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BMJ (Clinical Research Ed.) Jan 2024To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults... (Meta-Analysis)
Meta-Analysis
Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis.
OBJECTIVE
To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults with type 2 diabetes.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from database inception to 19 August 2023.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Eligible randomised controlled trials enrolled adults with type 2 diabetes who received GLP-1RA treatments and compared effects with placebo or any GLP-1RA drug, with a follow-up duration of at least 12 weeks. Trials with a crossover design, non-inferiority studies comparing GLP-1RA and other drug classes without a placebo group, using withdrawn drugs, and non-English studies were deemed ineligible.
RESULTS
76 eligible trials involving 15 GLP-1RA drugs and 39 246 participants were included in this network meta-analysis; all subsequent estimates refer to the comparison with placebo. All 15 GLP-1RAs effectively lowered haemoglobin A and fasting plasma glucose concentrations. Tirzepatide induced the largest reduction of haemoglobin A concentrations (mean difference -2.10% (95% confidence interval -2.47% to -1.74%), surface under the cumulative ranking curve 94.2%; high confidence of evidence), and fasting plasma glucose concentrations (-3.12 mmol/L (-3.59 to -2.66), 97.2%; high confidence), and proved the most effective GLP-1RA drug for glycaemic control. Furthermore, GLP-1RAs were shown to have strong benefits to weight management for patients with type 2 diabetes. CagriSema (semaglutide with cagrilintide) resulted in the highest weight loss (mean difference -14.03 kg (95% confidence interval -17.05 to -11.00); high confidence of evidence), followed by tirzepatide (-8.47 kg (-9.68 to -7.26); high confidence). Semaglutide was effective in lowering the concentration of low density lipoprotein (-0.16 mmol/L (-0.30 to -0.02)) and total cholesterol (-0.48 mmol/L (-0.84 to -0.11)). Moreover, this study also raises awareness of gastrointestinal adverse events induced by GLP-1RAs, and concerns about safety are especially warranted for high dose administration.
CONCLUSIONS
GLP-1RAs are efficacious in treating adults with type 2 diabetes. Compared with the placebo, tirzepatide was the most effective GLP-1RA drug for glycaemic control by reducing haemoglobin A and fasting plasma glucose concentrations. GLP-1RAs also significantly improved weight management for type 2 diabetes, with CagriSema performing the best for weight loss. The results prompt safety concerns for GLP-1RAs, especially with high dose administration, regarding gastrointestinal adverse events.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022342845.
Topics: Adult; Humans; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide-1 Receptor Agonists; Glycated Hemoglobin; Glycemic Control; Hypoglycemic Agents; Network Meta-Analysis; Weight Loss; Lipid Metabolism
PubMed: 38286487
DOI: 10.1136/bmj-2023-076410 -
European Heart Journal Jul 2023Due to growing environmental focus, plant-based diets are increasing steadily in popularity. Uncovering the effect on well-established risk factors for cardiovascular... (Meta-Analysis)
Meta-Analysis
AIMS
Due to growing environmental focus, plant-based diets are increasing steadily in popularity. Uncovering the effect on well-established risk factors for cardiovascular diseases, the leading cause of death worldwide, is thus highly relevant. Therefore, a systematic review and meta-analysis were conducted to estimate the effect of vegetarian and vegan diets on blood levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B.
METHODS AND RESULTS
Studies published between 1980 and October 2022 were searched for using PubMed, Embase, and references of previous reviews. Included studies were randomized controlled trials that quantified the effect of vegetarian or vegan diets vs. an omnivorous diet on blood lipids and lipoprotein levels in adults over 18 years. Estimates were calculated using a random-effects model. Thirty trials were included in the study. Compared with the omnivorous group, the plant-based diets reduced total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B levels with mean differences of -0.34 mmol/L (95% confidence interval, -0.44, -0.23; P = 1 × 10-9), -0.30 mmol/L (-0.40, -0.19; P = 4 × 10-8), and -12.92 mg/dL (-22.63, -3.20; P = 0.01), respectively. The effect sizes were similar across age, continent, duration of study, health status, intervention diet, intervention program, and study design. No significant difference was observed for triglyceride levels.
CONCLUSION
Vegetarian and vegan diets were associated with reduced concentrations of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B-effects that were consistent across various study and participant characteristics. Plant-based diets have the potential to lessen the atherosclerotic burden from atherogenic lipoproteins and thereby reduce the risk of cardiovascular disease.
