Research Article: 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

Date Published: April 26, 2019

Publisher: Public Library of Science

Author(s): Mar Masiá, Sergio Padilla, José A. García, Javier García-Abellán, Marta Fernández, Ignacio Bernardino, Marta Montero, Joaquim Peraire, Berta Pernas, Félix Gutiérrez, Jose Gutierrez.


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.

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.

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.

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.

Partial Text

The increase in life expectancy associated with effective antiretroviral therapy (ART) and the predominance of non-AIDS over AIDS events, has led physicians to focus attention of people living with HIV (PLWH) on common health problems that also affect the HIV-negative population. Cardiovascular disease is one of the leading causes of morbidity and mortality in PLWH [1]. Coronary and cerebrovascular events have been described to occur more frequently among HIV-infected persons than in their HIV-negative pairs [2,3], with most of the available data coming from Northern European countries and the USA, where the incidence of cardiovascular disease is relatively high.

The Cohort of adult PLWH of the AIDS Research Network (CoRIS) is an open, prospective, multicentre cohort of adult subjects with confirmed HIV infection, naïve to ART at study entry, who are recruited in HIV care units of the Spanish Public Health System [9], which constitutes the standard place of treatment for the great majority of persons in Spain. CoRIS was launched in 2004. Each centre recruits into the cohort all subjects seen for the first time in the centre who meet the following criteria: over 13 years of age, confirmed HIV diagnosis, and naive to ART. Written informed consent is obtained from all the patients. Demographic, clinical, laboratory, microbiological and treatment information is recorded. For these analyses, patients’ follow-up data were administratively censored on December 31, 2015.

Overall, 9,712 PLWH and 48,341 person-years of follow-up were analysed. Demographic and clinical characteristics of the participants are provided in Table 1. From 2004 to 2015, 147 persons developed 154 vascular events; 80 (54.42%) coronary-related events, 65 (44.22%) cerebrovascular-related events, and 9 (6.12%) PAD. Coronary events included AMI in 58 (72.50%) participants, angina in 17 (21.25%), and sudden death of probable coronary etiology in 5 (6.25%). Cerebrovascular disease included ischemic stroke/TIA in 54 (83.08%) participants, and haemorrhagic stroke in 11 (16.92%) (Table 1). Twenty-four (16.32%) of the persons developing vascular events died. Of them, 7 cases were attributed to cerebrovascular disease, 2 to coronary/heart disease and 15 to other causes (Table 1).

This study represents the first nationwide cohort study analyzing the incidence and spectrum of coronary, cerebrovascular and peripheral arterial disease in PLWH in Spain. CoRIS is a contemporary cohort that recruits patients at 28 sites from 13 of the 17 Autonomous Communities in Spain, and it covers most of the country, specifically those areas with the highest HIV/AIDS prevalence according to national surveillance [9]. Incident vascular events were collected from 2004 to 2015. In a previous cohort analysis, cardiovascular events constituted the fifth most common cause of non-AIDS events after psychiatric, hepatic, malignant and renal events [12]. As expected, the incidence of cardiovascular and cerebrovascular disease in the Spanish PLWH patients was lower compared to the rates described in North America and Northern Europe [2,4,15–17]. We found a similar incidence rate of AMI to that described in France [18]. Lifestyle habits, particularly the diet, and probably genetic factors seem to play a crucial role in the low rates of cardiovascular disease found in Mediterranean countries, despite high prevalence of cardiovascular risk factors, like smoking habit [19]. The lower frequency of atherosclerotic disease observed in our study is in agreement with the small number of PLWH with high estimated cardiovascular risk using different scores described in a subgroup of participants from CoRIS, even though the prevalence of smokers was 46% [7].




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