Abstract

Background: This study aims to assess differences in cardiorespiratory fitness improvement after phase II cardiac rehabilitation in coronary artery bypass grafting patients with various risk factor profiles and to investigate their correlation.

Methods: Between October 2023 and March 2024, a total of 45 patients (35 males, 10 females; mean age: 59.5±8.5 years; range, 55 to 64 years) who underwent phase II cardiac rehabilitation following coronary artery bypass grafting were retrospectively analyzed. Obesity, hypertension, diabetes mellitus, and dyslipidemia were assessed. The patients were classified according to the specific risk factors and risk factor count. Cardiorespiratory fitness parameters including 6-minute walk distance, maximal oxygen consumption, and metabolic equivalents before and after cardiac rehabilitation were recorded.

Results: The average risk factor count was 2.3 per patient, with dyslipidemia most prevalent (73.3%). The highest improvement in cardiorespiratory fitness was shown in patients with four risk factors and those who had obesity. A significant improvement in the cardiorespiratory fitness was observed in all patients, groups with one to four risk factors, and all specific risk factor groups (p<0.05). Patients with obesity showed significantly greater cardiorespiratory fitness improvement, compared to non-obese patients (p=0.009). There was no significant correlation between risk factor count and cardiorespiratory fitness improvement (p>0.05).

Conclusion: Cardiac rehabilitation significantly improved cardiorespiratory fitness in all post-coronary artery bypass grafting patients, regardless of risk factor profiles, with notably greater improvements observed in patients with obesity. Clinically, these findings underscore the importance of universally recommending phase II cardiac rehabilitation in this patient group, particularly emphasizing tailored interventions in individuals with obesity to maximize rehabilitation outcomes and potentially reduce cardiovascular morbidity and mortality.

Coronary artery disease (CAD) remains a major global health concern, with an estimated 315 million cases reported between 1990 and 2022. The global mortality rate averages 108 deaths per 100,000 cases, rising to 110.7 in Southeast Asia. In terms of disability, CAD accounts for 2,275.9 disability-adjusted life years per 100,000 globally and 2,501.3 per 100,000 in Southeast Asia.[1]

Coronary artery disease significantly impairs functional capacity, particularly cardiorespiratory fitness (CRF), which reflects the capacity of the cardiovascular and respiratory systems to deliver oxygen during physical activity.[2,3] The CRF is assessed via maximal oxygen consumption (VO_2max), commonly measured by cardiopulmonary exercise testing (CPET), or estimated using the 6-minute walk test (6MWT).[3] Compared to healthy individuals, men with CAD demonstrate lower functional capacity (10.9 vs. 12 metabolic equivalents [METs]) and a higher 10-year cardiovascular risk.[4] A decline of more than 2.0 METs in CRF is associated with a 74% increase in mortality risk.[5]

Coronary artery bypass grafting (CABG) is widely used to improve myocardial perfusion in patients with severe CAD.[6] Following surgery, cardiac rehabilitation (CR) is strongly recommended to enhance functional recovery and health-related quality of life (HRQoL). The evidence shows that exercise-based CR improves CRF, 6MWT distance, physical activity, and HRQoL.[7] Moreover, each 1-MET increase in CRF post-CR is linked to up to 28% reduction in mortality.[8]

Globally, key metabolic risk factors for CAD include hypertension, elevated low-density lipoprotein (LDL) cholesterol, high body mass index (BMI), diabetes mellitus (DM), and chronic kidney disease, with similar trends reported in Indonesia.[9,10] These risk factors contribute substantially to CADrelated morbidity and mortality, yet adherence to guideline-based management still remains suboptimal.[9]

Recent literature has highlighted that certain patient characteristics, including baseline fitness level, age, sex, obesity, and DM status, may influence the magnitude of CRF improvement during CR.[11] However, evidence regarding the role of obesity and other cardiovascular risk factors in predicting improvements in CRF following CR remains inconsistent. Several studies have explored the impact of these risk factors on CR outcomes, with varying results.[11-15] In the present study, we, therefore, aimed to evaluate whether variations in risk factor profiles, specifically obesity, hypertension, DM, and dyslipidemia, were associated with differential improvements in CRF following phase II CR and to contribute new insights which could help refine CR strategies and inform more tailored, risk factor-specific rehabilitation approaches.

