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1.
Lipid profile and risk of ovarian tumours: a meta-analysis.
Onwuka, JU, Okekunle, AP, Olutola, OM, Akpa, OM, Feng, R
BMC cancer. 2020;(1):200
Abstract
BACKGROUND Existing data from several reports on the association between lipid profile and ovarian tumour (OT) suggests divergent conclusions. Our aim was to examine whether circulating lipid profile: total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) differed between cases and non-cases of OT. METHODS Electronic repositories; PUBMED, EMBASE and Cochrane library were explored through December 2019 to retrieve published articles for inclusion in the meta-analysis after quality assessment. Heterogeneity was assessed using I2 statistics, the effect of individual studies on the overall effect size was tested using sensitivity analysis and funnel plot was used to evaluate publication bias. RESULTS Twelve studies, involving 1767 OT cases and 229,167 non-cases of OT were included in this meta-analysis and I2 statistics ranged between 97 and 99%. Mean circulating TC (- 16.60 [- 32.43, - 0.77]mg/dL; P = 0.04) and HDL (- 0.25[- 0.43, - 0.08]mmol/L; P = 0.005) were significantly lower among OT cases compared to non-OT cases. CONCLUSION Decreased TC and HDL profiles were observed among subjects with OT in this collection of reports. The implications of TC and HDL in tumour manifestations and growth need to be validated in a large multi-ethnic longitudinal cohort adjusting for relevant confounders.
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Triglyceride glucose index is an independent predictor for the progression of coronary artery calcification in the absence of heavy coronary artery calcification at baseline.
Won, KB, Park, EJ, Han, D, Lee, JH, Choi, SY, Chun, EJ, Park, SH, Han, HW, Sung, J, Jung, HO, et al
Cardiovascular diabetology. 2020;(1):34
Abstract
BACKGROUND Data on the relationship between the triglyceride glucose (TyG) index and coronary artery calcification (CAC) progression is limited. This longitudinal study evaluated the association of TyG index with CAC progression in asymptomatic adults. METHODS We enrolled 12,326 asymptomatic Korean adults who had at least two CAC evaluations. The TyG index was determined using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). CAC progression was defined as a difference ≥ 2.5 between the square roots (√) of the baseline and follow-up coronary artery calcium score (CACS) (Δ√transformed CACS). Annualized Δ√transformed CACS was defined as Δ√transformed CACS divided by the inter-scan period. RESULTS During a mean 3.3 years, the overall incidence of CAC progression was 30.6%. The incidence of CAC progression (group I [lowest]: 22.7% versus [vs.] group II: 31.7% vs. group III [highest]: 37.5%, P < 0.001) and annualized Δ√transformed CACS (group I: 0.46 ± 1.44 vs. group II: 0.71 ± 2.02 vs. group III: 0.87 ± 1.75, P < 0.001) were markedly elevated with increasing TyG index tertiles. Multivariate linear regression analysis showed that TyG index was associated with annualized Δ√transformed CACS (β = 0.066, P = 0.036). In multivariate logistic regression analysis, the TyG index was significantly associated with CAC progression in baseline CACS ≤ 100. CONCLUSION The TyG index is an independent predictor of CAC progression, especially in adults without heavy baseline CAC.
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3.
Triglyceride-Rich Lipoprotein Cholesterol, Small Dense LDL Cholesterol, and Incident Cardiovascular Disease.