Topics: Adult; Humans; Diet, Vegan; Diet, Vegetarian; Randomized Controlled Trials as Topic; Lipids; Vegetarians; Cholesterol, LDL; Lipoproteins; Cardiovascular Diseases; Atherosclerosis; Apolipoproteins
PubMed: 37226630
DOI: 10.1093/eurheartj/ehad211 -
JAMA Network Open Jul 2023Plant-based diets are known to improve cardiometabolic risk in the general population, but their effects on people at high risk of cardiovascular diseases (CVDs) remain... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Plant-based diets are known to improve cardiometabolic risk in the general population, but their effects on people at high risk of cardiovascular diseases (CVDs) remain inconclusive.
OBJECTIVE
To assess the association of vegetarian diets with major cardiometabolic risk factors, including low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and body weight in people with or at high risk of CVDs.
DATA SOURCES
This meta-analysis was registered before the study was conducted. Systematic searches performed included Embase, MEDLINE, CINAHL, and CENTRAL from inception until July 31, 2021.
STUDY SELECTION
Eligible randomized clinical trials (RCTs) that delivered vegetarian diets in adults with or at high risk of CVDs and measured LDL-C, HbA1c or SBP were included. Of the 7871 records screened, 29 (0.4%; 20 studies) met inclusion criteria.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data including demographics, study design, sample size, and diet description, and performed risk of bias assessment. A random-effects model was used to assess mean changes in LDL-C, HbA1c, SBP, and body weight. The overall certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool.
MAIN OUTCOMES AND MEASURES
Mean differences between groups in changes (preintervention vs postintervention) of LDL-C, HbA1c, and SBP; secondary outcomes were changes in body weight and energy intake.
RESULTS
Twenty RCTs involving 1878 participants (range of mean age, 28-64 years) were included, and mean duration of intervention was 25.4 weeks (range, 2 to 24 months). Four studies targeted people with CVDs, 7 focused on diabetes, and 9 included people with at least 2 CVD risk factors. Overall, relative to all comparison diets, meta-analyses showed that consuming vegetarian diets for an average of 6 months was associated with decreased LDL-C, HbA1c, and body weight by 6.6 mg/dL (95% CI, -10.1 to -3.1), 0.24% (95% CI, -0.40 to -0.07), and 3.4 kg (95% CI, -4.9 to -2.0), respectively, but the association with SBP was not significant (-0.1 mm Hg; 95% CI, -2.8 to 2.6). The GRADE assessment showed a moderate level of evidence for LDL-C and HbA1c reduction.
CONCLUSIONS AND RELEVANCE
In this study, consuming a vegetarian diet was associated with significant improvements in LDL-C, HbA1c and body weight beyond standard therapy in individuals at high risk of CVDs. Additional high-quality trials are warranted to further elucidate the effects of healthy plant-based diets in people with CVDs.
Topics: Adult; Humans; Middle Aged; Cardiovascular Diseases; Cholesterol, LDL; Glycated Hemoglobin; Vegetarians; Research Design; Body Weight
PubMed: 37490288
DOI: 10.1001/jamanetworkopen.2023.25658 -
Frontiers in Cardiovascular Medicine 2023Individuals diagnosed with atherosclerotic cardiovascular disease (ACD) are exposed to an increased risk of cardiovascular events. Reducing low-density lipoprotein... (Review)
Review
INTRODUCTION
Individuals diagnosed with atherosclerotic cardiovascular disease (ACD) are exposed to an increased risk of cardiovascular events. Reducing low-density lipoprotein cholesterol (LDL-C) levels has been established as an effective approach to mitigate these risks. However, a comprehensive and up-to-date meta-analysis investigating the LDL-C-lowering effectiveness and the impact on coronary atherosclerotic plaque compositions of Ezetimibe has been lacking.
METHODS
We conducted a systematic review by meticulously analyzing databases such as MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials that evaluated the efficacy of ezetimibe in lowering LDL-C levels and its influence on coronary atherosclerotic plaques among individuals with ACD. This review encompassed studies available until August 1, 2023. In our analysis, we employed the weighted mean difference (WMD) as the aggregated statistical measure, accompanied by the corresponding 95% confidence interval (CI).
RESULTS
We encompassed a total of 20 eligible studies. Our findings unveiled that the combined therapy involving ezetimibe alongside statins led to a more substantial absolute decrease in LDL-C in comparison to using statins alone. This difference in means amounted to (-14.06 mg/dl; 95% CI -18.0 to -10.0; = 0.0001). Furthermore, upon conducting subgroup analyses, it became evident that the intervention strategies proved effective in diminishing the volume of dense calcification (DC) in contrast to the control group.
