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Purpose of Review: To discuss the history of cardiovascular outcomes trials of cholesteryl ester transfer protein (CETP) inhibitors and to describe obicetrapib, a next-generation, oral, once-daily, low-dose CETP inhibitor in late-stage development for dyslipidemia and atherosclerotic cardiovascular disease (ASCVD). Recent Findings: Phase 1 and 2 trials have evaluated the safety and lipid/lipoprotein effects of obicetrapib as monotherapy, in conjunction with statins, on top of high-intensity statins (HIS), and with ezetimibe on top of HIS. In ROSE2, 10 mg obicetrapib monotherapy and combined with 10 mg ezetimibe, each on top of HIS, significantly reduced low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, total LDL particles, small LDL particles, small, dense LDL-C, and lipoprotein (a), and increased HDL-C. Phase 3 pivotal registration trials including a cardiovascular outcomes trial are underway. Summary: Obicetrapib has an excellent safety and tolerability profile and robustly lowers atherogenic lipoproteins and raises HDL-C. As such, obicetrapib may be a promising agent for the treatment of ASCVD. [ABSTRACT FROM AUTHOR]

Background: Fruit intake, including consumption of 100% fruit juice, is generally associated with a better diet quality and overall health. However, fruit and vegetable intakes are below recommendations in many countries. Methods: The present study examined fruit juice intake and total energy and nutrient intakes according to juice consumption or non‐consumption in participants in the National Dietary and Nutrition Survey Rolling Programme 2014–2016 in the UK (n = 2723) and the Individual and National Study on Food Consumption 2006–2007 (n = 4079) in France. Total energy and nutrient intakes were also estimated for scenarios in which orange juice with pomace was either added to the daily diet or replaced 100% orange juice or beverages containing fruit juice. Results: Fruit juice consumers had higher intakes of fruits and vegetables than non‐consumers, were more likely to reach 5‐a‐day targets for fruit and vegetable consumption, and had significantly higher intakes of folate, vitamin C, potassium, magnesium, and fibre. Juice consumers also had higher total energy and sugar intakes, but lower body mass index than non‐juice consumers. Modelling consumption of orange juice with pomace increased fibre and potassium intakes in orange juice consumers, and also increased fibre, most micronutrients, and 5‐a‐day achievements in non‐juice consumers. Conclusions: These national survey results demonstrate that fruit juice consumers in the UK and France had higher intakes of fruits and vegetables than fruit juice non‐consumers, and significantly higher intakes of several micronutrients and fibre. Furthermore, modelling of consumption of orange juice with pomace increased fibre and select micronutrient intakes, particularly among fruit juice non‐consumers. Key Points: Fruit intake is associated with better diet quality and overall health, but fruit and vegetable intakes are below recommendations in many countries. These national survey results from the UK and France show that fruit juice consumers had higher intakes of fruits and vegetables, several micronutrients (folate, vitamin C, potassium, magnesium) and fibre than non‐juice consumers. Modelling of consumption of orange juice with pomace, an edible byproduct of orange juice production that includes segments, broken pulp sacs, and a centre core, increased fibre and micronutrient intakes, especially among fruit juice non‐consumers. