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Summary: Background & aims: The metabolic syndrome (MetS) is a clustering of various metabolic abnormalities which is associated with increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus. Due to its increasing prevalence, it has become an important public health concern. Altered fatty acid (FA) composition and desaturase activities have been associated with several metabolic diseases, including MetS. The aim of the present study was to evaluate the relationship of the plasma FA profile and desaturase activities with the MetS in a Mediterranean population at high risk of CVD. Methods: Baseline data from 427 participants aged 55–80 years who took part in the interventional PREDIMED study were obtained. Individual FA was determined in plasma and desaturase activities were estimated from product/precursor ratios. Odds ratios (OR) and partial correlation coefficients were used to examine these relations with MetS and its components, respectively. Results: We found higher levels of C14:0, C16:0, C16:1n-7, estimated Δ9- or stearoyl-CoA desaturase (SCD), and estimated Δ6 desaturase (D6D), and lower levels of C18:2n-6 in people with MetS compared to those without it. After adjustment for several confounders, only higher quartiles of C14:0, C16:0, C16:1n-7, and D6D were found to be associated with an increasing prevalence of MetS, while higher quartiles of C18:2n-6 were inversely associated with MetS. High proportions of C14:0, C16:0, C16:1n-7, C20:3n-6, SCD, and D6D, and decreased proportions of C18:2n-6 and estimated Δ5-desaturase (D5D) were associated with adverse profiles of several metabolic risk factors. Women showed more unhealthy FA pattern and lipid profiles than men, but only among those with MetS. Conclusion: A FA composition and estimated desaturase activities consisting in high levels of SFA, SCD and D6D, and low levels of PUFA and D5D are associated with increased MetS probability and are characteristic of people presenting MetS, especially women. These findings support those observed in non-Mediterranean populations in which an altered FA profile and estimated desaturase activities are associated with MetS. [Copyright &y& Elsevier]

Lowering of low-density lipoprotein cholesterol levels is a worthwhile intervention in older (more than 65-70 years of age) subjects, since age itself is a powerful predictor of vascular disease risk. Although studies have not consistently demonstrated an overall beneficial effect on total mortality, cardiovascular morbidity and mortality are favorably affected. The drugs most extensively studied are statins, but similar results are at least suggested for other agents. The efficacy, safety, and benefits of statins make them the drugs of choice. Statin intolerance can be managed and should not lead immediately to an abandonment of therapy. In cases in which it cannot be overcome, other lipid-lowering drugs, either singly or in combination, can be used, although their side effects are generally more problematic and their benefits are less prominent. In older patients, prevention of disability from stroke, heart disease, or peripheral vascular diseases may be as important a goal as an overall beneficial effect on mortality, which, in the long run, is unavoidable. [ABSTRACT FROM AUTHOR]

Abstract: Two leptin receptor single nucleotide polymorphisms, Lys109Arg and Gln223Arg, have been shown to associate with several risk factors for cardiovascular disease. In addition, we have previously shown that Arg109 and Arg223 homozygotes displayed lower intima-media thickness in our well-defined OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study. This current research investigated the impact of these LEPR polymorphisms on cardiovascular events and related death as well as to total mortality in the 19-year follow-up of OPERA. Subjects were randomly selected, middle-aged drug-treated hypertensives and their age- and sex-matched control subjects recruited to the OPERA study between 1990 and 1993. Mortality and hospital events of 1045 subjects were followed up until 2009. A total of 151 coronary heart disease (CHD) and 211 cardiovascular disease (CVD) events or deaths including 58 CHD and 69 CVD deaths occurred. Furthermore, during this follow-up, a total of 165 subjects died. Logistic regression analysis was performed to assess the impact of Lys109Arg and Gln223Arg on the events and death. Further modeling was performed with Cox regression for Lys109Arg. The logistic regression analysis revealed a significant protective impact of Arg109Arg genotype on CHD (OR 0.433; CI 95% 0.217–0.863) and CVD (OR 0.540; CI 95% 0.309–0.942) events or death as well as on total mortality (OR 0.390; CI 95% 0.196–0.775) when adjusted with age, sex and study group. Even after further adjustment with BMI, smoking status, systolic blood pressure and low-density lipoprotein cholesterol, the protective effect of Arg109Arg on CHD events or death and total mortality still remained statistically significant (OR 0.463; CI 95% 0.230–0.931 and OR 0.442; CI 95% 0.218–0.896, respectively). Arg109Arg was also shown to confer protection against CHD mortality (HR 0.224; CI95% 0.055–0.919) and overall mortality (HR 0.413; CI95% 0.218–0.783) also in Cox regression analysis. In conclusion, the Arg109Arg genotype of LEPR seems to be protective from cardiovascular events and death and this phenomenon seems to be independent of the traditional risk factors for atherosclerosis. [Copyright &y& Elsevier]

Abstract: Background: Apolipoprotein A5 (APOA5) gene variants are associated with increased plasma triglycerides, a risk factor for metabolic syndrome (MS). The goal of the current study was the investigation of the distribution of T-1131C variant among obese adolescents with MS compared with healthy controls. Subjects and methods: The study included 150 obese adolescents (75 males and 75 females) with MS and 204 age and sex matched normal healthy controls (100 males and 104 females). The mean age of the patients was 15.47±2.54years, ranged from 17 to 20years. They were genotyped by polymerase chain reaction–restriction fragment length polymorphism for the mutation (T-1131C). Results: The blood pressure, triglyceride and HOMA-R levels were significantly higher and HDL-C levels were significantly lower in carrier (TC+CC) compared to non-carrier (TT) MS patients. There was accumulation of −1131C allele frequency in the MS group (31.33% vs. control group 11.76%), p<0.001. The genotypes were in Hardy–Weinberg equilibrium both in the patients with metabolic syndrome and in the control subjects. Results of analysis of multiple regression models showed that the ApoA5 −1131C carriers showed an increased incidence of MS (OR=1.73, 95% CI: 1.41–2.11). Conclusions: The present study suggests that the 1131T>C polymorphism is a risk factor for the development of metabolic syndrome in obese adolescents. [Copyright &y& Elsevier]

Objectives: This study sought to evaluate the safety and efficacy of rosuvastatin in preventing contrast-induced acute kidney injury (CI-AKI) in patients with diabetes mellitus (DM) and chronic kidney disease (CKD). Background: CI-AKI is an important complication after contrast medium injection. While small studies have shown positive results with statin therapy, the role of statin therapy in prevention of CI-AKI remains unknown. Methods: We randomized 2,998 patients with type 2 DM and concomitant CKD who were undergoing coronary/peripheral arterial angiography with or without percutaneous intervention to receive rosuvastatin, 10 mg/day (n = 1,498), for 5 days (2 days before, and 3 days after procedure) or standard-of-care (n = 1,500). Patients' renal function was assessed at baseline, 48 h, and 72 h after exposure to contrast medium. The primary endpoint of the study was the development of CI-AKI, which was defined as an increase in serum creatinine concentration ≥0.5 mg/dl (44.2 μmol/l) or 0.25% above baseline at 72 h after exposure to contrast medium. Results: Patients randomized to the rosuvastatin group had a significantly lower incidence of CI-AKI than controls (2.3% vs. 3.9%, respectively; p = 0.01). During 30 days' follow-up, the rate of worsening heart failure was significantly lower in the patients treated with rosuvastatin than that in the control group (2.6% vs. 4.3%, respectively; p = 0.02). Conclusions: Rosuvastatin significantly reduced the risk of CI-AKI in patients with DM and CKD undergoing arterial contrast medium injection. (Rosuvastatin Prevent Contrast Induced Acute Kidney Injury in Patients With Diabetes [TRACK-D]; NCT00786136) [ABSTRACT FROM AUTHOR]

Objective: To examine the influence of walking at different times of day on lipids and inflammatory markers in sedentary patients with coronary artery disease (CAD). Methods: A total of 330 patients recruited from Nanjing between September 2011 and November 2012 were randomly assigned to a control group (n=110), morning (n=110) or evening walking group (n=110). Both the walking groups were asked to walk 30min/day or more on at least 5days/week either in the morning or evening for 12weeks. Lipids and inflammatory markers were measured before and after exercise intervention. Results: Compared with baseline, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were improved in all groups. Significances were shown in the changes of fibrinogen, high sensitivity C-reactive protein (hsCRP), white blood cell (WBC) count, TC, triglycerides, LDL-C, lipoprotein(a) between groups. The evening walking group had a larger decrease in fibrinogen (0.16±0.19g/L, P<0.001), hsCRP (1.16±1.07mg/L, P<0.001), WBC count (0.76±1.53·109/L, P=0.004) and LDL-C (0.34±0.31mmol/L, P<0.001) than the other two groups. Conclusions: Our walking program successfully resulted in a favorable change in lipids and inflammatory markers. Patients in the evening walking group gained more benefits than those walking in the morning walking group. NCT01887093 [ABSTRACT FROM AUTHOR]

