Matthew J J D'Mello1, Stephanie A Ross1, Matthias Briel1, Sonia S Anand1, Hertzel Gerstein1, Guillaume Paré2. 1. From the Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada (M.J.J.D., S.A.R., S.S.A., H.G., G.P.); Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital, Basel, Switzerland (M.B.); and Department of Clinical Epidemiology and Biostatistics (M.B., S.S.A., H.G., G.P.), Department of Medicine (S.S.A., H.G.), and Department of Pathology and Molecular Medicine (G.P.), McMaster University, Hamilton, Ontario, Canada. 2. From the Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada (M.J.J.D., S.A.R., S.S.A., H.G., G.P.); Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital, Basel, Switzerland (M.B.); and Department of Clinical Epidemiology and Biostatistics (M.B., S.S.A., H.G., G.P.), Department of Medicine (S.S.A., H.G.), and Department of Pathology and Molecular Medicine (G.P.), McMaster University, Hamilton, Ontario, Canada. pareg@mcmaster.ca.
Abstract
BACKGROUND: Telomeres are repetitive, gene-poor regions that cap the ends of DNA and help maintain chromosomal integrity. Their shortening is caused by inflammation and oxidative stress within the cellular environment and ultimately leads to cellular senescence. Shortened leukocyte telomere length is hypothesized to be a novel biomarker for age and age-related diseases, yet reports on its association with cardiometabolic outcomes in the literature are conflicting. METHODS AND RESULTS: MEDLINE (1966 to present) and EMBASE (1980 to present) were last searched on September 9, 2013. Reference lists of retrieved citations were hand searched for relevant studies. No restrictions were placed on sample size, language, or publication type or date. Fifteen cohort and 12 case-control studies reporting the association between leukocyte telomere length and stroke, myocardial infarction, and type 2 diabetes mellitus were independently selected for inclusion by 2 reviewers. Data extraction and risk of bias assessment were completed independently by 2 reviewers using predefined criteria. Studies were pooled using the generic inverse variance method and both fixed and random effects models. A 1-SD decrease in leukocyte telomere length was significantly associated with stroke (odds ratio, 1.21; 95% confidence interval, 1.06-1.37; I(2)=61%), myocardial infarction (odds ratio, 1.24; 95% confidence interval, 1.04-1.47; I(2)=68%), and type 2 diabetes mellitus (odds ratio, 1.37; 95% confidence interval, 1.10-1.72; I(2)=91%). Stratification by measurement technique, study design, study size, and ethnicity explained heterogeneity in certain cardiometabolic outcomes. CONCLUSIONS: Shortened leukocyte telomere length demonstrates a significant association with stroke, myocardial infarction, and type 2 diabetes mellitus. Larger, well-designed studies are needed to confirm these findings and explore sources of heterogeneity.
BACKGROUND: Telomeres are repetitive, gene-poor regions that cap the ends of DNA and help maintain chromosomal integrity. Their shortening is caused by inflammation and oxidative stress within the cellular environment and ultimately leads to cellular senescence. Shortened leukocyte telomere length is hypothesized to be a novel biomarker for age and age-related diseases, yet reports on its association with cardiometabolic outcomes in the literature are conflicting. METHODS AND RESULTS: MEDLINE (1966 to present) and EMBASE (1980 to present) were last searched on September 9, 2013. Reference lists of retrieved citations were hand searched for relevant studies. No restrictions were placed on sample size, language, or publication type or date. Fifteen cohort and 12 case-control studies reporting the association between leukocyte telomere length and stroke, myocardial infarction, and type 2 diabetes mellitus were independently selected for inclusion by 2 reviewers. Data extraction and risk of bias assessment were completed independently by 2 reviewers using predefined criteria. Studies were pooled using the generic inverse variance method and both fixed and random effects models. A 1-SD decrease in leukocyte telomere length was significantly associated with stroke (odds ratio, 1.21; 95% confidence interval, 1.06-1.37; I(2)=61%), myocardial infarction (odds ratio, 1.24; 95% confidence interval, 1.04-1.47; I(2)=68%), and type 2 diabetes mellitus (odds ratio, 1.37; 95% confidence interval, 1.10-1.72; I(2)=91%). Stratification by measurement technique, study design, study size, and ethnicity explained heterogeneity in certain cardiometabolic outcomes. CONCLUSIONS: Shortened leukocyte telomere length demonstrates a significant association with stroke, myocardial infarction, and type 2 diabetes mellitus. Larger, well-designed studies are needed to confirm these findings and explore sources of heterogeneity.
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