Weight loss effect on inflammation and LDL oxidation in metabolically healthy but obese (MHO) individuals: low inflammation and LDL oxidation in MHO women

OBJECTIVE: Recently, a subtype of obesity characterized as a metabolically healthy but obese (MHO) individual has been identified. However, limited data are available on these MHO individuals' metabolic and inflammatory profiles, and the effect of weight loss on these profiles. We investigated metabolic and inflammatory markers in MHO women to determine the effects of a 12-week weight loss on those markers. SUBJECTS: One hundred and twenty-nine overweight-obese Korean women participated for 12 weeks in a clinical intervention study involving a 300 kcal/day intake reduction. The subjects were divided into two groups: MHO and metabolically abnormal obese (MAO) individuals. METHODS: Computed tomography was performed. C-reactive protein (CRP), interkeukin-6 (IL-6) and oxidized low-density lipoprotein (LDL), as well as blood lipids, glucose and insulin concentrations were determined at baseline and after weight loss. RESULTS:At baseline, plasma CRP (P<0.001), IL-6 (P<0.05) and oxidized LDL (P<0.001) levels were significantly lower in the MHO group than in the MAO group. Visceral fat at L1 (P<0.005) and visceral fat at L4 (P<0.001) were significantly lower in the MHO group than in the MAO group. The treatment induced weight loss averaging 3.11% of initial body weight, and the degree of weight loss between the two groups was similar. Visceral fat at L1 and L4 was reduced from its initial values by 3.2 and 5.4%, respectively, after weight loss. The levels of CRP (P<0.05) and oxidized LDL (P<0.01) were significantly reduced in the MAO group after the 12-week weight loss, whereas these effects were not seen in the MHO group. CONCLUSIONS: Our results showed that MHO individuals exhibited lower visceral fat accumulation and more favorable metabolic and inflammatory states than MAO individuals. After a 12-week weight loss program, significant reductions in blood lipids, CRP and oxidized LDL levels were observed in MAO individuals. However, there was no measurable effect of weight loss on lipid profiles and inflammation in MHO individuals, indicating differing effects of weight loss on these markers between MAO and MHO groups.     

Effects of simvastatin on C-reactive protein in mixed hyperlipidemic and hypertriglyceridemic patients

This study examined the effects of simvastatin on C-reactive protein (CRP) and other inflammatory markers in study subjects with significant elevations in triglyceride (TG) blood levels. CRP, vascular cellular adhesion molecule (VCAM), serum amyloid A (SAA), and interleukin 6 (IL-6) were measured in archived plasma samples from 2 multicenter, randomized, double-blind, placebo-controlled studies designed to examine the lipid-altering efficacy of simvastatin in study subjects with elevated TGs. In the first study, 130 study subjects with mixed hyperlipidemia (low-density lipoprotein [LDL] cholesterol > or =130 mg/dl; TGs 300 to 700 mg/dl) received placebo or simvastatin 40 or 80 mg once daily for three 6-week periods in a complete-block crossover design. In the second study, 195 study subjects with hypertriglyceridemia (TGs 300 to 900 mg/dl) received daily doses of placebo or simvastatin 20, 40, or 80 mg for 6 weeks. Significant but weak correlations were observed between baseline CRP values and baseline levels of LDL cholesterol and high-density lipoprotein (HDL) cholesterol, but not with TGs. CRP was also correlated with body mass index and fasting levels of glucose and insulin. Treatment with simvastatin 20, 40, and 80 mg led to significant reductions in CRP plasma levels versus placebo (p <0.05). Although CRP change was weakly correlated with changes in LDL cholesterol, TGs, and HDL cholesterol, results of regression analyses showed that only baseline CRP and treatment allocation were significant predictors of CRP response after 6 weeks of study drug administration. Simvastatin had no effect on VCAM, SAA, or IL-6. In summary, simvastatin significantly reduced CRP in patients with mixed hyperlipidemia and hypertriglyceridemia.     

Omega-3 fatty acids do not improve endothelial function in virologically suppressed HIV-infected men: a randomized placebo-controlled trial

Omega-3 fatty acids decrease cardiovascular disease (CVD) mortality possibly due to antiinflammatory effect. Inflammation and endothelial dysfunction likely play a role in the heightened CVD risk in HIV. Our goal was to evaluate the effect of omega-3 fatty acids primarily on endothelial function and inflammation in HIV-infected adults with moderate CVD risk on stable antiretroviral therapy. We conducted a 24-week, randomized, double-blind, placebo-controlled study to evaluate the effect of omega-3-acid ethyl esters 1 g twice a day. Flow-mediated dilation (FMD) of the brachial artery, lipoproteins and markers of inflammation, endothelial activation, coagulation, and insulin resistance were measured at entry and week 24. There were no within- or between-group differences in change in FMD over 24 weeks (mean change in FMD -0.13% vs. 1.5% for treatment vs. placebo; p=0.21). There were no between-group differences in changes in lipoprotein levels or biomarkers tested, except soluble tumor necrosis factor receptor-I, which favored omega-3-acid ethyl esters. Omega-3 fatty acids did not improve endothelial function or activation, coagulation, or insulin resistance in virologically suppressed, HIV-infected men with moderate CVD risk; however, inflammation tended to improve. This suggests that omega-3 fatty acids may not be potent enough to counteract the enhanced inflammation and endothelial dysfunction due to HIV and antiretrovirals.     

