Telomere length, traditional risk factors, HIV-related factors and coronary artery disease events in Swiss persons living with HIV. Clinical Infectious Disease
Engel et al. aimed to evaluate any independent association of leukocyte telomere length (TL) with coronary artery disease (CAD) events in persons living with human immunodeficiency virus (PLWH), in the context of all relevant clinical risk factors, HIV-related factors, and adverse antiretroviral exposures. Of note, TL shortens with age and is associated with CAD events in the general population.
The authors measured TL by quantitative polymerase chain reaction (PCR) in white Swiss HIV Cohort Study participants. Cases had a first CAD event during 1 January 2000 to 31 December 2017. They matched 1–3 PLWH controls without CAD events on sex, age, and observation time.
They included 333 cases (median age 54 years; 14% women; 83% with suppressed HIV RNA) and 745 controls. Median time (interquartile range) of TL measurement was 9.4 (5.9–13.8) years prior to CAD event. Compared to the 1st (shortest) TL quintile, participants in the 5th (longest) TL quintile had univariable and multivariable CAD event OR = 0.56 (95% confidence interval [CI], .35–.91) and OR = 0.54 (95% CI, .31–.96). Multivariable OR for current smoking was 1.93 (95% CI, 1.27–2.92), dyslipidemia OR = 1.92 (95% CI, 1.41–2.63), and for recent abacavir, cumulative lopinavir, indinavir, and darunavir exposure was OR = 1.82 (95% CI, 1.27–2.59), OR = 2.02 (95% CI, 1.34–3.04), OR = 3.42 (95% CI, 2.14–5.45), and OR = 1.66 (95% CI, 1.00–2.74), respectively. The TL-CAD association remained significant when adjusting only for Framingham risk score, when excluding TL outliers, and when adjusting for CMV-seropositivity, HCV-seropositivity, time spent with detectable HIV viremia, and injection drug use.
In conclusion, the study shows that TL was independently associated with CAD events in PLWH. The exact mechanisms of shorter TL in PLWH compared to the general population and the potential for accelerated TL shortening in PLWH remain incompletely understood. The study results suggest that short TL in PLWH matters, by documenting a relevant TL-CAD link in PLWH, and by putting the TL association into perspective with other relevant traditional and HIV-related risk factors. TL might therefore provide CAD risk information that current knowledge on CAD risk stratification in PLWH does not yet capture. As a clinical consequence, documenting short TL in a given patient might further emphasize the need to optimize management of CAD risk factors, including dyslipidemia, diabetes, and selection of appropriate ART. The clinical value of TL testing, however, will rely on demonstration of improved CAD risk stratification in other populations of PLWH and in prospective studies.