Association Between HIV Infection, Antiretroviral Therapy, and Risk of Acute Myocardial Infarction: A Cohort and Nested Case–Control Study Using Québecʼs Public Health Insurance Database

Internal Medicine Service, Centre Hopsitalier Universitaire de Montréal, Montréal, Canada.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 04/2011; 57(3):245-53. DOI: 10.1097/QAI.0b013e31821d33a5
Source: PubMed


Morbidity associated with cardiovascular disease is increasing in the HIV-infected population. We aimed to study the impact of HIV and of antiretrovirals on acute myocardial infarction (AMI).
We performed a cohort and a nested case-control study using the dataset of the Régie de l'Assurance Maladie du Québec. HIV-positive patients were identified using ICD-9 diagnostic codes and matched to HIV-negative patients. Within the HIV-positive cohort, cases of AMI were identified and matched to HIV-positive patients without AMI. The coprimary outcomes were the risk of AMI associated with HIV exposure in the cohort study and that associated with exposure to antiretrovirals in the case-control study. Data were analysed using Poisson and conditional logistic regression.
About 7053 HIV-positive patients were matched to 27,681 HIV-negative patients. Incidence rates of AMI in the HIV+ cohort was 3.88 95% confidence interval (CI) (3.26 to 4.58) per 1000 patient-years, compared to 2.21 95% CI (1.93 to 2.52) per 1000 patient-years in the HIV cohort. The adjusted incidence ratio of AMI for HIV-infected patients was 2.11 95%CI (1.69 to 2.63). Among HIV+ patients, 125 AMI cases were matched with 1084 HIV+ patients. We found increased odds ratio (95% CI) of AMI associated with any exposure to abacavir 1.79 (1.16 to 2.76), P = 0.02, efavirenz 1.83 (1.21 to 2.76) P = 0.004, lopinavir 1.98 (1.24 to 3.16) P = 0.004, and ritonavir 2.29 (1.48 to 3.54) P < 0.001.
HIV+ individuals were at higher risk of AMI than the general population, and several antiretrovirals were associated with an increased risk of AMI. Results should be interpreted with caution in absence of data on smoking and HIV clinical status.

