Telomere Length, Traditional Risk Factors, Factors Related to Human Immunodeficiency Virus (HIV) and Coronary Artery Disease Events in Swiss Persons Living With HIV

Abstract

Background Leukocyte telomere length (TL) shortens with age and is associated with coronary artery disease (CAD) events in the general population. Persons living with HIV (PLWH) may have accelerated atherosclerosis and shorter TL than the general population. It is unknown whether TL is associated with CAD in PLWH. Methods We measured TL by quantitative PCR in white Swiss HIV Cohort Study participants. Cases had a first CAD event during 01.01.2000-31.12.2017. We matched 1-3 PLWH controls without CAD events on sex, age, and observation time. We obtained univariable and multivariable odds ratios (OR) for CAD from conditional logistic regression analyses. Results We 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, 0.35-0.91) and OR=0.54 (0.31-0.96). Multivariable OR for current smoking was 1.93 (1.27-2.92), dyslipidemia OR=1.92 (1.41-2.63), and for recent abacavir, cumulative lopinavir, indinavir, and darunavir exposure was OR=1.82 (1.27-2.59), OR=2.02 (1.34-3.04), OR=3.42 (2.14-5.45), and OR=1.66 (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. Conclusion In PLWH, TL measured >9 years before, is independently associated with CAD events after adjusting for multiple traditional and HIV-related factors.

Coronary Artery Disease–Associated and Longevity-Associated Polygenic Risk Scores for Prediction of Coronary Artery Disease Events in Persons Living With Human Immunodeficiency Virus: The Swiss HIV Cohort Study

“…We included PLWH enrolled in the Swiss HIV Cohort Study (SHCS, www.shcs.ch) [17] who were participants of our previous CAD event prediction study. [18] The study was approved by the respective local ethics committees. Participants provided written informed consent for genetic testing.…”

Ageing with HIV: Challenges and biomarkers

“…66 Furthermore, in participants from the Swiss HIV Cohort Study (SHCS) TL -measured 9 years before the event-was independently associated with CVD after adjusting for traditional risk factors. 67 Nevertheless, no association between TL and cardiovascular risk was observed in women from the CARMA cohort. 68 Although these data suggest leucocyte TL could be a biomarker to measure ageing in PLWH, there are some technical and sample challenges.…”

Biological ageing with HIV infection: evaluating the geroscience hypothesis

“…23 In the context of chronic, treated HIV infection, shorter telomere length has been documented in the blood cells of people with HIV than in people without HIV, [24][25][26] and shorter blood telomere length has been linked to increased cardiovascular risk in people with HIV. 27 Telomere length is also shorter in the lung epithelia of people with HIV than in people without HIV, possibly increasing risk of lung disease. 28 Although there is evidence for excessive loss of telomere length in people with HIV, and associations of telomere attrition with disease progression, whether incremental declines in telomere length disproportionately increase the risk of disease onset, disease severity, and multimorbidity is unclear.…”

“…Telomere length in blood, 25,26 association of telomere loss with cardiovascular risk 27 and lung disease 28 Loss of proteostasis Proteostasis (autophagy markers and flux, chaperone proteins, protein aggregates) Disruption of autophagy in multiple cell types, [40][41][42] neurodegeneration, 44 and mitophagy in primary neurons 45…”