Abstract: The prevalence of obesity has steadily increased over the past three decades both in the United States and worldwide. Recent studies have shown the role of dietary polyphenols in the prevention of obesity and obesity-related chronic diseases. Here, we evaluated the impact of commonly consumed polyphenols, including green tea catechins, especially epigallocatechin gallates, resveratrol and curcumin, on obesity and obesity-related inflammation. Cellular studies demonstrated that these dietary polyphenols reduce viability of adipocytes and proliferation of preadipocytes, suppress adipocyte differentiation and triglyceride accumulation, stimulate lipolysis and fatty acid β-oxidation, and reduce inflammation. Concomitantly, the polyphenols modulate signaling pathways including the adenosine-monophosphate-activated protein kinase, peroxisome proliferator activated receptor γ, CCAAT/enhancer binding protein α, peroxisome proliferator activator receptor gamma activator 1-alpha, sirtuin 1, sterol regulatory element binding protein-1c, uncoupling proteins 1 and 2, and nuclear factor-κB that regulate adipogenesis, antioxidant and anti-inflammatory responses. Animal studies strongly suggest that commonly consumed polyphenols described in this review have a pronounced effect on obesity as shown by lower body weight, fat mass and triglycerides through enhancing energy expenditure and fat utilization, and modulating glucose hemostasis. Limited human studies have been conducted in this area and are inconsistent about the antiobesity impact of dietary polyphenols probably due to the various study designs and lengths, variation among subjects (age, gender, ethnicity), chemical forms of the dietary polyphenols used and confounding factors such as other weight-reducing agents. Future randomized controlled trials are warranted to reconcile the discrepancies between preclinical efficacies and inconclusive clinic outcomes of these polyphenols. [Copyright &y& Elsevier]

Highlights: [•] A novel proteoglycan, named FYGL, was isolated from G. lucidum. [•] FYGL, an antidiabetic agent, can protect against functional injuries in the kidneys. [•] FYGL is beneficial against oxidative stress and 8-OHdG expression. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Oral health conditions have a significant relationship with diabetes mellitus (DM) as well as dyslipidemia. In this study, we investigated the levels of apolipoprotein B (apoB) and oxidized low-density lipoprotein (oxLDL) in the gingival crevicular fluid (GCF) from patients with DM. Methods: GCF and blood samples from 18 DM patients and 18 healthy subjects were examined. GCF was collected with paper points without inflicting any harm. The apoB and oxLDL levels were measured by sandwich ELISA assays. Results: The number of teeth with a deep probing pocket depth and the number of teeth with bleeding on probing, two typical periodontal parameters, correlated with the DM parameters, such as hemoglobin A1c. The GCF volume and the concentrations of protein, apoB and oxLDL in GCF were significantly higher in the DM patients than in the healthy subjects. In particular, the apoB concentration in GCF was increased 6-fold in the DM patients. The GCF apoB concentration correlated well with the DM parameters in plasma. Conclusion: GCF could be a clinical source for examining not only the oral status of patients, but also certain systemic conditions. [Copyright &y& Elsevier]

Abstract: Background: OSAS, a frequently neglected, yet frequent comorbidity in T2DM, is associated with obesity, metabolic syndrome and central fat. OSAS is better documented in males, and this study explored novel gender dimorphisms in T2DM. Methods: Cross-sectional study: 815 T2DM (541 males; 274 females) classified into OSAS[−] and OSAS[+] were assessed for cardiometabolic risk factors, glucose homeostasis, micro/macroangiopathies, CV risk, autoimmune thyroid disease (AITD); and GAD65 antibodies. Results: There was a gender dimorphism in glucose control (worse in females), apolipoprotein B100 (higher in females), with apoB100/apoA1 and log(TG)/HDL-C sexually dimorphic. There was also a marked gender dimorphism in GAD65 positivity, higher (+793%) in OSAS[+] females vs. males. There were clear sexual dimorphisms in macro-/microangioathies, regarding stroke, retinopathy and polyneuropathy. OSAS was not sexually dimorphic regarding age; education; and diabetes duration. There was a significant dimorphism in ethnicity. There were no gender-specific dimorphisms related to OSAS in anthropometrics, nor in hypertension, insulin sensitivity, or hyperbolic product loss rate. Conclusion: We report a series of novel OSAS-related sexual dimorphisms, concerning GAD65 auto-antibodies; polyneuropathy; atherogenic dyslipidemia [all increased in females]; diabetic retinopathy; North-Caucasian ethnicity; metabolic control; and TIA/stroke prevalence [all lower in females]. These findings raise challenging questions regarding the reciprocal pathophysiology between obstructive sleep disorders and cardiometabolic risk in T2DM. [Copyright &y& Elsevier]

Abstract: Background and aims: Kiwifruit has the potential to improve markers of metabolic dysfunction, but the response may be influenced by inflammatory state. We aimed to investigate whether inflammatory state would modulate the effect of consuming two green kiwifruit daily on plasma lipids and markers of inflammation. Methods and results: Eighty-five hypercholesterolaemic men completed a 4-week healthy diet run-in, before randomisation to a controlled cross-over study of two 4-week interventions of two green kiwifruit/day plus healthy diet (intervention) or healthy diet alone (control). Anthropometric measures and fasting blood samples (plasma lipids, serum apolipoproteins A1 and B, high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6, tumour necrosis factor-alpha (TNF-α) and IL-10) were taken at baseline, 4 and 8 weeks. Subjects were divided into low and medium inflammatory groups, using pre-intervention hs-CRP concentrations (hs-CRP <1 and 1–3 mg/L, respectively). In the medium inflammatory group the kiwifruit intervention resulted in significant improvements in plasma high-density lipoprotein cholesterol (HDL-C) (mean difference 0.08 [95% CI: 0.03, 0.12] mmol/L [P < 0.001]), total cholesterol (TC)/HDL-C ratio (−0.29 [−0.45, −0.14] mmol/L [P = 0.001]), plasma hs-CRP (−22.1 [−33.6, −4.97]% [P = 0.01]) and IL-6 (−43.7 [−63.0, −14.1]% [P = 0.01]) compared to control treatment. No effects were seen in the low inflammatory group. There were significant between inflammation group differences for TC/HDL-C (P = 0.02), triglyceride (TG)/HDL-C (P = 0.05), and plasma IL-6 (P = 0.04). Conclusions: Inflammatory state modulated responses to the kiwifruit intervention by improving inflammatory markers and lipid profiles in subjects with modestly elevated CRP, suggesting this group may particularly benefit from the regular consumption of green kiwifruit. Registered 16th March 2010, Australian New Zealand Clinical Trials Registry (no. ACTRN12610000213044), www.ANZCTR.org.au. [Copyright &y& Elsevier]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Objective: Bilirubin, a natural product of heme catabolism by heme oxygenase, one of key antioxidant enzymes, has been recognized as a substance with potent antioxidant and cytoprotective properties. Several studies have shown a significant negative relationship between serum bilirubin levels and the risk of metabolic disorders, including type 2 diabetes. However, longitudinal studies investigating the association of elevated serum bilirubin levels and type 2 diabetes are lacking. In the present study, we aimed to investigate the longitudinal effects of baseline serum bilirubin concentrations on the development of type 2 diabetes in healthy Korean men. Materials and Methods: This 4year retrospective longitudinal observational study was conducted at the Asan Medical Center, Seoul, Republic of Korea. The study population consisted of 5960 men without type 2 diabetes who underwent routine health examinations in 2007 (baseline) and 2011 (follow-up). Baseline serum bilirubin concentrations were determined by the vanadate oxidation method. Results: During a 4year period, 409 incident cases of diabetes (6.9 %) were identified. Incident type 2 diabetes decreased across the baseline bilirubin quartile categories (P for trend <0.001). In multivariable-adjusted model, the relative risk (RR) for the development of type 2 diabetes was significantly lower in the highest (i.e., 1.30–2.00mg/dl) than in the lowest bilirubin quartile category (i.e., ≤0.90mg/dl), even after adjustment for confounding variables (RR=0.69, 95% confidence interval 0.48–0.99, P for trend=0.041). Conclusions: The results indicate that serum total bilirubin level may provide additional information for predicting future development of type 2 diabetes in healthy subjects. [Copyright &y& Elsevier]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: The purpose of this study was to test whether high-dose statin treatment would result in a reduction in periodontal inflammation as assessed by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT). Background: Periodontal disease (PD) is an independent risk factor for atherosclerosis. Methods: Eighty-three adults with risk factors or with established atherosclerosis and who were not taking high-dose statins were randomized to atorvastatin 80 mg vs. 10 mg in a multicenter, double-blind trial to evaluate the impact of atorvastatin on arterial inflammation. Subjects were evaluated using FDG-PET/CT at baseline and at 4 and 12 weeks. Arterial and periodontal tracer activity was assessed while blinded to treatment allocation, clinical characteristics, and temporal sequence. Periodontal bone loss (an index of PD severity) was evaluated using contrast-enhanced CT images while blinded to clinical and imaging data. Results: Seventy-one subjects completed the study, and 59 provided periodontal images for analysis. At baseline, areas of severe PD had higher target-to-background ratio (TBR) compared with areas without severe PD (mean TBR: 3.83 [95% confidence interval (CI): 3.36 to 4.30] vs. 3.18 [95% CI: 2.91 to 3.44], p = 0.004). After 12 weeks, there was a significant reduction in periodontal inflammation in patients randomized to atorvastatin 80 mg vs. 10 mg (ΔTBR 80 mg vs. 10 mg group: mean −0.43 [95% CI: −0.83 to −0.02], p = 0.04). Between-group differences were greater in patients with higher periodontal inflammation at baseline (mean −0.74 [95% CI: −1.29 to −0.19], p = 0.01) and in patients with severe bone loss at baseline (−0.61 [95% CI: −1.16 to −0.054], p = 0.03). Furthermore, the changes in periodontal inflammation correlated with changes in carotid inflammation (R = 0.61, p < 0.001). Conclusions: High-dose atorvastatin reduces periodontal inflammation, suggesting a newly recognized effect of statins. Given the concomitant changes observed in periodontal and arterial inflammation, these data raise the possibility that a portion of that beneficial impact of statins on atherosclerosis relate to reductions in extra-arterial inflammation, for example, periodontitis. (Evaluate the Utility of 18FDG-PET as a Tool to Quantify Atherosclerotic Plaque; NCT00703261) [Copyright &y& Elsevier]

