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The relationship of insulin resistance estimated by triglyceride glucose index and coronary plaque characteristics.
Won, KB, Kim, YS, Lee, BK, Heo, R, Han, D, Lee, JH, Lee, SE, Sung, JM, Cho, I, Park, HB, et al
Medicine. 2018;(21):e10726
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Abstract
The triglyceride glucose (TyG) index is a useful surrogate marker for insulin resistance, which is an important risk factor for coronary artery disease (CAD). However, data on the relationship of the TyG index and coronary plaque characteristics are limited.This study included 2840 participants with near-normal renal function who underwent coronary computed tomography angiography. CAD was defined as the presence of any plaques, and obstructive CAD was defined as the presence of plaques with ≥50% stenosis. The relationship between the TyG index and noncalcified plaque (NCP), calcified or mixed plaque (CMP), and coronary artery calcium score (CACS) was evaluated.All participants were stratified into 4 groups based on the quartiles of the TyG index. The prevalence of CAD and obstructive CAD significantly increased with increasing quartiles. The risk for NCP and obstructive NCP was not different among all groups. However, compared with group I (lowest quartile), the risk for CMP was higher in groups III (odds ratio [OR]: 1.438) and IV (highest quartile) (OR: 1.895) (P < .05), and that for obstructive CMP was higher in groups II (OR: 1.469), III (OR: 1.595), and IV (OR: 2.168) (P < .05). Multivariate regression analysis showed that the TyG index was associated with an increased risk for CAD (OR: 1.700), obstructive CAD (OR: 1.692), and CACS >400 (OR: 1.448) (P < .05).The TyG index was independently associated with the presence and severity of CAD due to an increased risk for CMP.
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The metabolic capacity of lipid droplet localized acyl-CoA synthetase 3 is not sufficient to support local triglyceride synthesis independent of the endoplasmic reticulum in A431 cells.
Poppelreuther, M, Sander, S, Minden, F, Dietz, MS, Exner, T, Du, C, Zhang, I, Ehehalt, F, Knüppel, L, Domschke, S, et al
Biochimica et biophysica acta. Molecular and cell biology of lipids. 2018;(6):614-624
Abstract
ACSL3 is the only long chain fatty acyl-CoA synthetase consistently found on growing and mature lipid droplets (LDs), suggesting that this specific localization has biological relevance. Current models for LD growth propose that triglycerides are synthesized by enzymes at the LD surface, with activated fatty acids provided by LD localized ACSL3, thus allowing growth independent of the ER. Here, we tested this hypothesis by quantifying ACSL3 on LDs from human A431 cells. RNAi of ACSL3 reduced the oleoyl-CoA synthetase activity by 83%, suggesting that ACSL3 is by far the dominant enzyme of A431 cells. Molar quantification revealed that there are 1.4 million ACSL3 molecules within a single cell. Metabolic labeling indicated that each ACSL3 molecule contributed a net gain of 3.1 oleoyl-CoA/s. 3D reconstruction of confocal images demonstrated that 530 individual lipid droplets were present in an average oleate fed A431 cell. A representative single lipid droplet with a diameter of 0.66 μm contained 680 ACSL3 molecules on the surface. Subcellular fractionation showed that at least 68% of ACSL3 remain at the ER even during extensive fatty acid supplementation. High resolution single molecule microscopy confirmed the abundance of cytoplasmic ACSL3 outside of LDs. Model calculations for triglyceride synthesis using only LD localized ACSL3 gave significant slower growth of LDs as observed experimentally. In conclusion, although ACSL3 is an abundant enzyme on A431 LDs, the metabolic capacity is not sufficient to account for LD growth solely by the local synthesis of triglycerides.
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Concurrent Training Promoted Sustained Anti-atherogenic Benefits in the Fasting Plasma Triacylglycerolemia of Postmenopausal Women at 1-Year Follow-up.