Duran, EK, Aday, AW, Cook, NR, Buring, JE, Ridker, PM, Pradhan, AD
Journal of the American College of Cardiology. 2020;(17):2122-2135
Abstract
BACKGROUND Elevated triglyceride-rich lipoprotein (TRL) and small-dense low-density lipoprotein (sdLDL) particles are hallmarks of atherogenic dyslipidemia, and their cholesterol content is hypothesized to drive atherosclerotic risk. Prospective epidemiological data pertaining to cholesterol content of TRLs and sdLDL in primary prevention populations are mostly limited to coronary heart disease. OBJECTIVES The purpose of this study was to prospectively evaluate whether triglyceride-rich lipoprotein cholesterol (TRL-C) and small-dense low-density lipoprotein cholesterol (sdLDL-C) concentrations associate with composite and individual incident cardiovascular disease (CVD) outcomes including myocardial infarction (MI), ischemic stroke (IS), and peripheral artery disease (PAD). METHODS In a prospective case-cohort study within the Women's Health Study, TRL-C and sdLDL-C (mg/dl) were directly measured in baseline blood specimens of case subjects (n = 480) and the reference subcohort (n = 496). Risk associations were evaluated for total CVD (MI, IS, PAD, and CVD death), coronary and cerebrovascular disease (MI, IS, CVD death), and individual outcomes (MI, IS, and PAD). Models were adjusted for traditional risk factors, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. RESULTS The risk of both composite outcomes significantly increased across quartiles of TRL-C and sdLDL-C. TRL-C was significantly associated with MI and PAD (MI hazard ratio [HR]Q4: 3.05 [95% confidence interval (CI): 1.46 to 6.39]; ptrend = 0.002; PAD HRQ4: 2.58 [95% CI: 1.18 to 5.63]; ptrend = 0.019), whereas sdLDL-C was significantly associated with MI alone (HRQ4: 3.71 [95% CI: 1.59 to 8.63]; ptrend < 0.001). Both markers weakly associated with IS. Association patterns were similar for continuous exposures and, for TRL-C, among subjects with low atherogenic particle concentrations (apolipoprotein B <100 mg/dl). CONCLUSIONS TRL-C strongly associates with future MI and PAD events, whereas sdLDL-C strongly associates with MI alone. These findings signal that the cholesterol content of TRLs and sdLDL influence atherogenesis independently of low-density lipoprotein cholesterol, and high sensitivity C-reactive protein, with potentially different potency across vascular beds. (Women's Health Study; NCT00000479).
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Elevated Triglycerides to High-Density Lipoprotein Cholesterol (TG/HDL-C) Ratio Predicts Long-Term Mortality in High-Risk Patients.
Sultani, R, Tong, DC, Peverelle, M, Lee, YS, Baradi, A, Wilson, AM
Heart, lung & circulation. 2020;(3):414-421
Abstract
BACKGROUND Elevated triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been utilised as a predictor of outcomes in patients with adverse cardiometabolic risk profiles. In this study, we examined the prognostic value of elevated TG/HDL-C level in an Australian population of patients with high clinical suspicion of coronary artery disease (CAD) presenting for coronary angiography. METHODS Follow-up data was collected for 482 patients who underwent coronary angiography in a prospective cohort study. The primary endpoint was all-cause mortality and the secondary endpoint was a major adverse cardiac event (MACE). Patients were stratified into two groups according to their baseline TG/HDL-C ratio, using a TG/HDL-C ratio cut point of 2.5. RESULTS The mean follow-up period was 5.1 ± 1.2 years, with 49 all-cause deaths. Coronary artery disease on coronary angiography was more prevalent in patients with TG/HDL-C ratio ≥2.5 (83.6% vs. 69.4%, p = 0.03). On the Kaplan-Meier analysis, patients with TG/HDL-C ratio ≥2.5 had worse long-term prognosis (p = 0.04). On multivariate Cox regression adjusting for established cardiovascular risk factors and CAD on coronary angiography, TG/HDL-C ratio ≥2.5 was an independent predictor of long-term all-cause mortality (hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.04-4.20, p = 0.04). On multivariate logistic regression adjusting for known cardiovascular risk factors and CAD on coronary angiography, TG/HDL-C ratio ≥2.5 was strongly associated with an increased risk of long-term MACE (odds ratio [OR] 2.72, 95% CI 1.42-5.20, p = 0.002). CONCLUSIONS Elevated TG/HDL-C ratio is an independent predictor of long-term all-cause mortality and is strongly associated with an increased risk of MACE.