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is an important driver of the increased mortality associated with chronic kidney disease (CKD). Higher left ventricular mass (LVM) predicts increased risk of adverse cardiovascular outcomes and total mortality, but previous reviews have shown no clear association between intervention-induced LVM change and all-cause or cardiovascular mortality in CKD. Methods: The primary objective of this meta-analysis was to investigate whether treatment-induced reductions in LVM over periods ≥12 months were associated with all-cause mortality in patients with CKD. Cardiovascular mortality was investigated as a secondary outcome. Measures of association in the form of relative risks (RRs) with associated variability and precision (95% confidence intervals [CIs]) were extracted directly from each study, when reported, or were calculated based on the published data, if possible, and pooled RR estimates were determined. Results: The meta-analysis included 42 trials with duration ≥12 months: 6 of erythropoietin stimulating agents treating to higher vs. lower hemoglobin targets, 10 of renin-angiotensin-aldosterone system inhibitors vs. placebo or another blood pressure lowering agent, 14 of modified hemodialysis regimens, and 12 of other types of interventions. All-cause mortality was reported in 121/2584 (4.86%) subjects in intervention groups and 168/2606 (6.45%) subjects in control groups. The pooled RR estimate of the 27 trials ≥12 months with ≥1 event in ≥1 group was 0.72 (95% CI 0.57 to 0.90, p = 0.005), with little heterogeneity across studies. Directionalities of the associations in intervention subgroups were the same. Sensitivity analyses of ≥6 months (34 trials), ≥9 months (29 trials), and >12 months (10 trials), and including studies with no events in either group, demonstrated similar risk reductions to the primary analysis. The point estimate for cardiovascular mortality was similar to all-cause mortality, but not statistically significant: RR 0.67, 95% CI 0.39 to 1.16. Conclusions: These results suggest that LVM regression may be a useful surrogate marker for benefits of interventions intended to reduce mortality risk in patients with CKD. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is an important driver of the increased mortality associated with chronic kidney disease (CKD). Higher left ventricular mass (LVM) predicts increased risk of adverse cardiovascular outcomes and total mortality, but previous reviews have shown no clear association between intervention-induced LVM change and all-cause or cardiovascular mortality in CKD. Methods: The primary objective of this meta-analysis was to investigate whether treatment-induced reductions in LVM over periods ≥12 months were associated with all-cause mortality in patients with CKD. Cardiovascular mortality was investigated as a secondary outcome. Measures of association in the form of relative risks (RRs) with associated variability and precision (95% confidence intervals [CIs]) were extracted directly from each study, when reported, or were calculated based on the published data, if possible, and pooled RR estimates were determined. Results: The meta-analysis included 42 trials with duration ≥12 months: 6 of erythropoietin stimulating agents treating to higher vs. lower hemoglobin targets, 10 of renin-angiotensin-aldosterone system inhibitors vs. placebo or another blood pressure lowering agent, 14 of modified hemodialysis regimens, and 12 of other types of interventions. All-cause mortality was reported in 121/2584 (4.86%) subjects in intervention groups and 168/2606 (6.45%) subjects in control groups. The pooled RR estimate of the 27 trials ≥12 months with ≥1 event in ≥1 group was 0.72 (95% CI 0.57 to 0.90, p = 0.005), with little heterogeneity across studies. Directionalities of the associations in intervention subgroups were the same. Sensitivity analyses of ≥6 months (34 trials), ≥9 months (29 trials), and >12 months (10 trials), and including studies with no events in either group, demonstrated similar risk reductions to the primary analysis. The point estimate for cardiovascular mortality was similar to all-cause mortality, but not statistically significant: RR 0.67, 95% CI 0.39 to 1.16. Conclusions: These results suggest that LVM regression may be a useful surrogate marker for benefits of interventions intended to reduce mortality risk in patients with CKD. [ABSTRACT FROM AUTHOR]