Methods

This single-center, retrospective, cross-sectional study was conducted at Dr. Hasan Sadikin General Hospital (RSHS), Department of Physical Medicine and Rehabilitation, Cardiorespiratory Rehabilitation Division between October 2023 and March 2024 The study population comprised adult patients who underwent phase II CR program following CABG surgery. In our center, all post-CABG patients scheduled for phase II CR undergo initial assessments, including risk stratification based on exercise or non-exercise testing (e.g., ejection fraction), as well as screening for absolute and relative contraindications to exercise. Regardless of risk classification, patients without contraindications are enrolled in phase II CR with individualized exercise prescriptions tailored to their clinical condition and risk profile. Inclusion criteria were post-CABG adult patients who completed standard phase II CR. Those were excluded if they did not complete the full duration (6 or 12 weeks) of the phase II CR program or lacked follow-up assessments after completing the CR program. Patients who did not show improvement were also excluded to specifically assess factors associated with measurable benefits from CR. Out of 66 participants in the study population, 45 (68.1%) met the inclusion and exclusion criteria. Twenty-one were excluded due to loss to follow-up (n=3), failure to complete one CR episode (n=2), and not meeting the inclusion criteria (n=16). Finally, a total of 45 patients (35 males, 10 females; mean age: 59.5±8.5 years; range, 55 to 64 years) were recruited for the study. Written informed consent was obtained from each patient. The study protocol was approved by Research Ethics Committee of R SHS ( Date: 2 4.02.2025, N o: D P.04.03/D. XIV.6.5/84/2025). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Data including age, sex, BMI, risk factor count per patient, and the number of cases per specific risk factor were analyzed. Four major cardiovascular risk factors were assessed in this study, including hypertension, type 2 DM, obesity, and dyslipidemia. Hypertension, type 2 DM, and dyslipidemia were defined based on a history of physician diagnosis and ongoing treatment. Obesity was defined as a BMI of ?25 kg/m² and further classified into obesity Grades 1 and 2. The standard phase II CR protocol implemented at RSHS adhered to the American College of Sports Medicine (ACSM) guidelines, comprising treadmill/walking aerobic exercise sessions performed three times per week (two in-hospital supervised sessions and one home session), lasting approximately 20 to 60 min per session. Exercise intensity was individualized, set at 40 to 80% of heart rate reserve or perceived exertion of 12 to 16 (Borg scale), gradually progressing according to patient tolerance.[2] Both pre- and post-rehabilitation assessments, along with their respective changes were recorded. The VO2max and METs were estimated from 6MWD using Nury's formula.[16] Each participant was categorized based on their risk factor profile, including both the presence of specific risk factors and the total number of risk factors per individual.

Statistical analysis
Statistical analysis was performed using the IBM SPSS version 27.0 software (IBM Corp., Armonk, NY, USA). Continuous variables were expressed in mean ± standard deviation (SD) or median (min-max), while categorical variables were expressed in number and frequency. Paired t-tests were used to assess within-group changes following the CR program. The Mann-Whitney U test was applied for comparisons between specific risk factor groups. One-way analysis of variance (ANOVA) was used to compare outcomes across groups categorized by risk factor count. The correlation between risk factor count and changes in CRF parameters was evaluated using Spearman rank correlation coefficient. A p value o f <0.05 w as considered statistically significant.

Results

The majority of the patients (53.3%) were classified as Grade 1 obesity (BMI 25-29.9 kg/m²). The risk factor profile averaged 2.3 risk factors/patient, with dyslipidemia being most prevalent (32.4%) (Table 1).

Table 1. Subject characteristics

Figure 1 and Table 2 present CRF parameter values before and after CR, with improvements across specific risk factor profile and risk factor count groups. Patients with obesity showed the greatest CRF improvement, followed by those with DM and those without dyslipidemia. The group with four risk factors had the highest CRF improvement, followed by those with no risk factors and two risk factors. Significant improvements occurred in all risk factor-specific groups and in patients with one to four risk factors (p<0.05), but not in those with zero risk factors (p=0.202). Overall, CRF improved significantly (p<0.001), with mean increases of 73.15±87.83 m in 6MWD, 3.87±4.65 mL/kg/min in VO2max, and 1.11±1.33 in METs. To assess risk factor profile effects, Table 2a-c shows differences between those with/without specific risk factors and by risk factor count. We found a significant difference only for obesity, with greater improvement in patients with obesity (Δ6MWD: 37.95±49.39 m vs. 101.32±101.7 m; p =0.009). However, t here were no significant differences among risk factor count groups (p=0.126). Correlation analysis showed no significant association between risk factor count and CRF improvement (p>0.05).

Figure 1. (a) Improvement in 6MWD by risk factor profiles. (b) Improvement in maximal oxygen uptake by risk factor profiles. (c) Improvement in metabolic equivalent by risk factor profiles.
6MWD: Six-minute walk distance; HT: Hypertension; DM: Diabetes mellitus; SD: Standard deviation; CR: Cardiac rehabilitation; RF: Risk factor; VO_2max: Via maximal oxygen consumption; METs: Metabolic equivalents.

