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Cholesterol efflux capacities (CECs) are negatively associated with cardiovascular disease risk, irrespective of plasma high-density lipoprotein (HDL) cholesterol levels. Whether interventions targeting lifestyle improve HDL-CECs is unknown. Our objective was to determine whether improving dietary quality and increasing physical activity levels improves HDL-CECs in men with abdominal obesity and dyslipidemia. Our study sample included men (48 ± 8.5 yr) with an elevated waist circumference (≥90 cm) associated with dyslipidemia (triglycerides ≥1.69 and/or HDL cholesterol <1.03 mmol/l); 113 men completed a 1-yr intervention, consisting of a healthy eating and physical activity/exercise program, and 32 were included in a control group. An oral lipid tolerance test (OLTT) was performed in a subsample of 28 men who completed the intervention, and blood was collected every 2 h for 8 h. HDL-CECs were measured using [ 3 H]cholesterol-labeled J774 macrophages and HepG2 hepatocytes. The lifestyle modification program led to an overall improvement in the cardiometabolic risk profile, increases in J774-HDL-CEC by 14.1% (+0.88 ± 1.09%, P < 0.0001), HepG2-HDL-CEC by 3.4% (+0.17 ± 0.75%, P = 0.01), and HDL cholesterol and apolipoprotein A-1 levels (13.5%, P < 0.0001 and 14.9%, P < 0.0001, respectively). J774-HDL-CECs and HepG2-HDL-CECs did not change in the control group. The best predictor for changes in HDL-CEC was apolipoprotein A-1 level. The lifestyle modification program also improved HDL-CEC response in postprandial lipemia during an OLTT. HDL-CEC did not change during the OLTT. Our results suggest that increasing physical activity levels and improving diet quality can have a positive impact on both HDL quantity and quality in men with abdominal obesity and dyslipidemia.

Objective: To assess whether plasma IGFBP-2 is independently associated with components of the lipoprotein-lipid profile and to suggest a cutoff value that could identify subjects with the features of the metabolic syndrome., Methods: In this cross-sectional study, 379 Caucasian men from the general population and covering a wide range of BMI were recruited through the media. Subjects with type 2 diabetes, BMI values > 40 kg/m(2), or taking medication targeting glucose or lipid metabolism or blood pressure were excluded. Anthropometric data were collected and plasma IGFBP-2 concentrations, glucose tolerance and an extensive plasma lipid profile were determined after an overnight fast., Results: Subjects with low IGFBP-2 levels were characterized by increased fat mass (p < 0.0001), impaired insulin sensitivity (p < 0.0001) and higher plasma triglyceride (TG) levels (p < 0.0001). When divided into 6 quantiles, only subjects with the highest IGFBP-2 levels (>221.5 ng/mL) did not meet the NCEP ATP III criteria for the clinical diagnosis of the metabolic syndrome. In addition, circulating IGFBP-2 levels were significantly associated with VLDL-TG (r = -0.51, p < 0.0001) and HDL-C (r = -0.27, p < 0.0001) levels. After adjustments, plasma IGFBP-2 was found to be independently associated with VLDL-TG levels but not with HDL-C concentrations., Conclusions: In our cohort, IGFBP-2 levels <221.5 ng/mL are incrementally associated with a detrimental plasma lipoprotein-lipid profile. After adjustment for covariates, IGFBP-2 remained independently associated with VLDL-TG but not HDL-C levels. This study supports further investigations in other populations and validation of IGFBP-2 as a biomarker of early dyslipidemia., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Cholesterol and triglyceride-rich Western diets are typically associated with an increased occurrence of type 2 diabetes and vascular diseases. This study aimed to assess the relative impact of dietary cholesterol and triglycerides on glucose tolerance, insulin sensitivity, atherosclerotic plaque formation, and endothelial function. C57BL6 wild-type (C57) mice were compared with atherosclerotic LDLr(-/-) ApoB(100/100) (LRKOB100) and atherosclerotic/diabetic IGF-II × LDLr(-/-) ApoB(100/100) (LRKOB100/IGF) mice. Each group was fed either a standard chow diet, a 0.2% cholesterol diet, a high-fat diet (HFD), or a high-fat 0.2% cholesterol diet for 6 mo. The triglyceride-rich HFD increased body weight, glucose intolerance, and insulin resistance but did not alter endothelial function or atherosclerotic plaque formation. Dietary cholesterol, however, increased plaque formation in LRKOB100 and LRKOB100/IGF animals and decreased endothelial function regardless of genotype. However, cholesterol was not associated with an increase of insulin resistance in LRKOB100 and LRKOB100/IGF mice and, unexpectedly, was even found to reduce the insulin-resistant effect of dietary triglycerides in these animals. Our data indicate that dietary triglycerides and cholesterol have distinct metabolic and vascular effects in obese atherogenic mouse models resulting in dissociation between the impairment of glucose homeostasis and the development of atherosclerosis.

Excess visceral adipose tissue (VAT) is associated with an increased cardiometabolic risk. The study examined whether changes in cardiometabolic risk markers after a 1-year lifestyle intervention in viscerally obese men were associated with changes in VAT or with changes in subcutaneous abdominal adipose tissue (SAT). The relative contributions of changes in global adiposity vs. changes in cardiorespiratory fitness to changes in VAT were also quantified. One hundred and forty four men were selected on the basis of an increased waist circumference (≥ 90 cm) associated with dyslipidemia (triglycerides ≥ 1.69 and/or high-density lipoprotein (HDL)-cholesterol <1.03 mmol/l); 117 men completed the 1-year intervention which consisted in a healthy eating, physical activity/exercise program. Body weight, body composition, and fat distribution were assessed by anthropometry and dual-energy X-ray absorptiometry (DEXA)/computed tomography. Cardiorespiratory fitness, plasma adipokine/inflammatory markers, fasting lipoprotein-lipid profile, and oral glucose tolerance test (OGTT) were assessed. VAT volume decreased by 26%, cardiorespiratory fitness improved by 20% (P < 0.0001) after 1 year. Plasma adipokine/inflammatory markers, lipids/lipoproteins, and glucose homeostasis were improved. One-year changes in triglyceride (r = 0.29), apolipoprotein B (r = 0.21), 120-min OGTT-glucose (r = 0.27), and fasting insulin (r = 0.27) levels correlated with changes in VAT (all P < 0.05) after adjustment for changes in SAT. Using a multilinear regression model, VAT reduction was independently associated with SAT reduction and with improvement in cardiorespiratory fitness (R(2) = 0.58, P < 0.0001). Therefore, this healthy eating-physical activity/exercise program improved the cardiometabolic risk profile of viscerally obese men in relation to the reduction of VAT. Furthermore, the reduction in VAT was independently related to the reduction in global adiposity and to the improvement in cardiorespiratory fitness.