Cholesteryl ester transfer protein (CETP) facilitates the exchange of cholesteryl esters and triglycerides (TG) between high-density lipoprotein (HDL) particles and TG-rich, apolipoprotein (apo) B-containing particles. Initially, these compounds were developed to raise plasma HDL cholesterol (HDL-C) levels, a mechanism that was previously thought to lower the risk of atherosclerotic cardiovascular disease (ASCVD). More recently, the focus changed and the use of pharmacologic CETP inhibitors to reduce low-density lipoprotein cholesterol (LDL-C), non-HDL-C and apoB concentrations became supported by several lines of evidence from animal models, observational investigations, randomized controlled trials and Mendelian randomization studies. Furthermore, a cardiovascular outcome trial of anacetrapib demonstrated that CETP inhibition significantly reduced the risk of major coronary events in patients with ASCVD in a manner directly proportional to the substantial reduction in LDL-C and apoB. These data have dramatically shifted the attention on CETP away from raising HDL-C instead to lowering apoB-containing lipoproteins, which is relevant since the newest CETP inhibitor, obicetrapib, reduces LDL-C by up to 51% and apoB by up to 30% when taken in combination with a high-intensity statin. An ongoing cardiovascular outcome trial of obicetrapib in patients with ASCVD is expected to provide further evidence of the ability of CETP inhibitors to reduce major adverse cardiovascular events by lowering apoB. The purpose of the present review is to provide an up-to-date understanding of CETP inhibition and its relationship to ASCVD risk reduction. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is an important driver of the increased mortality associated with chronic kidney disease (CKD). Higher left ventricular mass (LVM) predicts increased risk of adverse cardiovascular outcomes and total mortality, but previous reviews have shown no clear association between intervention-induced LVM change and all-cause or cardiovascular mortality in CKD.Methods: The primary objective of this meta-analysis was to investigate whether treatment-induced reductions in LVM over periods ≥12 months were associated with all-cause mortality in patients with CKD. Cardiovascular mortality was investigated as a secondary outcome. Measures of association in the form of relative risks (RRs) with associated variability and precision (95% confidence intervals [CIs]) were extracted directly from each study, when reported, or were calculated based on the published data, if possible, and pooled RR estimates were determined.Results: The meta-analysis included 42 trials with duration ≥12 months: 6 of erythropoietin stimulating agents treating to higher vs. lower hemoglobin targets, 10 of renin-angiotensin-aldosterone system inhibitors vs. placebo or another blood pressure lowering agent, 14 of modified hemodialysis regimens, and 12 of other types of interventions. All-cause mortality was reported in 121/2584 (4.86%) subjects in intervention groups and 168/2606 (6.45%) subjects in control groups. The pooled RR estimate of the 27 trials ≥12 months with ≥1 event in ≥1 group was 0.72 (95% CI 0.57 to 0.90, p = 0.005), with little heterogeneity across studies. Directionalities of the associations in intervention subgroups were the same. Sensitivity analyses of ≥6 months (34 trials), ≥9 months (29 trials), and >12 months (10 trials), and including studies with no events in either group, demonstrated similar risk reductions to the primary analysis. The point estimate for cardiovascular mortality was similar to all-cause mortality, but not statistically significant: RR 0.67, 95% CI 0.39 to 1.16.Conclusions: These results suggest that LVM regression may be a useful surrogate marker for benefits of interventions intended to reduce mortality risk in patients with CKD. [ABSTRACT FROM AUTHOR]

Primordial prevention is intended to prevent the development of ASCVD risk factors, whereas primary prevention is directed at early identification and treatment of risk factors and secondary prevention is aimed at reducing risk of additional ASCVD events in those who have already experienced an event. Atherosclerotic cardiovascular disease (ASCVD) is caused by plaque build-up in the walls of arteries which begins very early in life, progresses over decades, and, if not halted, may eventually lead to ASCVD events, generally in middle-age or later. Long-term secondary prevention of cardiovascular disease with a Mediterranean diet and a low-fat diet (CORDIOPREV): a randomised controlled trial. [Extracted from the article]