Abstract: Background: Although dietary treatments can successfully reduce blood lipids in hypercholesterolemic subjects, individual variation in that response has on occasion been linked to allelic differences. SNP rs12449157 has shown association with HDL-C concentrations in GWAS and falls in the glucose-fructose oxidoreductase domain containing 2 (GFOD2) locus. Of interest, previous data suggest that this SNP may be under environmentally driven selection. Thus, the aim of this study was to assess if rs12449157 may mediate the response of lipid traits to a dietary supplementation (DS) with soy protein and soluble fiber in a Mexican population with hypercholesterolemia. Methods: Forty-one subjects with hypercholesterolemia were given a low saturated fat diet (LSFD) for 1month, followed by a LSFD+DS that included 25g of soy protein and 15g of soluble fiber (S/SF) daily for 2months. Anthropometric, clinical, biochemical and dietary variables were determined. We analyzed the gene–diet interaction between the GFOD2 genotype, with the minor allele frequency of 0.24, and the DS on total cholesterol (TC) and LDL-C concentrations. Results: Hypercholesterolemic subjects with GFOD2 rs12449157 G allele had higher serum TC and LDL-C at the baseline and showed a greater response to the LSCD+S/SF (−83.9 and −57.5mg/dl, respectively) than those with GFOD2 AA genotype (−40.1 and −21.8mg/dl, respectively) (P =0.006 for TC, 0.025 for LDL-C, respectively). Conclusion: The observed differences in allele-driven, diet-induced changes in blood lipids may be the result of a recent environmentally driven selection on the rs12449157 minor allele. Variation in the GFOD2 gene contributes to the genetic basis for a differential response to a cholesterol- or lipid-lowering diet. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: The dried succulent stem of Cistanche tubulosa (Schenk) R. Wight is one component of traditional Chinese medicine prescriptions for diabetes. However, there have been no modern scientific reports to confirm this traditional claim for the Cistanche species until now. Thus, we investigated the effects of Cistanche tubulosa on glucose homeostasis and serum lipids in male BKS.Cg-Dock7 m +/+ Lepr db /J (db/db) mice, a model of type 2 diabetes. Materials and methods: The verbascoside and echinacoside contents of Cistanche tubulosa powder were evaluated using HPLC. The total phenolic content, polysaccharide content and antioxidant activity of Cistanche tubulosa powder were also evaluated. Then, different doses of Cistanche tubulosa (equivalent to 120.9, 72.6 or 24.2mg verbascoside/kg) were administered orally once daily for 45 days to male db/db mice. Age matched db/+ mice were used as normal controls. Body weight, fasting blood glucose, postprandial blood glucose and insulin tolerance test were measured during the experiment. At the time of sacrifice, blood was collected for measurement of insulin level, the homeostatic model assessment of insulin resistance (HOMA-IR), and total cholesterol, triglyceride, HDL-c, LDL-c and VLDL-c levels; liver and muscle were harvested for measurement of glycogen levels. Results: Cistanche tubulosa significantly suppressed the elevated fasting blood glucose and postprandial blood glucose levels, improved insulin resistance and dyslipidemia, and suppressed body weight loss in db/db mice. However, Cistanche tubulosa did not significantly affect serum insulin levels or hepatic and muscle glycogen levels. Conclusion: This study provides scientific evidence for the traditional use of Cistanche tubulosa to treat diabetes, suggesting that Cistanche tubulosa has the potential for development into a functional food ingredient or drug to prevent hyperglycemia and treat hyperlipidemia. [Copyright &y& Elsevier]

Abstract: Inflammation is a major contributor to the development of atherosclerotic plaque, yet the involvement of liver and visceral adipose tissue inflammatory status in atherosclerotic lesion development has yet to be fully elucidated. We hypothesized that an atherogenic diet would increase inflammatory response and lipid accumulation in the liver and gonadal adipose tissue (GAT) and would correlate with systemic inflammation and aortic lesion formation in low-density lipoprotein (LDL) receptor null (LDLr−/−) mice. For 32 weeks, LDLr−/− mice (n = 10/group) were fed either an atherogenic (high saturated fat and cholesterol) or control (low fat and cholesterol) diet. Hepatic and GAT lipid content and expression of inflammatory factors were measured using standard procedures. Compared with the control diet, the atherogenic diet significantly increased hepatic triglyceride and total cholesterol (TC), primarily esterified cholesterol, and GAT triglyceride content. These changes were accompanied by increased expression of acyl-CoA synthetase long-chain family member 5, CD36, ATP-binding cassette, subfamily A, member 1 and scavenger receptor B class 1, and they decreased the expression of cytochrome P450, family 7 and subfamily a, polypeptide 1 in GAT. Aortic TC content was positively associated with hepatic TC, triglyceride, and GAT triglyceride contents as well as plasma interleukin 6 and monocyte chemoattractant protein-1 concentrations. Although when compared with the control diet, the atherogenic diet increased hepatic tumor necrosis factor α production, they were not associated with aortic TC content. These data suggest that the LDLr−/− mice responded to the atherogenic diet by increasing lipid accumulation in the liver and GAT, which may have increased inflammatory response. Aortic TC content was positively associated with systemic inflammation but not hepatic and GAT inflammatory status. [Copyright &y& Elsevier]

Abstract: We hypothesized that dietary monounsaturated fatty acids (MUFA) and exercise increase high-density lipoprotein cholesterol (HDL-C) by independent mechanisms, so there would be additive effects between a single, intensive session of exercise and high-MUFA ground beef on HDL-C and blood risk factors for cardiovascular disease. Seventeen postmenopausal women completed a 2-way crossover design in which they consumed five 114-g ground beef patties per week for two 6-week periods separated by a 4-week washout (habitual diet) period. The ground beef patties contained 21% total fat with either 9.97 (low-MUFA) or 12.72 (high-MUFA) g total MUFA. Blood was taken at entry, at the end of each 6-week diet period, after the 4-week washout period, and 24 hours after aerobic exercise sessions (75% VO2peak, 2.07 MJ). After the ground beef intervention, the high-MUFA ground beef increased plasma palmitoleic acid and oleic acid, low-density lipoprotein (LDL) particle density, HDL-C, and HDL2b-C (all P < .05), whereas the low-MUFA ground beef increased LDL density. After the washout (habitual diet) period, the single exercise session increased serum LDL cholesterol, HDL-C, and HDL2a and decreased TAG and oleic acid. After the low-MUFA ground beef diet, exercise increased LDL size and HDL density and decreased LDL density and very low-density lipoprotein cholesterol, but had no effect on HDL-C fractions. After the high-MUFA ground beef intervention, exercise decreased palmitioleic acid, oleic acid, HDL-C, and HDL2a-C, but not HDL2b-C. Contrary to our hypothesis, the effects of exercise and a high-MUFA diet were not additive; instead, exercise attenuated the effects of the high-MUFA ground beef on HDL-C and plasma MUFAs. The differential effects of high-MUFA ground beef and exercise on HDL2a-C and HDL2b-C indicate that diet and exercise affect HDL-C by different mechanisms. [Copyright &y& Elsevier]

