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European Journal of Clinical... Nov 2022Patients with severe hypertriglyceridaemia (sHTG) are often refractory to lipid-lowering therapy. Apolipoprotein (Apo) CIII inhibition could be promising to treat... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with severe hypertriglyceridaemia (sHTG) are often refractory to lipid-lowering therapy. Apolipoprotein (Apo) CIII inhibition could be promising to treat subjects with sHTG. The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat sHTG. We performed a systematic review and meta-analysis of RCTs on the efficacy and safety of volanesorsen as compared to placebo treatment in patients with severe HTG.
METHODS
Studies were systematically searched in the PubMed, Web of Science and Scopus databases according to PRISMA guidelines. The last search was performed on 7 February 2022.
RESULTS
Four studies showed significant reduction in TG after 3 months of treatment with volanesorsen as compared with placebo (MD: -73.9%; 95%CI: -93.5%, -54.2; p < .001 I = 89.05%; p < .001); VLDL-C level (MD: -71.0%; 95%CI: -76.6%, -65.4%; p < .001 I = 94.1%; p < .001); Apo-B48 level (MD: -69.03%; 95%CI: -98.59.4%, -39.47%; p < .001, I = 93.51%; p < .001) and Apo-CIII level (MD: -80.0%; 95%CI: -97.5%, -62.5; p < .001 I = 94.1%; p < .001) with an increase in HDL-C level (MD: +45.92%, 95%CI: +37.24%, +54.60%; p < .001 I = 94.34%; p < .001) and in LDL-C level (MD: +68.6%, 95%CI: +7.0%, +130.1%; p < .001 I = 96.18%; p < .001) without a significant elevation of Apo-B100 level (MD: +4.58%, 95%CI: -5.64%, +14.79%; p = .380 I = 95.09%; p < .001) in 139 volanesorsen patients as compared to 100 placebo-treated controls. Most of adverse events were mild and related to local injection site reactions.
CONCLUSIONS
In patients with severe HTG, volanesorsen is associated with a significant reduction in TG, VLDL-C, Apo-B48 and non-HDL-C and increment of HDL-C as compared to placebo. Documented efficacy is accompanied by an acceptable safety profile.
Topics: Apolipoprotein B-48; Apolipoprotein C-III; Cholesterol, LDL; Humans; Hyperlipidemias; Hypertriglyceridemia; Oligonucleotides; Oligonucleotides, Antisense; RNA, Messenger; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 35851450
DOI: 10.1111/eci.13841 -
European Journal of Preventive... Aug 2020The effect of therapeutic lowering of apolipoprotein B (apoB) on mortality and major adverse cardiovascular events is uncertain. It is also unclear whether these... (Meta-Analysis)
Meta-Analysis
AIMS
The effect of therapeutic lowering of apolipoprotein B (apoB) on mortality and major adverse cardiovascular events is uncertain. It is also unclear whether these potential effects vary by different lipid-lowering strategies.
METHODS
A total of 29 randomized controlled trials were selected using PubMed, Cochrane Library and EMBASE through 2018. We selected trials of therapies which ultimately clear apolipoprotein B particles by upregulating low-density lipoprotein receptor (LDL-R) expression (statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, bile acid sequestrants) or therapies which reduce apolipoprotein B independent of LDL-R (cholesteryl ester transfer protein inhibitor, fibrates, niacin, omega-3 fatty acids) with sample size of ≥1000 patients and follow-up of ≥1 year. The meta-regression and meta-analyses were constructed using a random effects model.
RESULTS
In 332,912 patients, meta-regression analyses showed relative risks of 0.95 for all-cause mortality (95% confidence interval 0.92-0.99) and 0.93 (0.88-0.98) for cardiovascular mortality for every 10 mg/dL decrease in apolipoprotein B by all interventions combined. Reduction in all-cause mortality was limited to statins (0.92 (0.86-0.98)). For MACE, the relative risk per 10 mg/dL reduction in apolipoprotein B was 0.93 (0.90-0.97) for all therapies combined, with both statin (0.88 (0.83-0.93)) and non-statin therapies (0.96 (0.94-0.99)). which clear apolipoprotein B by upregulating LDL-R showing significant reductions; whereas interventions which lower apolipoprotein B independent of LDL-R did not demonstrate this effect (1.02 (0.81-1.30)).