Background: Observational evidence suggests that red meat intake is associated with type 2 diabetes (T2D) and cardiovascular disease incidence, but few randomized controlled trials have assessed effects of lean, unprocessed red meat intake on insulin sensitivity and other cardiometabolic risk factors.Objective: This study compared the USDA Healthy US-Style Eating Pattern, low in saturated fat and red meat (<40 g/d red meat; USDA-CON), with a modified version with an additional 150 g/d lean beef as an isocaloric replacement for carbohydrate (USDA-LB) on insulin sensitivity and cardiometabolic risk markers.Methods: Participants (7 men, 26 women; 44.4 y old) with overweight/obesity [BMI (kg/m2) = 31.3] and prediabetes and/or metabolic syndrome completed this randomized, crossover, controlled-feeding trial consisting of two 28-d treatments (USDA-CON and USDA-LB) separated by a ≥14-day washout. Insulin sensitivity (primary outcome variable), lipoprotein lipids, apolipoproteins (apoA-I and apoB), and high-sensitivity C-reactive protein (hs-CRP) (secondary outcome variables), in plasma or serum, and blood pressures were assessed at baseline and the end of each diet period.Results: USDA-LB and USDA-CON did not differ significantly in effects on whole-body insulin sensitivity and other indicators of carbohydrate metabolism, lipoprotein lipids, apoA-I and apoB, hs-CRP, and blood pressures. USDA-LB produced a shift toward less cholesterol carried by smaller LDL subfractions compared with USDA-CON [least-squares geometric mean ratios for LDL1+2 cholesterol of 1.20 (P = 0.016) and LDL3+4 cholesterol of 0.89 (P = 0.044)] and increased peak LDL time versus USDA-CON (1.01; P = 0.008).Conclusions: Substituting lean, unprocessed beef for carbohydrate in a Healthy US-Style Eating Pattern resulted in a shift toward larger, more buoyant LDL subfractions, but otherwise had no significant effects on the cardiometabolic risk factor profile in men and women with prediabetes and/or metabolic syndrome.This trial was registered at clinicaltrials.gov as NCT03202680. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to assess the effects of replacing high-carbohydrate (CHO) foods with raw almonds on insulin sensitivity and cardiometabolic health markers in overweight or obese adults with prediabetes.Method: This randomized crossover study consisted of two 6-week dietary intervention periods, separated by a ≥ 4-week washout. Subjects incorporated 1.5 oz of raw almonds twice daily or isocaloric CHO-based foods into their diets, with instructions to maintain body weight. Dietary intakes as well as insulin sensitivity, CHO metabolism indices, lipoprotein lipids and particles, and inflammatory markers were assessed.Results: Thirty-three subjects (17 male, 16 female), mean age 48.3 ± 2.2 years and body mass index 30.5 ± 0.7 kg/m2, provided evaluable data. Compared to CHO, almonds resulted in significantly (p < 0.01) higher intakes of protein, fat (unsaturated fatty acids), fiber, and magnesium and significantly (p < 0.001) lower intakes of CHO and sugars. No differences were observed between diet conditions for changes from baseline in the insulin sensitivity index from a short intravenous glucose tolerance test or other indices of glucose homeostasis. No significant differences were observed in biomarkers of cardiovascular risk except that the CHO intervention led to a shift toward a higher concentration of cholesterol in small, dense low-density lipoprotein subfraction 3+4 (LDL3 + 4) particles (p = 0.024 vs almonds).Conclusions: Intake of 3.0 oz/d raw almonds, vs energy-matched CHO foods, improved the dietary nutrient profile, but did not significantly affect insulin sensitivity and most markers of cardiometabolic health in overweight and obese men and women with prediabetes. [ABSTRACT FROM AUTHOR]

Objectives: To assess effects of egg-based versus non-egg, higher-carbohydrate (CHO) breakfast meals on cardiometabolic health markers in overweight or obese adults with prediabetes and/or metabolic syndrome.Methods: This randomized, crossover study included two 4-week dietary interventions, separated by a ≥4-week washout. Subjects incorporated into their habitual diets breakfast meals containing either 2 eggs/day for 6 days/week (Egg condition), or energy-matched, non-egg, higher-CHO-based foods (Non-Egg condition). Dietary intakes, insulin sensitivity, and other CHO metabolism indices, lipid biomarkers, high-sensitivity C-reactive protein, and blood pressures were measured.Results: Thirty men and women with mean age 54.1 ± 1.9 years and body mass index 31.9 ± 0.7 kg/m2 provided data. Neither diet condition significantly altered insulin sensitivity indices, but the homeostasis model assessment for insulin resistance was significantly (p = 0.028) higher after the Non-Egg vs. the Egg condition. Low-density lipoprotein cholesterol (LDL-C) was decreased from baseline (119 mg/dL) by 2.9 and 6.0% with Egg and Non-Egg breakfasts, respectively (p = 0.023). Systolic blood pressure was reduced from baseline (127 mm Hg) by 2.7 and 0.0% with Egg and Non-Egg, respectively (p = 0.018). Diet records indicated 149 kcal/day higher (p = 0.008) energy intake from non-study foods during the Egg condition; however, weight change from baseline did not differ between conditions.Conclusion: Compared with the baseline diet, consumption of 12 eggs/week for 4 weeks at breakfast was associated with less reduction in LDL-C, and more lowering of systolic blood pressure, than observed with non-egg-based, energy-matched, control foods higher in CHO. [ABSTRACT FROM AUTHOR]