Abstract: Objectives: Waist circumference (WC) is highly associated with metabolic risk factor clusters (RFC) for chronic non-communicable diseases (NCDs). In this study, we evaluated the use of WC measurements to detect hyperglycemia and dyslipidemia in children and adolescents using the WC cutoff points reported in the Bogalusa Heart study and the New Zealand study. Design and methods: Students (n=1011; aged 6 to 14years) were enrolled in a cross-sectional study. Anthropometric indices, fasting glucose, and lipid profiles were measured. The associations between WC measures and serum parameters were investigated by logistic regression models, and the clinical accuracy of the studied parameters was assessed using receiver operating characteristic (ROC) curve analysis. Results: The prevalence of increased WC was 30.2% using the New Zealand cutoff points and 13.7% using the Bogalusa cutoff values. In general, children with increased WC exhibited higher concentrations of total cholesterol, triglycerides, LDL-cholesterol, and non-HDL-cholesterol and lower levels of HDL-cholesterol. The areas under the ROC curves (AUC) of the WC measurements were 0.770 (95% CI: 0.744–0.797) and 0.600 (95% CI: 0.569–0.631) using, respectively, the New Zealand and Bogalusa cutoff points for WC, indicating the prediction of simultaneous hyperglycemia, increased levels of non-HDL-cholesterol, and reduced HDL-cholesterol for students with increased WC. There was a significant difference between AUC values (P =0.001). Furthermore, the sensitivity of using WC for detecting RFC in students was 2.0 to 2.5-fold higher with the New Zealand study cutoff values for WC than with those from the Bogalusa study. Logistic regression analysis revealed that increased WC was associated with simultaneous hyperglycemia and dyslipidemia after controlling for differences in sex and age (P <0.01 for all). Conclusions: Children and adolescents exhibited a high prevalence of increased WC associated with other RFCs for NCDs. Increased WC may be used to screen and identify students with elevated clusters of metabolic risk factors for NCDs. [Copyright &y& Elsevier]

Abstract: Background: Elevation of adiponectin levels is a potential therapeutic tool against cardiovascular and metabolic diseases. Clinical evidence suggests differences between fibrates and statins in improving circulating concentrations of adiponectin. Aim: To compare the efficacy of fibrates vs. statins on circulating concentrations of adiponectin by meta-analysis of randomized head-to-head trials. Methods: A systematic literature search of Medline was conducted to identify randomized head-to-head comparative trials investigating the efficacy of fibrates vs. statins on circulating levels of adiponectin. Inverse variance-weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated for net changes in adiponectin concentrations using a random-effects model. Random-effects meta-regression was performed to assess the effect of putative moderators on adiponectin levels. Results: Six trials with a total of 326 subjects (166 in the fibrate and 160 in the statin group) met the eligibility criteria and were selected for this meta-analysis. The estimated effect size for fibrate versus statin therapy was 0.42μg/mL (95% CI: −0.34–1.17). This effect size was robust in the leave-one-out sensitivity analysis and not sensitive to any single study. Meta-regression indicated a borderline significant association between duration of treatment and the effect of fibrates vs. statins on adiponectin concentrations (slope: −0.20; 95% CI: −0.41–0.01; p =0.06). However, baseline body mass index, glucose and lipid levels did not predict the effect of fibrate vs. statin therapy on circulating adiponectin concentrations (p >0.05). Conclusions: Monotherapy with either fibrates or statins has comparable effects on circulating concentrations of adiponectin. Thus, differential effects of statins and fibrates on the occurrence of cardiovascular events may not be attributed to the corresponding changes in adiponectin levels. [Copyright &y& Elsevier]

Opinion statement: Familial hypercholesterolemia is a genetic disorder of the low-density lipoprotein cholesterol (LDL-c) receptor leading to severe elevations in plasma levels of LDL-c which results in premature atherosclerosis and cardiovascular events. Statins, ezetimibe, and bile acid sequestrants significantly lower LDL-c levels in these patients and subsequently markedly improve survival; however, even with these interventions LDL-c goals often are not met. Several new drug classes are in development and have the potential to make reaching these cholesterol goals easier. In this article we review the most recent trials of several classes of drugs with the potential to change the future of familial hypercholesterolemia management: microsomal triglyceride transfer protein (MTP) inhibitors, apolipoprotein B synthesis inhibitors (mipomersen), cholesterol ester transfer protein (CETP) inhibitors and inhibitors of pro-protein convertase subtilisin/kexin 9 (PCSK9). Each class has shown promise with regard to their effects on the lipid profile. However, the potential side-effects of each drug are also being determined and have limited the development of certain agents. Therefore, the long-term effects of these drug classes, both in terms of side-effects and their effect on clinical outcomes such as cardiovascular events and mortality, continue to be determined. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease. Background: Higher circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA2 inhibitor (varespladib) was stopped prematurely for lack of efficacy. Methods: We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA2-IIA isoenzyme, as an instrumental variable. Results: PLA2G2A rs11573156 C allele associated with lower circulating sPLA2-IIA mass (38% to 44%) and sPLA2 enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA2-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. Conclusions: Reducing sPLA2-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events. [Copyright &y& Elsevier]

Objectives: This study sought to examine patient-level discordance between population percentiles of non–high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Background: Non–HDL-C is an alternative to LDL-C for risk stratification and lipid-lowering therapy. The justification for the present guideline-based non–HDL-C cutpoints of 30 mg/dl higher than the LDL-C cutpoints remains largely untested. Methods: We assigned population percentiles to non–HDL-C and Friedewald-estimated LDL-C values of 1,310,440 U.S. adults with triglyceride levels <400 mg/dl who underwent lipid testing by vertical spin density gradient ultracentrifugation (Atherotech, Birmingham, Alabama) from 2009 to 2011. Results: LDL-C cutpoints of 70, 100, 130, 160, and 190 mg/dl were in the same population percentiles as non–HDL-C values of 93, 125, 157, 190, and 223 mg/dl, respectively. Non–HDL-C values reclassified a significant proportion of patients within or to a higher treatment category compared with Friedewald LDL-C values, especially at LDL-C levels in the treatment range of high-risk patients and at triglyceride levels ≥150 mg/dl. Of patients with LDL-C levels <70 mg/dl, 15% had a non–HDL-C level ≥100 mg/dl (guideline-based cutpoint) and 25% had a non–HDL-C level ≥93 mg/dl (percentile-based cutpoint); if triglyceride levels were 150 to 199 mg/dl concurrently, these values were 22% and 50%, respectively. Conclusions: There is significant patient-level discordance between non–HDL-C and LDL-C percentiles at lower LDL-C and higher triglyceride levels, which has implications for the treatment of high-risk patients. Current non–HDL-C cutpoints for high-risk patients may need to be lowered to match percentiles of LDL-C cutpoints. Relatively small absolute reductions in non–HDL-C cutpoints result in substantial reclassification of patients to higher treatment categories with potential implications for risk assessment and treatment. (The Very Large Database of Lipids [VLDL-2]; NCT01698489) [Copyright &y& Elsevier]

Objectives: This study sought to assess the independent effect of high-density lipoprotein-cholesterol (HDL-C) level on cardiovascular risk in patients with stable ischemic heart disease (SIHD) who were receiving optimal medical therapy (OMT). Background: Although low HDL-C level is a powerful and independent predictor of cardiovascular risk, recent data suggest that this may not apply when low-density lipoprotein-cholesterol (LDL-C) is reduced to optimal levels using intensive statin therapy. Methods: We performed a post-hoc analysis in 2,193 men and women with SIHD from the COURAGE trial. The primary outcome measure was the composite of death from any cause or nonfatal myocardial infarction (MI). The independent association between HDL-C levels measured after 6 months on OMT and the rate of cardiovascular events after 4 years was assessed. Similar analyses were performed separately in subjects with LDL-C levels below 70 mg/dl (1.8 mmol/l). Results: In the overall population, the rate of death/MI was 33% lower in the highest HDL-C quartile as compared with the lowest quartile, with quartile of HDL-C being a significant, independent predictor of death/MI (p = 0.05), but with no interaction for LDL-C category (p = 0.40). Among subjects with LDL-C levels <70 mg/dl, those in the highest quintile of HDL-C had a 65% relative risk reduction in death or MI as compared with the lowest quintile, with HDL-C quintile demonstrating a significant, inverse predictive effect (p = 0.02). Conclusions: In this post-hoc analysis, patients with SIHD continued to experience incremental cardiovascular risk associated with low HDL-C levels despite OMT during long-term follow-up. This relationship persisted and appeared more prominent even when LDL-C was reduced to optimal levels with intensive dyslipidemic therapy. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657) [Copyright &y& Elsevier]

Objectives: The aim of this study was to examine the prescribing patterns of medications quantified by the performance measures for acute myocardial infarction (AMI). Background: Current performance measures for AMI are designed to improve quality by quantifying the use of evidence-based treatments. However, these measures only assess medication prescription. Whether patients receive optimal dosing of secondary prevention medications at the time of and after discharge after AMI is unknown. Methods: We assessed treatment doses of beta-blockers, statins, and angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARBs) at discharge and 12 months after AMI among 6,748 patients from 31 hospitals enrolled in 2 U.S. registries (2003 to 2008). Prescribed doses were categorized as none, low (<50% target [defined from seminal clinical trials]), moderate (50% to 74% target), or goal (≥75% target). Patients with contraindications were excluded from analyses for that medication. Results: Most eligible patients (>87%) were prescribed some dose of each medication at discharge, although only 1 in 3 patients were prescribed these medications at goal doses. Of patients not discharged on goal doses, up-titration during follow-up occurred infrequently (approximately 25% of patients for each medication). At 12 months, goal doses of beta-blockers, statins, and ACEI/ARBs were achieved in only 12%, 26%, and 32% of eligible patients, respectively. After multivariable adjustment, prescription of goal dose at discharge was strongly associated with being at goal dose at follow-up: beta-blockers, adjusted odds ratio (OR): 6.08 (95% confidence interval [CI]: 3.70 to 10.01); statins, adjusted OR: 8.22 (95% CI: 6.20 to 10.90); ACEI/ARBs, adjusted OR: 5.80 (95% CI: 2.56 to 13.16); p < 0.001 for each. Conclusions: Although nearly all patients after an AMI are discharged on appropriate secondary prevention medications, dose increases occur infrequently, and most patients are prescribed doses below those with proven efficacy in clinical trials. Integration of dose intensity into performance measures might help improve the use of optimal medical therapy after AMI. [Copyright &y& Elsevier]

