Search

Background: Although rosiglitazone favorably affects myriad intermediate markers of atherosclerosis, it appears to increase myocardial infarction (MI) risk. We analyzed the effects of rosiglitazone on a panel of 8 novel circulating biomarkers, 4 of which are independently associated with atherosclerosis: lymphotoxin β receptor, peptidoglycan recognition protein 1, chemokine ligand 23, and soluble receptor for advanced glycation end products (sRAGE) as well as on high-sensitivity C-reactive protein (hs-CRP). Methods: Blood samples were analyzed at baseline and after 6 months of study treatment from subjects with type 2 diabetes with or at high risk for coronary artery disease in a randomized trial comparing rosiglitazone versus placebo. Results: Data from 111 subjects (rosiglitazone 55, placebo 56) were analyzed. Mean age was 56 years, 41% were women, and 66% were nonwhite. Compared with baseline values, rosiglitazone adversely affected levels of lymphotoxin β receptor (1.7 vs 2.4 ng/mL, P = .002), peptidoglycan recognition protein 1 (29.0 vs 30.1 ng/mL, P = .01), and chemokine ligand 23 (0.76 vs 0.84 ng/mL, P = .02) and favorably affected levels of sRAGE (inversely associated with atherosclerosis, 1.1 vs 1.4 ng/mL, P = .003) and hs-CRP (0.42 vs 0.31 ng/mL, P = .02); no changes were observed with rosiglitazone in the other biomarkers. In the placebo group, change was observed only for sRAGE (1.0 vs 1.1 ng/mL, P = .046). Conclusion: Rosiglitazone adversely affected 3 novel biomarkers and favorably affected a fourth previously associated with atherosclerosis while improving hs-CRP, as has previously been shown. Whether these complex effects on circulating inflammatory biomarkers contribute to the signal of increased MI risk with rosiglitazone and whether pioglitazone has similar effects warrant further investigation. [Copyright &y& Elsevier]

Objectives: This study sought to evaluate the associations between different measures of obesity and prevalent atherosclerosis in a large population-based cohort. Background: Although obesity is associated with cardiovascular mortality, it is unclear whether this relationship is mediated by increased atherosclerotic burden. Methods: Using data from the Dallas Heart Study, we assessed the association between gender-specific obesity measures (i.e., body mass index [BMI]; waist circumference [WC]; waist-to-hip ratio [WHR]) and prevalent atherosclerosis defined as coronary artery calcium (CAC) score >10 Agatston units measured by electron-beam computed tomography and detectable aortic plaque measured by magnetic resonance imaging. Results: In univariable analyses (n = 2,744), CAC prevalence was significantly greater only in the fifth versus first quintile of BMI, whereas it increased stepwise across quintiles of WC and WHR (p trend <0.001 for each). After multivariable adjustment for standard risk factors, prevalent CAC was more frequent in the fifth versus first quintile of WHR (odds ratio 1.91, 95% confidence interval 1.30 to 2.80), whereas no independent positive association was observed for BMI or WC. Similar results were observed for aortic plaque in both univariable and multivariable-adjusted analyses. The c-statistic for discrimination of prevalent CAC was greater for WHR compared with BMI and WC in women and men (p < 0.001 vs. BMI; p < 0.01 vs. WC). Conclusions: We discovered that WHR was independently associated with prevalent atherosclerosis and provided better discrimination than either BMI or WC. The associations between obesity measurements and atherosclerosis mirror those observed between obesity and cardiovascular mortality, suggesting that obesity contributes to cardiovascular mortality via increased atherosclerotic burden. [Copyright &y& Elsevier]

Abstract: Aims: Most lipoprotein-associated phospholipase A2 (Lp-PLA2) studies included mainly white men. We sought to determine whether Lp-PLA2 levels differ according to race and sex. Methods: Lp-PLA2 mass and activity were measured in 3332 subjects age 30–65 participating in the Dallas Heart Study, a multiethnic, population-based, probability sample. Lp-PLA2 levels were compared between different race and sex groups. Results: Mean age was 45±9 years and 44% were men; 30% were white, 17% hispanic, and 53% black. Mean Lp-PLA2 activity and mass were 146±40nmol/min/mL and 191±60ng/mL, respectively. Lp-PLA2 activity was lower in women compared with men (134±35 vs. 161±40, p =0.001) and was lowest in black (136±38), intermediate in hispanic (151±36), and highest in white subjects (161±39) (trend p =0.0001). In multivariable linear regression models, after adjusting for age, body mass index (BMI), smoking, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides and high sensitivity C-reactive protein (hsCRP), Lp-PLA2 activity was 19nmol/min/mL higher in men vs. women (p <0.001); compared with black subjects, adjusted Lp-PLA2 activity was 11 and 20nmol/min/mL higher in white and hispanic subjects, respectively (both p <0.001). Similar race and sex differences were observed for Lp-PLA2 mass. Conclusion: Race and sex independently influence Lp-PLA2 activity and mass. Thresholds to define Lp-PLA2 elevation may need to be sex and race specific. [Copyright &y& Elsevier]