Background
Statins have pleiotropic effects beyond lowering LDL cholesterol, offering benefits in multiple cardiometabolic conditions and reducing chronic inflammation. These effects have the potential to also influence biological aging trajectories, reflected by frailty. The objective of this study was to compare frailty trajectories, in people with HIV (PWH) who used statins for primary cardiovascular prevention with those who did not.
Methods
This was an observational longitudinal study including antiretroviral therapy (ART)-experienced PWH attending the Modena HIV Metabolic Clinic (Italy) who had no prior statin exposure at baseline (BL) and with at least 3 frailty assessments during follow-up. PWH with a history of cardiovascular events were excluded. BL was defined as the first visit with available FI, and follow-up was defined as the last visit with available FI. Statin users and non-users were matched based on median time between BL and initiation of the statin therapy in the first group. Time 0 was defined as the initiation of the statin therapy. Frailty was assessed using a validated 37-item frailty index (FI), ranging from 0 to 1. Frailty trajectories were analysed using a linear mixed model (LMM) adjusted for statin use, age, sex, follow-up time, diabetes, hypertension, smoking (pack year), and BL LDL cholesterol.
Results
A total of 3,543 PWH were included, 1,100 (31%) were women. The median age at BL was 44.7 yrs, median time since HIV diagnosis was 14 yrs, median current CD4 cell count was 558.5/microL with 88.6% having undetectable HIV viral load. At BL, PWH who started statin were older (48.4 vs 43.6 yrs, p<0.001), had a higher: FI (0.3 vs 0.2; p<0.001), BMI (23.9 vs 23 kg/m2; p<0.001), LDL cholesterol (129 vs 109 mg/dL; p<0.001), prevalence of hypertension (31.8 vs 15.4%; p<0.001), diabetes (11.5 vs 4.7%; p<0.001). In LMM, statin use (β= -0.0171, 95% confidence interval (CI): -0.0345, -0.0009) was a significant predictor of FI reduction (Figure 1). Other factors associated with FI were: female sex (β= -0.0123, 95% CI: -0.0194, -0.0052), diabetes (β= 0.0305, 95% CI: -0.0248, 0.0362), hypertension (β=0.0389, 95% CI: 0.0349, 0.0429).
Conclusions
Statin use significantly reduces frailty over time. Although PWH who started statins had a higher FI at baseline, they were able to reverse the BL difference, reaching a lower FI compared to the control group by the end of follow-up. These findings suggest that statins may have a geroprotective effect in PWH.
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