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PLoS Medicine Jul 2020Bempedoic acid is a first-in-class lipid-lowering drug recommended by guidelines for the treatment of hypercholesterolemia. Our objective was to estimate its average... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bempedoic acid is a first-in-class lipid-lowering drug recommended by guidelines for the treatment of hypercholesterolemia. Our objective was to estimate its average effect on plasma lipids in humans and its safety profile.
METHODS AND FINDINGS
We carried out a systematic review and meta-analysis of phase II and III randomized controlled trials on bempedoic acid (PROSPERO: CRD42019129687). PubMed (Medline), Scopus, Google Scholar, and Web of Science databases were searched, with no language restriction, from inception to 5 August 2019. We included 10 RCTs (n = 3,788) comprising 26 arms (active arm [n = 2,460]; control arm [n = 1,328]). Effect sizes for changes in lipids and high-sensitivity C-reactive protein (hsCRP) serum concentration were expressed as mean differences (MDs) and 95% confidence intervals (CIs). For safety analyses, odds ratios (ORs) and 95% CIs were calculated using the Mantel-Haenszel method. Bempedoic acid significantly reduced total cholesterol (MD -14.94%; 95% CI -17.31%, -12.57%; p < 0.001), non-high-density lipoprotein cholesterol (MD -18.17%; 95% CI -21.14%, -15.19%; p < 0.001), low-density lipoprotein cholesterol (MD -22.94%; 95% CI -26.63%, -19.25%; p < 0.001), low-density lipoprotein particle number (MD -20.67%; 95% CI -23.84%, -17.48%; p < 0.001), apolipoprotein B (MD -15.18%; 95% CI -17.41%, -12.95%; p < 0.001), high-density lipoprotein cholesterol (MD -5.83%; 95% CI -6.14%, -5.52%; p < 0.001), high-density lipoprotein particle number (MD -3.21%; 95% CI -6.40%, -0.02%; p = 0.049), and hsCRP (MD -27.03%; 95% CI -31.42%, -22.64%; p < 0.001). Bempedoic acid did not significantly modify triglyceride level (MD -1.51%; 95% CI -3.75%, 0.74%; p = 0.189), very-low-density lipoprotein particle number (MD 3.79%; 95% CI -9.81%, 17.39%; p = 0.585), and apolipoprotein A-1 (MD -1.83%; 95% CI -5.23%, 1.56%; p = 0.290). Treatment with bempedoic acid was positively associated with an increased risk of discontinuation of treatment (OR 1.37; 95% CI 1.06, 1.76; p = 0.015), elevated serum uric acid (OR 3.55; 95% CI 1.03, 12.27; p = 0.045), elevated liver enzymes (OR 4.28; 95% CI 1.34, 13.71; p = 0.014), and elevated creatine kinase (OR 3.79; 95% CI 1.06, 13.51; p = 0.04), though it was strongly associated with a decreased risk of new onset or worsening diabetes (OR 0.59; 95% CI 0.39, 0.90; p = 0.01). The main limitation of this meta-analysis is related to the relatively small number of individuals involved in the studies, which were often short or middle term in length.
CONCLUSIONS
Our results show that bempedoic acid has favorable effects on lipid profile and hsCRP levels and an acceptable safety profile. Further well-designed studies are needed to explore its longer-term safety.
Topics: Anticholesteremic Agents; Apolipoproteins B; Cholesterol; Cholesterol, LDL; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dicarboxylic Acids; Fatty Acids; Humans; Hypercholesterolemia; Peptide Fragments; Randomized Controlled Trials as Topic
PubMed: 32673317
DOI: 10.1371/journal.pmed.1003121 -
Journal of Lipid Research Dec 2016The burden caused by familial hypercholesterolemia (FH) varies among countries and ethnic groups. The prevalence and characteristics of FH in Latin American (LA)... (Review)
Review
The burden caused by familial hypercholesterolemia (FH) varies among countries and ethnic groups. The prevalence and characteristics of FH in Latin American (LA) countries is largely unknown. We present a systematic review (following the PRISMA statement) of FH in LA countries. The epidemiology, genetics, screening, management, and unique challenges encountered in these countries are discussed. Published reports discussing FH in Hispanic or LA groups was considered for analysis. Thirty studies were included representing 10 countries. The bulk of the data was generated in Brazil and Mexico. Few countries have registries and there was little commonality in FH mutations between LA countries. LDL receptor mutations predominate; APOB and PCSK9 mutations are rare. No mutation was found in an FH gene in nearly 50% of cases. In addition, some country-specific mutations have been reported. Scant information exists regarding models of care, cascade screening, cost, treatment effectiveness, morbidity, and mortality. In conclusion, FH is largely underdiagnosed and undertreated in the LA region. The genetic admixture with indigenous populations, producing mestizo's groups, may influence the mutational findings in Latin America. Potential opportunities to close gaps in knowledge and health care are identified.