Effect of nutritional counseling on low-density lipoprotein cholesterol among Thai HIV-infected adults receiving antiretroviral therapy

HIV-infected patients receiving antiretroviral therapy have increased risk of metabolic syndrome, including dyslipidemia. In this study, we determined whether individual nutritional counseling reduced dyslipidemia, particularly low-density lipoprotein (LDL) cholesterol, among HIV-infected patients with dyslipidemia not currently taking lipid-lowering medication. We conducted a randomized 24-week trial among HIV-infected patients with dyslipidemia who were on antiretroviral therapy and were eligible to initiate therapeutic lifestyle changes according to the Thai National Cholesterol Education Program. Participants were randomly assigned to an intervention group that received individual counseling with a nutritionist for seven sessions (baseline, weeks 2, 4, 8, 12, 18, and 24) and a control group that received standard verbal diet information at baseline and nutritional counseling only at week 24. A 24-h recall technique was used to assess dietary intake for both groups at baseline and week 24. Lipid profile (total cholesterol, LDL, high-density lipoprotein (HDL), and triglyceride) was measured at baseline and after 12 and 24 weeks of therapy. An intention-to-treat and linear mixed model were used. Seventy-two patients were randomly assigned, and 62 (86%) participants completed their lipid profile test. After 12 weeks of follow-up, there were significant reductions in the intervention group for total cholesterol (?14.4?±?4.6?mg/dL, P?=?.002), LDL cholesterol (?13.7?±?4.1?mg/dL, P?=?.001), and triglyceride (?30.4?±?13.8?mg/dL, P?=?.03). A significant reduction in LDL cholesterol was also observed in the control group (?7.7?±?3.8?mg/dL, P?=?.04), but there were no significant differences in change of mean lipid levels between the groups at 12 weeks of follow-up. After 24 weeks, participants assigned to the intervention group demonstrated significantly greater decreases in serum total cholesterol (?19.0?±?4.6?vs. 0.2?±?4.3?mg/dL, P?=?.003) and LDL cholesterol (?21.5?±?4.1?vs. ?6.8?±?3.8?mg/dL, P?=?.009). There were no significant changes in HDL cholesterol or triglyceride levels in either group.     

Low-density lipoprotein-dependent and -independent effects of cholesterol-lowering therapies on C-reactive protein: a meta-analysis.

OBJECTIVES: This study sought to assess the contribution of low-density lipoprotein (LDL)-dependent and LDL-independent effects of LDL-lowering therapies to changes in C-reactive protein (CRP) in healthy or stable subjects. BACKGROUND: Correlations of change in LDL and CRP in individuals are lowered by their measurement variability. By using average changes in LDL and CRP in study groups, meta-analysis reduces this variability to better assess their correlation. METHODS: A systematic search for randomized placebo-controlled trials reporting change in LDL and CRP with LDL-lowering interventions retrieved 23 studies with 57 groups treated with a variety of statins, nonstatin drugs, or other regimens. Meta-analysis techniques assessed the relationships between average mean differences (placebo - treatment) in change in CRP and LDL. RESULTS: The overall reduction in CRP was 28% (95% confidence interval 26% to 30%). Significantly greater CRP reduction occurred in statin and statin-ezetimibe interventions, interventions using 80 mg/day of statins, and with greater LDL lowering. Meta-regression analysis showed a strong correlation between the change in LDL and CRP (r = 0.80, p < 0.001). Statin therapies had no significant effect on CRP after adjusting for the change in LDL. In a multivariate model applied to a range of LDL reduction typically seen with statins (20% to 60%), 89% to 98% of CRP change was related to LDL lowering and 2% to 11% was related to non-LDL effects of statins. CONCLUSIONS: In clinical practice, most of the anti-inflammatory effect of LDL-lowering therapies is related to the magnitude of change in LDL. The potential non-LDL effects of statins on inflammation are much smaller in magnitude.     

Acid dissociation increases the sensitivity of p24 antigen detection for the evaluation of antiviral therapy and disease progression in asymptomatic human immunodeficiency virus-infected persons.

Because the time from primary infection to symptoms in human immunodeficiency virus type 1 (HIV-1) infection is typically 8-10 years, the use of surrogate markers to monitor disease progression and therapeutic efficacy is of interest. An acid dissociation procedure that disrupts the p24 antigen-antibody complexes found in early HIV-1 infection has greatly increased the sensitivity of p24 detection assays. The utility of p24 antigen after acid treatment as a surrogate marker of disease progression and therapeutic effect in asymptomatic HIV-infected subjects receiving zidovudine (AZT) was determined. After acid treatment, the sensitivity of p24 antigen detection increased fivefold. The proportion of subjects who were antigenemic increased over the 48-week follow-up in the placebo group; approximately 50% of subjects who were p24 antigen-positive at entry and who received AZT showed clearance or a greater than 50% reduction in baseline p24 antigen levels at 16 and 32 weeks. Thus, acid treatment of plasma may allow the use of p24 antigen as a marker of disease progression and therapeutic response.