The Association Between Shortened Leukocyte Telomere Length and Cardio-Metabolic Outcomes: A Systematic Review and Meta-Analysis.

D'Mello MJ1, Ross SA1, Briel M2, Anand SS3, Gerstein H3, Paré G4.

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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 (LTL) is hypothesized to be a novel biomarker for age and age-related diseases, yet reports on its association with cardio-metabolic outcomes in the literature are conflicting.

METHODS AND RESULTS:

-MEDLINE (1966-present), and EMBASE (1980-present) were last searched on September 9th 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. 15 Cohort and 12 case-control studies reporting the association between LTL and stroke, myocardial infarction, and type 2 diabetes were independently selected for inclusion by two reviewers. Data extraction and risk of bias assessment were completed independently by two reviewers using pre-defined criteria. Studies were pooled using the generic inverse variance method and both fixed and random effects models. A 1-standard deviation decrease in LTL was significantly associated with stroke (OR=1.21, 95% CI=1.06-1.37; I2=61%), myocardial infarction (OR=1.24, 95% CI=1.04-1.47; I2=68%), and type 2 diabetes (OR=1.37, 95% CI=1.10-1.72; I2=91%). Stratification by measurement technique, study design, study size, and ethnicity explained heterogeneity in certain cardio-metabolic outcomes.

CONCLUSIONS:

-Shortened LTL demonstrates a significant association with stroke, myocardial infarction, and type 2 diabetes. Larger, well-designed studies are needed to confirm these findings and explore sources of heterogeneity.