The aim of the present study was to compare the ability of the hypertriglyceridemic waist phenotype and the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) clinical criteria to predict coronary artery disease (CAD) risk in a sample of women. We studied 254 women among whom the presence/absence of CAD was assessed by angiography. The hypertriglyceridemic waist phenotype was defined as having both a high waist circumference (≥85 cm) and increased fasting triglyceride levels (≥1.5 mmol/L), whereas the presence of at least 3 of the 5 NCEP-ATP III criteria was used as the "reference" screening approach to identify women with the features of the metabolic syndrome. Women with hypertriglyceridemic waist were characterized by higher adiposity indices as well as by a more disturbed fasting metabolic risk profile compared with women without this phenotype. Similar differences were observed when comparing the metabolic profile of women with vs without at least 3 of the NCEP-ATP III clinical criteria. Moreover, differences in the Framingham risk score were essentially similar when women were considered at low or high risk by either hypertriglyceridemic waist or by NCEP-ATP III clinical criteria (P < .0001). Finally, both clinical phenotypes were predictive of CAD (hypertriglyceridemic waist: relative odds ratio, 2.1; 95% confidence interval, 1.1-3.8; P = .02; NCEP-ATP III clinical criteria: relative odds ratio, 2.5; 95% confidence interval, 1.4-4.6; P < .003). These results suggest that hypertriglyceridemic waist is a simple screening tool to identify women with clustering metabolic abnormalities and at increased CAD risk., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: This study was designed to test the hypothesis that at any low-density lipoprotein cholesterol (LDL-C) level, other lipid parameters such as non-high-density lipoprotein cholesterol (HDL-C) levels, triglyceride (TG) levels, and the total cholesterol (TC)/HDL-C are still associated with an increased coronary heart disease (CHD) risk., Background: Although LDL-C is considered to be the primary target of lipid-lowering therapy, other parameters of the lipoprotein-lipid profile may more closely associated with CHD risk., Methods: In the EPIC (European Prospective Investigation Into Cancer and Nutrition)-Norfolk prospective population study, 21,448 participants without diabetes or CHD between age 45 and 79 years were followed for 11.0 years. A total of 2,086 participants developed CHD during follow-up., Results: Among individuals with low LDL-C levels (<100 mg/dl), after adjustment for age, sex, smoking, systolic blood pressure, waist circumference, physical activity, and hormone replacement therapy (in women), those with non-HDL-C >130 mg/dl had a hazard ratio (HR) for future CHD of 1.84 (95% confidence interval [CI]: 1.12 to 3.04) when compared with those with non-HDL-C levels <130 mg/dl. In a similar model, individuals with TG levels >150 mg/dl had an HR of 1.63 (95% CI: 1.02 to 2.59) when compared with those with TG levels <150 mg/dl, and individuals with a TC/HDL-C ratio >5 had an HR of 2.19 (95% CI: 1.22 to 3.93) when compared with those with a TC/HDL-C ratio <5., Conclusions: In this prospective study, independently of their plasma LDL-C levels, participants with high non-HDL-C levels, high TG levels, or with an elevated TC/HDL-C ratio were at increased CHD risk. CHD risk assessment algorithms as well as lipid targets of lipid-lowering trials may also need to consider other easily available parameters such as non-HDL-C., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The hypertriglyceridemic waist phenotype, the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria, and the International Diabetes Federation (IDF) criteria have been proposed as screening tools to identify subjects with features of the metabolic syndrome and therefore at increased cardiometabolic risk. The aim of the present study was to compare the ability of these 3 clinical approaches to identify individuals at increased cardiometabolic risk as suggested by the presence of deteriorated markers such as hyperinsulinemia, elevated apolipoprotein B levels, small low-density lipoprotein particles, high C-reactive protein concentrations, and low adiponectin levels. For that purpose, physical and cardiometabolic characteristics of a sample of 272 white men recruited for various metabolic investigations were studied. The hypertriglyceridemic waist phenotype was defined as having both a high waist circumference (>or=90 cm) and increased fasting triglyceride levels (>or=2.0 mmol/L). Having at least 3 of the 5 NCEP-ATP III criteria or waist circumference of at least 94 cm plus any 2 of the 4 additional IDF criteria was also used to identify individuals at increased cardiometabolic risk. A large proportion of men with the hypertriglyceridemic waist phenotype also met the NCEP-ATP III (82.7%) or IDF (89.2%) criteria. Men with the hypertriglyceridemic waist phenotype were characterized by alterations in their lipoprotein-lipid profile that included small low-density lipoprotein particles, increased apolipoprotein B and insulin levels, as well as reduced adiponectin concentrations, which were similar to individuals meeting the NCEP-ATP III or the IDF criteria. Moreover, the Framingham risk score of men meeting any of the 3 screening tools criteria was higher and was similar across the 3 approaches (4.2, 3.8, and 3.7, respectively). These results suggest that hypertriglyceridemic waist may be as discriminant as the NCEP-ATP III or the IDF criteria and could be used as an initial screening approach to identify individuals with deteriorated cardiometabolic risk markers.

