Physical exercise volume, type, and intensity and risk of all-cause mortality and cardiovascular events in patients with cardiovascular disease: a mediation analysis

Nadia E Bonekamp; Anne M May; Martin Halle; Jannick A N Dorresteijn; Manon G van der Meer; Ynte M Ruigrok; Gert J de Borst; Johanna M Geleijnse; Frank L J Visseren; Charlotte Koopal

doi:10.1093/ehjopen/oead057

Physical exercise volume, type, and intensity and risk of all-cause mortality and cardiovascular events in patients with cardiovascular disease: a mediation analysis

Eur Heart J Open. 2023 Jun 13;3(3):oead057. doi: 10.1093/ehjopen/oead057. eCollection 2023 May.

Affiliations

¹ Department of Vascular Medicine, University Medical Center Utrecht, Utrecht University, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
² Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
³ Department of Prevention and Sports Medicine, School of Medicine, University Hospital Klinikum rechts der Isar, Technical University Munich, Ismaninger Straße 22, D-81675 München, Germany.
⁴ Department of Cardiology, University Medical Centre Utrecht, Utrecht University, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
⁵ UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht University, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
⁶ Department of Vascular Surgery, University Medical Center Utrecht, Utrecht University, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
⁷ Division of Human Nutrition and Health, Wageningen University, Stippeneng 4, 6708 WE Wageningen, The Netherlands.

Abstract

Aims: To estimate the relation between physical exercise volume, type, and intensity with all-cause mortality and recurrent vascular events in patients with cardiovascular disease (CVD) and to quantify to what extent traditional cardiovascular risk factors mediate these relations.

Methods and results: In the prospective UCC-SMART cohort (N = 8660), the associations of clinical endpoints and physical exercise volume (metabolic equivalent of task hours per week, METh/wk), type (endurance vs. endurance + resistance), and intensity (moderate vs. vigorous) were estimated using multivariable-adjusted Cox models. The proportion mediated effect (PME) through body mass index, systolic blood pressure, low-density lipoprotein cholesterol, insulin sensitivity, and systemic inflammation was assessed using structural equation models. Sixty-one percent of patients (73% male, age 61 ± 10 years, >70% receiving lipid-lowering and blood pressure-lowering medications) reported that they did not exercise. Over a median follow-up of 9.5 years [interquartile range (IQR) 5.1-14.0], 2256 deaths and 1828 recurrent vascular events occurred. The association between exercise volume had a reverse J-shape with a nadir at 29 (95% CI 24-29) METh/wk, corresponding with a HR 0.56 (95% CI 0.48-0.64) for all-cause mortality and HR 0.63 (95% CI 0.55-0.73) for recurrent vascular events compared with no exercise. Up to 38% (95% CI 24-61) of the association was mediated through the assessed risk factors of which insulin sensitivity (PME up to 12%, 95% CI 5-25) and systemic inflammation (PME up to 18%, 95% CI 9-37) were the most important.

Conclusion: Regular physical exercise is significantly related with reduced risks of all-cause mortality and recurrent vascular events in patients with CVD. In this population with high rates of lipid-lowering and blood pressure--lowering medication use, exercise benefits were mainly mediated through systemic inflammation and insulin resistance.

Keywords: Cardiovascular disease; Endurance training; Low-grade inflammation; Mediation analysis; Physical exercise; Resistance training.