Role of metabolic syndrome components in human immunodeficiency virus–associated stroke

Abstract

Metabolic syndrome (MetS) is a cluster of risk factors, including elevated mean arterial pressure (MAP), atherogenic dyslipidemia (elevated triglycerides [TRG]), abdominal obesity (increased body mass index [BMI]), glucose intolerance (elevated glucose [GLU]), and prothrombotic/inflammatory state (increases in uric acid [UA]), that are associated with increased risk of cerebrovascular disease. We studied if an association existed between MetS components and human immunodeficiency virus (HIV)-associated cryptogenic strokes-those not caused by HIV complications, endocarditis, or stimulant abuse. We performed a retrospective case-control study. Eleven cryptogenic strokes were identified from 2346 HIV-infected (HIV+) participants. Each case was matched by age, sex, and date of stroke diagnosis to five HIV+ controls without stroke. Nonparametric stratified Wilcoxon ranked sum tests with subsequent mixed effect logistic regression determined the influence of each MetS component on HIV-associated cryptogenic stroke. Although each MetS component appeared higher for HIV+ cases with cryptogenic strokes than HIV+ controls, only MAP (odds ratio [OR] = 5.70, 95% confidence interval [CI] = 1.15-28.3) and UA (OR = 1.88, 95% CI = 1.06-3.32) were statistically different. A significantly higher percentage of HIV-associated cryptogenic stroke cases met criteria for MetS (4/11 = 36%) compared to HIV+ controls (6/55 = 11%). This observational study suggests a possible role for MetS components in HIV+ cryptogenic stroke cases. Although MetS is defined as a constellation of disorders, elevated hypertension and hyperuricemia may be involved in stroke pathogenesis. Reducing MetS component levels in HIV+ patients could therefore protect them from subsequent stroke.

Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment

“…The cohort was unique and different from those previously described due to its size (N= 240), age (40% older than 50 years), and duration of infection (60% were infected more than 10 years and nearly 10% more than 20 years), reflecting the established benefits of ART on survival. Several studies have reported that despite these benefits, subjects are facing a number of complications related to the effects of aging, chronic immune activation or treatment, including lipodystrophies, metabolic disorder and cardiovascular disease [35, 36]. More recently, there is some evidence suggesting that chronically infected yet stable subjects may be developing cognitive impairment [37, 38].…”

“…Age had a profound effect on certain metabolites, notably MI/Cr and Glx/Cr. Interestingly, GLx/Cr levels approached those observed in older healthy individuals suggesting that HIV infection may be accelerating age-related processes in the brain similar to its effects on the cardiovascular system [35, 36]. The observed decreases in MI/Cr in the FWM with age and in the BG with increasing duration of disease may reflect age related disturbances in glial cell metabolism or the effects of chronic “burnt out” brain disease.…”

Predictors of CNS injury as measured by proton magnetic resonance spectroscopy in the setting of chronic HIV infection and CART

“…The study demonstrates that host and viral factors, particularly those linked to current disease status and HIV disease history along with their interactions are predictive of specific patterns of metabolite abnormalities that reflect pathological processes occurring in the chronically infected and treated brain. However, other factors not examined in these models may also be contributing to these changes, including the effects of various chemokines (Navia and Rostasy, 2005, Letendre et al 2011, Kaul and Lipton, 1999) and co-morbid disorders such as hepatitis C and cardiovascular risk factors (Letendre et al, 2004, Valcour et al, 2005, van Gorp and Hinkin, 2005, Perry et al, 2008, Ances et al, 2009) which have been associated with cognitive impairment or brain injury. Future studies will address the relative contributions of these factors to patterns of brain injury and cognitive impairment.…”

Increasing incidence of ischemic stroke in patients with HIV infection

“…Over the study period, the weighted number of total primary stroke diagnoses in the United States generally declined, with 71,742 fewer incident strokes (7 Web site at www.neurology.org show that in the general HIV-negative population, stroke hospitalization rates decreased from 375 hospitalizations per 100,000 persons in 1998 to 311 hospitalizations per 100,000 persons in 2006 ( p Ͻ 0.0001), a 17% rate decrease. As seen in figure e-2 and table e-1, the results in the HIVϩ population were less pronounced after taking into account population size, since the observed increase in the absolute number of strokes was largely explained by a growing HIVϩ US population which increased by close to 40% from 1998 to 2006.…”

“…HIV infection can cause stroke via several mechanisms including HIV-stimulated endothelial activation (predisposing to accelerated atherosclerosis), opportunistic infections, neoplasia, HIV-induced cardiac disease, HIV-associated cerebral vasculopathy, HIV-induced systemic vasculitis, prothrombosis, and metabolic derangements. [4][5][6][7][8] So for instance, the observed increase in several metabolic factors over time may have predisposed these patients to greater risk for developing strokes. It is also possible that recently there has been greatly increased action by the virus in facilitating these mechanisms to the extent that ischemic stroke incidence in particular is much higher, but this would seem unlikely without any supportive evidence.…”