Background: Rimonabant, the first selective cannabinoid type 1 (CB1) receptor antagonist, improves cardiometabolic risk factors in overweight/obese patients. ADAGIO-Lipids assessed the effect of rimonabant on cardiometabolic risk factors and intraabdominal and liver fat., Methods and Results: 803 abdominally obese patients with atherogenic dyslipidemia (increased triglycerides [TG] or reduced high-density lipoprotein-cholesterol [HDL-C]) were randomized to placebo or rimonabant 20 mg/d for 1 year. HDL-C and TG were coprimary end points. Intraabdominal (visceral) and liver fat were measured by computed tomography in a subgroup of 231 patients. In total, 73% of rimonabant- and 70% of placebo-treated patients completed the study treatment. Rimonabant 20 mg produced significantly greater changes from baseline versus placebo in HDL-C (+7.4%) and TG levels (-18%; P<0.0001), as well as low-density lipoprotein (LDL) and HDL particle sizes, apolipoprotein A1 and B, HDL2, HDL3, C-reactive protein, and adiponectin levels (all P<0.05). Rimonabant decreased abdominal subcutaneous adipose tissue (AT) cross-sectional area by 5.1% compared to placebo (P<0.005), with a greater reduction in visceral AT (-10.1% compared to placebo; P<0.0005), thereby reducing the ratio of visceral/subcutaneous AT (P<0.05). Rimonabant significantly reduced liver fat content (liver/spleen attenuation ratio; P<0.005). Systolic (-3.3 mm Hg) and diastolic (-2.4 mm Hg) blood pressure were significantly reduced with rimonabant versus placebo (P<0.0001). The safety profile of rimonabant was consistent with previous studies; gastrointestinal, nervous system, psychiatric, and general adverse events were more common with rimonabant 20 mg., Conclusions: In abdominally obese patients with atherogenic dyslipidemia, rimonabant 20 mg significantly improved multiple cardiometabolic risk markers and induced significant reductions in both intraabdominal and liver fat.

This study tested the hypothesis that the "hypertriglyceridemic waist" phenotype (waist girth >90 cm [35.4 inches] in men and >85 cm [33.5 inches] in women, along with a plasma triglyceride concentration of >or=2.0 mmol/L [177 mg/dl]) as a covariate of metabolic syndrome features (hyperinsulinemia, hyperapolipoprotein B, and small low-density lipoprotein particles), is predictive of premature coronary artery disease (CAD) among patients with glucose intolerance or type 2 diabetes. Glucose intolerance and type 2 diabetes were assessed after an oral glucose tolerance test among 1,190 men and women using the American Diabetes Association criteria. Glycemic control was evaluated using hemoglobin A1c levels. CAD was considered present on the basis of a clinical history of retrosternal pains on exertion, electrophysiologically and clinically documented myocardial infarction, or angiographic evidence of coronary lesions. More than 53% of men (n = 103) with a waist circumference >or=90 cm (35.4 inches) and nearly 80% of women (n = 122) with a waist circumference >or=85 cm (33.5 in.) with triglyceride levels >or=2 mmol/L (177 mg/dl) were diagnosed with glucose intolerance or type 2 diabetes. Survival models revealed that those with glucose intolerance or type 2 diabetes with the "hypertriglyceridemic waist" phenotype experienced their first CAD symptoms 5 years earlier than those without this phenotype. This elevated and earlier risk of CAD was statistically significant (hazard ratio 2.0, 95% confidence interval 1.2 to 3.7, p = 0.02). In conclusion, the "hypertriglyceridemic waist" phenotype, an inexpensive and simple tool identifying subjects with metabolic syndrome features, is a significant marker of CAD manifestations occurring at an earlier age in those with glucose intolerance or type 2 diabetes.

To determine whether a common quantitative trait locus (QTL) influences the variation of fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels, we used a bivariate multipoint linkage analysis with 654 polymorphic markers in 99 white and 101 black families. The phenotypes were investigated under two conditions: at baseline and after a 20-week exercise training intervention. A maximum genome-wide bivariate LOD score of 3.0 (p = 0.00010) was found on chromosome 12q23-q24, located within the IGF1 gene (insulin-like growth factor 1, at 107 cM) for TG and HDL-C at baseline in whites. This bivariate linkage peak is considerably higher than the univariate linkage results at the same chromosome location for either trait (for TG, LOD = 2.07, p = 0.00108; for HDL-C, LOD = 2.04, p = 0.00101). The genetic correlations between baseline TG and HDL-C levels were -0.14 for the residual and -0.33 for the QTL components. Moreover, association analysis showed that TG, HDL-C, and IGF1 are significantly associated (p = 0.04). In conclusion, these results suggest that a QTL on chromosome 12q23-q24 influences the variation of plasma TG and HDL-C levels. Further investigation should confirm whether IGF1 or another nearby gene is responsible for the concomitant variation in TG and HDL-C levels.

Fasting triglyceride (TG) levels in total plasma and in lipoprotein subfractions were assessed both at baseline and after a 20-week exercise training intervention in 99 White and 101 Black families. A genome-wide multipoint variance component linkage analysis was performed separately by race, using 509 markers. The strongest evidence of linkage was for the TG subfractions of low-density lipoprotein (LDL-TG) and high-density lipoprotein (HDL-TG) rather than for overall levels of TG. For baseline levels, the maximum LOD score was 3.8 on 13q12-q14 with HDL-TG in Whites. Additional linkage evidence was found on 14q31 (LOD=3.2) and 10p14 (LOD=2.9) for baseline LDL-TG in Whites. Suggestive linkage signal at baseline in Whites was detected for HDL-TG (LOD=2.6) on 12q24 and for LDL-TG on 19p13. For training response in Whites, suggestive signal (LOD=2.2) was observed on 13q12-q14 with LDL-TG and for HDL-TG on 10q23. For Blacks, weak signals (LODs<2.0) were found either for baseline and responses to training, perhaps due to small sample sizes that reduced the power of the linkage analysis. These results represent the first report of linkage for the lipoprotein subfractions and for the lipid and lipoprotein responses to exercise training. It is interesting that the strongest signals were found for the LDL-TG and HDL-TG subfractions, given their particular relationships with the atherogenic lipid profile including dense LDL and HDL particles.