Abstract: Although hormone therapy using estrogens plus progestogens (EPT) is effective for the management of menopausal symptoms (e.g., vasomotor symptoms and vulvar/vaginal atrophy) and prevention/treatment of postmenopausal osteoporosis, EPT is associated with safety and tolerability concerns. A new alternative to EPT is the tissue selective estrogen complex (TSEC), which partners a selective estrogen receptor modulator (SERM) with one or more estrogens and is designed to treat menopausal symptoms and prevent postmenopausal osteoporosis without the tolerability concerns associated with EPT. The first TSEC to reach advanced clinical development is a combination of the SERM bazedoxifene (BZA) with conjugated estrogens (CE). BZA has been shown to inhibit the stimulatory activity of CE on uterine tissue and breast in vitro and in vivo. In clinical studies, BZA/CE treatment has been associated with significant improvements in menopausal symptoms including hot flushes and vulvar/vaginal atrophy and significant increases in bone mineral density, coupled with reductions in bone turnover marker levels and improvements in sleep and health-related quality of life. Additionally, BZA/CE has been shown to have a neutral effect on endometrial and breast tissue because BZA inhibits the stimulatory effects of estrogens in tissue-selective fashion in these 2 organs. Taken together, results of these preclinical and clinical studies indicate that the benefits of estrogens for treating menopausal symptoms are maintained with BZA/CE without endometrial or breast stimulation, resulting in a safe and effective treatment for symptomatic postmenopausal women. [Copyright &y& Elsevier]

Abstract: Statins positively impact plasma low-density lipoprotein cholesterol, inflammation and vascular endothelial function (VEF). Carbohydrate restricted diets (CRD) improve atherogenic dyslipidemia, and similar to statins, have been shown to favorably affect markers of inflammation and VEF. No studies have examined whether a CRD provides additional benefit beyond that achieved by habitual statin use. We hypothesized that a CRD (<50 g carbohydrate/d) for 6 weeks would improve lipid profiles and insulin sensitivity, reduce blood pressure, decrease cellular adhesion and inflammatory biomarkers, and augment VEF (flow-mediated dilation and forearm blood flow) in statin users. Participants (n = 21; 59.3 ± 9.3 y, 29.5 ± 3.0 kg/m2) decreased total caloric intake by approximately 415 kcal at 6 weeks (P < .001). Daily nutrient intakes at baseline (46/36/17% carb/fat/pro) and averaged across the intervention (11/58/28% carb/fat/pro) demonstrated dietary compliance, with carbohydrate intake at baseline nearly 5-fold greater than during the intervention (P < .001). Compared to baseline, both systolic and diastolic blood pressure decreased after 3 and 6 weeks (P < .01). Peak forearm blood flow, but not flow-mediated dilation, increased at week 6 compared to baseline and week 3 (P ≤ .03). Serum triglyceride, insulin, soluble E-Selectin and intracellular adhesion molecule-1 decreased (P < .01) from baseline at week 3, and this effect was maintained at week 6. In conclusion, these findings demonstrate that individuals undergoing statin therapy experience additional improvements in metabolic and vascular health from a 6 weeks CRD as evidenced by increased insulin sensitivity and resistance vessel endothelial function, and decreased blood pressure, triglycerides, and adhesion molecules. [Copyright &y& Elsevier]

Abstract: Objectives: Relaxin-2 has been found to alleviate fibrosis in experimental diabetic cardiomyopathy. In addition, the levels of serum relaxin-3 were increased and correlated with all the component traits of metabolic syndrome. We investigated the levels of plasma relaxin-2 or relaxin-3 and their relationship to component traits in patients with diabetes. Design and methods: We studied 33 newly diagnosed type 2 diabetes patients and 38 age-matched healthy subjects. Blood samples were taken at study entry, and relaxin-3, relaxin-2, fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, serum insulin and hemoglobin A1c (HbA1c) levels were measured. Results: Relaxin-2 levels were significantly lower in patients with diabetes than in controls: the median plasma relaxin-2 concentration was 34.68pg/mL (range, <29.00–50.81pg/mL) in patients with diabetes and 45.80pg/mL (range, <37.42–54.46pg/mL) in controls (p =0.0150). However, no differences in relaxin-3 levels were observed between the diabetes group and controls (p =0.6550). The plasma levels of relaxin-2 or relaxin-3 were not correlated with systolic blood pressure (BP), diastolic BP, total cholesterol, LDL-C, HDL-C, triglyceride, fasting blood glucose, fasting insulin and HbA1c in patients with diabetes. Additionally, there was no correlation between the plasma concentrations of relaxin-2 and relaxin-3 in patients with diabetes (rs =0.225; p =0.208). Conclusions: We conclude that the plasma levels of relaxin-2 in diabetes patients were lower than in controls, however, there are no difference in plasma relaxin-3 concentrations between controls and patients with diabetes. Relaxin-2 or relaxin-3 levels are not related to component traits in patients with diabetes. [Copyright &y& Elsevier]

Abstract: Introduction: Probucol (PB) and cilostazol (CZ) both exhibit anti-atherogenic effects. However, their combinatorial effects are unclear. This study was designed to investigate their combinatorial anti-atherogenic effect in cholesterol-fed rabbits. Materials and Methods: Rabbits were fed a cholesterol diet with PB or CZ alone or both PB and CZ for 16weeks. The plasma levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, C-reactive protein, superoxide dismutase, malondialdehyde, and nitric oxide (NO) were measured. The aortic atherosclerotic lesions were grossly and microscopically evaluated. Additionally, in vitro experiments were conducted using human umbilical vein endothelial cells. Results and Conclusion: We found that the PB group and the PB+CZ group exhibited a reduction in the lesion areas (70% in the PB+CZ group, 56% in the PB group) compared with the vehicle group. However, although PB alone and PB+CZ led to a reduction in the lesion size, the histological analysis revealed that only PB+CZ significantly decreased the macrophage accumulation and smooth muscle cell proliferation in the lesions compared with the vehicle group. The plasma levels of total cholesterol in the PB+CZ group were decreased compared with the vehicle group, Moreover, PB+CZ exerted obvious anti-oxidant and anti-inflammatory effects. Interestingly, the PB+CZ treatment led to a marked increase in the levels of plasma NO. The in vitro experiments showed that the combinatorial treatment up-regulated the levels of NO and protein S-nitrosylation in endothelial cells treated with oxidized LDL. In summary, these results suggest that PB and CZ exert combinatorial anti-atherogenic effects. [Copyright &y& Elsevier]

Abstract: Objective: To explore the relationship between adiponectin and albuminuria in a large group of overweight and obese nondiabetic individuals after controlling for potential confounders. Material and Methods: Detailed anthropometry, computed tomography-measured visceral abdominal adipose tissue, 24-h albuminuria, adiponectin and a series of biochemical parameters were assessed. Four hundred forty patients, predominantly of Caucasian origin, were included (80.2% female). A multiple linear regression model was developed, with albuminuria as the dependent variable and potential predictors as independent variables. Results: The mean age was 40±13years, the mean body mass index was 35.7±6.6kg/m2, and the median visceral abdominal adipose tissue was 142.4 (92.3–194.0)cm2. 10.9% of subjects exhibited microalbuminuria. The median adiponectin level was 9.08 (6.23–12.94)μg/ml, and the median fasting serum glucose level was 83 (77–89)mg/dl. The strongest significant univariate correlations with albuminuria were visceral abdominal adipose tissue (r=0.258, p<0.001), adiponectin (r=−0.265, p<0.001), waist circumference (r=0.250, p<0.001), waist-to-hip ratio (r=0.236, p<0.001) and high-density lipoprotein cholesterol (r=−0.211, p<0.001). The multiple linear regression model revealed a significant positive independent correlation between visceral abdominal adipose tissue and albuminuria (r=0.134, p=0.033), between fasting glucose levels and albuminuria (r=0.390, p=0.029) and between gender and albuminuria (r=0.107, p=0.038). A significant independent negative correlation was identified between adiponectin and albuminuria (r=−0.255, p=0.022). Conclusions: We observed an independent inverse relationship between adiponectin and albuminuria in overweight and obese nondiabetic individuals. Further investigations are needed to confirm this finding and to clarify whether adiponectin is a risk marker or plays a causative role in developing obesity-induced nephropathy. [Copyright &y& Elsevier]

