Effects of Increasing Exercise Intensity and Dose on Multiple Measures of HDL (High-Density Lipoprotein) Function

Abstract

Objective: Measures of HDL (high-density lipoprotein) function are associated with cardiovascular disease. However, the effects of regular exercise on these measures is largely unknown. Thus, we examined the effects of different doses of exercise on 3 measures of HDL function in 2 randomized clinical exercise trials.

Approach and results: Radiolabeled and boron dipyrromethene difluoride-labeled cholesterol efflux capacity and HDL-apoA-I (apolipoprotein A-I) exchange were assessed before and after 6 months of exercise training in 2 cohorts: STRRIDE-PD (Studies of Targeted Risk Reduction Interventions through Defined Exercise, in individuals with Pre-Diabetes; n=106) and E-MECHANIC (Examination of Mechanisms of exercise-induced weight compensation; n=90). STRRIDE-PD participants completed 1 of 4 exercise interventions differing in amount and intensity. E-MECHANIC participants were randomized into 1 of 2 exercise groups (8 or 20 kcal/kg per week) or a control group. HDL-C significantly increased in the high-amount/vigorous-intensity group (3±5 mg/dL; P=0.02) of STRRIDE-PD, whereas no changes in HDL-C were observed in E-MECHANIC. In STRRIDE-PD, global radiolabeled efflux capacity significantly increased 6.2% (SEM, 0.06) in the high-amount/vigorous-intensity group compared with all other STRRIDE-PD groups (range, -2.4 to -8.4%; SEM, 0.06). In E-MECHANIC, non-ABCA1 (ATP-binding cassette transporter A1) radiolabeled efflux significantly increased 5.7% (95% CI, 1.2-10.2%) in the 20 kcal/kg per week group compared with the control group, with no change in the 8 kcal/kg per week group (2.6%; 95% CI, -1.4 to 6.7%). This association was attenuated when adjusting for change in HDL-C. Exercise training did not affect BODIPY-labeled cholesterol efflux capacity or HDL-apoA-I exchange in either study.

Conclusions: Regular prolonged vigorous exercise improves some but not all measures of HDL function. Future studies are warranted to investigate whether the effects of exercise on cardiovascular disease are mediated in part by improving HDL function.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00962962 and NCT01264406.

Keywords: apolipoproteins; cholesterol; clinical trial; longitudinal studies; metabolic syndrome; overweight; prediabetic state.

Conflict of interest statement

Disclosures

MAS is a consultant for Genetic Direction, LLC. MNO is a founder of and owns a significant stake in Seer Biologics, Inc. AR has a research grant from Merck and is a consultant for Merck, CSL Limited, HDL Diagnostics, and Cleveland HeartLabs. The other authors declare no conflicts.

© 2018 American Heart Association, Inc.

Figures

Figure 1

Adjusted mean (SEM) percent change of radiolabeled global efflux (A) and BODIPY-labeled global efflux (B) in response to exercise training in STRRIDE-PD. Values adjusted for age, sex, race, baseline BMI, and baseline value. ap=0.005 and bp<0.05 for difference from High-Vig.

Figure 2

Adjusted mean (SEM) percent change of radiolabeled global (A), ABCA1 (B), and non-ABCA1 (C) efflux, and BODIPY-labeled global efflux (D) in response to exercise training in E-MECHANIC. Values adjusted for age, sex, race, baseline BMI, and baseline value. ap=0.01 for difference from control group.