Rossi, FE, Diniz, TA, Fortaleza, ACS, Neves, LM, Picolo, MR, Monteiro, PA, Buonani, C, Lira, FS, Freitas, IF
Journal of strength and conditioning research. 2018;(12):3564-3573
Abstract
Rossi, FE, Diniz, TA, Fortaleza, ACS, Neves, LM, Picolo, MR, Monteiro, PA, Buonani, C, Lira, FS, and Freitas, IF Jr. Concurrent training promoted sustained anti-atherogenic benefits in the fasting plasma triacylglycerolemia of postmenopausal women at 1-year follow-up. J Strength Cond Res 32(12): 3573-3582, 2018-The aim of this study was to compare the effects of aerobic and concurrent training (aerobic plus strength training) on the lipid profiles of normotriacylglycerolemic and hypertriacylglycerolemic postmenopausal women and to verify whether the benefits of aerobic and concurrent training were sustained after 1 year. Total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol, triacylglycerol (TAG), and glucose were assessed in 46 normotriacylglycerolemic (TAG < 150 mg·dl) postmenopausal women divided into 3 groups: aerobic training, concurrent training (CT), and a control group. For CT group, hypertriacylglycerolemic postmenopausal women were recruited (TAG ≥ 150 mg·dl, n = 14). Total daily caloric consumption and free-living physical activity were evaluated by dietary questionnaires and accelerometer, respectively, and fat mass by DXA. In 16 weeks, CT was effective in increasing HDL-c (normotriacylglycerolemic: pre = 57.1 ± 17.3 mg·dl × post = 64.3 ± 16.1 mg·dl p = 0.020 and hypertriacylglycerolemic: pre = 44.7 ± 9.6 mg·dl × post = 50.3 ± 15.3 mg·dl; p = 0.012) and reducing the atherogenic index in normotriacylglycerolemic (pre = 3.6 ± 0.9 mg·dl × post = 3.0 ± 0.6 mg·dl; p = 0.003) and hypertriacylglycerolemic (pre = 5.2 ± 1.1 mg·dl × post = 4.7 ± 1.2 mg·dl; p = 0.018) postmenopausal women. In addition, the effects were sustained at the 1-year follow-up only among the hypertriacylglycerolemic postmenopausal women. The anti-atherogenic status in normotriacylglycerolemic and hypertriacylglycerolemic postmenopausal women was changed by CT but without significant differences between groups. Furthermore, these benefits are sustained at the 1-year follow-up among the hypertriacylglycerolemic subjects.
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Reducing prolonged sedentary time using a treadmill desk acutely improves cardiometabolic risk markers in male and female adults.
Champion, RB, Smith, LR, Smith, J, Hirlav, B, Maylor, BD, White, SL, Bailey, DP
Journal of sports sciences. 2018;(21):2484-2491
Abstract
This study evaluated the acute effects of interrupting prolonged sitting with an accumulated 2 h of light-intensity walking on postprandial cardiometabolic risk markers. In this randomised crossover trial, 24 participants (twelve males) aged 18-55 years took part in two, 6.5 h conditions: 1) prolonged sitting (SIT) and 2) sitting interrupted hourly with 20 min light-intensity treadmill desk walking at between 1.2-3.5 km/h-1 (INT-SIT). Standardized meals were provided at 0 h and 3 h. Blood samples and blood pressure measures were taken hourly. Statistical analyses were completed using linear mixed models. Postprandial incremental area under the curve responses (mmol/L∙6.5 h) for glucose (4.52 [3.47, 5.56] and 6.66 [5.62, 7.71] for INT-SIT and SIT, respectively) and triglycerides (1.96 [0.96, 2.96] and 2.71 [1.70, 3.71] for INT-SIT and SIT, respectively) were significantly lower in INT-SIT than SIT. Mean systolic and diastolic blood pressure responses were lower by 3% and 4%, respectively, in INT-SIT than SIT (P < 0.05). There was no significant condition x sex interaction effect for any outcomes (P > 0.05). These findings suggest that interrupting sitting with an accumulated 2 h of light-intensity walking acutely improves cardiometabolic risk levels in males and females compared with prolonged sitting.
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Adiposity and Genetic Factors in Relation to Triglycerides and Triglyceride-Rich Lipoproteins in the Women's Genome Health Study.
Ahmad, S, Mora, S, Franks, PW, Orho-Melander, M, Ridker, PM, Hu, FB, Chasman, DI
Clinical chemistry. 2018;(1):231-241
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Abstract
BACKGROUND Previous results from Scandinavian cohorts have shown that obesity accentuates the effects of common genetic susceptibility variants on increased triglycerides (TG). Whether such interactions are present in the US population and further selective for particular TG-rich lipoprotein subfractions is unknown. METHODS We examined these questions using body mass index (BMI) and waist circumference (WC) among women of European ancestry from the Women's Genome Health Study (WGHS) (n = 21840 for BMI; n = 19313 for WC). A weighted genetic risk score (TG-wGRS) based on 40 published TG-associated single-nucleotide polymorphisms was calculated using published effect estimates. RESULTS Comparing overweight (BMI ≥ 25 kg/m2) and normal weight (BMI < 25 kg/m2) WGHS women, each unit increase of TG-wGRS was associated with TG increases of 1.013% and 1.011%, respectively, and this differential association was significant (Pinteraction = 0.014). Metaanalyses combining results for WGHS BMI with the 4 Scandinavian cohorts (INTER99, HEALTH2006, GLACIER, MDC) (total n = 40026) yielded a more significant interaction (Pinteraction = 0.001). Similarly, we observed differential association of the TG-wGRS with TG (Pinteraction = 0.006) in strata of WC (<80 cm vs ≥80 cm). Metaanalysis with 2 additional cohorts reporting WC (INTER99 and HEALTH2006) (total n = 27834) was significant with consistent effects (Pinteraction = 0.006). We also observed highly significant interactions of the TG-wGRS across the strata of BMI with very large, medium, and small TG-rich lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy (all Pinteractions < 0.0001). The differential effects were strongest for very large TG-rich lipoprotein. CONCLUSIONS Our results support the original findings and suggest that obese individuals may be more susceptible to aggregated genetic risk associated with common TG-raising alleles, with effects accentuated in the large TG-rich lipoprotein subfraction.
