Jason Lazar

Low CD4+ T cell count as a major atherosclerosis risk factor in HIV-infected women and men

Objective:To assess the association of HIV infection, HIV disease parameters (including CD4+ T-cell counts, HIV viral load, and AIDS) and antiretroviral medication use with subclinical carotid artery atherosclerosis. Design:Cross-sectional study nested within a prospective cohort study. Methods:Among participants in the Womens Interagency HIV Study (1331 HIV-infected women, 534 HIV-uninfected women) and Multicenter AIDS Cohort Study (600 HIV-infected men, 325 HIV-uninfected men), we measured subclinical carotid artery lesions and common carotid artery intima-media thickness using B-mode ultrasound. We estimated adjusted mean carotid artery intima-media thickness differences and prevalence ratios for carotid lesions associated with HIV-related disease and treatments, with multivariate adjustment to control for possible confounding variables. Results:Among HIV-infected individuals, a low CD4+ T-cell count was independently associated with an increased prevalence of carotid lesions. Compared with the reference group of HIV-uninfected individuals, the adjusted prevalence ratio for lesions among HIV-infected individuals with CD4+ T-cell count less than 200 cells/μl was 2.00 (95% confidence interval, 1.22–3.28) in women and 1.74 (95% confidence interval, 1.04–2.93) in men. No consistent association of antiretroviral medications with carotid atherosclerosis was observed, except for a borderline significant association between protease inhibitor use and carotid lesions in men (with no association among women). History of clinical AIDS and HIV viral load were not significantly associated with carotid atherosclerosis. Conclusion:Beyond traditional cardiovascular disease risk factors, low CD4+ T-cell count is the most robust risk factor for increased subclinical carotid atherosclerosis in HIV-infected women and men.

Ten-Year Predicted Coronary Heart Disease Risk in HIV-Infected Men and Women

BACKGROUND Highly active antiretroviral therapy (HAART), in addition to traditional vascular risk factors, may affect coronary heart disease (CHD) risk in individuals with human immunodeficiency virus (HIV) infection. METHODS Among HIV-infected (931 men and 1455 women) and HIV-uninfected (1099 men and 576 women) adults, the predicted risk of CHD was estimated on the basis of age, sex, lipid and blood pressure levels, the presence of diabetes, and smoking status. RESULTS Among HIV-infected men, 2% had moderate predicted risk of CHD (10-year CHD risk, 15%-25%), and 17% had high predicted risk (10-year CHD risk of > or = 25% or diabetes). Among HIV-infected women, 2% had moderate predicted CHD risk, and 12% had high predicted CHD risk. Compared with users of protease inhibitor-based HAART, the adjusted odds ratio (OR) for moderate-to-high risk of CHD was significantly lower among HAART-naive individuals (OR, 0.57; 95% confidence interval [CI], 0.36-0.89). Users of HAART that was not protease inhibitor based (OR, 0.74; 95% CI, 0.53-1.01) and former HAART users (OR, 0.68; 95% CI, 0.46-1.03) were also less likely than users of protease inhibitor-based HAART to have moderate-to-high CHD risk, although 95% CIs overlapped the null. Low income was associated with increased likelihood of moderate-to-high CHD risk (for annual income <

Autonomic consequences of kainic acid–induced limbic cortical seizures in rats: Peripheral autonomic nerve activity, acute cardiovascular changes, and death

10,000 vs. >

Association Between Human Immunodeficiency Virus Infection and Stiffness of the Common Carotid Artery

40,000: OR, 2.32; 95% CI, 1.51-3.56 ). Elevated body mass index (calculated as weight in kilograms divided by the square of height in meters) predicted increased likelihood of moderate-to-high CHD risk (for BMI of 18.5-24.9 vs. BMI of 25-30: OR, 1.41 [95% CI, 1.03-1.93]; for BMI of 18.5-24.9 vs. BMI > or = 30: OR, 1.79 [95% CI, 1.25-2.56]). CONCLUSIONS Among HIV-infected adults, in addition to antiretroviral drug exposures, being overweight and having a low income level were associated with increased predicted CHD risk. This suggests a need to target HIV-infected men and women with these characteristics for vascular risk factor screening.

Cardiac Rupture in Takotsubo Cardiomyopathy: A Systematic Review

Purpose: Autonomic consequences of seizures are common, but can be severe. We sought to define changes in autonomic activity from limbic cortical seizures and their impact on the heart.

Microalbuminuria is associated with all-cause and AIDS mortality in women with HIV infection.

Background and Purpose— Individuals with human immunodeficiency virus (HIV) who use highly active antiretroviral therapy (HAART) may have an increased risk for cardiovascular-related events, although the underlying mechanism remains unclear. We tested the hypothesis that carotid arterial stiffness was higher among persons using HAART compared to HAART-naïve and HIV-uninfected persons. Methods— Between 2004 and 2006, we performed high-resolution B-mode ultrasound on 2789 HIV-infected and HIV-uninfected participants of the Womens Interagency HIV Study (1865 women) and the Multicenter AIDS Cohort Study (924 men) and determined carotid arterial distensibility, which is a direct measure of carotid arterial stiffness. We used generalized estimating equations to evaluate the association between distensibility and HIV infection, CD4+ cell count, and exposure to HAART adjusted for demographic, behavioral, and clinical characteristics. Results— In multivariable analysis, distensibility was 4.3% lower (95% confidence interval, −7.4% to −1.1%) among HIV-infected vs uninfected participants. Among HIV-infected participants with <200 CD4+ cells, distensibility was 10.5% lower (95% confidence interval, −14.5% to −6.2%) than that among HIV-uninfected participants, and this effect did not differ significantly by cohort or race. Concurrent HAART use was independently associated with lower distensibility among Multicenter AIDS Cohort Study participants but not among Womens Interagency HIV Study participants. Conclusions— Our finding that advanced HIV-related immunosuppression was associated with increased carotid arterial stiffness independent from the effects of traditional atherosclerosis risk factors suggests that the etiologic mechanism underlying reports of an increased cardiovascular disease risk among HIV-infected individuals might involve HIV-related immunosuppression leading to vascular dysfunction and arterial stiffening.