Background: Few trials have examined the effects of coconut oil consumption in comparison with polyunsaturated fatty acid-rich oils such as corn oil.Objective: This trial assessed the effects of consuming foods made with corn oil compared with coconut oil on lipids, glucose homeostasis, and inflammation.Methods: This was a preliminary randomized crossover study of men (n = 12) and women (n = 13) with a mean age of 45.2 y, mean body mass index (in kg/m2) of 27.7, fasting LDL cholesterol ≥115 mg/dL and <190 mg/dL, and triglycerides (TGs) ≤375 mg/dL. Subjects consumed muffins and rolls providing 4 tablespoons (∼54 g) per day of corn oil or coconut oil as part of their habitual diets for 4 wk, with a 3-wk washout between conditions. Fasting plasma lipids and high-sensitivity C-reactive protein (hs-CRP) and glucose metabolism were assessed via an intravenous glucose tolerance test at baseline and 15 and 29 d of treatment. Responses were compared between treatments by ANCOVA.Results: Median baseline concentrations of LDL cholesterol, non-HDL cholesterol, total cholesterol (total-C), HDL cholesterol, total-C:HDL cholesterol, and TGs were 123, 144, 188, 46.0, 4.21, and 92.5 mg/dL, respectively. Changes from baseline for corn oil and coconut oil conditions, respectively, were: LDL cholesterol (primary outcome; -2.7% compared with +4.6%), non-HDL cholesterol (-3.0% compared with +5.8%), total-C (-0.5% compared with +7.1%), HDL cholesterol (+5.4% compared with +6.5%), total-C:HDL cholesterol (-4.3% compared with -3.3%), and TGs (-2.1% compared with +6.0%). Non-HDL cholesterol responses were significantly different between corn and coconut oil conditions (P = 0.034); differences between conditions in total-C and LDL cholesterol approached significance (both P = 0.06). Responses for hs-CRP and carbohydrate homeostasis parameters did not differ significantly between diet conditions.Conclusions: When incorporated into the habitual diet, consumption of foods providing ∼54 g of corn oil/d produced a more favorable plasma lipid profile than did coconut oil in adults with elevated cholesterol. This trial was registered at clinicaltrials.gov as NCT03202654. [ABSTRACT FROM AUTHOR]

Objective: This randomized crossover trial assessed the effects of 5 weeks of consuming low-fat dairy (one serving/day each of 1% fluid milk, low-fat cheese, and low-fat yogurt) versus nondairy products (one serving/day each of apple juice, pretzels, and cereal bar) on systolic and diastolic blood pressures (SBP and DBP), vascular function (reactive hyperemia index [RHI] and augmentation index), and plasma lipids.Methods: Patients were 62 men and women (mean age 54.5 years, body mass index 29.2 kg/m(2)) with prehypertension or stage 1 hypertension (mean resting SBP/DBP 129.8 mmHg/80.8 mmHg) while not receiving antihypertensive medications. A standard breakfast meal challenge including two servings of study products was administered at the end of each treatment period.Results: Dairy and nondairy treatments did not produce significantly different mean SBP or DBP in the resting postprandial state or from premeal to 3.5 hours postmeal (SBP, 126.3 mmHg versus 124.9 mmHg; DBP, 76.5 mmHg versus 75.7 mmHg), premeal (2.35 versus 2.20) or 2 hours postmeal (2.33 versus 2.30) RHI, and premeal (22.5 versus 23.8) or 2 hours postmeal (12.4 versus 13.2) augmentation index. Among subjects with endothelial dysfunction (RHI ≤ 1.67; n = 14) during the control treatment, premeal RHI was significantly higher in the dairy versus nondairy condition (2.32 versus 1.50, P = 0.002). Fasting lipoprotein lipid values were not significantly different between treatments overall, or in subgroup analyses.Conclusion: No significant effects of consuming low-fat dairy products, compared with low-fat nondairy products, were observed for blood pressures, measures of vascular function, or lipid variables in the overall sample, but results from subgroup analyses were consistent with the hypothesis that dairy foods might improve RHI in those with endothelial dysfunction. [ABSTRACT FROM AUTHOR]