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Hypertriglyceridemia and omega-3 fatty acids: Their often overlooked role in cardiovascular disease prevention.
Arca, M, Borghi, C, Pontremoli, R, De Ferrari, GM, Colivicchi, F, Desideri, G, Temporelli, PL
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2018;(3):197-205
Abstract
AIMS: This review aims to describe the pathogenic role of triglycerides in cardiometabolic risk, and the potential role of omega-3 fatty acids in the management of hypertriglyceridemia and cardiovascular disease. DATA SYNTHESIS In epidemiological studies, hypertriglyceridemia correlates with an increased risk of cardiovascular disease, even after adjustment for low density lipoprotein cholesterol (LDL-C) levels. This has been further supported by Mendelian randomization studies where triglyceride-raising common single nucleotide polymorphisms confer an increased risk of developing cardiovascular disease. Although guidelines vary in their definition of hypertriglyceridemia, they consistently define a normal triglyceride level as <150 mg/dL (or <1.7 mmol/L). For patients with moderately elevated triglyceride levels, LDL-C remains the primary target for treatment in both European and US guidelines. However, since any triglyceride level in excess of normal increases the risk of cardiovascular disease, even in patients with optimally managed LDL-C levels, triglycerides are an important secondary target in both assessment and treatment. Dietary changes are a key element of first-line lifestyle intervention, but pharmacological treatment including omega-3 fatty acids may be indicated in people with persistently high triglyceride levels. Moreover, in patients with pre-existing cardiovascular disease, omega-3 supplements significantly reduce the risk of sudden death, cardiac death and myocardial infarction and are generally well tolerated. CONCLUSIONS Targeting resistant hypertriglyceridemia should be considered as a part of clinical management of cardiovascular risk. Omega-3 fatty acids may represent a valuable resource to this aim.
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Corn Oil Lowers Plasma Cholesterol Compared with Coconut Oil in Adults with Above-Desirable Levels of Cholesterol in a Randomized Crossover Trial.
Maki, KC, Hasse, W, Dicklin, MR, Bell, M, Buggia, MA, Cassens, ME, Eren, F
The Journal of nutrition. 2018;(10):1556-1563
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Abstract
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.
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Plant sterols lower LDL-cholesterol and triglycerides in dyslipidemic individuals with or at risk of developing type 2 diabetes; a randomized, double-blind, placebo-controlled study.
Trautwein, EA, Koppenol, WP, de Jong, A, Hiemstra, H, Vermeer, MA, Noakes, M, Luscombe-Marsh, ND
Nutrition & diabetes. 2018;(1):30
Abstract
BACKGROUND Managing cardiovascular disease (CVD) risk factors, e.g., dyslipidemia in type-2 diabetes mellitus (T2DM) is critically important as CVD is the most common cause of death in T2DM patients. This study aimed to investigate the effect of plant sterols (PS) on lowering both elevated low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). METHODS In a double-blind, randomized, placebo-controlled, parallel study, 161 individuals at increased risk of and with established T2DM, consumed low-fat spreads without or with added PS (2 g/d) for 6 weeks after a 2-week run-in period. Increased risk of developing T2DM was defined by the Australian T2DM Risk Assessment Tool (AUSDRISK). Fasting serum/plasma total cholesterol (TC), LDL-C, TG, high-density lipoprotein cholesterol (HDL-C), glucose and insulin were measured at baseline and after 6 weeks. Effects on acute and chronic postprandial blood lipids, glucose and insulin were measured over 4-h in 39 individuals with T2DM following a mixed meal challenge without and with added 2 g/d PS at week 6. The study was registered at clinicaltrials.gov (NCT02288585). RESULTS Hundred fifty-one individuals completed the study and 138 (57% men, 43% women; 44 with and 94 at risk of T2DM) were included in per protocol analysis. Baseline LDL-C and TG were 3.8 ± 1.0 and 2.5 ± 0.8 mmol/l, respectively. PS intake significantly lowered fasting LDL-C (-4.6%, 95%CI -1.2; -8.0; p = 0.009), TC (-4.2%, 95%CI -1.2; -7.1; p = 0.006) and TG (-8.3%, 95% -1.1, -15.0; p = 0.024) with no significant changes in HDL-C, glucose or insulin. Postprandial lipid (TG, TC, LDL-C, HDL-C, remnant cholesterol), glucose and insulin responses did not differ. CONCLUSIONS In individuals at risk of and with established T2DM and with elevated TG and LDL-C, 2 g/d of PS results in dual LDL-C plus TG lowering. Postprandial lipid or glycemic responses did not differ between PS and control treatment.