Purpose: This study explores sex and race differences in the association between changes in fat mass (FM), abdominal visceral fat (AVF), and abdominal subcutaneous fat (ASF) on blood lipid changes consequent to aerobic exercise training., Methods: The sample included 613 participants (428 white and 185 black, 46% men) from the HERITAGE Family Study. Total FM was determined by densitometry, whereas AVF and ASF cross-sectional areas were determined by computed tomography at the L4-L5 level. Blood lipid measurements included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and the TC/HDL-C ratio, which were obtained before and after 20 wk of supervised aerobic exercise. Canonical correlation was used to determine the multivariate associations between body fatness and blood lipids at baseline and the changes induced by exercise training., Results: Body fat accounted for 26-36% of the variance in baseline blood lipids, and changes in body fat accounted for 7-21% of the variance in changes in blood lipids with exercise training. The pattern of loadings indicated similar relationships between body fatness and blood lipids at baseline, and their respective changes with exercise training among the four sex-by-race groups. Greater fat loss, characterized by loss of FM, AVF, and ASF, was associated with a greater blood lipid response characterized by an increase in HDL-C and decreases in LDL-C, TG, TC, and TC/HDL-C. Although the pattern of loadings was similar in all groups, the strength of the association was stronger in blacks than in whites., Conclusion: The multivariate associations among fat loss and changes in blood lipids consequent to aerobic exercise training are similar in black and white men and women.

Many factors are involved in the development of the insulin resistance syndrome, such as visceral obesity and the type of dietary fat. The main purpose of this study was to investigate the relationships between fatty acid content of triglyceride (TG), visceral adipose tissue (AT) accumulation, and metabolic components of the insulin resistance syndrome in a group of 97 Caucasian men with a mean age of 45.1 +/- 7.2 years (29 to 63 years). To reach these objectives, Spearman correlations, group comparisons, and stepwise multiple regression analyses were performed. The proportion of palmitic acid (16:0) in the TG fraction was positively associated with plasma fasting insulin (r =.25, P =.03), diastolic (r =.45, P <.001), and systolic (r =.29, P =.003) blood pressure. On the other hand, the proportion of alpha-linolenic acid (18:3n-3) was associated negatively with apolipoprotein (apo) B (r = -.29, P =.005) and positively with low-density lipoprotein (LDL) diameter (r =.29, P =.007), while the proportion of gamma-linolenic acid (18:3n-6) was associated negatively with plasma TG (r = -.33, P =.003), diastolic (r = -.29, P =.01), and systolic (r = -.35, P =.002) blood pressure and plasma fasting insulin (r = -.37, P =.0005) and positively with high-density lipoprotein (HDL)(2)-cholesterol (r =.27, P =.01) and LDL diameter (r =.25, P =.02). Stepwise multiple regression analyses were conducted to determine the contribution of visceral AT, body fat mass, and the fatty acid content of TG to the variance of metabolic variables studied. It was found that visceral AT contributed significantly to the variance in plasma TG (R(2) = 20.7%, P <.0001), apo B (R(2) = 9.0%, P =.007), HDL(2)-cholesterol (R(2) = 17.9%, P <.0001), LDL diameter (R(2) = 4.9%, P =.02), and area under the glucose curve (AUC-glucose) (R(2) = 8.2%, P =.006). On the other hand, body fat mass contributed significantly to the variance in fasting insulin (R(2) = 19.7%, P <.0001) and diastolic (R(2) = 6.8%, P =.007) and systolic (R(2) = 10.5%, P =.01) blood pressure. At least one fatty acid made a significant contribution to the variance of each metabolic variable studied. In fact, the proportion of 18:3n-6 contributed significantly to the variance in both TG (R(2) = 8.9%, P = 0.007) and HDL(2)-cholesterol (R(2) = 6.0%, P =.01). Moreover, 18:3n-3 contributed to the variance of apo B (R(2) = 7.0%, P =.02), while 18:3n-6 made the largest contribution to the variance of LDL diameter (R(2) = 7.6%, P =.02). Finally, 16:0 significantly contributed to the variance of AUC-glucose (R(2) = 11.4%, P =.0003), diastolic (R(2) = 25.2%, P <.0001), and systolic (R(2) = 6.8%, P =.002) blood pressure. In summary, results of this study suggest that the fatty acid content of TG is associated with many metabolic variables of the insulin resistance syndrome independently of body fat mass or visceral AT accumulation.

Fasting hypertriglyceridemia has been reported to be predictive of an exaggerated triglyceride (TG) response to an oral fat load. Abdominal obesity has also been associated with postprandial hyperlipidemia. The objective of the present study was to quantify the contribution of abdominal obesity and fasting hypertriglyceridemia to the magnitude of postprandial lipemia. For that purpose, potential differences in postprandial TG-rich lipoprotein (TRL) levels were examined among men characterized by the absence/presence of the "hypertriglyceridemic waist" phenotype following a standardized breakfast with a high fat content (64% calories as fat). Sixty-nine men (mean age +/- S.D.: 45.1 +/- 10.5 years) were classified according to waist girth (< 90 or >/ or = 90 cm) and fasting TG concentrations (< 2.0 or > or = 2.0 mmol/l). Subjects characterized by "hypertriglyceridemic waist" (waist > or = 90 cm and fasting TG > or = 2.0 mmol/l) showed the highest TRL-TG concentrations (P < 0.0001) throughout the entire postprandial period (8 h) as well as elevated concentrations of apolipoprotein (apo) B-48 and apo B-100 in all TRL fractions (large, medium and small) compared to subjects with low fasting TG levels who had waist girth values either above or below 90 cm. These higher postprandial TRL-TG levels among carriers of the "hypertriglyceridemic waist" phenotype also led to significantly greater postprandial TG-total area under the curve (AUC) in total TRLs resulting mainly from the increased concentrations of large- and medium-sized TRLs. Furthermore, subjects characterized by the "hypertriglyceridemic waist" phenotype displayed higher fasting insulin concentrations and postprandial insulin AUC compared to men with low fasting plasma TG levels and low waist girth values. In conclusion, results of the present study indicate that postprandial hyperlipidemia is associated with the simultaneous presence of abdominal obesity and elevated fasting TG concentrations: a condition that we have described as the "hypertriglyceridemic waist" phenotype., (Copyright 2003 Elsevier Ireland Ltd.)