"Owing to uncertainty regarding the contribution of the various proposed pathophysiologic links between hypertriglyceridemia and cardiovascular disease risk, the optimal treatment strategy for patients with mild-to-moderate hypertriglyceridemia is unclear." [ABSTRACT FROM AUTHOR]

This randomized, placebo-controlled, crossover trial assessed the lipid-altering efficacy of a dietary supplement (tablet form) providing 1.8 g/day free (non-esterified) plant sterols and stanols versus placebo for 6 weeks as part of a therapeutic lifestyle changes (TLC) diet in 32 men and women with primary hypercholesterolaemia. Mean ± SE baseline (end of a 5-week TLC diet lead-in) lipid concentrations (mmol/l) were total cholesterol (TC), 5.88 ± 0.08; non-high-density lipoprotein cholesterol (non-HDL-C), 4.71 ± 0.09; low-density lipoprotein cholesterol (LDL-C), 4.02 ± 0.08; HDL-C, 1.17 ± 0.06 and triglycerides (TGs), 1.51 ± 0.12. Differences from control in responses (plant sterol/stanol - control) were significant (p < 0.05) for LDL-C ( - 4.9%), non-HDL-C ( - 3.6%) and TC ( - 2.8%). HDL-C and TG responses were not significantly different between treatment conditions. These results indicate that 1.8 g/day free plant sterols/stanols administered in a tablet produced favourable lipoprotein lipid changes in men and women with hypercholesterolaemia. [ABSTRACT FROM AUTHOR]

This randomized, placebo-controlled, crossover trial assessed the lipid-altering efficacy of a dietary supplement (tablet form) providing 1.8 g/day free (non-esterified) plant sterols and stanols versus placebo for 6 weeks as part of a therapeutic lifestyle changes (TLC) diet in 32 men and women with primary hypercholesterolaemia. Mean ± SE baseline (end of a 5-week TLC diet lead-in) lipid concentrations (mmol/l) were total cholesterol (TC), 5.88 ± 0.08; non-high-density lipoprotein cholesterol (non-HDL-C), 4.71 ± 0.09; low-density lipoprotein cholesterol (LDL-C), 4.02 ± 0.08; HDL-C, 1.17 ± 0.06 and triglycerides (TGs), 1.51 ± 0.12. Differences from control in responses (plant sterol/stanol − control) were significant ( p < 0.05) for LDL-C ( − 4.9%), non-HDL-C ( − 3.6%) and TC ( − 2.8%). HDL-C and TG responses were not significantly different between treatment conditions. These results indicate that 1.8 g/day free plant sterols/stanols administered in a tablet produced favourable lipoprotein lipid changes in men and women with hypercholesterolaemia. [ABSTRACT FROM AUTHOR]

Objective: Progression of carotid intima-media thickness (CIMT) is a surrogate indicator for the early stages of atherosclerosis. Methods: The study investigated relationships between baseline lipoprotein cholesterol, triglyceride (TG), and apolipoprotein (Apo) B levels assessed with density gradient ultracentrifugation (DGU) and progression of posterior wall common CIMT in men (45-75 years of age) and women (55-74 years of age) in the control arm of a clinical trial. Participants had baseline posterior wall CIMT 0.7-2.0 mm, without significant stenosis. CIMT was assessed using B-mode ultrasound at baseline, and 12 and ~18 months. A DGU cholesterol panel that assessed the major lipoprotein classes and subclasses, plus triglycerides, lipoprotein (a) cholesterol, low-density lipoprotein (LDL) peak time (inversely related to LDL particle density), and Apo B were performed on fasting baseline samples. Apo B was also measured using an enzyme linked immunosorbent assay. Results: Baseline CIMT was inversely associated (P < 0.001) with CIMT progression. After adjustment for baseline CIMT, significant predictors of posterior wall CIMT progression in linear regression analyses included LDL peak time (inverse, P = 0.045), total high-density lipoprotein cholesterol (HDL-C) (inverse, P = 0.001), HDL2-C (inverse, P = 0.005), HDL3-C (inverse, P = 0.003), very low-density lipoprotein (VLDL)-C (P = 0.037), and VLDL1+2-C (P = 0.016). Conclusion: These data indicate that DGU-derived indicators of the "atherogenic lipoprotein phenotype," including increased TG-rich lipoprotein cholesterol, lower HDL-C and HDL-C subfractions, and a greater proportion of LDL-C carried by more dense LDL particles, are associated with CIMT progression in men and women at moderate risk for coronary heart disease. [ABSTRACT FROM AUTHOR]