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Objectives: This study sought to examine the relationship between baseline and on-study apolipoproteins (apo) A-1 and B and lipoprotein(a) [Lp(a)] levels and the development of subsequent cardiovascular (CV) events in the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes) trial. Background: Niacin has been reported to lower apoB and Lp(a) and to raise apoA-1. Methods: Individuals with CV disease and low baseline levels of high-density lipoprotein cholesterol were randomized to simvastatin plus placebo or simvastatin, plus extended-release niacin ([ERN], 1,500 to 2,000 mg/day), with ezetimibe added as needed, in both groups, to maintain an on-treatment low-density lipoprotein cholesterol in the range of 40 to 80 mg/dl. Hazard ratios (HRs) were used to evaluate the relationship between levels of apoA-1, apoB, and Lp(a), and CV events in each treatment group. Results: Baseline apoB and the apoB/apoA-I ratio were significantly predictive of CV events only for the placebo group (HR: 1.17 [p = 0.018] and HR: 1.19 [p = 0.016]). Baseline and on-study Lp(a) were predictive of CV events in both simvastatin plus placebo (baseline HR: 1.24 [p = 0.002] and on-study HR: 1.21 [p = 0.017]) and the simvastatin plus ERN group (baseline HR: 1.25 [p = 0.001] and on-study HR: 1.18 [p = 0.028]). The ERN modestly increased 1-year apoA-1 (7%), decreased apoB (13%), decreased the ApoB/ApoA-1 ratio (19%), and decreased Lp(a) 21%, but did not reduce CV events. Conclusions: Lp(a) was associated with increased CV risk in both treatment groups indicating that it contributes to residual CV risk. However, there was no evidence that ERN reduced CV risk, despite favorable lipoprotein changes. [Copyright &y& Elsevier]

Objectives: This study sought to examine the relationship between niacin treatment, lipoproteins, and cardiovascular (CV) outcomes in this secondary analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes) trial. Background: During a 3-year follow-up in 3,414 patients with established CV disease and low high-density lipoprotein cholesterol (HDL-C) levels, combined niacin + low-density lipoprotein cholesterol (LDL-C)–lowering therapy did not reduce CV events compared with LDL-C–lowering therapy alone. Methods: Subjects taking simvastatin and/or ezetimibe were randomized to receive extended-release (ER) niacin 1,500 to 2,000 mg or minimal immediate-release niacin (≤150 mg) as placebo at bedtime. LDL-C levels in both groups were maintained from 40 to 80 mg/dl. Hazard ratios were estimated by using Cox proportional hazards models for relationships between lipoproteins and the composite endpoint of CV death, myocardial infarction, acute coronary syndrome, ischemic stroke, or symptom-driven revascularization. Results: CV outcomes were not associated with ER niacin in any baseline lipoprotein tertile. In a subset of patients in both the highest triglyceride (≥198 mg/dl) and lowest HDL-C (<33 mg/dl) tertiles, ER niacin showed a trend toward benefit (hazard ratio: 0.74, p = 0.073). In-trial LDL-C levels, non–HDL-C levels, and the total cholesterol/HDL-C ratio were positively associated with CV events in the control group, but these relationships were absent in the ER niacin group. Conclusions: Baseline lipoprotein tertiles did not predict differential benefit or harm with ER niacin added to LDL-C–lowering therapy, but a small dyslipidemic subgroup may benefit. ER niacin attenuated expected relationships of lipoprotein risk factors with CV events, raising the possibility that nonlipoprotein actions of niacin could affect risk. (Niacin Plus Statin to Prevent Vascular Events [AIM-HIGH]; NCT00120289) [Copyright &y& Elsevier]

Hypercholesterolemia is a major risk factor for cardiovascular diseases, increasing the incidence of myocardial infarction and death. Statin-induced lowering of low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular morbidity and mortality. However, many individuals treated with statins do not achieve their target levels of LDL-C, and thus, LDL-associated residual risk remains. Gain-of-function mutations of the proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with hypercholesterolemia and increased risk of cardiovascular events. Conversely, loss-of-function mutations are linked to low plasma LDL-C levels and a reduction of cardiovascular risk without known unwanted effects on individual health. Experimental studies have revealed that PCSK9 reduces the hepatic uptake of LDL-C by increasing the endosomal and lysosomal degradation of LDL receptors (LDLR). Low intracellular cholesterol levels in response to statin treatment activate the sterol regulatory element-binding protein-2 (SREBP-2), resulting in coexpression of LDLR and PCSK9. Although this self-regulatory mechanism contributes to maintain cholesterol homeostasis preventing excessive cholesterol uptake, it may limit the therapeutic effect of statins. A number of clinical studies have demonstrated that inhibition of PCSK9 alone and in addition to statins potently reduces serum LDL-C concentrations. Moreover, experimental studies indicate that PCSK9 might accelerate atherosclerosis by promoting inflammation, endothelial dysfunction, and hypertension by mechanisms independent of the LDLR. Further research is needed to characterize the potential therapeutic and to rule out unwanted off-target effects of PCSK9 inhibition. In this review we elucidate the role of PCSK9 in lipid homeostasis, highlight the impact of PCSK9 on atherosclerosis, and summarize current therapeutic strategies targeting PCSK9. [Copyright &y& Elsevier]

Abstract: Background: Farnesyltransferase (FT), an essential enzyme at the downstream of mevalonate pathway, was reported to be upregulated in hypertrophic cardiomyocytes of spontaneously hypertensive rats (SHRs) compared with myocardium of Wistar-Kyoto rats (WKYs). This upregulation was accompanied with cardiac remodeling. This study was designed to determine whether FT inhibition can alter cardiac remodeling in SHRs. Methods: Twelve-week-old SHRs were randomized to receive infusion of either NS or FTI-276 (307μg/kg/d i.v. each n=10). WKY rats served as normal controls (n=6). Echocardiography was performed before and after intervention. SHR hearts were perfused ex vivo for the evaluation of cardiac performance, collagen deposition and biochemical changes (activation of Ras, extracellular-signal regulated kinases/ERK1/2, procollagen type І/Ш, TGF-β1, connective tissue growth factor/CTGF, and bone morphogenetic protein-7/BMP-7 expression). Results: FTI-276 intervention decreased interventricular septum wall thickness at end- diastole (IVSd) and relative wall thickness (RWT) of SHRs (P<0.05). Three week intervention with FTI-276 attenuated hydroxyproline content (P <0.05), collagen deposition (P <0.01), Ras activation, ERK1/2 phosphorylation (P <0.01) and mRNA expression of procollagen type I, TGF-β1 and CTGF and elevated mRNA expression of BMP-7 (P <0.05) in left ventricle of SHRs. Conclusion: The present study indicated that FT inhibition could attenuate myocardial fibrosis and partly improve cardiac remodeling in SHRs. The beneficial effects might be mediated through suppression of the activation of Ras and ERK1/2 phosphorylation pathway. The enhanced mRNA expression of BMP-7 with inhibition of TGF-β1 and CTGF mRNA expression might be an important mechanism. [Copyright &y& Elsevier]

Abstract: Objective: Statin pleiotropy is still an evolving concept, and the lack of clarity on this subject is due at least in part to the lack of a definitive biomarker for statin pleiotropy. Using plasma mRNA analysis as a novel research tool for the non-invasive in vivo assessment of gene expression in vascular beds, we hypothesised that atorvastatin lowers the plasma mRNA level from statin pleiotropy-target genes, and the reduction is independent of the reduction of low-density lipoprotein cholesterol (LDL-C). Design and methods: Forty-four patients with stable angina received atorvastatin therapy (20mg/day, 10weeks). Plasma chemokine (C-C motif) ligand 2 (CCL2) and intercellular adhesion molecule-1 (ICAM1) mRNA levels and their protein concentrations (MCP-1, sICAM-1) were analysed before and after the treatment. Plasma vascular adhesion molecule-1 (sVCAM-1) concentrations were also analysed. Results: Atorvastatin lowered plasma mRNA levels (CCL2: −31.76%, p=0.037; ICAM1: −34.09%, p<0.001) and MCP-1 protein concentration (−18.88%, p=0.008) but did not lower sICAM-1 and sVCAM-1 protein concentrations, and the decreases appeared to be independent from the lowering of LDL-C. The plasma mRNA levels correlated with their protein concentrations following statin treatment only. Conclusion: Our results significantly strengthen the clinical evidence in support of statin pleiotropy. Furthermore, this unique simultaneous measurement of plasma mRNAs and their protein concentrations offers an advanced non-invasive in vivo assessment of the circulation pathology. [Copyright &y& Elsevier]