Topics: Apolipoproteins B; Humans; Hyperlipoproteinemia Type II; Latin America; Mutation; Receptors, LDL; Risk Factors
PubMed: 27777316
DOI: 10.1194/jlr.R072231 -
European Eating Disorders Review : the... Mar 2016Oxidative stress markers seem to be higher in patients with anorexia nervosa (AN) than healthy controls, but the potentially beneficial effects of weight gain is not... (Meta-Analysis)
Meta-Analysis Review
Oxidative stress markers seem to be higher in patients with anorexia nervosa (AN) than healthy controls, but the potentially beneficial effects of weight gain is not known. We calculated random effects standardised mean differences (SMDs) as effect size measures of oxidative stress marker changes after re-alimentation reported in two or more studies, summarising others descriptively. Seven longitudinal studies (n = 104) were included. After a median follow-up period of 8 weeks, AN patients significantly increased their body mass index (15.1 ± 2.1 to 17.1 ± 2.2, p < 0.0001). This weight gain was followed by a significant increase in serum levels of the antioxidant albumin (studies = 6, SMD = 0.50, 95%CI = 0.18; 0.82, p = 0.002; I(2) = 16%) and a significant decrease in the oxidative stress marker Apolipoprotein B (studies = 2, n = 19, SMD = -0.85, 95%CI = -1.53; -0.17, p = 0.01; I(2) = 0). In one study, catalase and total antioxidant capacity increased, whilst superoxide dismutase significantly decreased. In conclusion, oral re-alimentation, even without full-weight normalisation, seems to improve oxidative stress in people with AN.
Topics: Albumins; Anorexia Nervosa; Antioxidants; Apolipoprotein B-100; Biomarkers; Catalase; Humans; Longitudinal Studies; Oxidative Stress; Superoxide Dismutase; Weight Gain
PubMed: 26663703
DOI: 10.1002/erv.2420 -
Advances in Nutrition (Bethesda, Md.) Nov 2015High-oleic acid soybean oil (H-OSBO) is a trait-enhanced vegetable oil containing >70% oleic acid. Developed as an alternative for trans-FA (TFA)-containing vegetable... (Review)
Review
A systematic review of high-oleic vegetable oil substitutions for other fats and oils on cardiovascular disease risk factors: implications for novel high-oleic soybean oils.
High-oleic acid soybean oil (H-OSBO) is a trait-enhanced vegetable oil containing >70% oleic acid. Developed as an alternative for trans-FA (TFA)-containing vegetable oils, H-OSBO is predicted to replace large amounts of soybean oil in the US diet. However, there is little evidence concerning the effects of H-OSBO on coronary heart disease (CHD)(6) risk factors and CHD risk. We examined and quantified the effects of substituting high-oleic acid (HO) oils for fats and oils rich in saturated FAs (SFAs), TFAs, or n-6 (ω-6) polyunsaturated FAs (PUFAs) on blood lipids in controlled clinical trials. Searches of online databases through June 2014 were used to select studies that defined subject characteristics; described control and intervention diets; substituted HO oils compositionally similar to H-OSBO (i.e., ≥70% oleic acid) for equivalent amounts of oils high in SFAs, TFAs, or n-6 PUFAs for ≥3 wk; and reported changes in blood lipids. Studies that replaced saturated fats or oils with HO oils showed significant reductions in total cholesterol (TC), LDL cholesterol, and apolipoprotein B (apoB) (P < 0.05; mean percentage of change: -8.0%, -10.9%, -7.9%, respectively), whereas most showed no changes in HDL cholesterol, triglycerides (TGs), the ratio of TC to HDL cholesterol (TC:HDL cholesterol), and apolipoprotein A-1 (apoA-1). Replacing TFA-containing oil sources with HO oils showed significant reductions in TC, LDL cholesterol, apoB, TGs, TC:HDL cholesterol and increased HDL cholesterol and apoA-1 (mean percentage of change: -5.7%, -9.2%, -7.3%, -11.7%, -12.1%, 5.6%, 3.7%, respectively; P < 0.05). In most studies that replaced oils high in n-6 PUFAs with equivalent amounts of HO oils, TC, LDL cholesterol, TGs, HDL cholesterol, apoA-1, and TC:HDL cholesterol did not change. These findings suggest that replacing fats and oils high in SFAs or TFAs with either H-OSBO or oils high in n-6 PUFAs would have favorable and comparable effects on plasma lipid risk factors and overall CHD risk.