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Risk Factor Control and Cardiovascular Event Risk in People With Type 2 Diabetes in Primary and Secondary Prevention Settings.
Wright, AK, Suarez-Ortegon, MF, Read, SH, Kontopantelis, E, Buchan, I, Emsley, R, Sattar, N, Ashcroft, DM, Wild, SH, Rutter, MK
Circulation. 2020;(20):1925-1936
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Abstract
BACKGROUND To examine the association between the degree of risk factor control and cardiovascular disease (CVD) risk in type 2 diabetes and to assess if the presence of cardio-renal disease modifies these relationships. METHODS A retrospective cohort study using data from English practices from CPRD GOLD (Clinical Practice Research Datalink) and the SCI-Diabetes dataset (Scottish Care Information-Diabetes), with linkage to hospital and mortality data. We identified 101 749 with type 2 diabetes (T2D) in CPRD matched with 378 938 controls without diabetes and 330 892 with type 2 diabetes in SCI-Diabetes between 2006 and 2015. The main exposure was number of optimized risk factors: nonsmoker, total cholesterol ≤4 mmol/L, triglycerides ≤1.7 mmol/L, glycated haemoglobin (HbA1c) ≤53 mmol/mol (≤7.0%), systolic blood pressure <140mm Hg, or <130 mm Hg if high risk. Cox models were used to assess cardiovascular risk associated with levels of risk factor control. RESULTS In CPRD, the mean baseline age in T2D was 63 years and 28% had cardio-renal disease (SCI-Diabetes: 62 years; 35% cardio-renal disease). Over 3 years follow-up (SCI-Diabetes: 6 years), CVD events occurred among 27 900 (27%) CPRD-T2D, 101 362 (31%) SCI-Diabetes-T2D, and 75 520 (19%) CPRD-controls. In CPRD, compared with controls, T2D participants with optimal risk factor control (all risk factors controlled) had a higher risk of CVD events (adjusted hazard ratio, 1.21; 95% confidence interval, 1.12-1.29). In T2D participants from CPRD and SCI-Diabetes, pooled hazard ratios for CVD associated with 5 risk factors being elevated versus optimal risk factor control were 1.09 (95% confidence interval, 1.01-1.17) in people with cardio-renal disease but 1.96 (95% confidence interval, 1.82-2.12) in people without cardio-renal disease. People without cardio-renal disease were younger and more likely to have likely to have suboptimal risk factor control but had fewer prescriptions for risk factor modifying medications than those with cardio-renal disease. CONCLUSIONS Optimally managed people with T2D have a 21% higher CVD risk when compared with controls. People with T2D without cardio-renal disease would be predicted to benefit greatly from CVD risk factor intervention.
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Feasibility, Safety, and Beneficial Effects of MCT-Based Ketogenic Diet for Breast Cancer Treatment: A Randomized Controlled Trial Study.
Khodabakhshi, A, Akbari, ME, Mirzaei, HR, Mehrad-Majd, H, Kalamian, M, Davoodi, SH
Nutrition and cancer. 2020;(4):627-634
Abstract
The present study was aimed to evaluate the safety, tolerability, and beneficial effects of a ketogenic diet (KD) on body composition and blood parameters and survival in patients with breast cancer. In this randomized, controlled trial, 60 patients with locally advanced or metastatic breast cancer and planned chemotherapy, were randomly assigned to a group receiving KDs (n = 30) or to a control group with standard diet (n = 30) for 3 months. Serum biochemical parameters and body composition were analyzed at baseline, every 3 weeks and end of each arm. Compliance and safety of KD were also checked weekly. Fasting blood sugar (FBS) was significantly decreased in intervention group compared to the baseline (84.5 ± 11.3 vs. 100.4 ± 11.8, P = 0.001). A significant inter-group difference was also observed for FBS level at end of intervention. There was an increasing trend in serum levels of ketone bodies in intervention group (0.007-0.92, P < 0.001). Compared to the control group, BMI, body weight, and fat% were significantly decreased in intervention group in last visit (P < 0.001). No severe adverse side effect was found regarding lipid profile and kidney or liver marker. Overall survival was higher in KD group compared to the control group in neoadjuvant patients (P = 0.04). Our results suggested that chemotherapy combined with KDs can improve the biochemical parameters, body composition, and overall survival with no substantial side effects in patients with breast cancer.