CONCLUSION
While both statin and established non-statin therapies (PCSK9 inhibitor and ezetimibe) reduced cardiovascular risk per decrease in apolipoprotein B, interventions which reduce apolipoprotein B independently of LDL-R were not associated with cardiovascular benefit.
Topics: Apolipoproteins B; Biomarkers; Cardiovascular Diseases; Humans; Hypolipidemic Agents; Prognosis; Risk Factors
PubMed: 31475865
DOI: 10.1177/2047487319871733 -
Cardiovascular Drugs and Therapy Feb 2021Despite advances in the development of lipid-lowering therapies, clinical trials have shown that a significant residual risk of cardiovascular disease persists....
BACKGROUND
Despite advances in the development of lipid-lowering therapies, clinical trials have shown that a significant residual risk of cardiovascular disease persists. Specifically, new drugs are needed for non-responding or statin-intolerant subjects or patients considered at very high risk for cardiovascular events even though are already on treatment with the best standard of care.
RESULTS AND CONCLUSIONS
Besides, genetic and epidemiological studies and Mendelian randomization analyses have strengthened the linear correlation between the concentration of low-density lipoprotein cholesterol (LDL-C) and the incidence of cardiovascular events and highlighted various novel therapeutic targets. This review describes the novel strategies to reduce the levels of LDL-C, non-HDL-C, triglyceride, apolipoprotein B, and Lp(a), focusing on those developed using biotechnology-based strategies.
Topics: Antibodies, Monoclonal, Humanized; Apolipoproteins B; Cholesterol, LDL; Clinical Trials as Topic; Dyslipidemias; Genetic Therapy; Humans; Hypolipidemic Agents; Lysophospholipids; Oligonucleotides, Antisense; RNA, Small Interfering; Triglycerides
PubMed: 32519066
DOI: 10.1007/s10557-020-07017-6 -
Current Medical Research and Opinion Dec 2015To assess the efficacy of fenofibrate and statin dual therapy versus a double or equivalent dose of statin monotherapy. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To assess the efficacy of fenofibrate and statin dual therapy versus a double or equivalent dose of statin monotherapy.
METHODS
A systematic literature search and meta-analysis was performed for publications before 1 January 2014 in MEDLINE, Embase, and BIOSIS Previews, among others.
RESULTS
The difference in percentage change from baseline was in favor of dual therapy versus a double dose of statin monotherapy for triglycerides (difference -20%; standard error [SE] 2.6%) and HDL-C (8.7%; SE 1.2%), but not for LDL-C (8.4%; SE 1.5%), non-HDL-C (2.8%; SE 1.1%), total cholesterol (4.5%; SE 1.0%) and apolipoprotein B (2.6%; SE 1.1%). For high intensity statins, the difference in percentage change from baseline was in favor of dual therapy versus equivalent statin monotherapy for triglycerides (-17%; SE 2.6%) and for HDL-C (8.7%; SE 1.9%). The difference in percentage change from baseline for LDL-C was 6% (SE 1.7%), implying a greater reduction in LDL-C with statin monotherapy. For moderate intensity statins, the difference in percentage change from baseline was in favor of dual therapy versus equivalent statin monotherapy for triglycerides (-24.2%; SE 1.2%) and HDL-C (8.2%; SE 0.9%). LDL-C decreased 2.2% (SE 1.4%) more with dual therapy.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
When aiming to change HDL-C or triglycerides, dual therapy is to be preferred to doubling the statin dose; conversely, doubling the statin dose is to be preferred when aiming to reduce LDL-C. If the aim is both to change HDL-C or triglycerides and to reduce LDL-C, the importance of the three outcomes may need to be weighed depending on the intensity of the statin. Combining high intensity statin therapy with fenofibrate improves the effect on HDL-C and triglycerides, but lowers the effect on LDL-C. Combining a moderate intensity statin with fenofibrate improves the effect on HDL-C and triglycerides without reducing the effect on LDL-C. There is a need for long-term randomized clinical trials to compare dual therapy versus doubling the statin dose to assess the importance of improvement in HDL-C and triglycerides versus improvement in LDL-C in terms of cardiovascular outcomes. Further, the addition of ezetimibe to statin/fenofibrate therapy may be of interest.