Topics: Adult; Aged; Apolipoproteins B; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dietary Fats; Dietary Fats, Unsaturated; Fatty Acids, Omega-6; Female; Humans; Lipids; Male; Middle Aged; Oleic Acid; Risk Factors; Soybean Oil; Triglycerides
PubMed: 26567193
DOI: 10.3945/an.115.008979 -
Experimental and Clinical Endocrinology... Apr 2013Carnitine is an endogenous metabolite and exogenous nutrient with a pivotal role in lipid metabolism. Plasma levels of carnitine are reduced in type 2 Diabetes Mellitus... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Carnitine is an endogenous metabolite and exogenous nutrient with a pivotal role in lipid metabolism. Plasma levels of carnitine are reduced in type 2 Diabetes Mellitus (T2DM). The aim was to evaluate the metabolic effects of the administration of L-carnitine in T2DM.
METHOD
A systematic review was performed. Relevant randomized, controlled-trials trials were searched in Pubmed, Trip Database and Cochrane Library, and selected when they had enough methodological quality assessed with the Jadad scale. Article search strategy included "Carnitine" OR "L-carnitine" AND "Diabetes -Mellitus" OR "Diabetes mellitus, type 2" OR "Noninsulindependent-diabetes mellitus". Meta-analysis was performed, and the difference of means calculated with a 95% confidence interval. Heterogeneity was evaluated with the Q statistic.
RESULTS
The systematic review included 4 trials with 284 patients. Oral L-carnitine lowered fasting plasma glucose [-14.3 mg/dl (CI95% - 23.2 to -5.4); p=0,002], total cholesterol [-7.8 mg/dL (95%CI -15.5 to -0.1); p=0.09], low density lipoprotein [-8.8 mg/dl (CI95% -12.2 to -8.5), p<0.0001], apolipoprotein-B100 [-7.6 mg/dl (CI95% -13.6 to -1.6); p=0.013] and apolipoprotein-A1 [-6.0 mg/dl (CI95% -10.5 a -1.5); p=0.523]. There was no significant heterogeneity. The changes in triglycerides, lipoprotein (a) or HbA(1c) were not significant.
CONCLUSION
The administration of L-carnitine in type 2 diabetes mellitus is associated with an improvement in glycaemia and plasma lipids.
Topics: Apolipoprotein A-I; Apolipoprotein B-100; Blood Glucose; Carnitine; Cholesterol; Diabetes Mellitus, Type 2; Fasting; Humans; Insulin; Lipids; Lipoproteins, LDL; MEDLINE; Postprandial Period; Randomized Controlled Trials as Topic
PubMed: 23430574
DOI: 10.1055/s-0033-1333688 -
Atherosclerosis Nov 2012Lipoprotein association phospholipase A2 (Lp-PLA(2)), an enzyme which has been found in atherosclerotic plaque is currently under investigation in large Phase III... (Review)
Review
BACKGROUND
Lipoprotein association phospholipase A2 (Lp-PLA(2)), an enzyme which has been found in atherosclerotic plaque is currently under investigation in large Phase III clinical trials of vascular disease prevention. We assessed in a variety of different population settings variation of Lp-PLA(2) mass and activity across gender, ethnicity, diabetes, kidney disease and metabolic syndrome. We also assessed correlations with measures of circulating lipids, systemic inflammation and adiposity.