Macrophage Inflammatory Markers Are Associated With Subclinical Carotid Artery Disease in Women With Human Immunodeficiency Virus or Hepatitis C Virus Infection

Takotsubo cardiomyopathy (TSC) and its complications, such as cardiac rupture (CR), are increasingly being reported in the literature. CR is associated with rapid clinical decline and is uniformly fatal if not surgically repaired. To identify patients who developed CR we performed an analysis of all available indexed cases in the literature and compared them with a control group of patients with TSC without rupture.

Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment.

Objectives:Prevalence of microalbuminuria is increased in patients with HIV. Microalbuminuria is associated with increased mortality in other populations, including diabetics, for whom microalbuminuria testing is standard of care. We investigated whether microalbuminuria is associated with mortality in HIV-infected women not receiving antiretroviral therapy. Methods:Urinalysis for proteinuria and semiquantitative testing for microalbuminuria were performed in specimens from 2 consecutive visits in 1547 HIV-infected women enrolled in the Womens Interagency HIV Study in 1994-1995. Time to death was modeled using proportional hazards analysis. Results:Compared with women without albuminuria, the hazard ratio (HR) for all-cause mortality was increased in women with 1 (HR: 3.4; 95% CI: 2.2 to 5.2) or 2 specimens positive for either proteinuria or microalbuminuria (HR: 3.9; 95% CI: 2.1 to 7.0). The highest risk was observed in women with both specimens positive for proteinuria (HR: 5.8; 95% CI: 3.4 to 9.8). The association between albuminuria and all-cause mortality risk remained significant after adjustment for demographics, HIV disease severity, and related comorbidities. Similar results were obtained for AIDS death. Conclusions:We identified a graded relationship between albuminuria and the risk of all-cause and AIDS mortality.

Cardiac repolarization indices in epilepsy patients.

Objective—Infection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) may be associated with atherosclerosis and vascular disease. Macrophages are a major component of atherosclerotic plaque, and classically activated (M1) macrophages contribute to plaque instability. Our goal was to identify plasma biomarkers that reflect macrophage inflammation and are associated with subclinical atherosclerosis. Approach and Results—We tested whether M1 macrophages produce galectin-3–binding protein in vitro. Then, we measured galectin-3–binding protein and the soluble macrophage biomarkers soluble cluster of differentiation (CD) 163 and soluble CD14 in 264 participants in the Women’s Interagency HIV Study. Women were positive for HIV, HCV, both, or neither (66 in each group, matched for age, race/ethnicity, and smoking status). Carotid artery disease was assessed by ultrasound measurement of right distal common carotid artery intima-media thickness, distensibility, and presence of atherosclerotic lesions (intima-media thickness >1.5 mm). Plasma galectin-3–binding protein was higher in HCV+ than HCV− women (P<0.01) but did not differ by HIV status. The 3 inflammatory macrophage markers were significantly correlated with each other and negatively correlated with CD4+ counts in HIV-infected women. We defined a macrophage score as 1, 2, or 3 biomarkers elevated above the median. In models adjusted for traditional risk factors, higher macrophage scores were significantly associated with increased atherosclerotic lesions and lower carotid distensibility. Receiver-operator curve analysis of lesions revealed that the markers added predictive value beyond traditional risk factors and C-reactive protein. Conclusions—The macrophage inflammatory markers galectin-3–binding protein, soluble CD163, and soluble CD14 are significantly associated with carotid artery disease in the setting of HIV and HCV infection.

Association of hepatitis C virus and HIV infection with subclinical atherosclerosis in the women's interagency HIV study

Background: Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly active antiretroviral therapy (HAART). Methods: In the Womens Interagency HIV Study, 127 HIV-infected women studied pre and post HAART were matched to HIV-uninfected controls. Six semiannual measurements of soluble CD14, tumor necrosis factor (TNF) alfa, soluble interleukin (IL) 2 receptor, IL-6, IL-10, monocyte chemoattractant protein 1, D-dimer, and fibrinogen were obtained. Carotid artery intima–media thickness was measured by B-mode ultrasound. Results: Relative to HIV-uninfected controls, HAART-naive HIV-infected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P < 0.0001), TNF-&agr; (6.3 vs 3.4 pg/mL, P < 0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P < 0.0001), IL-10 (3.3 vs 1.9 pg/mL, P < 0.0001), monocyte chemoattractant protein 1 (190 vs 163 pg/mL, P < 0.0001), and D-dimer (0.43 vs 0.31 &mgr;g/mL, P < 0.01). Elevated biomarker levels declined after HAART. Although most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-&agr; levels remained elevated compared with HIV-uninfected women (+0.8 pg/mL, P = 0.0002). Higher post-HAART levels of soluble IL-2 receptor (P = 0.02), IL-6 (P = 0.05), and D-dimer (P = 0.03) were associated with increased carotid artery intima–media thickness. Conclusions: Untreated HIV infection is associated with abnormal hemostasis (eg, D-dimer), proatherogenic (eg, TNF-&agr;), and antiatherogenic (eg, IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV-infected patients, even with effective therapy.