Topics: Apolipoproteins B; Cholesterol; Drug Therapy, Combination; Fenofibrate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 26397380
DOI: 10.1185/03007995.2015.1098597 -
Nutrition Reviews Apr 2022Moderate alcohol consumption is associated with decreased risk of cardiovascular disease (CVD) and improvement in cardiovascular risk markers, including lipoproteins and...
CONTEXT
Moderate alcohol consumption is associated with decreased risk of cardiovascular disease (CVD) and improvement in cardiovascular risk markers, including lipoproteins and lipoprotein subfractions.
OBJECTIVE
To systematically review the relationship between moderate alcohol intake, lipoprotein subfractions, and related mechanisms.
DATA SOURCES
Following PRISMA, all human and ex vivo studies with an alcohol intake up to 60 g/d were included from 8 databases.
DATA EXTRACTION
A total of 17 478 studies were screened, and data were extracted from 37 intervention and 77 observational studies.
RESULTS
Alcohol intake was positively associated with all HDL subfractions. A few studies found lower levels of small LDLs, increased average LDL particle size, and nonlinear relationships to apolipoprotein B-containing lipoproteins. Cholesterol efflux capacity and paraoxonase activity were consistently increased. Several studies had unclear or high risk of bias, and heterogeneous laboratory methods restricted comparability between studies.
CONCLUSIONS
Up to 60 g/d alcohol can cause changes in lipoprotein subfractions and related mechanisms that could influence cardiovascular health.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration no. 98955.
Topics: Alcohol Drinking; Apolipoproteins B; Cardiovascular Diseases; Cholesterol, HDL; Humans; Lipoproteins; Lipoproteins, LDL
PubMed: 34957513
DOI: 10.1093/nutrit/nuab102 -
Multiple Sclerosis and Related Disorders Jan 2016Multiple sclerosis (MS) is a chronic central nervous system disease that is associated with progressive loss of myelin and subsequent axonal degeneration. Cholesterol is... (Review)
Review
Multiple sclerosis (MS) is a chronic central nervous system disease that is associated with progressive loss of myelin and subsequent axonal degeneration. Cholesterol is an essential component of mammalian cellular and myelin membranes. In this systematic review, we examined the relationship between levels of cholesterol and markers of cholesterol turnover in circulation and/or cerebrospinal fluid (CSF) and disease outcomes in adults with clinically isolated syndrome (CIS) or confirmed MS. Studies suggest that elevated levels of circulating low density lipoprotein cholesterol (LDL), total cholesterol, and particularly, apolipoprotein B and oxidized LDL are associated with adverse clinical and MRI outcomes in MS. These relationships were observed as early as CIS. The studies also suggest that oxysterols, cholesterol precursors, and apolipoprotein E may be markers of specific disease processes in MS, but more research is required to elucidate these processes and relationships. Taken together, the data indicate that cholesterol and markers of cholesterol turnover have potential to be used clinically as biomarkers of disease activity and may even be implicated in the pathogenesis of MS.
Topics: Apolipoproteins; Apolipoproteins B; Biomarkers; Cholesterol; Cholesterol, LDL; Humans; Multiple Sclerosis
PubMed: 26856944
DOI: 10.1016/j.msard.2015.10.005 -
European Journal of Clinical Nutrition Nov 2016There has been recent interest in barley as a therapeutic food owing to its high content of beta-glucan (β-glucan), a viscous soluble fiber recognized for its... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis of randomized controlled trials of the effect of barley β-glucan on LDL-C, non-HDL-C and apoB for cardiovascular disease risk reduction.
BACKGROUND/OBJECTIVES
There has been recent interest in barley as a therapeutic food owing to its high content of beta-glucan (β-glucan), a viscous soluble fiber recognized for its cholesterol-lowering properties. The objective of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the cholesterol-lowering potential of barley β-glucan on low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (apoB) for cardiovascular disease (CVD) risk reduction.
METHODS
MEDLINE, Embase, CINAHL and the Cochrane CENTRAL were searched. We included RCTs of ⩾3-week duration assessing the effect of diets enriched with barley β-glucan compared with controlled diets on LDL-C, non-HDL-C or apoB. Two independent reviewers extracted relevant data and assessed study quality and risk of bias. Data were pooled using the generic inverse-variance method with random effects models and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed by the Cochran Q-statistic and quantified by the I statistic.
