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Association of lowering apolipoprotein B with cardiovascular outcomes across various lipid-lowering therapies: Systematic review and meta-analysis of trials.
Khan, SU, Khan, MU, Valavoor, S, Khan, MS, Okunrintemi, V, Mamas, MA, Leucker, TM, Blaha, MJ, Michos, ED
European journal of preventive cardiology. 2020;(12):1255-1268
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Abstract
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.
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Effect of psyllium (Plantago ovata) fiber on LDL cholesterol and alternative lipid targets, non-HDL cholesterol and apolipoprotein B: a systematic review and meta-analysis of randomized controlled trials.
Jovanovski, E, Yashpal, S, Komishon, A, Zurbau, A, Blanco Mejia, S, Ho, HVT, Li, D, Sievenpiper, J, Duvnjak, L, Vuksan, V
The American journal of clinical nutrition. 2018;(5):922-932
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Abstract
BACKGROUND Studies have identified viscous dietary fiber as potentially attenuating cholesterol, including psyllium, which reduces LDL cholesterol and thus may complement cardiovascular disease (CVD) treatment. OBJECTIVES The aims of this study were to update evidence on the effect of psyllium on LDL cholesterol and to provide an assessment of its impact on alternate markers: non-HDL cholesterol and apolipoprotein B (apoB). DESIGN Medline, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials were searched through 3 October 2017. Independent reviewers extracted relevant data and assessed risk of bias. We included randomized controlled trials with a duration of ≥3 wk that assessed the effect of psyllium on blood lipids in individuals with or without hypercholesterolemia. Data were pooled by using the generic inverse variance method with random-effects models and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by Cochran's Q statistic and quantified by the I2 statistic. Overall quality of the evidence was assessed by using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. RESULTS We included 28 trials in our analysis (n = 1924). Supplementation of a median dose of ∼10.2 g psyllium significantly reduced LDL cholesterol (MD = -0.33 mmol/L; 95% CI: -0.38, -0.27 mmol/L; P < 0.00001), non-HDL cholesterol (MD = -0.39 mmol/L; 95% CI: -0.50, -0.27 mmol/L; P < 0.00001), and apoB (MD = -0.05 g/L; 95% CI: -0.08, -0.03 g/L; P < 0.0001). Effect estimates for LDL cholesterol and non-HDL cholesterol were graded as moderate quality on the basis of downgrades for inconsistency and graded as high quality for apoB. CONCLUSION Psyllium fiber effectively improves conventional and alternative lipids markers, potentially delaying the process of atherosclerosis-associated CVD risk in those with or without hypercholesterolemia. This trial is registered at www.clinicaltrials.gov as NCT03346733.