The fasting atherogenic dyslipidemia of visceral obesity, which includes the presence of small, dense low-density lipoprotein (LDL) particles, is predictive of an increased risk of coronary heart disease (CHD). It has also been suggested that progression of atherosclerosis may be accelerated in the presence of postprandial hyperlipidemia independently from the fasting dyslipidemic state. Studies have shown that the best predictor of postprandial hyperlipidemia and of the small, dense LDL phenotype is fasting triglyceride (TG) concentration. In the present study, we evaluated the impact of postprandial hypertriglyceridemia on the variation in LDL particle size. Fasting (0 hour) and postprandial changes (2, 4, 6, and 8 hours) in LDL particle size were measured by nondenaturing 2% to 16% polyacrylamide gel electrophoresis in a sample of 49 men (mean age +/- SD: 46.6 +/- 9.2 years) who underwent a standardized breakfast with a high-fat (64% calories as fat) content. The postprandial increase in TG levels was associated with a transient reduction in LDL particle size, the most substantial reduction being observed 4 hours (-1.0 +/- 2.4 A) after the oral fat load. Although there were strong correlations between TG-rich lipoprotein (TRL)-TG levels and LDL particle size in the fasting state (r=-0.71, P<.0001) as well as 4 hours after the oral fat load (r=-0.70, P<.0001), changes in TRL-TG concentrations during the postprandial state (from time 0 to 4 hours) were not associated with changes in LDL particle size during this period (r=-0.04, not significant [NS]). However, among subgroups of men matched for similar fasting TRL-TG levels (n=12), subjects with the highest total area under the curve (AUC) of TRL-TG after the fat load were characterized by smaller LDL particle size at 6 and 8 hours compared with men with the lowest AUC TRL-TG (P<.02). Men displaying the highest postprandial AUC TRL-TG were also characterized by the greatest accumulation of visceral adipose tissue (AT) (P<.05). These results indicate that the hypertriglyceridemic (hyperTG) state induced by a high-fat meal is associated with a transient reduction in LDL peak particle diameter, which is not proportionate, however, to the level of TG achieved in the postprandial state. Furthermore, despite similar TG levels at baseline, viscerally obese men with an impaired postprandial lipemia had smaller LDL particles at the end of the oral fat load than obese men with a lower accumulation of visceral AT.

Background: Apolipoprotein (apo) CIII plays an important role in the catabolism of triglyceride-rich lipoproteins as it is a potent inhibitor of lipoprotein lipase (LPL). A low LPL activity has been simultaneously associated with hypertriglyceridemia, low HDL cholesterol and with small LDL particles., Aim: To compare the effects of a 12-week treatment with micronized fenofibrate (200 mg) versus atorvastatin (10 mg) on apo CIII and lipoprotein-lipid levels including LDL size., Method: After a 4-week washout period, dyslipidemic patients were randomized to either micronized fenofibrate (n = 64) or atorvastatin (n = 72)., Results: Both fenofibrate and atorvastatin significantly decreased apo CIII levels by -0.03 +/- 0.03 versus -0.01 +/- 0.03 g/l respectively, and increased LDL size by 4.9 +/- 3.3 versus 1.8 +/- 2.9 A. Improvements in these parameters were significantly greater with fenofibrate (P < 0.0001). Significant relationships were found between changes in triglycerides and changes in apo CIII (r = 0.81 and r = 0.59, P < 0.0001) as well as between changes in LDL size and changes in apo CIII (r = -0.41 and r = -0.45, P < 0.001), in both fenofibrate and atorvastatin groups. respectively., Conclusion: The substantial reduction in apo CIII induced by micronized fenofibrate plays an important role in the greater effect of micronized fenofibrate than atorvastatin on plasma triglycerides and LDL size.

High overall nutritional quality (NQ) is an important component of ideal cardiovascular health, a concept introduced in 2010 by the American Heart Association. However, data on the independent contribution of overall NQ to the variation in the cardiometabolic risk (CMR) profile are limited. This observational study aimed to investigate the association between overall NQ and the CMR profile in 4785 participants (65⋅4 % of men, age 43⋅3 (sd 10⋅8) years) who underwent a cardiometabolic health evaluation, including lifestyle habits, anthropometric measurements, blood pressure, lipid profile and HbA1c concentrations. In addition, a submaximal exercise test was conducted to assess cardiorespiratory fitness (CRF). Using a standardised NQ questionnaire (twenty-five items food-based questionnaire), participants were classified into three subgroups: (1) low, (2) moderate or (3) high NQ and variance and multiple linear regression analyses were performed. Results showed that less than 15 % of participants presented a high NQ. A high NQ was associated with a healthier lifestyle habits and a more favourable CMR profile (lower values of waist circumference and cholesterol:HDL-cholesterol ratio, lower concentrations of non-HDL-cholesterol, TAG and HbA1c). Some of these associations were independent of age, physical activity level (PAL) and CRF. A better NQ was also associated with a lower proportion of participants presenting the hypertriacylglycerolaemic waist phenotype independently of both PAL and CRF. The present study suggests that overall NQ can be assessed with a short food-based questionnaire and should be considered in clinical practice as a new 'vital sign' associated with other health behaviours and cardiometabolic health. [ABSTRACT FROM AUTHOR]

