Evolving understanding of cardiovascular, cerebrovascular and peripheral arterial disease in people living with HIV and role of novel biomarkers. A study of the Spanish CoRIS cohort, 2004-2015

OBJECTIVES: To analyze the incidence rates (IR) and spectrum of vascular events in people living with HIV (PLWH) in Spain from 2004 to 2015. Serial measurements of different plasma cardiovascular biomarkers were assessed in relation to disease development. METHODS: Longitudinal study in a nationwide contemporary multicenter cohort of PLWH. A nested case-control study was performed to evaluate the predictive value of cardiovascular biomarkers. Additive generalized and Cox mixed models were used for the analyses. RESULTS: 9,712 PLWH and 48,341 person-years of follow-up were analysed. During 2004–2015, 147 persons developed 154 vascular events; 80 (54.42%) coronary-related; 65 (44.22%) cerebrovascular-related, and 9 (6.12%) peripheral arterial disease. The 2004–2015 IR (95% confidence interval) of vascular events was 3.17 (2.69–3.71) x1,000 person-years; 1.64 (1.30–2.05) for coronary events; 1.34 (1.03–1.70) for cerebrovascular events; and 0.19 (0.09–0.35) for peripheral arterial disease (p<0.001). IR of vascular events gradually increased from 0.37 (0.12–0.85) x1,000 patient-years in the stratum 25-34-years to 19.65 (6.38–45.85) x1,000 patient-years in the stratum 75-84-years. Compared to the general population, there was a higher incidence of acute myocardial infarction (AMI) in men (sIR ratio 1.29 [95% CI 1.16–1.42]), of cerebrovascular events in women (sIR ratio 2.44 [95% CI 1.68–3.19]), and of both types of events specifically among the younger age-strata. CD4 count (hazard ratio 0.80, [95% CI, 0.79–0.81]), age (1.86 [1.47–2.34] for 45–65 years and 3.44 [2.37–4.97] for >65 years) and vascular event (1.81 [1.12–2.94]) were associated with total mortality. Adjusted levels of intercellular-adhesion-molecule (sICAM), pro-b-type-natriuretic-peptide (pro-BNP) and marginally sCD14, were higher among patients who subsequently developed vascular events. CONCLUSION: Vascular events in PLWH do preferentially occur in the older age-strata, they are associated with increased mortality and, compared to the general population, the excess risk occurs at younger ages. Peripheral arterial disease is unusual. Vascular events are preceded by increased levels of sICAM, pro-BNP and, marginally, sCD14.