The lipid-lowering effect of metabolic adaptations during cardiac rehabilitation in coronary artery disease patients

Background Cardiac rehabilitation (CR) is a multidisciplinary intervention recommended for patients with coronary artery disease (CAD). While the benefits of exercise-based rehabilitation on cardiorespiratory fitness and health-related quality of life are well documented, its metabolic effects are less well explored. Purpose This study investigated fat oxidation (FatOx) and carbohydrate oxidation (ChOx) during exercise as an indirect measure of mitochondrial oxidative capacity during CR and evaluated dependent changes in lipid profiles in CAD patients. Methods 458 CAD patients (23% women, 55.3±7.3 years) after myocardial infarction and/or percutaneous coronary intervention referred to 3–4 weeks of inpatient CR underwent cardiopulmonary exercise testing at admission and before discharge. Breath-by-breath spiroergometric data were used to stoichiometrically determine substrate oxidation rates. Data were expressed relative to peak oxygen uptake (VO₂peak). Mean area under the curve (AUC) with 95% confidence interval as well as linear regression slopes from start to peak were calculated. Responder analyses were conducted for submaximal and peak exercise capacity based on VO₂ at ventilatory threshold 1 (VT1) and VO₂peak, as well as for maximal fat oxidation (MFO), using the typical-error method. Results FatOx was impaired in CAD patients (MFOpre: 0.32±0.15 g/min; AUCpre: 9.7[9.2–10.2]) compared to healthy controls (MFO: 0.46±0.17 g/min; p<0.001), while ChOx was largely unaffected. CR induced significant improvements in FatOx (+14.3%; AUCpost: 11.1[10.6–11.7]; p<0.001) and MFO (MFOpost: 0.34±0.15 g/min; p<0.0001). Improvements were smaller in women, older patients, and patients with reduced ejection fraction (+8.0%, +7.6%, and +8.7%) compared to their respective counterparts (+15.9%, +20.8%, and +15.6%). Responder analyses revealed that 37% of patients showed a response in VO2@VT1, 41% in VO2peak and 31% improved in MFO. However, a subgroup of metabolic responders (“metabolic phenotype”; ~10%) was identified that improved significantly in metabolic endpoints (+0.14±0.06 g/min in MFO, +90.4% in FatOx, +15.4% in ChOx) but showed no changes in VO2-based outcomes. Patients with the metabolic phenotype exhibited significantly larger reductions in blood lipid profiles, including total cholesterol, LDL cholesterol and triglycerides (all p≤0.031) compared to VO2-based responders. The lipid-lowering effect was independent of medication. Conclusion CAD patients exhibited improved FatOx capacity in response to CR indicating enhanced mitochondrial oxidative capacity. Adaptations were less-pronounced in women, older patients, and those with reduced EF suggesting subgroup-specific differences in metabolic responsiveness. In addition to traditional outcome assessments based on VO₂ uptake, MFO may identify CR responders in terms of beneficial metabolic adaptations accompanied by larger reductions in blood lipid levels.