Background: To provide an initial evaluation of insulin sensitivity and secretion indices derived from a standard liquid meal tolerance test protocol in subjects with normal (NFG), impaired fasting glucose (IFG) or type 2 diabetes mellitus. Methods: Areas under the curve (AUC) for glucose, insulin and C-peptide from pre-meal to 120 min after consumption of a liquid meal were calculated, as were homeostasis model assessments of insulin resistance (HOMA2-IR) and the Matsuda index of insulin sensitivity. Results: Subjects with NFG (n = 19), IFG (n = 19), and diabetes (n = 35) had mean ± SEM HOMA2- IR values of 1.0 ± 0.1, 1.6 ± 0.2 and 2.5 ± 0.3 and Matsuda insulin sensitivity index values of 15.6 ± 2.0, 8.8 ± 1.2 and 6.0 ± 0.6, respectively. The log-transformed values for these variables were highly correlated overall and within each fasting glucose category (r = -0.91 to -0.94, all p < 0.001). Values for the product of the insulin/glucose AUC ratio and the Matsuda index, an indicator of the ability of the pancreas to match insulin secretion to the degree of insulin resistance, were 995.6 ± 80.7 (NFG), 684.0 ± 57.3 (IFG) and 188.3 ± 16.1 (diabetes) and discriminated significantly between fasting glucose categories (p < 0.001 for each comparison). Conclusion: These results provide initial evidence to support the usefulness of a standard liquid meal tolerance test for evaluation of insulin secretion and sensitivity in clinical and population studies. [ABSTRACT FROM AUTHOR]

Background: Diacylglycerol is a natural component of edible oils that has metabolic characteristics that are distinct from those of triacylglycerol. Objective: We assessed the efficacy of an oil containing mainly 1,3-diacylglycerol in reducing body weight and fat mass when incorporated into a reduced-energy diet. Design: The study was a randomized, double-blind, parallel intervention trial that was conducted at an outpatient clinical research center. The subjects (n = 131) were overweight or obese men (waist circumference ⩾ 90 cm) and women (waist circumference ⩾ 87 cm). Food products (muffins, crackers, soup, cookies, and granola bars) containing diacylglycerol or triacylglycerol oil and having the same fatty acid composition were incorporated into a reduced-energy diet (2100-3350-kJ/d deficit) for 24 wk. Percentages of change in body weight, fat mass, and intraabdominal fat area were assessed. Results: In an intention-to-treat analysis, body weight and fat mass decreased significantly more in the diacylglycerol group than in the triacylglycerol group (P = 0.025 and 0.037, respectively). By the end of the trial, mean body weight had decreased 3.6% and 2.5% in the diacylglycerol and triacylglycerol groups, respectively. Fat mass decreased 8.3% and 5.6% in the diacylglycerol and triacylglycerol groups, respectively. Conclusion: Foods containing diacylglycerol oil promoted weight loss and body fat reduction and may be useful as an adjunct to diet therapy in the management of obesity. [ABSTRACT FROM AUTHOR]