Objective: Previous studies suggested that decreased serum vaspin levels were associated with coronary artery disease (CAD). The present study aimed to investigate the association between plasma vaspin levels and different states of CAD. Design and methods: A total of 162 patients with coronary angiography (CAG) proved that CAD was enrolled. Additional 103 patients complained with “chest discomfort” with negative CAG, and 60 normal subjects were enrolled in this study. The levels of plasma vaspin, adiponectin, clinical parameters, lipid profile and C reactive protein (CRP) were measured. Results: The levels of plasma vaspin were significantly lower in the CAD group (0.47±0.63μg/L) than those in the healthy group and CAG (−) group (all p<0.001). In CAD group, the pos hoc analysis showed that serum vaspin concentration in acute myocardial infarction group (0.21±0.19μg/L) was significantly lower than that in the unstable angina pectoris group (0.40±0.37μg/L) (p=0.012), and serum vaspin concentration in unstable angina pectoris was significantly lower than that in stable angina pectoris group (0.92±0.94μg/L) (p=0.013). The plasma vaspin concentration was also negatively correlated with the severity of CAD (1-vessel: 0.86±0.90μg/L; 2-vessel: 0.36±0.39μg/L; 3-vessel: 0.21±0.16μg/L). The plasma vaspin concentration in CAG (−) group with “chest discomfort” (1.93±2.57μg/L) was similar to the healthy control group (2.18±3.49μg/L). Conclusions: The plasma vaspin concentration correlated to the severity of CAD. Furthermore, plasma vaspin has a value of avoiding patients without CAD from unnecessary CAG. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) consist of heterogeneous particles whose subpopulations may have different atherogenic characteristics. This study investigated the associations between these subpopulations and other lipids, lipoproteins and atherosclerosis-related markers. Design and methods: A total of 416 subjects (124 males and 292 females, mean age: 50.8years) were enrolled in this study. Using polyacrylamide gel electrophoresis, serum lipoproteins were separated according to their specific electrophoretic mobility based on particle size. The IDL particles were separated into three midbands (MID-A to C), and the LDL particles were separated into seven subfractions (LDL1 to 7). Results: MID-B, MID-C, LDL2 and LDL3 to 6 (as a small LDL fraction) were significantly and positively correlated with very LDL (VLDL), while MID-A and LDL1 were significantly and inversely correlated with VLDL. MID-A and LDL1 were significantly and positively correlated with high-density lipoprotein (HDL). The correlation patterns between MID-A or LDL1 and triglycerides, apolipoprotein A-I, glucose, the insulin resistance index, creatinine and the mean LDL particle size had similar trends to those between HDL and these parameters. Conclusions: The respective subpopulations of IDL and LDL particles can vary in their ability to predict cardiovascular disease risks. These variations may partially explain why quantitative assessments using LDL-cholesterol concentrations, as typically performed in conventional practice, are not perfect predictors of cardiovascular disease. Further studies are required to determine the clinical relevance of analyzing the IDL and LDL subpopulations. [Copyright &y& Elsevier]

Objective: To evaluate endothelial function in children within 5 years after the onset of Kawasaki disease (KD). Study design: A total of 46 children were enrolled prospectively as follows: 9 patients with KD and coronary artery lesions composed group 1, 15 patients with KD but without coronary artery lesions composed group 2, and 22 healthy age- and sex-matched children composed group 3. Flow-mediated dilatation (FMD) of the brachial artery, intima-media thickness of the common carotid artery, and biologic characteristics were compared among the 3 groups. Differences in the factors associated with endothelial function after KD were examined as well. Results: The mean age of the study group was 6.5 ± 1.7 years. The patients with KD were studied at a median interval of 3.3 years (IQR, 2.0-4.4 years) from the onset of disease. The percent FMD (%FMD) was significantly lower in group 1 patients (median, 4.4%; IQR, 2.6%-5.7%) compared with both group 2 (median, 9.1%; IQR 6.6%-10.7%; P < .01) and group 3 (median, 11.1%; IQR, 10.1%-13.9%, P < .01). The %FMD was statistically significantly lower in group 2 compared with group 3 (P < .05). There were no significant differences in the intima-media thickness among the 3 groups. There was a significant negative correlation between %FMD and the total duration of fever (r = −0.50; P = .013). Conclusion: The children with KD already had arterial endothelial dysfunction within 5 years after the onset of illness. The longer the duration of fever, the greater the risk of inflammation-induced endothelial dysfunction. [Copyright &y& Elsevier]

Objectives: The aim of this study was to assess the lipid-altering efficacy and safety of ETC-1002 in subjects with hypercholesterolemia. Background: ETC-1002 is a small molecule that modulates pathways of cholesterol, fatty acid, and carbohydrate metabolism and may have therapeutic benefits in treating hypercholesterolemia and other cardiometabolic risk factors. Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial evaluated patients (n = 177) with elevated low-density lipoprotein cholesterol (LDL-C) (130 to 220 mg/dl), who were stratified by baseline triglycerides (not elevated [<150 mg/dl] or elevated [150–<400 mg/dl]) and randomized to receive 40, 80, or 120 mg of ETC-1002 or placebo once daily for 12 weeks. Outcomes included changes in LDL-C (primary endpoint), other lipids, and cardiometabolic risk factors; and safety. Results: ETC-1002 40, 80, and 120 mg lowered least-squares mean ± SE LDL-C levels by 17.9 ± 2.2%, 25.0 ± 2.1%, and 26.6 ± 2.2%, respectively, versus a reduction of 2.1 ± 2.2% with placebo (all, p < 0.0001); LDL-C lowering was similar between the subgroups with nonelevated and elevated triglycerides. ETC-1002 also lowered non–high-density lipoprotein cholesterol (non–HDL-C), apolipoprotein B, and LDL particle number (all, p < 0.0001) in a dose-dependent manner; HDL-C and triglyceride levels were relatively unchanged. Post-hoc analyses suggest that ETC-1002 may have favorable effects on other cardiometabolic risk factors. The ETC-1002 and placebo groups did not demonstrate clinically meaningful differences in adverse events or other safety assessments. Conclusions: ETC-1002 significantly lowered LDL-C levels up to 27% across a broad range of baseline triglycerides and was generally safe and well tolerated. ETC-1002 has a novel mechanism of action and may be useful for reducing LDL-C. (A Study to Assess the Efficacy and Safety of ETC-1002 in Subjects With Elevated Blood Cholesterol and Either Normal or Elevated Triglycerides; NCT01262638) [ABSTRACT FROM AUTHOR]

Abstract: There is emerging interest in the potential of the phenolic compounds of Asiatic plantain (Plantago asiatica L.) to attenuate in vitro and in vivo oxidative stress. We hypothesized that a single administration of Asiatic plantain beverage may exert protective effects against postprandial oxidative stress. This preliminary study was designed to compare the ability of different doses of Asiatic plantain beverage to mitigate the postprandial effects of a high-fat meal on the oxidation of lipids and DNA in overweight hyperlipidemic subjects. In a randomized, double-blind, placebo-controlled parallel design (n = 10/group), 40 subjects were administered a single high-fat meal with either a placebo or 1 of 3 Asiatic plantain extract beverages (low, intermediate, or high dose). Blood samples were obtained at fasting and 60, 120, 240, and 360 minutes (total of 5 samples) after intervention. The data showed a tendency for plasma free fatty acid levels to decrease in response to high-dose Asiatic plantain at all time points. Plasma oxidized low-density lipoprotein levels were significantly reduced with high-dose Asiatic plantain at 120 minutes (P = .0251 vs placebo). A comet assay revealed that DNA damage in lymphocytes was significantly decreased by Asiatic plantain at 360 minutes (P = .0225 vs placebo). There were no treatment differences in triglyceride or malondialdehyde levels. The maximum suppression was achieved with a high dose (20 g Asiatic plantain extract/80 mL). These results suggest that by protecting low-density lipoprotein and DNA, an Asiatic plantain beverage may be useful to enhance antioxidant. [Copyright &y& Elsevier]

Abstract: Objective: Ankle–brachial index (ABI) screening is recommended for the detection of asymptomatic peripheral arterial disease (PAD) in at-risk populations, including diabetics. A low ABI identifies obstructive lower extremity vascular disease and predicts CVD events and increased mortality. A high ABI represents non-compressible arterial disease (NCAD), and is also associated with increased mortality and vascular events. Our objective is to investigate whether low and high ABI have distinct patterns of association with cardiovascular disease (CVD) risk factors and subclinical atherosclerosis in individuals with type-II diabetes mellitus. Methods: The Penn Diabetes Heart Study (PDHS) is a prospective observational cohort of diabetic individuals without clinically evident CVD. Multivariate logistic and Tobit linear regression were used to compare CVD risk factors and coronary artery (CAC) among 1863 subjects with PAD (ABI ≤ 0.9), NCAD (ABI ≥ 1.4 or non-compressible) or normal ABI (0.91–1.39). Results: Compared to those with normal ABI, PAD was associated with smoking, obesity, and lower HDL-c; while diabetes duration and reduced renal function were associated with NCAD. Both PAD and NCAD were independently associated with increased CAC compared to those with normal ABI, and these relationships were not attenuated in multiply adjusted models. Conclusion: NCAD bears a distinct relationship to traditional CVD risk factors among diabetics, though like PAD is independently associated with increased CAC. These findings support the recognition of NCAD as a high-risk phenotype and provide additional relevance to ABI screening in diabetics. [Copyright &y& Elsevier]

