Effect of Exercise Training on Apolipoproteins: Meta-analysis and Trial Sequence Analysis

We conducted a systematic review and meta-analysis of the effect of exercise training on common lipid subunits. We systematically searched PubMed, Web of Science and the Cochrane Library of Controlled Trials for randomized, controlled trials of exercise training versus sedentary controls that reported lipid subunits including apolipoprotein-AI, apolipoprotein-AII, apolipoprotein-B, high density cholesterol-2, high density cholesterol-3 and lipoprotein (a) up until January 31, 2024. Our search identified 2,363 potential studies. We included 25 studies with 34 intervention groups, and a total of 1,429 participants, 775 exercise training and 654 control. We found significant favourable anti-atherogenic changes in apolipoprotein-AI with a mean difference of 8.17 mg/dL and a 95% confidence interval of 5.80-10.55, lipoprotein (a) with a mean difference of -2.52 mg/dL and a 95% confidence interval of -4.33 to -0.72), apolipoprotein-B with a mean difference of -0.11 mg/dL and a 95% confidence interval 0f -0.19 to -0.04, and high density cholesterol-2 with a mean difference of 1.28 mg/dL and a 95% CI of 0.28-2.28. Our trial sequence analysis showed that futility was achieved for apolipoprotein-AI, but not for lipoprotein (a), apolipoprotein-B and high density cholesterol-2. The minimal clinically important differences for apolipoprotein-AI, lipoprotein (a), apolipoprotein-B and high density cholesterol-2 were 0.76, 0.46, 0.02 and 0.26 mg/dL, respectively. Analyses of apolipoprotein-AII and high density cholesterol-3 were not significant and these trial sequence analyses failed to show futility. Exercise training produces significant improvements in apolipoprotein-AI, lipoprotein (a), apolipoprotein-B and high density cholesterol-2, with the minimal clinically important differences being achieved. The effect of exercise training on apolipoprotein-AII and high density cholesterol-3 is unclear.