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Improvement of endothelial dysfunction is mediated through reduction of remnant lipoprotein after statin therapy in patients with coronary artery disease.
Nakamura, T, Uematsu, M, Yoshizaki, T, Kobayashi, T, Watanabe, Y, Kugiyama, K
Journal of cardiology. 2020;(3):270-274
Abstract
BACKGROUND Remnant lipoproteinemia with high levels of low-density lipoprotein cholesterol (LDL-C) is a high risk for endothelial dysfunction. Statins are the first-line lipid-lowering drugs for this combined hyperlipidemia. However, it remains undetermined whether reduction of remnant lipoprotein mediates the relationship between improvement in endothelial dysfunction and reduction of LDL-C level after statin treatment. METHODS A total of 122 coronary artery disease (CAD) patients with impaired flow-mediated dilation (FMD; <5.5%), high levels of LDL-C (≥100 mg/dL), and remnant-like lipoprotein particle cholesterol (RLP-C) (≥5 mg/dL) were examined in this study. The lipid profiles and FMD were measured before and after 6-9 months of statin treatment. The association between changes in LDL-C levels and its relationship with changes in FMD was investigated. Furthermore, mediation analysis was performed to assess the changes in RLP-C level as a mediator of the relationship between the reduction in LDL-C level and improvement of FMD. RESULTS Treatment with statins improved FMD in 69 (56.5%) patients. Patients with improved FMD showed lower percent changes of LDL-C, triglyceride (TG), RLP-C, RLP-C/TG, and C-reactive protein (CRP) levels, and higher percent change of HDL-C level, compared to patients who did not show improved FMD. The percent changes in FMD levels had a significant inverse correlation with the percent changes in LDL-C, (r = -0.18, p = 0.03), RLP-C (r = -0.39, p < 0.001), RLP-C/TG (r = -0.34, p < 0.001), and CRP (r = -0.27, p < 0.01). Mediation analysis showed that the relationship between reduction in LDL-C and improvement of FMD was mediated by reduction of RLP-C (34.5%), RLP-C/TG (24.4%), and CRP (24.9%) levels. CONCLUSION Improvement of remnant lipoproteinemia may be an important mediator for the relationship between improvement of endothelial dysfunction and LDL-lowering after statin treatment in patients with CAD.
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Short-Term Efficacy (at 12 Weeks) and Long-Term Safety (up to 52 Weeks) of Omega-3 Free Fatty Acids (AZD0585) for the Treatment of Japanese Patients With Dyslipidemia - A Randomized, Double-Blind, Placebo-Controlled, Phase III Study.
Yokote, K, Niwa, K, Hakoda, T, Oh, F, Kajimoto, Y, Fukui, T, Kim, H, Noda, Y, Lundström, T, Yajima, T
Circulation journal : official journal of the Japanese Circulation Society. 2020;(6):994-1003
Abstract
BACKGROUND This study is the first to evaluate the short-term efficacy and long-term safety of AZD0585, a mixture of omega-3 free fatty acids, in Japanese patients with dyslipidemia.Methods and Results:In this randomized double-blind placebo-controlled Phase III study, 383 patients were randomized to 2 g AZD0585, 4 g AZD0585, or placebo once daily for 52 weeks. Eligible patients had low-density lipoprotein cholesterol (LDL-C) levels controlled regardless of statin use, and triglyceride levels between 150 and 499 mg/dL. The least-squares (LS) mean percentage changes in triglyceride concentrations from baseline to the 12-week endpoint (mean of measurements at Weeks 10 and 12) in the 2 and 4 g AZD0585 and placebo groups were -15.57%, -21.75%, and 11.15% respectively (P<0.0001 for both AZD0585 doses vs. placebo). No clinically significant changes from baseline to the 12-week endpoint in total cholesterol, LDL-C, and LDL-C/apolipoprotein (Apo) B were found with AZD0585. High-density lipoprotein cholesterol (HDL-C) was slightly increased and very low-density lipoprotein cholesterol, non-HDL-C, ApoC-II, and ApoC-III were decreased with AZD0585 compared with placebo at the 12-week endpoint. Lipid profiles up to Week 52 were consistent with those up to the 12-week endpoint. No clinically important safety concerns were raised. CONCLUSIONS AZD0585 significantly decreased serum triglyceride levels compared with placebo at the 12-week endpoint and was generally safe and well tolerated in Japanese patients with dyslipidemia.