Abstract: Familial hyperlipidemia is an inherited metabolic disorder characterized by elevated lipid and/or lipoprotein levels in the blood. Despite improvements in lipid-lowering therapy during the last decades, it still remains a substantial contributor to the incidence of cardiovascular disease since patients on current conventional therapies do not achieve their target LDL-cholesterol levels. With a view to lower LDL-cholesterol levels, a number of new therapeutic strategies have been developed over recent years. In this review, we provide an overview of these treatment options that are currently in clinical development and may offer alternative or adjunctive therapies for this high-risk population. [Copyright &y& Elsevier]

Abstract: Objective: It is unclear how lipids change in response to lifestyle modification or metformin among postmenopausal glucose intolerant women using and not using hormone therapy (HT). We examined the one-year changes in lipids among postmenopausal, prediabetic women in the Diabetes Prevention Program (DPP), and whether changes were mediated by sex hormones. Materials/Methods: We performed a secondary analysis of a randomized controlled trial of 342 women who used HT at baseline and year 1 and 382 women who did not use HT at either time point. Interventions included intensive lifestyle (ILS) with goals of weight reduction of at least 7% of initial weight and 150minutes per week of moderate intensity exercise, or metformin or placebo administered 850mg up to twice a day. Women were not randomized to HT. Main outcome measures were changes between baseline and study year 1 in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Results: Compared to placebo, both ILS and metformin significantly reduced LDL-C and raised HDL-C among HT users, changes partially explained by change in estradiol and testosterone but independent of changes in waist circumference and 1/fasting insulin. In contrast, DPP interventions had no effect on LDL-C and HDL-C among non-HT users. ILS significantly lowered triglycerides among non-users but did not significantly change triglycerides among HT users. Metformin did not significantly change triglycerides among non-users but increased triglycerides among HT users. Conclusions: The beneficial effects of ILS and metformin on lowering LDL-C and raising HDL-C differ depending upon concurrent HT use. [Copyright &y& Elsevier]

Objectives: The aim of this study was to determine whether baseline and on-statin C-reactive protein (CRP) are independent predictors of cardiovascular (CV) outcome beyond low-density lipoprotein cholesterol (LDL-C). Background: Use of CRP as a predictor of statin treatment remains controversial. Methods: We investigated the relationship of baseline and on-treatment CRP with subsequent CV events in Cox models using a subset of white subjects with no history of CV disease from the UK ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial). Results: During 5.5 years of follow-up, a total of 488 subjects experienced a CV event. CV risk increased with baseline CRP (hazard ratio [HR] per 1 SD: 1.21; 95% confidence interval [CI]: 1.09 to 1.33) in an adjusted model. In ASCOT Lipid-Lowering Arm, the relative statin effect in preventing CV events did not differ according to tertiles of baseline CRP (p = 0.69). After 6 months of atorvastatin therapy, the median LDL-C and CRP were reduced by 38.7% and 25.8%, respectively. Those who achieved LDL-C below the median had a reduced CV risk (HR: 0.58; 95% CI: 0.34 to 0.97) compared with those who did not. In contrast, those who achieved a CRP level below the median did not have a reduced risk of CV events (HR: 0.95; 95% CI: 0.59 to 1.55). Among those who achieved LDL-C below the median, there was no difference in CV risk whether they also achieved a CRP level below (HR: 0.55; 95% CI: 0.30 to 1.02) or above the median (HR: 0.56; 95% CI: 0.30 to 1.03). Conclusions: In these primary prevention patients, although baseline CRP independently predicted CV event risk, the achieved CRP level on while statin therapy did not predict CV events, either alone or in combination with LDL-C. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to compare Friedewald-estimated and directly measured low-density lipoprotein cholesterol (LDL-C) values. Background: LDL-C is routinely estimated by the Friedewald equation to guide treatment; however, compatibility with direct measurement has received relatively little scrutiny, especially at levels <70 mg/dl now targeted in high-risk patients. Methods: We examined 1,340,614 U.S. adults who underwent lipid profiling by vertical spin density gradient ultracentrifugation (Atherotech, Birmingham, Alabama) from 2009 to 2011. Following standard practice, Friedewald LDL-C was not estimated if triglyceride levels were ≥400 mg/dl (n = 30,174), yielding 1,310,440 total patients and 191,333 patients with Friedewald LDL-C <70 mg/dl. Results: Patients were 59 ± 15 years of age and 52% were women. Lipid distributions closely matched those in the National Health and Nutrition Examination Survey. A greater difference in the Friedewald-estimated versus directly measured LDL-C occurred at lower LDL-C and higher triglyceride levels. If the Friedewald-estimated LDL-C was <70 mg/dl, the median directly measured LDL-C was 9.0 mg/dl higher (5th to 95th percentiles, 1.8 to 15.4 mg/dl) when triglyceride levels were 150 to 199 mg/dl and 18.4 mg/dl higher (5th to 95th percentiles, 6.6 to 36.0 mg/dl) when triglyceride levels were 200 to 399 mg/dl. Of patients with a Friedewald-estimated LDL-C <70 mg/dl, 23% had a directly measured LDL-C ≥70 mg/dl (39% if triglyceride levels were concurrently 150 to 199 mg/dl; 59% if triglyceride levels were concurrently 200 to 399 mg/dl). Conclusions: The Friedewald equation tends to underestimate LDL-C most when accuracy is most crucial. Especially if triglyceride levels are ≥150 mg/dl, Friedewald estimation commonly classifies LDL-C as <70 mg/dl despite directly measured levels ≥70 mg/dl, and therefore additional evaluation is warranted in high-risk patients. [Copyright &y& Elsevier]

Objectives: This study sought to determine if simvastatin impairs exercise training adaptations. Background: Statins are commonly prescribed in combination with therapeutic lifestyle changes, including exercise, to reduce cardiovascular disease risk in patients with metabolic syndrome. Statin use has been linked to skeletal muscle myopathy and impaired mitochondrial function, but it is unclear whether statin use alters adaptations to exercise training. Methods: This study examined the effects of simvastatin on changes in cardiorespiratory fitness and skeletal muscle mitochondrial content in response to aerobic exercise training. Sedentary overweight or obese adults with at least 2 metabolic syndrome risk factors (defined according to National Cholesterol Education Panel Adult Treatment Panel III criteria) were randomized to 12 weeks of aerobic exercise training or to exercise in combination with simvastatin (40 mg/day). The primary outcomes were cardiorespiratory fitness and skeletal muscle (vastus lateralis) mitochondrial content (citrate synthase enzyme activity). Results: Thirty-seven participants (exercise plus statins: n = 18; exercise only: n = 19) completed the study. Cardiorespiratory fitness increased by 10% (p < 0.05) in response to exercise training alone, but was blunted by the addition of simvastatin resulting in only a 1.5% increase (p < 0.005 for group by time interaction). Similarly, skeletal muscle citrate synthase activity increased by 13% in the exercise-only group (p < 0.05), but decreased by 4.5% in the simvastatin-plus-exercise group (p < 0.05 for group-by-time interaction). Conclusions: Simvastatin attenuates increases in cardiorespiratory fitness and skeletal muscle mitochondrial content when combined with exercise training in overweight or obese patients at risk of the metabolic syndrome. (Exercise, Statins, and the Metabolic Syndrome; NCT01700530) [Copyright &y& Elsevier]

Abstract: It is hypothesized that healthy dietary and physical activity choices will be inversely associated with coronary heart disease (CHD) risk factors. Results from a cross-sectional study of 294 first-year University of Rhode Island students were used for the analyses. The presence of CHD risk factors was defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines. Diet was assessed by three 24-hour food recalls, and physical activity was assessed by the International Physical Activity Questionnaire. Logistic regression models adjusted for sex estimated the odds of having CHD risk factors. A higher percent of kilocalories from alcohol was associated with a 9.9% increased risk for elevated triacylglycerol (odds ratio [OR], 1.099; 95% confidence interval [CI], 1.000-1.207). Sugar intake (OR, 1.015; 95% CI, 1.004-1.026), saccharin intake (OR, 1.047; 95% CI, 1.015-1.080), and body mass index (BMI; OR, 1.139; 95% CI, 1.037-1.252) were associated with an increased risk of low high-density lipoprotein cholesterol; dietary fiber intake (OR, 0.934; 95% CI, 0.873-1.000) was associated with a decreased risk of low high-density lipoprotein cholesterol. Participants with a higher BMI were 9.4% more likely to have elevated fasting glucose (OR, 1.094; 95% CI, 1.004-1.192) and 193.6% more likely to have a larger waist circumference (OR, 2.936; 95% CI, 1.543-5.586). Dietary factors and BMI are better indicators of CHD risk than physical activity is in this population. [Copyright &y& Elsevier]