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

Abstract

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.

High incidence of subclinical peripheral artery disease in people with HIV

“…In Iceland and Israel, the annual incidence of intermittent claudication was 0.1% and 1.0% [6], and among men in the Netherlands in age groups comparable to those of our cohort, the annual incidence of ABI <0.95 per 1000 person-years was 1.7 and 1.5 for those aged 40-54 years and 55-64 years, respectively [29]. In previous registry studies examining PAD in PWH, incidence rate estimates ranged from 0.19 to 3.17 per 1000 person-years [15][16][17]30]. Notably, a study from the Veterans Ageing Cohort Study (VACS) found an incidence of 11.9 per 1000 person-years corresponding to a cumulative 2.5-year PAD incidence of around 2% [18].…”

“…Few studies have investigated the incidence of PAD in PWH. These studies were retrospective and based on registry data or patient records, thereby excluding subclinical cases and underestimating the disease burden [15][16][17][18][19]. It remains to be determined to what extent traditional risk factors contribute to the risk of PAD, and whether HIV-related risk factors are involved in the PAD pathogenesis.…”

Prognosis of Stroke Among People Living With HIV and Its Relationship With Admission to Specialized Stroke Units

“…We diagnosed a total of 43 strokes, excluding transient ischemic attacks (that were also excluded by Crane et al), which corresponded to a global incidence rate of 1.9 cases per 1000 patient-year, like the ones reported by other authors in our country. 2 This incidence has progressively increased during time, starting from 0.63 cases per 1000 patient-year during the 1993–2006 period to 3.3 cases per 1000 patient-year during the 2013–2017 period. The mean age of patients was 51 years, and 81% were men.…”

Residual Viremia Is Linked to a Specific Immune Activation Profile in HIV-1-Infected Adults Under Efficient Antiretroviral Therapy

“…To further test this hypothesis, tissue evaluation of the IA, particularly in secondary lymphoid organs, and functional assays would be necessary. According to this model, the fact that we have shown that residual viremia is associated with a marker of monocyte activation (sCD14), two markers of endothelial activation (sEPCR and tPA), and a marker of coagulation (D-dimer), three forms of activation known to favor atherothrombosis (33)(34)(35), should encourage us to search for a link between residual viremia and atherosclerosis.…”