CONCLUSIONS
Our study findings indicate that the inclusion of ezetimibe in conjunction with statin therapy leads to a modest yet meaningful additional reduction in LDL-C levels when compared to using statins in isolation. Importantly, the introduction of ezetimibe resulted in a significant decrease in the volume of DC. However, it is worth noting that further investigation is warranted to delve deeper into this phenomenon.
PubMed: 38075958
DOI: 10.3389/fcvm.2023.1269172 -
The association between lipoprotein(a) and atrial fibrillation: A systemic review and meta-analysis.Clinical Cardiology Aug 2023Lipoprotein(a) (Lp[a]) is a particle consisting of a low-density lipoprotein (LDL)-like core connected to an apolipoprotein(a) chain, which is an established risk factor... (Meta-Analysis)
Meta-Analysis Review
Lipoprotein(a) (Lp[a]) is a particle consisting of a low-density lipoprotein (LDL)-like core connected to an apolipoprotein(a) chain, which is an established risk factor for cardiovascular disease. However, studies addressing the relationship between atrial fibrillation (AF) and Lp(a) demonstrated conflicted results. Thus, we sought to evaluate this relationship by conducting this systemic review and meta-analysis. We performed a comprehensive systematic search of health science databases, including PubMed, Embase, Cochrane Library, Web of Science, MEDLINE, and ScienceDirect, to identify all relevant literature from their inception to March 1, 2023. We identified nine related articles, which were eventually included in this study. Our study showed no association between Lp(a) with new-onset AF (HR = 1.45, 95% confidence interval [CI]: 0.57-3.67, p = .432). In addition, genetically elevated Lp(a) was not associated with the risk of atrial fibrillation (OR = 1.00, 95% CI: 1.00-1.00, p = .461). Different stratification of Lp(a) levels may have different outcomes. Also, higher Lp(a) levels may be inversely associated with the risk of developing AF compared to those with lower levels. Lp(a) levels were not associated with incident AF. Further research is needed to identify the mechanism underlying these results and better understand Lp(a) stratification for AF and the possible inverse association between Lp(a) and AF.
Topics: Humans; Atrial Fibrillation; Lipoprotein(a); Risk Factors
PubMed: 37436817
DOI: 10.1002/clc.24086 -
BMJ Open Nov 2023To report a systematic review and meta-analysis of the association between dry eye disease (DED) and dyslipidaemia. (Meta-Analysis)
Meta-Analysis
PURPOSE
To report a systematic review and meta-analysis of the association between dry eye disease (DED) and dyslipidaemia.
METHODS
PubMed, Embase, Web of Science and Cochrane Library were systematically searched from January 2000 to December 2021. We included observational studies to assess the correlation of DED with meibomian gland dysfunction and dyslipidaemia without any language restrictions. The pooled OR with 95% CI was calculated in Stata V.15.
RESULTS
Of 6727 identified studies, 18 studies (21 databases) with a total of 2 663 126 patients were analysed in our meta-analysis. The results showed that DED risk was associated with dyslipidaemia (OR=1.53, 95% CI: 1.41 to 1.66, p=0.001), especially elevated total cholesterol levels (OR=1.57, 95% CI: 1.25 to 1.99, p<0.001), elevated low-density lipoprotein cholesterol levels (OR=1.13, 95% CI: 1.06 to 1.20, p<0.001) and high-density lipoprotein cholesterol levels (OR=1.06, 95% CI: 1.01 to 1.11, p<0.001), but not with serum triglyceride levels. Moreover, having a history of lipid-lowering drug use (OR=1.41, 95% CI: 1.19 to 1.67, p<0.001) was also found to be positively associated with DED risk.
CONCLUSIONS
The findings suggested that dyslipidaemia and lipid-lowering drug use might be associated with an increased risk of DED. More evidence is needed to confirm the findings by prospective studies.
PROSPERO REGISTRATION NUMBER
CRD42022296664.
Topics: Humans; Prospective Studies; Dyslipidemias; Dry Eye Syndromes; Cholesterol; Lipids
PubMed: 37989379
DOI: 10.1136/bmjopen-2022-069283 -
Cardiovascular Diabetology Nov 2023Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with hypercholesterolemia.
METHODS
PubMed, Scopus, and Cochrane library databases were searched for randomised controlled trials evaluating the efficacy and/or safety of BA compared with placebo. Trials investigating dosages other than 180 mg/die were excluded. Major adverse cardiovascular events (MACE) were the primary efficacy endpoint. LDL-cholesterol reduction was the primary laboratory endpoint. Pre-specified safety endpoints included muscle-related adverse events, new-onset diabetes, and gout. The protocol was registered on PROSPERO (temporary ID:399,867).
