Efficacy of cholesterol uptake inhibition added to statin therapy among subjects following a low-carbohydrate diet: a randomized controlled trial.

BACKGROUND: Low-carbohydrate diets are frequently used as part of weight-loss programs. These are typically associated with increased fat intake. Therefore, cholesterol absorption inhibition is a logical therapeutic strategy to lower low-density lipoprotein cholesterol (LDL-C) in subjects following a low-carbohydrate diet. However, the efficacy of cholesterol absorption inhibition added to statin therapy has not been studied in this common clinical setting. METHODS: We performed a randomized controlled trial to compare the effects of ezetimibe on LDL-C when added to simvastatin among subjects following a low-carbohydrate diet. We enrolled 65 subjects who were overweight or obese (body mass index 25-45 kg/m(2)) and had a moderately elevated LDL-C (130-190 mg/dL). During a 4-week diet run-in, subjects were instructed to restrict carbohydrate intake to <30 g/day. Subjects demonstrating adequate adherence to a low-carbohydrate diet (n = 58) were randomized to simvastatin (20 mg) or simvastatin (20 mg) plus ezetimibe (10 mg) for 8 weeks. RESULTS: Body weight decreased by 3.1% (95% CI 2.1%-4.0%, P < .0001), but the magnitude of weight change did not differ between the groups (P = .92). The LDL-C decreased by 32 mg/dL (95% CI 21-42 mg/dL) in the simvastatin arm and 60 mg/dL (95% CI 45-75 mg/dL) in the combined simvastatin-ezetimibe arm (P = .002). This corresponded to a 20.9% reduction (95% CI 14.5%-27.4%) in LDL-C on simvastatin alone, compared with a 37.4% reduction (95% CI 29.3%-45.6%) on simvastatin-ezetimibe (P = .002). A significant 15.8% reduction in triglycerides was observed among enrolled subjects, which did not differ between the groups. CONCLUSIONS: Among subjects following a low-carbohydrate diet, combined statin and cholesterol absorption inhibitor therapy is more effective than statin monotherapy for LDL-C lowering.

Avoiding the Major Causes of Death: Does Childhood Misfortune Reduce the Likelihood of Being Disease Free in Later Life?

Objectives: Although previous research reveals the detrimental effects of early misfortune on the development of chronic diseases in later life, few studies have investigated its effects on remaining disease free. This study draws on cumulative inequality theory to investigate whether experiencing childhood misfortune reduces the likelihood of remaining disease free over time. Method: This study utilizes five waves of data from the Health and Retirement Study to test whether five domains of childhood misfortune predict being disease free at baseline (2004) and developing disease over time (2004-2012). Results: Respondents reporting risky parental behaviors during childhood were less likely to be disease free at baseline and had an increased risk of disease onset over time, the latter driven by having a guardian who smoked in combination with more pack-years smoked in adulthood. Furthermore, we find that adult resources, that is wealth, help to mitigate the noxious effects of other misfortunes, notably poor socioeconomic conditions. Discussion: Consistent with cumulative inequality theory, these findings reveal that experiencing multiple types of misfortune during childhood decreases the likelihood of remaining disease free in later life, but engaging in health behaviors, such as physical activity, can help to ameliorate some of the noxious effects of early misfortune.

Effects of rosiglitazone on lipids, adipokines, and inflammatory markers in nondiabetic patients with low high-density lipoprotein cholesterol and metabolic syndrome.

BACKGROUND: PPAR-gamma agonists improve insulin sensitivity and glycemic control in type 2 diabetes and may reduce atherosclerosis progression. Thus, PPAR-gamma agonists may be an effective therapy for metabolic syndrome. However, the full spectrum of potentially antiatherogenic mechanisms of PPAR-gamma agonists have not been fully tested in nondiabetic patients with metabolic syndrome. METHODS AND RESULTS: We performed a prospective, double-blinded, placebo-controlled study of 60 nondiabetic subjects with low high-density lipoprotein cholesterol (HDL-C) level and metabolic syndrome to rosiglitazone 8 mg daily or placebo for 12 weeks. We found no significant effect of rosiglitazone on HDL-C (+5.5% versus +5.8%, P=0.89), and an increase in total cholesterol (+8% versus -1%; P=0.03). Nevertheless, rosiglitazone significantly increased adiponectin (+168% versus +25%; P<0.001), and lowered resistin (-6% versus +4%; P=0.009), C-reactive protein (-32% versus +36%, P=0.002), interleukin (IL)-6 (-22% versus +4%, P<0.001), and soluble tumor-necrosis factor-alpha receptor-2 (-5% versus +7%, P<0.001). CONCLUSIONS: These findings suggest that rosiglitazone, presumably through its PPAR-gamma agonist properties, has direct effects on inflammatory markers and adipokines in the absence of favorable lipid effects. These findings may help explain the mechanism underlying the possible antiatherosclerotic effects of rosiglitazone.

Diverse Aging and Health Inequality by Race and Ethnicity.

Although gerontologists have long embraced the concept of heterogeneity in theories and models of aging, recent research reveals the importance of racial and ethnic diversity on life course processes leading to health inequality. This article examines research on health inequality by race and ethnicity and identifies theoretical and methodological innovations that are transforming the study of health disparities. Drawing from cumulative inequality theory, we propose greater use of life course analysis, more attention to variability within racial and ethnic groups, and better integration of environmental context into the study of accumulation processes leading to health disparities.

Does Neighborhood Disorder Predict Recovery From Mobility Limitation? Findings From the Health and Retirement Study.

OBJECTIVE: This research explores whether perceptions of physical neighborhood disorder predict recovery from mobility limitation over a 2-year period and examines whether psychosocial factors (i.e., depressive symptomology and mastery) and physical activity are salient mediators. METHOD: Using data from the Health and Retirement Study (HRS): Participant Lifestyle Questionnaire (2008-2010), odds ratio estimates of recovery were ascertained using binary logistic regression, and post hoc Sobel tests were conducted to formally assess mediation. RESULTS: Net of demographic characteristics and socioeconomic status, increased neighborhood disorder was associated with lower odds of recovery. However, both psychosocial indicators and physical activity were significant individual partial mediators, which suggest neighborhood disorder influences recovery from physical impairment via psychosocial processes and barriers to physical activity. DISCUSSION: Reducing neighborhood disorder may enhance older residents' psychosocial well-being and improve participation in physical activity, thus increasing recovery from mobility limitation and preventing subsequent disability.