Leukocyte Telomere Length And Risk Of Stroke: The Strong Heart Family Study

Introduction: Leukocyte telomere length (LTL) is a potential biomarker of aging and associated with several age-related diseases. Current research on an association between LTL and incident stroke has had inconclusive results. We hypothesized that LTL is associated with incident stroke among American Indians (AI) in the Strong Heart Family Study (SHFS). Methods: The SHFS is a population-based cohort study of cardiovascular disease (CVD) and its risk factors. Participants (n=2,769) recruited from regions in Arizona, Oklahoma and the Dakotas were assessed for LTL and CVD risk factors during a clinic visit between 2001 and 2003. Incident stroke events were identified through the end of 2018 (mean follow-up: 16.4 years). We assessed the association between LTL and incident stroke using frailty models based on the proportional hazards, accounting for family relatedness and established stroke risk factors that include sex, geographical location, education, smoking, atrial fibrillation, diabetes mellitus, and hypertension. Results: Among 2,769 participants, the mean age was 40.6±17.2 and 41.4% were male. During follow-up, there were 79 (2.9%) incident stroke cases. In the primary model, which adjusted for demographic variables (sex, location and education), the hazard ratios (HR) for stroke in participants in the first and second LTL quartiles were significantly higher than those in the highest (longest) LTL quartile, with HRs of 3.1 (95%CI: 1.4 - 6.6) and 3.5 (95%CI: 1.7 - 7.5), respectively. After adjusting for smoking, atrial fibrillation, diabetes mellitus, and hypertension, the association between LTL and stroke was attenuated, but remained significant when comparing the second shortest LTL quartile to the longest LTL quartile, HR: 2.3 (95% CI: 1.1 – 5.0). Conclusions: In summary, LTL was associated with incident stroke among SHFS participants. Those with shorter LTL have higher risk of stroke. Longer follow-up time may add more power to data analyses since the SHFS is relatively young, with an average baseline age of 40 years. If results are confirmed in other populations, LTL may serve as a biomarker identifying high risk individuals for the purpose of stroke prevention.