METHODS
Systematic review of studies measuring Lp-PLA(2) and at least one of the relevant characteristics in >50 participants.
RESULTS
We identified a total of 77 studies involving 102,499 participants meeting the inclusion criteria. Lp-PLA(2) mass and activity were consistently approximately 10% higher in males than females and 15% higher in Caucasians than African Americans or Hispanics. There were no clear associations of Lp-PLA(2) mass or activity with type II diabetes, markers of systemic inflammation (C-reactive protein, fibrinogen) or with body mass index. Correlations of Lp-PLA(2) mass or activity with low density lipoprotein cholesterol and apolipoprotein B were moderate and positive, whilst correlations with high density lipoprotein cholesterol were negative and moderate to weak. There was no clear differences in associations with any of the above characteristics in groups defined based upon prevalent cardiovascular disease or its risk factors.
CONCLUSIONS
Despite considerable variability in absolute levels of Lp-PLA(2) across studies, the variability of Lp-PLA(2) across gender, ethnicity, and levels of circulating lipids and markers of systemic inflammation are more consistent and appear not to vary importantly across categories defined by CVD or its risk factors.
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Black or African American; Animals; Apolipoproteins B; Biomarkers; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Inflammation; Lipids; Male; Risk Factors; Sex Factors; White People
PubMed: 22784637
DOI: 10.1016/j.atherosclerosis.2012.06.020 -
Atherosclerosis Oct 2017Genetic studies have been reported on the association between APOA5, APOB, APOC3 and ABCA1 gene polymorphisms and ischemic stroke, but results remain controversial.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Genetic studies have been reported on the association between APOA5, APOB, APOC3 and ABCA1 gene polymorphisms and ischemic stroke, but results remain controversial. Hence, this meta-analysis aimed to infer the causal relationships of APOA5 (rs662799, rs3135506), APOB (rs693, rs1042031, rs1801701), APOC3 (rs4520, rs5128, rs2854116, rs2854117) and ABCA1 rs2230806 with ischemic stroke risk.
METHODS
A systematic review was performed for all the articles retrieved from multiple databases, up until March 2017. Data were extracted from all eligible studies, and meta-analysis was carried out using RevMan 5.3 and R package 3.2.1. The strength of association between each studied polymorphism and ischemic stroke risk was measured as odds ratios (ORs) and 95% confidence intervals (CIs), under fixed- and random-effect models.
RESULTS
A total of 79 studies reporting on the association between the studied polymorphisms and ischemic stroke risk were identified. The pooled data indicated that all genetic models of APOA5 rs662799 (ORs = 1.23-1.43), allelic and over-dominant models of APOA5 rs3135506 (ORs = 1.77-1.97), APOB rs1801701 (ORs = 1.72-2.13) and APOB rs1042031 (ORs = 1.66-1.88) as well as dominant model of ABCA1 rs2230806 (OR = 1.31) were significantly associated with higher risk of ischemic stroke. However, no significant associations were observed between ischemic stroke and the other five polymorphisms, namely ApoB (rs693) and APOC3 (rs4520, rs5128, rs2854116 and rs2854117), under any genetic model.
CONCLUSIONS
The present meta-analysis confirmed a significant association of APOA5 rs662799 CC, APOA5 rs3135506 CG, APOB rs1801701 GA, APOB rs1042031 GA and ABCA1 rs2230806 GG with increased risk of ischemic stroke.