Background: Plant sterol esters reduce cholesterol absorption and lower circulating blood cholesterol concentrations when incorporated into the habitual diet. Objective: This randomized, double-blind, 3-group parallel, controlled study evaluated the influence of esterified plant sterols on serum lipid concentrations in adults with mild-to-moderate primary hypercholesterolemia. Design: Subjects incorporated a conventional 50%-fat spread into a National Cholesterol Education Program Step I diet for a 4-wk lead-in period, followed by a 5-wk intervention period of the diet plus either a control reduced-fat spread (40% fat; n = 92) or a reduced-fat spread enriched with plant sterol esters to achieve intakes of 1.1 g/d (n = 92; low-sterol group) or 2.2 g/d (n = 40; high-sterol group). Results: Subjects in the low- and high-sterol groups who consumed > 80% of the scheduled servings (per-protocol analyses) had total cholesterol values that were 5.2% and 6.6% lower, LDL-cholesterol values that were 7.6% and 8.1% lower, apolipoprotein B values that were 6.2% and 8.4% lower, and ratios of total to HDL cholesterol that were 5.9% and 8.1% lower, respectively, than values for the control group (P < 0.001 for all). Additionally, triacylglycerol concentrations decreased by 10.4% in the high-sterol group. Serum concentrations of fat-soluble vitamins and carotenoids were generally within reference ranges at baseline and postintervention. Serum plant sterol concentrations increased from baseline (0.48% of total sterol by wt) to 0.64% and 0.71% by wt for the low- and high-sterol groups, respectively (P < 0.05 compared with control). Conclusion: A reduced-fat spread containing plant sterol esters incorporated into a low-fat diet is a beneficial adjunct in the dietary management of hypercholesterolemia. [ABSTRACT FROM AUTHOR]

There has been a great deal of controversy in recent years about the potential role of dietary supplementation with long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) in the prevention of cardiovascular disease (CVD). Four recent meta-analyses have been published that evaluated randomized, controlled trial (RCT) data from studies that assessed the effects of supplemental n-3 PUFA intake on CVD endpoints. The authors of those reports reached disparate conclusions. This review explores the reasons informed experts have drawn different conclusions from the evidence, and addresses implications for future investigation. Although RCT data accumulated to date have failed to provide unequivocal evidence of CVD risk reduction with n-3 PUFA supplementation, many studies were limited by design issues, including low dosage, no assessment of n-3 status, and absence of a clear biological target or pathophysiologic hypothesis for the intervention. The most promising evidence supports n-3 PUFA supplementation for prevention of cardiac death. Two ongoing trials have enrolled high cardiovascular risk subjects with hypertriglyceridemia and are administering larger dosages of n-3 PUFA than employed in previous RCTs. These are expected to clarify the potential role of long-chain n-3 PUFA supplementation in CVD risk management. [ABSTRACT FROM AUTHOR]

Purpose of Review: The aims of this review are to provide perspective on evaluation of relative and absolute cardiovascular disease (CVD) risk reductions for assessing the efficacy of preventive therapies and to summarize methods for evaluation of CVD risk in clinical practice.Recent Findings: Major CVD risk factors can be used to stratify patients into risk categories. Results from recent trials reinforce the view that benefits of preventive therapies will be greatest in those with the highest absolute risk and in those with the most severe disturbance in the risk factor targeted. In evaluating clinical utility, it is necessary to assess the impact of an intervention on both relative and absolute risk. Quantitative risk scoring using major CVD risk factors is effective for identifying those at low, moderate, and high CVD risk. When there is uncertainty about the appropriate treatment strategy, additional testing may be used to refine risk assessment. This may include measurement of inflammatory markers, subclinical indicators of atherosclerosis (e.g., coronary artery calcium and ankle brachial index), urinary albumin/creatinine ratio, and the level of lipoprotein (a).Summary: The benefit of a preventive therapy will generally be the greatest in those with the highest absolute risk and in those with the most severe disturbance in the risk factor targeted. Quantitative risk scoring with major CVD risk factors can be supplemented with additional testing for refinement of risk assessment in patients for whom decisions about pharmacotherapy, or the intensity of therapy, for risk factor modification are uncertain. [ABSTRACT FROM AUTHOR]