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Optimizing Lipid Pattern by Adding a Combined Nutraceutical or Pravastatin to Fenofibrate Treatment in Hypertriglyceridemic Subjects: Single Site, Randomized, Open-Label, Post-Market Clinical Investigation.
Cicero, AFG, Fogacci, F, Bove, M, Ventura, F, Giovannini, M, Borghi, C
High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension. 2018;(4):355-359
Abstract
INTRODUCTION Fenofibrate is an effective and safe treatment for hypertriglyceridemia. However, after TG reduction a residual dyslipidemia could appear and require further treatment. AIM: To comparatively evaluate the short-term tolerability and efficacy of a combined lipid-lowering nutraceutical and pravastatin 40 mg in fenofibrate treated patients. METHOD We prospectively enrolled 40 patients well-tolerating treatment with micronized fenofibrate 145 mg/day and with residual dyslipidemia (LDL-C > 115 mg/dL and TG > 150 mg/dL). Exclusion criteria have been type 2 diabetes, Familial Hypercholesterolemia, previous cardiovascular diseases and severe chronic kidney disease. Then, we have randomly assigned the patients to treatment with pravastatin 40 mg or a combined lipid-lowering nutraceutical (Armolipid Plus®, containing monacolin 3 mg and berberine 500 mg). RESULTS After 8 weeks of treatment, 80% of pravastatin treated patients (N. 16/20) and 75% of those treated with Armolipid Plus® (N. 15/20) reached the desired LDL-C target, while 50% of pravastatin treated patients (N. 10/20) and 80% of the Armolipid Plus® treated ones reached the desired TG target (N. 16/20). No one adverse event has been registered during Armolipid Plus®, while 1 patient claimed myalgia and 1 reported significant increase of CPK (> 3 ULN) during pravastatin treatment. Both patients were then treated with Armolipid Plus® with resolution of symptoms and CPK increase, respectively. CONCLUSION In hypertriglyceridemic patients treated with fenofibrate, the association with a combined lipid lowering nutraceutical seem to be more effective in optimizing residual hypertriglyceridemia than pravastatin 40 mg, while being more tolerable and having similar effect on LDL-C plasma level.
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Cardiovascular outcomes during extended follow-up of the AIM-HIGH trial cohort.
Probstfield, JL, Boden, WE, Anderson, T, Branch, K, Kashyap, M, Fleg, JL, Desvigne-Nickens, P, McBride, R, McGovern, M, ,
Journal of clinical lipidology. 2018;(6):1413-1419
Abstract
BACKGROUND Epidemiologic studies have shown that low levels of high-density lipoprotein-cholesterol (HDL-C) and elevated triglycerides are independent predictors of cardiovascular (CV) events, though randomized trials of HDL-C-raising therapies to reduce clinical events have been largely disappointing. The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) trial failed to show that extended release niacin (ERN) reduced CV events in patients with atherogenic dyslipidemia who were on statin-based therapy. OBJECTIVE We sought to determine whether extended follow-up of AIM-HIGH participants changed these null results. METHODS AIM-HIGH was a placebo-controlled trial of 3414 patients with established CV disease, low baseline HDL-C, and elevated triglycerides levels randomized to ERN 1500-2000 mg/d vs placebo. Participants also received simvastatin with or without ezetimibe to attain on-treatment low-density lipoprotein cholesterol levels of 40-80 mg/dL. The trial was halted after a mean 3-year follow-up because of futility. RESULTS Among 3236 participants alive at the end of blinded study, 2613 (81%; ERN = 1,312, placebo = 1301) were followed a mean 1.1 additional years. Ninety-five percent of subjects remained on statin, but only 4% on ERN. At a mean total follow-up of 4.1 years, there were 343 primary CV endpoints in the ERN arm and 305 CV endpoints in placebo participants (HR 1.11, 95% CI 0.96, 1.30). Ischemic stroke was also not significantly different after extended follow-up in the two groups (2.2% vs 1.5%, P = .13). CONCLUSIONS In patients with CV disease and atherogenic dyslipidemia on statin-based therapy, 3 years of ERN treatment did not lower CV event rates. An additional year of follow-up off assigned treatment did not alter these findings.