Long term prognostic value of silent myocardial ischaemia in asymptomatic people with HIV

Background and Aims People living with HIV (PWH) are at higher risk of coronary heart disease (CHD). There is a need for improved cardiovascular (CV) risk stratification. We assessed the long-term prognostic value of silent myocardial ischaemia (SMI) for major adverse cardiovascular events (MACE) in asymptomatic PWH without known CHD. Methods Between 2003 and 2016, consecutive asymptomatic PWH without known CHD underwent systematic CV evaluation, including non-invasive screening for CHD. Clinical events were collected up to 2023. The primary endpoint was 4-point MACE (CV death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularisation). Secondary endpoints were 3-point MACE, coronary events, and all atherothrombotic events. Predicted risk using SCORE2 and ASCVD risk scores was compared with observed risk. Results Among 810 eligible PWH, overall loss to follow-up was exceptionally low at 0.6% (5/810). The final analysis included 756 participants (mean age 51.1 ± 8.3 years; 85.3% men) with long-standing, well-controlled HIV (median known duration 19.8 years; 15.9 years on ART; 89% virologically suppressed). Median SCORE2 and ASCVD risk scores were 3.7 (IQR 2.5–5.5) and 6.0 (IQR 3.0–11.0), respectively. Among 756 participants, 29 (3.8%) had a positive ischaemia test at baseline. Over a median follow-up of 11.0 years, the 10-year cumulative incidence of CV events was 18.4%. These events were significantly more frequent in patients with a positive vs negative test (39.3% vs 17.5%; P = 0.004). The primary endpoint (4-point MACE) occurred in 8.5% of the cohort (incidence 9.7/1,000 person-years), with significantly lower 10-year event-free survival in the positive test group (log-rank P = 0.009).This difference was consistent across all secondary endpoints (all log-rank P ≤ 0.03). Sudden cardiac death accounted for 57.7% of CV deaths. In multivariable analysis, a positive baseline stress test was independently associated with 4-point MACE (adjusted HR 2.42, 95% CI 1.03–5.68; P = 0.043). HIV-specific variables (including HIV seropositivity duration and cumulative ART exposure) were not associated with outcomes. Risk prediction using SCORE2 and ASCVD was modest (C-statistics 0.64 and 0.63, respectively) with discordant calibration patterns. Specifically, SCORE2 underestimated risk in low-to-moderate categories, while ASCVD overestimated it. Conclusions In asymptomatic PWH without known CHD, SMI was infrequent (3.8%) but independently associated with a 2.4-fold higher risk of 4-point MACE over long-term follow-up, identifying a high-risk cardiovascular phenotype. Conventional risk scores showed modest discrimination and imperfect calibration. These findings highlight the heterogeneity of cardiovascular risk in asymptomatic PWH and support targeted non-invasive ischaemia testing for risk refinement.