Background Patients with coronary artery disease (CAD) are characterized by an impaired cardiometabolic risk profile including high levels of atherogenic apolipoprotein (apo) B-containing lipoprotein levels. Genetic studies have highlighted a critical role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipoprotein metabolism and CAD risk. Objective To determine whether improving dietary quality and increasing physical activity levels improve parameters of the cardiometabolic risk profile such as plasma apoB and PCSK9 levels in patients with CAD. Methods We recruited 86 men aged between 39 and 80 years (82 of them on statins) undergoing coronary artery bypass graft (CABG) surgery. These patients participated in a 1-year lifestyle modification program aiming at achieving a minimum of 150 minutes/week of physical activity and improving diet quality by following dietary guidelines. We used magnetic resonance imaging to measure visceral adipose tissue and a modified Bruce protocol to measure fitness levels before and after the intervention. Results Plasma apoB and low-density lipoprotein cholesterol levels were not modified by the intervention (−3.0%, P = .08 and 1.3%, P = .56, respectively), whereas non-HDL cholesterol decreased by 4.5% ( P = .04) and triglycerides by 13% ( P = .002). In contrast, PCSK9 levels increased by 5.2% after the intervention ( P = .05). HDL cholesterol and apolipoprotein A-I levels also increased (+12%, P < .0001 and + 6%, P < .0001, respectively). PCSK9 levels increased with improvements in fitness ( r = 0.23, P = .04) and visceral fat mobilization ( r = −0.23, P = .04). Conclusion In post-CABG patients, a lifestyle modification program lead to significant improvements in some parameters of the lipoprotein profile but unexpectedly increased plasma PCSK9 levels. [ABSTRACT FROM AUTHOR]

With regard to the beneficial impact of lifestyle interventions on weight and abdominal obesity management, our objective was to identify which components of a lifestyle-intervention program [physical activity (PA), energy and macronutrient intake, diet quality] had an influence on visceral adipose tissue (VAT) loss. The present lifestyle intervention targeted a daily energy deficit (500 kcal), coupled with a PA program (160 min/wk). From the 144 participants initially recruited, 93 viscerally obese men (age: 49 ± 1 y; waist circumference: 108 ± 9 cm; plasma triglyceride concentration: 2.46 ± 0.09 mmol/L) who completed a 3-d dietary journal both at baseline and after 1 y of intervention and a daily PA journal for 1 y were considered in the present analyses. Body composition and fat distribution were assessed by using dual-energy X-ray absorptiometry and computed tomography. After 1 y, abdominally obese men significantly improved their diet quality, as assessed by the Dietary Approaches to Stop Hypertension (DASH)-derived diet quality (DQ) score (P < 0.0001). Improved DQ and higher levels of PA were both independently and significantly associated with reductions in body weight, fat mass, VAT, and thigh muscle fat content, beyond reported energy intake or diet macronutrient composition. When stratified according to the level of PA and DQ [PA- (low PA), DQ- (low DQ), PA+ (high PA), DQ+ (high DQ)], the PA+/DQ+ group showed reductions in VAT that were 20% greater than in the PA-/DQ+ group, 28% greater than in the PA+/DQ- group, and 50% (P < 0.05) greater than in the PA-/DQ- group. Our results highlight the strong contribution of DQ beyond macronutrient and energy content to changes in body composition and suggest that synergistic changes in both DQ and PA levels optimally reduce VAT in men with features of metabolic syndrome. [ABSTRACT FROM AUTHOR]

The global prevalence of obesity is increasing at a rapid pace and is likely to have an impact on the prevalence of Type 2 diabetes and cardiovascular disease (CVD). Identifying individuals carrying a high-risk obesity phenotype, such as those patients with an accumulation of visceral or intra-abdominal fat, goes beyond the assessment of the BMI and even waist circumference. An increasing amount of population-based studies have shown that the hypertriglyceridemic waist phenotype (the combination of an elevated waist girth and triglyceride levels) could identify individuals with increased amounts of visceral fat that are characterized by a concomitant deteriorated cardiometabolic risk profile and prospectively, with an increased risk of developing both Type 2 diabetes and CVD. Our objective is to review the evidence on the relationship between the hypertriglyceridemic waist phenotype and the risk of CVD and Type 2 diabetes as well as to discuss how to identify and manage individuals who have this high-risk obesity phenotype. [ABSTRACT FROM AUTHOR]

Obesity is the most common cause of secondary hyperlipidemia. Atherogenic dyslipidemia refers to elevated triglycerides, low HDL-cholesterol and small dense LDL associated with visceral obesity and metabolic syndrome. Obesity may also be associated with isolated low HDL-cholesterol or high triglycerides and postprandial hyperlipidemia. While some obese patients have high LDL cholesterol concentrations, obesity has a more pronounced effect on other atherogenic lipids and lipoproteins. Obesity may aggravate familial lipid disorders. Lipid disorders in obesity are responsive to weight loss, pharmacotherapy and weight loss surgery. Statins are the lipid-lowering drug of choice, together with lifestyle change. Hard clinical end point data to support combinations of statins with other drugs is lacking. After weight loss surgery, the absolute risk of cardiovascular disease should be reassessed, but tools to facilitate risk assessment need to be developed. [ABSTRACT FROM AUTHOR]

