Estimating the Effect of Aerobic Exercise Training on Novel Lipid Biomarkers: A Systematic Review and Multivariate Meta-Analysis of Randomized Controlled Trials

Abstract
Background Aerobic exercise training (AET) prescribed as lipid management treatment positively affects the standard lipid profile and reduces cardiovascular disease (CVD) risk. Apolipoproteins, lipid and apolipoprotein ratios, and lipoprotein sub-fractions may more effectively predict CVD risk than the standard lipid profile but an AET response in these biomarkers has not been established. Objectives We conducted a quantitative systematic review of randomised controlled trials (RCTs) to (1) determine the effects of AET on lipoprotein sub-fractions, apolipoproteins and relevant ratios; and (2) identify study or intervention covariates associated with change in these biomarkers. Methods We searched PubMed, EMBASE, all Web of Science and EBSCO health and medical online databases from inception to 31 December 2021. We included published RCTs of adult humans with ≥ 10 per group of participants; an AET intervention duration ≥ 12 weeks of at least moderate intensity (> 40% maximum oxygen consumption); and reporting pre/post measurements. Non-sedentary subjects, or those with chronic disease other than Metabolic Syndrome factors, or pregnant/lactating, as well as trials testing diet/medications, or resistance/isometric/unconventional training interventions, were excluded. Results Fifty-seven RCTs totalling 3194 participants were analysed. Multivariate meta-analysis showed AET significantly raised antiatherogenic apolipoproteins and lipoprotein sub-fractions (mmol/L mean difference (MD) 0.047 (95% confidence interval (CI) 0.011, 0.082), P = .01); lowered atherogenic apoliproteins and lipoprotein sub-fractions (mmol/L MD − 0.08 (95% CI − 0.161, 0.0003), P = .05); and improved atherogenic lipid ratios (MD − 0.201 (95% CI − 0.291, − 0.111), P < .0001). Multivariate meta-regression showed intervention variables contributed to change in lipid, sub-fraction, and apoliprotein ratios. Conclusion Aerobic exercise training positively impacts atherogenic lipid and apolipoprotein ratios, alipoproteins, and lipoprotein sub-fractions; and antiatherogenic apolipoproteins and lipoprotein sub-fractions. Cardiovascular disease risk predicted by these biomarkers may be lowered when AET is prescribed as treatment or prevention. PROSPERO ID CRD42020151925.