DNA methylation-based telomere length is more strongly associated with long-term all-cause mortality than quantitative polymerase chain reaction-based telomere length among middle-aged and older hypertensive adults.

Background: Telomere length (TL) has been linked to mortality risk across various populations. However, its predictive value for mortality risk specifically in hypertensive adults remains unclear.

Methods: This cohort study utilized data from the 1999-2000 and 2001-2002 cycles of the National Health and Nutrition Examination Survey (NHANES). TL was assessed using DNA methylation (DNAmTL) and quantitative polymerase chain reaction (qPCRTL). Cox proportional hazards models were employed to examine the relationship between TL and mortality risk.

Results: This study included 1601 participants, with 988 deaths occurring during a median follow-up of 184 months, including 279 from cardiovascular disease (CVD). Deceased participants exhibited significantly lower levels of DNAmTL (6.45 ± 0.30 vs. 6.70 ± 0.28, P < 0.001) and qPCRTL (0.89 ± 0.22 vs. 0.99 ± 0.24, P < 0.001) compared to survivors. After full adjustment, each 1-kb decrement in DNAmTL and qPCRTL was associated with a 52% and 38% reduction in all-cause mortality risk, respectively. Participants in the highest TL quartile (Q4) for DNAmTL and qPCRTL had a 36% and 25% reduced risk of all-cause mortality than those in the lowest quartile (Q1), respectively. Receiver operating characteristic (ROC) curves demonstrated that DNAmTL had superior predictive value compared to qPCRTL (area under curve [AUC] 0.73 vs. 0.63, P < 0.001).

Conclusion: TL is inversely associated with all-cause mortality risk in middle-aged and older hypertensive adults, with DNAmTL showing greater predictive accuracy for long-term mortality than qPCRTL.