RESULTS
Fourteen trials (N=615) were included in the final analysis. A median dose of 6.5 and 6.9 g/day of barley β-glucan for a median duration of 4 weeks significantly reduced LDL-C (MD=-0.25 mmol/l (95% CI: -0.30, -0.20)) and non-HDL-C (MD=-0.31 mmol/l (95% CI: -0.39, -0.23)), respectively, with no significant changes to apoB levels, compared with control diets. There was evidence of considerable unexplained heterogeneity in the analysis of non-HDL-C (I=98%).
CONCLUSIONS
Pooled analyses show that barley β-glucan has a lowering effect on LDL-C and non-HDL-C. Inclusion of barley-containing foods may be a strategy for achieving targets in CVD risk reduction.
Topics: Apolipoproteins B; Biomarkers; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Dietary Supplements; Hordeum; Humans; Randomized Controlled Trials as Topic; beta-Glucans
PubMed: 27273067
DOI: 10.1038/ejcn.2016.89 -
Lipids in Health and Disease Aug 2023The purpose of this study was to comprehensively evaluate the lipid profiles in patients with juvenile idiopathic arthritis (JIA). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The purpose of this study was to comprehensively evaluate the lipid profiles in patients with juvenile idiopathic arthritis (JIA).
METHODS
The literature and relevant reviews were searched for published clinical studies on the relationship between JIA and blood lipid levels. The Newcastle-Ottawa scale (NOS) was applied to evaluate the risk and methodological value of the included case‒control and cohort studies. Standardized mean differences (SMDs) and 95% confidence intervals were derived for all variables with adequate unprocessed data. This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines.
RESULTS
In total, 16 studies were incorporated through screening. The analysis findings revealed that the levels of very low-density lipoprotein cholesterol [SMD=-0.411, 95% CI (-0.774~-0.048), P = 0.026], high-density lipoprotein cholesterol [SMD=-0.528, 95% CI (-0.976~-0.079), P = 0.021], and apolipoprotein A1 [SMD=-1.050, 95% CI (-1.452~-0.647), P = 0.000] in JIA patients were statistically lower than those observed in healthy controls. The level of low-density lipoprotein cholesterol [SMD = 0.202, 95% CI (0.003 ~ 0.400), P = 0.046] was significantly higher in JIA patients than in healthy controls. In JIA patients, body mass index [SMD=-0.189, 95% CI (-0.690 ~ 0.311), P = 0.459], high-density lipoprotein [SMD =-1.235, 95% CI (-2.845 ~ 0.374), P = 0.133), low-density lipoprotein [SMD = 0.616, 95% CI (-0.813 ~ 2.046), P = 0.398), triglycerides (SMD = 0.278, 95% CI (-0.182 ~ 0.738), P = 0.236], total cholesterol [SMD=-0.073, 95% CI (-0.438 ~ 0.293), P = 0.696] and apolipoprotein B levels [SMD = 0.226, 95% CI (-0.133 ~ 0.585), P = 0.217] were not significantly different from those in healthy controls.
CONCLUSIONS
The outcomes of this meta-analysis suggest that dyslipidemia is common in JIA patients compared to healthy controls. Patients with JIA have a significantly increased risk of atherosclerosis and cardiovascular disease later in life.
Topics: Humans; Arthritis, Juvenile; Apolipoproteins B; Cholesterol, HDL; Cholesterol, LDL; Lipoproteins, HDL
PubMed: 37626321
DOI: 10.1186/s12944-023-01885-1 -
Journal of the American Heart... Sep 2015Debate over the role of fructose in mediating cardiovascular risk remains active. To update the evidence on the effect of fructose on established therapeutic lipid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Debate over the role of fructose in mediating cardiovascular risk remains active. To update the evidence on the effect of fructose on established therapeutic lipid targets for cardiovascular disease (low-density lipoprotein cholesterol [LDL]-C, apolipoprotein B, non-high-density lipoprotein cholesterol [HDL-C]), and metabolic syndrome (triglycerides and HDL-C), we conducted a systematic review and meta-analysis of controlled feeding trials.
