HIV infection and cocaine use induce endothelial damage and dysfunction in African Americans

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Abstract

Background

Clinical and epidemiological evidence suggests that HIV infection and cocaine use are associated with an increased risk of premature atherosclerosis. The underlying mechanisms linking HIV infection and cocaine use with early atherosclerosis remain elusive.

Methods and results

Endothelin-1 (ET-1) levels in 360 African American participants in Baltimore, Maryland were measured. Quantile regression analysis was performed to examine the associations between ET-1, HIV infection, cocaine use, and other relevant clinical factors. The median of ET-1 in plasma, (1.05 pg/mL with interquartile range: 0.73, 1.40) for those with HIV infection was significantly higher than values for those without HIV infection (0.74 pg/mL with interquartile range: 0.61, 0.93). The median of ET-1 was markedly higher in chronic cocaine users (0.96 pg/mL with interquartile range: 0.71, 1.36) than that in non-cocaine users (0.72 pg/mL with interquartile range: 0.58, 1.06). Multivariate quantile regression suggested that HIV infection and duration of cocaine use were independently associated with plasma ET-1 levels after controlling for potential confounding factors.

Conclusions

This study may provide insight into the mechanism of premature atherosclerosis in HIV-infected cocaine users and suggest that measurement of ET-1 in plasma can be used as a marker of early atherosclerosis in HIV infected patients and cocaine users.

Introduction

HIV infection is implicated in the development of premature cardiovascular disease [1], [2]. Despite the extensive research attempting to explain the increased incidence of coronary artery disease (CAD) among persons with HIV infection, the mechanisms linking HIV infection with early atherosclerosis are not well described. In our previous publications, we have demonstrated that both HIV infection and cocaine use are associated with an increase risk of atherosclerosis [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]. Endothelial dysfunction represents the first step in the pathogenesis of atherosclerosis [14]. It has been demonstrated that early coronary atherosclerosis in humans is characterized by increased coronary and circulating ET-1 and is associated with coronary endothelial dysfunction [15].

In many patient populations, particularly our patient population, drug abuse is found in patients with HIV. The drug cocaine has been especially implicated in a wide variety of cardiac pathology. Despite recognition that cocaine abuse promotes atherosclerosis, most human studies of the impact of cocaine use on atherosclerosis have focused on clinical cardiovascular disease. Most importantly since patients with HIV may use cocaine, it is important to study the effect of cocaine in patients with HIV who may have endothelial dysfunction related to HIV infection. Our study objectives are (1) to explore whether HIV infection and cocaine use, especially duration of cocaine use are independently associated with endothelial damage or dysfunction, measured with the use of ET-1 levels; and (2) to examine whether HIV infection and cocaine use influence ET-1 levels differently for those with average ET-1 levels than for those with elevated ET-1 levels.

Section snippets

Study participants

Between June 2008 and September 2009, 360 African American participants were consecutively enrolled in an observational study investigating novel circulating biochemical markers of atherosclerosis in relation to HIV infection and chronic cocaine use at the Johns Hopkins Hospital, Baltimore, Maryland.

Inclusion criteria were age of 25 years or older and African American race (self-designated). Exclusion criteria were (1) any clinical, scintigraphic or laboratory evidence of CAD, (2) any symptoms

General characteristics

The demographic and clinical characteristics of the study participants are presented in Table 1. The median age was 45 years and 42% were women. Among the 360 participants, 72% were chronic cocaine users, and 71% were HIV infected. The median of duration of cocaine use was 7.0 years (interquartile range: 0.0–16.0). The median systolic blood pressure was 120 mm Hg (interquartile range: 109, 130) and the median diastolic blood pressure was 78 mm Hg (interquartile range: 69, 84). Sixty-two participants

Discussion

The findings of this study show that HIV infection, duration of cocaine use, age and triglycerides levels were independently associated with ET-1 levels in African American adults. We found that the duration of cocaine use was linearly associated with plasma ET-1 levels. Although previous studies have shown cocaine use increased the ET-1 release in vitro and in vivo [16], [17], [18], our results suggest a response-relationship between duration of cocaine use and plasma ET-1 levels in this

Conflict of interest

None declared.

Acknowledgments

This research was supported by grantsR01-DA12777 and DA25524 from the National Institute on Drug Abuse and National Institutes of Health. We thank the study participants for their contributions.

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [30].

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