Topics: ATP Binding Cassette Transporter 1; Apolipoprotein A-V; Apolipoprotein B-100; Apolipoprotein C-III; Brain Ischemia; Case-Control Studies; Chi-Square Distribution; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Odds Ratio; Phenotype; Polymorphism, Single Nucleotide; Risk Factors; Stroke
PubMed: 28865324
DOI: 10.1016/j.atherosclerosis.2017.08.003 -
European Journal of Clinical Nutrition Jan 2024To investigate the effects of rapeseed oil on body composition, blood glucose and lipid metabolism in people with overweight and obesity compared to other cooking oils.... (Meta-Analysis)
Meta-Analysis Review
To investigate the effects of rapeseed oil on body composition, blood glucose and lipid metabolism in people with overweight and obesity compared to other cooking oils. We searched eight databases for randomized controlled studies (including randomized crossover trials). The risk of bias for the included studies was assessed using the Cochrane Risk of Bias 2.0 tool. The Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria were used to evaluate the quality of the outcomes. The methodological quality of the included studies was assessed using the Physiotherapy Evidence Database (PEDro) scale. Sensitivity analysis was used to check the stability of the pooled results. Statistical analysis was carried out using Review Manager 5.3 software. As a result, fifteen randomized controlled studies (including six parallel studies and nine crossover studies) were included in this study. Compared to other edible oils, rapeseed oil significantly reduced low density lipoprotein cholesterol (LDL-C) (MD = -0.14 mmol/L, 95% CI: -0.21, -0.08, I = 0%, P < 0.0001), apolipoprotein B (ApoB) (MD = -0.03 g/L, 95% CI: -0.05, -0.01, I = 0%, P = 0.0003), ApoB/ApoA1 (MD = -0.02, 95% CI: -0.04, -0.00, I = 0%, P = 0.02) and insulin (MD = -12.45 pmol/L, 95% CI: -19.61, -5.29, I = 37%, P = 0.0007) levels, and increased fasting glucose (MD = 0.16 mmol/L, 95% CI: 0.05, 0.27, I = 27%, P = 0.003) levels. However, the differences in body weight and body composition between rapeseed oil and control oils were not significant. In a word, rapeseed oil is effective in reducing LDL-C, ApoB and ApoB/ApoA1 levels in people with overweight and obesity, which is helpful in preventing and reducing the risk of atherosclerosis. PROSPERO registration number: CRD42022333436.
Topics: Humans; Overweight; Rapeseed Oil; Cholesterol, LDL; Obesity; Body Composition; Apolipoproteins B
PubMed: 37740067
DOI: 10.1038/s41430-023-01344-1 -
Frontiers in Endocrinology 2022Subclinical hypothyroidism (SCH) is usually treated with levothyroxine, but there is controversy as to whether SCH should be treated, especially for older patients. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Subclinical hypothyroidism (SCH) is usually treated with levothyroxine, but there is controversy as to whether SCH should be treated, especially for older patients. The aim of the systematic review and meta-analysis was to evaluate whether levothyroxine has a beneficial or harmful effect on older patients with SCH.
METHODS
Databases including PubMed, Embase, Cochrane Library, Web of Science, Wanfang, Weipu and China National Knowledge Infrastructure were searched from inception until December 21, 2021. Subjects must be diagnosed with SCH, and older than or equal to 60 years of age. Interventions should be thyroid hormone therapy (e.g. levothyroxine). The literature was independently screened by 2 researchers. Statistical analysis was performed using RevMan5.3 software.
RESULTS
A total of 13 articles were included. Meta-analysis results showed that in older SCH patients, levothyroxine can significantly reduce cholesterol (TC) ( < 0.00001), triglyceride (TG) ( < 0.00001), low-density lipoprotein cholesterol (LDL-C) ( = 0.03) and apolipoprotein B (ApoB) ( < 0.00001). In addition, levothyroxine had no significant effect on bone mineral density, fatigue, hypothyroidism symptoms, quality of life, BMI, cognitive function, depression, blood pressure, etc. in older SCH patients, and also did not significantly increase the incidence of adverse events.
CONCLUSIONS
Among older SCH patients, levothyroxine treatment may reduce TC, TG, LDL-C, and ApoB.
Topics: Aged; Apolipoproteins B; Cholesterol; Cholesterol, LDL; Humans; Hypothyroidism; Quality of Life; Thyroxine; Triglycerides
PubMed: 35909574
DOI: 10.3389/fendo.2022.913749 -
The Breast Journal Jul 2019
Topics: Apolipoprotein B-100; Breast Neoplasms; Case-Control Studies; Cohort Studies; Female; Heterozygote; Humans; Hypobetalipoproteinemia, Familial, Apolipoprotein B; Hypobetalipoproteinemias; Lipoproteins, LDL; Risk Factors
PubMed: 31111608
DOI: 10.1111/tbj.13341