpatrick, Annette L and Kimura, Masayuki and Aviv, Abraham and Starr, Jacqueline R} }