Small dense lipoproteins, apolipoprotein B, and risk of coronary events in HIV-infected patients on antiretroviral therapy: the Swiss HIV Cohort Study.
ABSTRACT HIV infection and exposure to certain antiretroviral drugs is associated with dyslipidemia and increased risk for coronary events. Whether this risk is mediated by highly atherogenic lipoproteins is unclear. We investigated the association of highly atherogenic small dense low-density lipoproteins (LDLs) and apolipoprotein B and coronary events in HIV-infected individuals receiving antiretroviral therapy.
We conducted a case-control study nested into the Swiss HIV Cohort Study to investigate the association of small dense LDL and apolipoprotein B and coronary events in 98 antiretroviral drug-treated patients with a first coronary event (19 fatal and 79 nonfatal coronary events with 53 definite and 15 possible myocardial infarctions, 11 angioplasties or bypasses) and 393 treated controls matched for age, gender, and smoking status. Lipids were measured by ultracentrifugation.
In models including cholesterol, triglycerides, high-density lipoprotein cholesterol, blood pressure, central obesity, diabetes, and family history, there was an independent association between small dense LDL and coronary events [odds ratio (OR) for 1 mg/dL increase: 1.06, 95% confidence interval (CI): 1.00 to 1.11] and apolipoprotein B (OR for 10 mg/dL increase: 1.16, 95% CI: 1.02 to 1.32). When adding HIV and antiretroviral therapy-related variables, ORs were 1.04 (95% CI: 0.99 to 1.10) for small dense LDL and 1.13 (95% CI: 0.99 to 1.30) for apolipoprotein B. In both models, blood pressure and HIV viral load was independently associated with the odds for coronary events.
HIV-infected patients receiving antiretroviral therapy with elevate small dense LDL and apolipoprotein B are at increased risk for coronary events as are patients without sustained HIV suppression.
- [Show abstract] [Hide abstract]
ABSTRACT: Higher levels of small low-density lipoprotein (LDL) and lower levels of high-density lipoprotein (HDL) subclasses have been associated with increased risk of cardiovascular disease. The extent to which HIV infection and HIV/HCV coinfection are associated with abnormalities of lipoprotein subclasses is unknown. Lipoprotein subclasses were measured by nuclear magnetic resonance (NMR) spectroscopy in plasma samples from 569 HIV-infected and 5948 control participants in the FRAM, CARDIA and MESA studies. Multivariable regression was used to estimate the association of HIV and HIV/HCV coinfection with lipoprotein measures with adjustment for demographics, lifestyle factors, and waist-to-hip ratio. Relative to controls, small LDL levels were higher in HIV-monoinfected persons (+381 nmol/L, p < .0001), with no increase seen in HIV/HCV coinfection (-16.6 nmol/L). Levels of large LDL levels were lower (-196 nmol/L, p < .0001) and small HDL were higher (+8.2 μmol/L, p < .0001) in HIV-monoinfection with intermediate values seen in HIV/HCV-coinfection. Large HDL levels were higher in HIV/HCV-coinfected persons relative to controls (+1.70 μmol/L, p < .0001), whereas little difference was seen in HIV-monoinfected persons (+0.33, p=0.075). Within HIV-infected participants, HCV was associated independently with lower levels of small LDL (-329 nmol/L, p < .0001) and small HDL (-4.6 μmol/L, p < .0001), even after adjusting for demographic and traditional cardiovascular risk factors. HIV-monoinfected participants had worse levels of atherogenic LDL lipoprotein subclasses compared with controls. HIV/HCV coinfection attenuates these changes, perhaps by altering hepatic factors affecting lipoprotein production and/or metabolism. The effect of HIV/HCV coinfection on atherosclerosis and the clinical consequences of low small subclasses remain to be determined.AIDS (London, England) 10/2013; · 6.56 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Objectives: To examine whether the lipid parameters are predicting factors for human immunodeficiency virus (HIV)-associated lipodystrophy. Methods: Whole-body fat compositions of HIV-positive patients receiving stavudine-containing antiretroviral regimens (n = 79) were determined. Lipodystrophy was defined as a ratio of trunk fat mass/lower limb fat mass greater than 2.28. Blood samples were analyzed for total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), small-dense LDL-C (sdLDL-C), apoAI, apoB, lipoprotein(a), and CD4 cell counts. Large-buoyant LDL-C (lbLDL-C) was calculated (LDL-C minus sdLDL-C). Results: Twenty-six patients were classified as having lipodystrophy. The mean values of triglycerides, HDL-C, sdLDL-C, apoB, TC/HDL-C, apolipoprotein (apo) B/apoAI, and sdLDL-C/lbLDL-C showed significant differences between patients with and without lipodystrophy (P < .02). Using logistic regression analysis, sdLDL-C/lbLDL-C was identified as a significant predictor of lipodystrophy (P < .001). At a ratio of 0.554, the odds ratio was 17.8 with a likelihood ratio of 5.5. Conclusions: The sdLDL-C/lbLDL-C ratio is an excellent marker for indicating lipodystrophy in HIV-infected patients.American Journal of Clinical Pathology 10/2013; 140(4):506-15. · 2.88 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: With the success of antiretroviral therapy (ART), non-human immunodeficiency virus (HIV)-related comorbidities like cardiovascular diseases (CVDs) are of increasing concern. We describe important recent research developments on the epidemiology of CVD in HIV infection, ART-related metabolic changes, and cardioprotective anti-inflammatory mechanisms, and summarize management strategies for CVD risk reduction. We systematically identified and analysed systematic reviews and most cited literature published in the last 3 years and supplemented findings with selected evidence based on clinical expertise. Among HIV-infected individuals, the prevalence of CVD risk factors and the risk for CVD is higher compared with HIV negatives. Antiretroviral drugs may induce dyslipidaemia, reduce insulin sensitivity, and promote body fat redistribution that additionally contributes to CVD risk. Some antiretroviral drugs may increase risk for CVD events, but the absolute risk increase is moderate and has to be put into perspective with the massive HIV-related benefits. Sustained HIV suppression reduces systemic inflammatory markers and is associated with a moderate reduction in CVD events. Regular CVD risk assessment and counselling to stop smoking must be regularly done in all HIV-infected individuals. Statins are effective for the treatment of dyslipidaemia in HIV infection, but drug interactions with ART need to be considered. Human immunodeficiency virus-infected individuals are at increased risk for CVD. Timely initiation of ART with consequent viral suppression is likely to reduce CVD events and to offset potential side effects from ART-induced metabolic changes. Reduction in smoking in HIV-infected individuals is a public health priority.European Heart Journal 01/2014; · 14.72 Impact Factor