Background: Screening for increased waist circumference and hypertriglyceridemia (the hypertriglyceridemic-waist phenotype) has been proposed as an inexpensive approach to identify patients with excess intra-abdominal adiposity and associated metabolic abnormalities. We examined the relationship between the hypertriglyceridemic-waist phenotype to the risk of coronary artery disease in apparently healthy individuals. Methods: A total of 21 787 participants aged 45-79 years were followed for a mean of 9.8 (standard deviation 1.7) years. Coronary artery disease developed in 2109 of them during follow-up. The hypertriglyceridemic-waist phenotype was defined as a waist circumference of 90 cm or more and a triglyceride level of 2.0 mmol/L or more in men, and a waist circumference of 85 cm or more and a triglyceride level of 1.5 mmol/L or more in women. Results: Compared with participants who had a waist circumference and triglyceride level below the threshold, those with the hypertriglyceridemic-waist phenotype had higher blood pressure indices, higher levels of apolipoprotein B and C-reactive protein, lower levels of high-density lipoprotein cholesterol and apolipoprotein A-I, and smaller low-density lipoprotein particles. Among men, those with the hypertriglyceridemic- waist phenotype had an unadjusted hazard ratio for future coronary artery disease of 2.40 (95% confidence interval [CI] 2.02-2.87) compared with men who did not have the phenotype. Women with the phenotype had an unadjusted hazard ratio of 3.84 (95% CI 3.20-4.62) compared with women who did not have the phenotype. Interpretation: Among participants from a European cohort representative of a contemporary Western population, the hypertriglyceridemic- waist phenotype was associated with a deteriorated cardiometabolic risk profile and an increased risk for coronary artery disease. [ABSTRACT FROM AUTHOR]

Microsomal triglyceride transfer protein (MTP) plays a critical role in the assembly of lipoproteins. The aim of this study was first to seek new MTP gene variants and then to verify whether MTP gene polymorphisms were associated with plasma lipoprotein/lipid levels in men with visceral obesity. Molecular screening of the MTP gene revealed 11 polymorphisms. The carriers of the c.933A allele and c.1151C allele or -400A/A homozygotes were characterized by increased levels of abdominal visceral adipose tissue (AT) measured by computed tomography (P=0.02,P=0.04,P=0.03, respectively). After dividing each genotype group into subgroups using 130 cm2 as a cutoff point for visceral AT, significantly higher low-density lipoprotein (LDL)-apolipoprotein B (apoB) concentrations were found in obese men bearing the c.891G allele, the -400 T allele, as well as for 282G/G homozygotes, 933C/C homozygotes, and 1151A/A homozygotes when compared to their lean counterparts. Haplotypes were not associated with phenotypes under study. In conclusion, some MTP gene polymorphisms in the French Canadian population are associated with the amount of abdominal visceral AT and plasma LDL-apoB concentrations. [ABSTRACT FROM AUTHOR]

We compared the effects of ad libitum consumption of a defined high complex carbohydrate (CHO) diet (% of energy: CHO, 58.3; fat, 25.8) vs. a defined high monounsaturated fatty acid (MUFA) diet (% of energy: CHO, 44.7; fat, 40.1; MUFA, 22.5) on LDL electrophoretic characteristics. Healthy men [n = 65; age, 37.5 +/- 11.2 (mean +/- SD) y; BMI, 29.2 +/- 4.9 kg/m2] were randomly assigned to one of the two diets that they consumed for 6-7 wk. The high CHO diet significantly reduced body weight (-2%). The diet-induced reduction in plasma LDL cholesterol (C) levels in the high-CHO diet group was due mainly to concurrent reductions in the cholesterol content of small (<25.5 nm, P < 0.01) and medium-sized LDL (25.5-26.0 nm, P = 0.01). The high MUFA diet also reduced body weight, and LDL-C and LDL-apolipoprotein (apo)B levels, which were comparable to those in the high CHO group. The cholesterol levels of small LDL particles tended to be reduced (P = 0.24) in the high MUFA group (-12%), similar to changes in the high CHO group. These results suggest that, when associated with weight loss, ad libitum consumption of high CHO and high MUFA diets may be considered to be equally beneficial for the management of LDL-related atherogenic dyslipidemia. However, the high MUFA diet more favorably affected triglyceride levels, suggesting that it may be preferable to a high CHO diet in cardiovascular disease prevention. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Purpose: Low-attenuation muscle (LAM) area at mid-thigh, a computed tomography (CT)–derived index of intramuscular lipids, is associated with insulin resistance, obesity, and type 2 diabetes. The present study aimed at testing the hypothesis that changes in LAM area in trunk muscles from a single abdominal scan could provide relevant information to evaluate the effects of a lifestyle intervention without the use of a mid-thigh CT scan. Methods: Cardiometabolic risk variables, including waist circumference, lipoprotein–lipid profile, glucose tolerance, and cardiorespiratory fitness, were assessed in a sample of 102 dyslipidemic viscerally obese men at baseline and after a 1-yr lifestyle intervention. Abdominal (L4–L5) and mid-thigh CT scans were performed and abdominal muscles classified as psoas and core muscles. Scans were segmented to calculate muscle areas, LAM areas, and mean attenuation values. Results: All muscle groups showed a decrease in LAM areas (P < 0.0001) in response to the lifestyle intervention. Changes in LAM areas were significantly associated with changes in triglycerides, high-density lipoprotein (HDL) cholesterol, cholesterol/HDL cholesterol ratio and log triglycerides/HDL cholesterol ratio (mid-thigh, 0.20 ≤ | r | ≤ 0.29; psoas, 0.28 ≤ | r | ≤ 0.38; core, 0.29 ≤ | r | ≤ 0.34, P < 0.05). Changes in core LAM area were significantly associated with changes in 2-h glucose levels, glucose area measured during the oral glucose tolerance test and homeostasis model assessment of insulin resistance (0.21 ≤ r ≤ 0.34, P < 0.05). Stepwise regression analyses showed that changes in LAM psoas area were associated with changes in HDL cholesterol and the cholesterol/HDL cholesterol ratio independently from changes in visceral adiposity. Conclusions: Changes in trunk LAM areas are useful indices of changes in mid-thigh LAM area observed with a 1-yr lifestyle intervention. Thus, an additional mid-thigh scan is not necessary to evaluate muscle lipid content by CT when an abdominal CT scan is available. [ABSTRACT FROM AUTHOR]