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    • "The adjusted analysis included smoking, previous diagnosis of AIDS, CD4 count, HIV viral load, and duration of HAART. Durand et al. (2011) (42) conducted a nested case-control analysis of two administrative databases widely used in Québec, Canada, for those with public insurance to assess the association between ART and acute MI, selecting up to 10 controls per case within the HIV-infected cohort that did not have an acute MI, matched on age, gender, and cohort entry date Acute MI was assessed by diagnostic codes and review of discharge summaries. A dichotomous measure of alcohol abuse at any time before acute MI or end of follow-up was identified through the administrative databases. "
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    ABSTRACT: People living with HIV-infection (PLWH) have higher prevalence and earlier onset of cardiovascular disease (CVD), compared to uninfected populations. It is unclear how alcohol consumption is related to CVD among PLWH. To summarize the current literature and strength of evidence regarding alcohol consumption as a risk factor for CVD among PLWH, to generate summary estimates for the effect of alcohol consumption on CVD outcomes, and to make recommendations for clinical practice and future research based on the findings and limitations of existing studies. A systematic review was conducted using Pubmed/Medline to identify relevant peer-reviewed articles published between 1 January 1999 and 1 January 2014. After critical review of the literature, 13 studies were identified. Risk ratios were extracted or calculated and sample size weighted summary estimates were calculated. The prevalence of a CVD diagnosis or event ranged from 5.7-24.0%. The weighted pooled crude effect sizes were 1.75 (95% CI 1.06, 3.17) for general and 1.78 (95% CI 1.09, 2.93) for heavy alcohol use on CVD. The pooled adjusted effect size was 1.37 (95% CI 1.02, 1.84) for heavy alcohol use on CVD. Pooled estimates differed by CVD outcome and alcohol measure; alcohol consumption was most significant for cerebral/ischemic events. HIV clinicians should consider risk factors that are not included in the traditional risk factor framework, particularly heavy alcohol consumption. Neglect of this risk factor may lead to underestimation of risk, and thus under-treatment among PLWH.
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    • "5672 HIV+ Yes Mary–Krause M [25] 34, 976 HIV+ Yes Durand M [26] "
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    ABSTRACT: The successful roll-out of highly active antiretroviral therapy (HAART) has extended life expectancy and enhanced the overall well-being of HIV-positive individuals. There are, however, increased concerns regarding HAART-mediated metabolic derangements and its potential risk for cardiovascular diseases (CVD) in the long-term. Here certain classes of antiretroviral drugs such as the HIV protease inhibitors (PIs) are strongly implicated in this process. This article largely focuses on the direct PI-linked development of cardio-metabolic complications, and reviews the inter-linked roles of oxidative stress and the ubiquitin proteasome system (UPS) as key mediators driving this process. It is proposed that PIs trigger reactive oxygen species (ROS) production that leads to serious downstream consequences such as cell death, impaired mitochondrial function, and UPS dysregulation. Moreover, we advocate that HIV PIs may also directly lower myocardial UPS function. The attenuation of cardiac UPS can initiate transcriptional changes that contribute to perturbed lipid metabolism, thereby fueling a pro-atherogenic milieu. It may also directly alter ionic channels and interfere with electrical signaling in the myocardium. Therefore HIV PI-induced ROS together with a dysfunctional UPS elicit detrimental effects on the cardiovascular system that will eventually result in the onset of heart diseases. Thus while HIV PIs substantially improve life expectancy and quality of life in HIV-positive patients, its longer-term side-effects on the cardiovascular system should lead to a) greater clinical awareness regarding its benefit-harm paradigm, and b) the development and evaluation of novel co-treatment strategies.
    Full-text · Article · Nov 2013 · Biochimica et Biophysica Acta
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    • "Efavirenz was not found to be associated with CVD events in the D:A:D cohort. However, a large case-control study from Quebec suggested an increased risk of acute myocardial infarction with the use of efavirenz as well with the use of the protease inhibitor lopinavir [20]. These observational cohort data though may include unmeasured confounders that would perhaps nullify these associations. "
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    ABSTRACT: Changes in endothelial function, measured as flow-mediated dilation (FMD) of the brachial artery, has not been systematically assessed beyond 6 months of initiation of antiretroviral therapy (ART) when drug-related effects might offset initial improvements with virologic control. We assessed 6 and 12 month changes in FMD [presented as median (quartile 1, quartile 3)] and circulating HIV and cardiovascular biomarkers in 23 subjects initiating ART. There were no significant changes in FMD at 6 or 12 months overall despite significant increases in CD4 cell count and HDL-C and reductions in HIV RNA level, MCP-1, IP-10, sVCAM-1, sTNFR2, and sCD14. However, there were significant differences (P = 0.04) in the changes in FMD between those receiving efavirenz [N = 12; -3.50% (-4.90%, 0.68%)] vs. protease inhibitors at 12 months [N = 11; 1.50% (-0.86%, 4.56%)]. The differences in changes in FMD between those receiving and not receiving emtricitabine/tenofovir/efavirenz were more pronounced and were significantly different at both 6 and 12 months (P<0.02 for both). Additional studies showed no significant differences in changes in 25-(OH)-vitamin D, PTH, FGF-23, of F2-isoprostane levels between efavirenz and PI use or between those receiving and not receiving emtricitabine/tenofovir/efavirenz. Efavirenz use was associated with reduced FMD at 12 months compared to PI-based regimens while emtricitabine/tenofovir/efavirenz was associated with reduced FMD at both 6 and 12 months compared to those not receiving this combination. Long-term effects of antiretrovirals on endothelial function may play an important role in the risk of cardiovascular disease in HIV-infected patients.
    Full-text · Article · Oct 2012 · PLoS ONE
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