RESULTS
Study search identified 275 deduplicated results. 11 studies, encompassing 18,315 patients (9854 on BA vs 8461 on placebo/no treatment) were included. BA was associated with a reduced risk of MACE (OR 0.86, 95% CI 0.79-0.95), myocardial infarction (OR 0.76, 95% CI 0.64-0.88) and unstable angina (OR 0.69, 95% CI 0.54-0.88) compared to control, over a median follow up of 87 (15-162) weeks. BA was associated with a reduction of LDL-Cholesterol (mean difference [MD]-22.42,95% CI - 24.02% to - 20.82%), total cholesterol (- 16.50%,95% - 19.21% to - 13.79%), Apo-B lipoprotein (- 19.55%, - 22.68% to - 16.42%) and high-sensitivity CRP (- 27.83%, - 31.71% to - 23.96%) at 12 weeks. BA was associated with a higher risk of gout (OR 1.55, 95% CI 1.27-1.90) as compared with placebo. Efficacy on laboratory endpoints was confirmed, with a variable extent, across patients on statin or ezetimibe background therapy.
CONCLUSIONS
The improved cholesterol control achieved with BA translates into a reduced risk of MACE, including myocardial infarction and coronary revascularisation. The drug has a satisfactory safety profile except for an increased risk of gout.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol, LDL; Cholesterol; Myocardial Infarction; Gout; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38017541
DOI: 10.1186/s12933-023-02022-z -
Atherosclerosis Plus Dec 2023To systematically investigate all relevant evidence on the association between high-density lipoprotein cholesterol (HDL-C) and multiple myeloma (MM).
BACKGROUND AND AIMS
To systematically investigate all relevant evidence on the association between high-density lipoprotein cholesterol (HDL-C) and multiple myeloma (MM).
METHODS
We searched PubMed and Cochrane library databases (up to 20 September 2022) for studies with evidence on HDL-C in patients with MM. A qualitative synthesis of published prospective and retrospective studies for the role of HDL-C and other lipid profile parameters in MM was performed. Additionally, a meta-analysis on HDL-C mean differences (MD) between MM cases and controls was performed.
RESULTS
Fourteen studies (3 prospective, 11 retrospective) including 895 MM patients were eligible for this systematic review. Ten studies compared HDL-C levels in MM patients with healthy controls. In these 10 studies (n = 17,213), pooled analyses showed that MM patients had significantly lower HDL-C levels compared to healthy controls (MD: -13.07 mg/dl, 95% CI: -17.83, -8.32, p < 0.00001). Regarding secondary endpoints, total cholesterol (TC) (MD: -22.19 mg/dl, 95% CI: -39.08, -5.30) and apolipoprotein A-I (apoA-I) (-40.20 mg/dl, 95% CI: -55.00, -25.39) demonstrated significant decreases, while differences in low-density lipoprotein cholesterol (LDL-C) (MD: -11.33 mg/dl, 95% CI: -36.95, 14.30) and triglycerides (MD: 9.93 mg/dl, 95% CI: -3.40, 23.26) were not shown to be significant.
CONCLUSIONS
HDL-C, as well as TC and apoA-I, levels are significantly decreased in MM. Hence, lipid profile parameters should be taken into account when assessing such patients.
PubMed: 37780686
DOI: 10.1016/j.athplu.2023.09.003 -
Advances in Nutrition (Bethesda, Md.) Sep 2023Cardiovascular disease (CVD) is the leading cause of death globally. Habitual consumption of tree nuts and peanuts is associated with cardioprotective benefits.... (Meta-Analysis)
Meta-Analysis Review
Cardiovascular disease (CVD) is the leading cause of death globally. Habitual consumption of tree nuts and peanuts is associated with cardioprotective benefits. Food-based dietary guidelines globally recommend nuts as a key component of a healthy diet. This systematic review and meta-analysis were conducted to examine the relationship between tree nut and peanut consumption and risk factors for CVD in randomized controlled trials (RCTs) (PROSPERO: CRD42022309156). MEDLINE, PubMed, CINAHL, and Cochrane Central databases were searched up to 26 September, 2021. All RCT studies that assessed the effects of tree nut or peanut consumption of any dose on CVD risk factors were included. Review Manager software was used to conduct a random effect meta-analysis for CVD outcomes from RCTs. Forest plots were generated for each outcome, between-study heterogeneity was estimated using the I test statistic and funnel plots and Egger's test for outcomes with ≥10 strata. The quality assessment used the Health Canada Quality Appraisal Tool, and the certainty of the evidence was assessed using grading of recommendations assessment, development, and evaluation (GRADE). A total of 153 articles describing 139 studies (81 parallel design and 58 cross-over design) were included in the systematic review, with 129 studies in the meta-analysis. The meta-analysis showed a significant decrease for low-density lipoprotein (LDL) cholesterol, total cholesterol (TC), triglycerides (TG), TC:high-density lipoprotein (HDL) cholesterol, LDL cholesterol:HDL cholesterol, and apolipoprotein B (apoB) following nut consumption. However, the quality of evidence was "low" for only 18 intervention studies. The certainty of the body of evidence for TC:HDL cholesterol, LDL cholesterol:HDL cholesterol, and apoB were "moderate" because of inconsistency, for TG were "low," and for LDL cholesterol and TC were "very low" because of inconsistency and the likelihood of publication bias. The findings of this review provide evidence of a combined effect of tree nuts and peanuts on a range of biomarkers to create an overall CVD risk reduction.