METHODS AND RESULTS
MEDLINE, EMBASE, CINHAL, and the Cochrane Library were searched through July 7, 2015 for controlled feeding trials with follow-up ≥7 days, which investigated the effect of oral fructose compared to a control carbohydrate on lipids (LDL-C, apolipoprotein B, non-HDL-C, triglycerides, and HDL-C) in participants of all health backgrounds. Two independent reviewers extracted relevant data. Data were pooled using random effects models and expressed as mean difference with 95% CI. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic). Eligibility criteria were met by 51 isocaloric trials (n=943), in which fructose was provided in isocaloric exchange for other carbohydrates, and 8 hypercaloric trials (n=125), in which fructose supplemented control diets with excess calories compared to the control diets alone without the excess calories. Fructose had no effect on LDL-C, non-HDL-C, apolipoprotein B, triglycerides, or HDL-C in isocaloric trials. However, in hypercaloric trials, fructose increased apolipoprotein B (n=2 trials; mean difference = 0.18 mmol/L; 95% CI: 0.05, 0.30; P=0.005) and triglycerides (n=8 trials; mean difference = 0.26 mmol/L; 95% CI: 0.11, 0.41; P<0.001). The study is limited by small sample sizes, limited follow-up, and low quality scores of the included trials.
CONCLUSIONS
Pooled analyses showed that fructose only had an adverse effect on established lipid targets when added to existing diets so as to provide excess calories (+21% to 35% energy). When isocalorically exchanged for other carbohydrates, fructose had no adverse effects on blood lipids. More trials that are larger, longer, and higher quality are required.
CLINICAL TRIALS REGISTRATION
URL: https://www.clinicaltrials.gov/. Unique Identifier: NCT01363791.
Topics: Apolipoprotein B-100; Biomarkers; Cardiovascular Diseases; Chi-Square Distribution; Cholesterol, HDL; Cholesterol, LDL; Controlled Clinical Trials as Topic; Dietary Carbohydrates; Dyslipidemias; Energy Intake; Fructose; Humans; Lipids; Metabolic Syndrome; Risk Factors; Time Factors; Triglycerides
PubMed: 26358358
DOI: 10.1161/JAHA.114.001700 -
Advances in Nutrition (Bethesda, Md.) Nov 2019Evidence suggests that eating nuts may reduce the risk of cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of randomized controlled... (Meta-Analysis)
Meta-Analysis
Evidence suggests that eating nuts may reduce the risk of cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating almond consumption and risk factors for CVD. MEDLINE, Cochrane Central, Commonwealth Agricultural Bureau, and previous systematic reviews were searched from 1990 through June 2017 for RCTs of ≥3 wk duration that evaluated almond compared with no almond consumption in adults who were either healthy or at risk for CVD. The most appropriate stratum was selected with an almond dose closer to 42.5 g, with a control most closely matched for macronutrient composition, energy intake, and similar intervention duration. The outcomes included risk factors for CVD. Random-effects model meta-analyses and subgroup meta-analyses were performed. Fifteen eligible trials analyzed a total of 534 subjects. Almond intervention significantly decreased total cholesterol (summary net change: -10.69 mg/dL; 95% CI: -16.75, -4.63 mg/dL), LDL cholesterol (summary net change: -5.83 mg/dL; 95% CI: -9.91, -1.75 mg/dL); body weight (summary net change: -1.39 kg; 95% CI: -2.49, -0.30 kg), HDL cholesterol (summary net change: -1.26 mg/dL; 95% CI: -2.47, -0.05 mg/dL), and apolipoprotein B (apoB) (summary net change: -6.67 mg/dL; 95% CI: -12.63, -0.72 mg/dL). Triglycerides, systolic blood pressure, apolipoprotein A1, high-sensitivity C-reactive protein, and lipoprotein (a) showed no difference between almond and control in the main and subgroup analyses. Fasting blood glucose, diastolic blood pressure, and body mass index significantly decreased with almond consumption of >42.5 g compared with ≤42.5 g. Almond consumption may reduce the risk of CVD by improving blood lipids and by decreasing body weight and apoB. Substantial heterogeneity in eligible studies regarding almond interventions and dosages precludes firmer conclusions.
Topics: Adult; Apolipoproteins B; Biomarkers; Body Weight; Cardiovascular Diseases; Diet; Female; Humans; Lipids; MEDLINE; Male; Nuts; Prunus dulcis; Randomized Controlled Trials as Topic
PubMed: 31243439
DOI: 10.1093/advances/nmz043