Abstract: Background: The association of metabolic syndrome and risk of CHD is now well established. The association between ‘metabolic dyslipidemia’ as defined by high triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels and the risk of coronary heart disease (CHD) risk is not known. The aim of this study was to investigate the association between metabolic dyslipidemia, and risk of coronary heart disease (CHD) in apparently healthy men and women. Methods: Metabolic dyslipidemia was defined by combination of increased triglyceride (TG) levels (≥150 mg/dl) and low high-density lipoprotein cholesterol (HDL-C) levels (≤50 mg/dl for women and ≤40 mg/dl for men). In the EPIC-Norfolk prospective population study, 21,340 participants without diabetes (9326 men and 12,014 women) were followed for a mean of 11.4 years during which 2075 CHD events occurred. Three multivariate models were used adjusting for other metabolic risk factors including low-density lipoprotein cholesterol (LDL-C). Results: Compared to men with normal HDL and normal TG, men with metabolic dyslipidemia had an increased risk for CHD (HR 1.61, 95% CI 1.40–1.86). The increased risk remained significant after adjustment for LDL-C and other metabolic risk factors. Among women, metabolic dyslipidemia was associated with increased CHD risk (HR 1.78, 95% CI 1.47–2.15). This association was lost when the model was additionally adjusted for other metabolic syndrome risk factors. In men and women Kaplan-Meier survival curves according to HDL and TG levels revealed that participants with metabolic dyslipidemia had poorer survival compared to people without metabolic dyslipidemia (logrank p <0.001 for each). Conclusions: Metabolic dyslipidemia is associated with an increased risk of CHD. This relationship was independent from LDL-C and other risk factors of the metabolic syndrome in men, but not in women. A better management of this phenotype via lifestyle modification or pharmacotherapy may be warranted. [Copyright &y& Elsevier]

Background: This study evaluated the prevalence of the atherogenic metabolic triad and the hypothesis that waist circumference and fasting triglyceride concentrations could be used as screening tools for identification of the atherogenic metabolic triad in a population of heart transplant men. It also evaluated the relationship between the atherogenic metabolic triad and coronary artery disease (CAD). Methods: In the study group of 83 consecutive male heart transplant patients having their routine annual coronarography, 23 patients (28%) were characterized by the atherogenic metabolic triad defined by the presence of elevated fasting insulin and apolipoprotein B concentrations and by small low-density lipoprotein (LDL) particles. Results: Seventy-seven per cent of patients with waist circumference values ≥ 90 cm and with elevated triglyceride levels (≥2.0 mmol/liter) were characterized by this atherogenic metabolic triad. Patients with the atherogenic metabolic triad were at markedly increased risk of CAD (odds ratio of 25.3, 95% CI: 1.11–577.3, p &#60; 0.04) compared to heart transplant patients without the atherogenic metabolic triad. Conclusions: About 30% of heart transplant patients showed the features of the atherogenic metabolic triad. Measurement and interpretation of waist circumference and fasting triglycerides could be used among heart transplant patients to early identify men characterized by the presence of elevated fasting insulin and apolipoprotein B concentrations and small LDL particles. The presence of the atherogenic metabolic triad identified patients at high risk of CAD even in the heart transplant population. [Copyright &y& Elsevier]

The dyslipidemic state of visceral obesity is characterized by increased plasma triglyceride (TG) levels, low HDL-cholesterol concentrations and alterations in LDL composition and concentration. A functional, non-coding −514C>T single nucleotide polymorphism (SNP) of the hepatic lipase gene (LIPC) has been related to variation in HDL-cholesterol concentrations.Objectives: To investigate the hypotheses that the LIPC −514C>T polymorphism may be associated with a deteriorated lipoprotein-lipid profile and that environmental factor, such as abdominal obesity, alters this association.Methods: A total of 235 French-Canadian men from the greater Quebec City area were assigned into three groups on the basis of their LIPC −514C>T SNP, including 149 CC homozygotes, 75 CT heterozygotes, and 11 TT homozygotes.Results: In the present study, the highest values of BMI, waist circumference, and accumulation of visceral adipose tissue (VAT) were observed among TT homozygotes (p<0.05). After adjustment for age and BMI, TT homozygotes still showed higher plasma apolipoprotein (apo) AI and HDL-TG concentrations than the two other groups (p<0.05). When the two genotype groups (CC vs CT/TT) were further divided on the basis of VAT accumulation using a cut-off point of 130 cm2 (high vs low) it appears that irrespective of the genotype subjects with low VAT had higher HDL2-cholesterol concentrations (p<0.0001). However, lean carriers of the T allele had higher plasma HDL2-cholesterol levels than lean CC homozygotes. The beneficial effect of the T allele on plasma HDL2-cholesterol levels was abolished in the presence of visceral obesity (VAT>130 cm2).Conclusion: In summary, the presence of visceral obesity attenuates the impact of the LIPC −514C>T polymorphism on plasma HDL2-cholesterol levels. [Copyright &y& Elsevier]

A low plasma HDL-cholesterol concentration is an important risk factor for coronary heart disease (CHD) and is often accompanied by increased triglyceride concentrations. Women have generally higher HDL-cholesterol and lower triglyceride concentrations and concomitantly are at lower risk of CHD than men. As HDL particle size is a new and potentially important marker of CHD risk, we have examined the potential gender difference in HDL particle size, assessed by nondenaturing 4–30% polyacrylamide gradient gel electrophoresis, in a sample of men (n=231) and women (n=183). Overall, men were characterized by a less favorable lipoprotein–lipid profile, which was accompanied by smaller HDL particle size compared to women. However, when men and women were matched for HDL particle size and compared for their metabolic profile, it was found that both genders were characterized by similar plasma lipoprotein–lipid profile despite the fact that women were characterized by higher levels of total body fat but lower waist girth than men. In summary, HDL particle size is a strong marker of the gender-related difference in the determination of the metabolic risk profile. [Copyright &y& Elsevier]

Increased numbers of small, dense low-density lipoprotein particles may be present in patients with low high-density lipoprotein cholesterol and normal plasma triglycerides and cholesterol. Measurment of apolipoprotein B is the key to diagnosis and such patients should be considered for statin therapy. [ABSTRACT FROM AUTHOR]