Topics: Humans; Cardiovascular Diseases; Nuts; Arachis; Cholesterol, LDL; Cholesterol, HDL; Randomized Controlled Trials as Topic; Cholesterol; Triglycerides; Apolipoproteins B
PubMed: 37149262
DOI: 10.1016/j.advnut.2023.05.004 -
Journal of the Academy of Nutrition and... Feb 2024Avocados are a rich source of unsaturated fats and bioactives, however, their role in altering cardiometabolic risk factors is unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Avocados are a rich source of unsaturated fats and bioactives, however, their role in altering cardiometabolic risk factors is unclear.
OBJECTIVE
The aim was to review the effects of consuming diets containing avocado compared with control diets containing no or low amounts of avocado on cardiometabolic risk factors in adults who were healthy, had clinical cardiovascular disease, or were at increased risk of cardiovascular disease.
METHODS
Five electronic databases were searched (PubMed, Web of Science, Scopus, ProQuest, and a Clinical Trials Registry) along with Google Scholar to identify studies published between January 1990 and November 10, 2021. Randomized controlled trials ≥3 weeks and prospective cohort studies were included. Ten studies-9 randomized controlled trials (n = 503 participants) and 1 prospective observational study (n = 55,407)-met the inclusion criteria. Outcomes assessed by means of meta-analysis were low-density lipoprotein cholesterol (LDL-C) (primary), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Outcomes assessed by narrative review were TC to HDL-C ratio, non-HDL-C, apolipoprotein B, blood pressure, body weight, body mass index (calculated as kg/m), waist circumference, waist-to-hip ratio, body composition, and blood glucose and insulin concentrations. Risk of bias was assessed using the Cochrane Risk of Bias tool, version 2.0 and Newcastle-Ottawa Scale; quality of evidence was examined using the Grading of Recommendations, Assessment, Development and Evaluation method. Random-effects models meta-analyses were performed when there were ≥3 studies of the same design (ie, randomized controlled trial) and reporting the same outcome. Statistical heterogeneity was assessed by calculating χ and I statistics and publication bias was assessed by funnel plots.
RESULTS
Overall, there was a small, significant reduction in TC (-5.08 mg/dL [to convert to mmol/L, divide by 38.67]; 95% CI -9.29 to -0.87 mg/dL; P = .02) in avocado vs the control groups and no significant difference in LDL-C, HDL-C, or triglycerides. Subgroup analysis demonstrated significant reductions in LDL-C (-9.4 mg/dL [to convert to mmol/L, divide by 38.67]; 95% CI -10.84 to -7.95 mg/dL; P < .00001) and TC (-7.54 mg/dL; 95% CI -9.40 to -5.68 mg/dL; P < .00001) in avocado vs control groups in hypercholesterolemic populations, and no differences were seen in normocholesterolemic populations. However, the certainty in the findings was graded as low to very low. Body weight and composition were not negatively affected by avocado consumption.
CONCLUSIONS
Avocado consumption may reduce TC and LDL-C in people with hypercholesterolemia. Avocado consumption does not negatively impact body weight. Larger, well-conducted studies are needed to have greater confidence in the role of avocado consumption on cardiovascular disease risk factors.
Topics: Adult; Humans; Persea; Cardiovascular Diseases; Cholesterol, LDL; Prospective Studies; Cholesterol; Triglycerides; Body Weight; Cholesterol, HDL; Observational Studies as Topic
PubMed: 36565850
DOI: 10.1016/j.jand.2022.12.008