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Familial chylomicronemia syndrome: A rare but devastating autosomal recessive disorder characterized by refractory hypertriglyceridemia and recurrent pancreatitis.
Chyzhyk, V, Brown, AS
Trends in cardiovascular medicine. 2020;(2):80-85
Abstract
Familial Chylomicronemia Syndrome (FCS) is a rare autosomal recessive lipid disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis. Because the disorder is often misdiagnosed or not diagnosed and because traditional triglyceride lowering medications are often ineffective, the disease leads to a tremendous physical, social and emotional burden on afflicted patients and their caretakers. Mutations in 5 different genes have been implicated in the development of FCS, all of which have an effect on the activity of lipoprotein lipase. Lipoprotein lipase(LPL) is responsible for removing triglycerides from chylomicrons and other triglyceride rich lipoproteins in the circulation, breaking them down into free fatty acids for use as energy. Patients with FCS have loss of function of their LPL leading to severely elevated chylomicrons in the circulation and hence, severe hypertriglyceridemia. The principle treatment for FCS is to reduce chylomicron formation in the gut by placing the patient on an extremely low fat diet. New medications in development hold significant promise for improving the quality of life for FCS patients.
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Incorporating Milk Protein Isolate into an Energy-Restricted Western-Style Eating Pattern Augments Improvements in Blood Pressure and Triglycerides, but Not Body Composition Changes in Adults Classified as Overweight or Obese: A Randomized Controlled Trial.
Hudson, JL, Zhou, J, Kim, JE, Campbell, WW
Nutrients. 2020;(3)
Abstract
Unhealthy Western-style eating patterns (WSEP) predominate, adversely affecting health. Resistance to improving dietary patterns prompts interest to incorporate a potentially health-promoting ingredient into typical WSEP foods and beverages. We assessed the effect of incorporating isocalorically matched carbohydrates versus milk protein isolate (MPI) into a WSEP on weight loss-induced changes in cardiometabolic health and body composition. In a randomized, double-blind, parallel-design study, 44 participants (age 52 ± 1 years, body mass index (BMI) 31.4 ± 0.5 kg/m2, mean ± standard error) consumed a weight maintenance WSEP (0.8 g total protein/kg/day) for 3 weeks (baseline). After, participants consumed an energy-restricted (750 kcal/day below estimated requirement) WSEP for 16 weeks, randomly assigned to contain either an additional 0.7 g carbohydrate/kg/d (CON: n = 23, 0.8 g total protein/kg/day) or 0.7 g protein/kg/d from MPI (MPI: n = 21, 1.5 g total protein/kg/day) incorporated into foods and beverages. Compared to CON, the MPI favored reductions in average 24 h and sleeping systolic and diastolic blood pressures (BP), waking hours systolic BP, and fasting plasma triglyceride concentrations. Reductions in fasting plasma insulin, glucose, total cholesterol, and low-density lipoprotein cholesterol concentrations were not different between groups. Among all participants, whole body mass, lean mass, fat mass, and thigh muscle area, each decreased over time. For adults finding it difficult to deviate from a WSEP, replacing a portion of their carbohydrate with foods and beverages containing MPI may be an effective dietary strategy to reduce BP after weight loss.