Table 2a. Pre- and post-rehabilitation 6MWD stratified by cardiovascular risk factor profile

Table 2b. Pre- and post-rehabilitation

Table 2c. Pre- and post-rehabilitation metabolic equivalent changes stratified by cardiovascular risk factor profile

Table 3. Spearman correlation between RF count and improvements in CRF parameters after phase II CR

Discussion

In the present study, we evaluated the impact of phase II CR on CRF in CAD patients post-CABG with varying cardiovascular risk factor profiles. While the association between risk factors and CR outcomes still remains underexplored, our findingsconfirm that phase II CR significantly enhances CRF, consistent with previously established clinical expectations.[17]

The improvement in CRF aligns with well-documented reductions in morbidity and mortality, where incremental gains in exercise capacity, as reflected by MET, have been associated with substantial survival benefits.[8] These outcomes are largely attributed to the physiological benefits of exercise, rather than to changes in conventional risk factors.

Among the analyzed risk factor profiles, obesity emerged as a factor significantly associated with greater improvements in CRF. Several mechanisms have been proposed to explain this finding, including low baseline functional capacity, more significant cardiovascular adaptations, improvements in body composition, enhanced oxidative metabolism, and reductions in systemic inflammation.[18,19] The law of initial value, or the inverse response principle in exercise physiology, suggests that individuals with lower baseline fitness tend to experience greater absolute improvements following an intervention due to a larger room for improvement compared to those with higher initial fitness levels.[19] Despite the strong association between excess adiposity and the development of cardiovascular diseases (CVDs), considerable evidence indicates the presence of the obesity paradox in patients with CVDs, characterized by better prognosis in overweight and patients with mild obesity, compared to their leaner counterparts.[19,20]

Individuals with obesity typically experience higher cardiovascular load during physical activity, as excess body weight increases oxygen demand, cardiac output, and blood pressure. When these individuals undergo aerobic exercise programs, their cardiovascular systems are required to adapt to greater loads, resulting in more rapid improvements in cardiac function, vascularization, and metabolic efficiency. Moreover, aerobic exercise in individuals with obesity often enhances skeletal muscle oxidative capacity, increases mitochondrial density and function, and promotes greater utilization of fatty acids as an energy source. These processes contribute to improved cardiovascular efficiency and reduced insulin resistance, which together enhance vascular function.[21]

In addition to physiological adaptations, individuals with obesity who improve their fitness often report enhanced functional capacity, reduced dyspnea and fatigue, and improved HRQoL, which may further promote increased physical activity and additional cardiovascular benefits.[22] Weight loss and improvements in body composition following exercise have also been associated with increased CRF in patients with obesity.[19]

In individuals with obesity and heart disease, exercise-based CR has been shown to reduce C-reactive protein (CRP) levels, a key marker of systemic inflammation, while simultaneously improving CRF. The most significant reductions in CRP have been observed in patients with obesity along with CAD, suggesting that the anti-inflammatory effects of exercise are more pronounced in this population.[18] Another study has supported the association between higher VO_2max levels and lower CRP concentrations, even after adjusting for BMI, underscoring the essential role of CRF improvement in reducing obesity-related inflammation.[23]

In contrast, another study showed greater improvements in non-obese patients, highlighting the influence of baseline fitness levels and specific intervention characteristics on CR outcomes.[8,18] Individuals with lower initial capacity, regardless of risk factor profiles, often exhibit greater relative improvements following exercise interventions.[8,18] The absence of significant differences in CRF outcomes among patients with hypertension, DM, or dyslipidemia may reflect effective medical control of these conditions during the CR program, thereby reducing variability in exercise responses.

The influence of hypertension on CRF remains equivocal. While some reviews suggest that physical activity improves VO2max and 6MWD in individuals with hypertension, type 2 DM, or CVD, others indicate functional limitations in hypertensive adults.[14] Similarly, although patients with diabetes may start CR with lower physical capacity, their relative improvements post-rehabilitation appear comparable to those without DM.[13] Another study, however, reported attenuated improvement in this subgroup, likely due to higher baseline risk factor burdens.[15]

Numerous factors influence CRF responses, including program intensity, adherence, comorbidities, and disease severity. Our phase II CR protocol follows ACSM guidelines, and program adherence was high, exceeding 70%, supporting its effectiveness.[2,24] More intriguingly, the present study found no significant differences in CRF improvement across specific risk factors or risk factor burden. Prior research has established that risk factors often reduce physical activity, which contributes to diminished CRF.[25] Individuals with obesity and those with hypertension tend to have lower exercise tolerance and greater oxygen consumption per workload, resulting in reduced reserves.[25] Furthermore, resting heart rate, affected by age and BMI, may also limit exercise capacity.

The baseline physical activity in our cohort appeared low, as reflected by initial functional capacity values. As reported in earlier studies, individuals with lower baseline activity levels usually experience greater functional gains after CR.[8,25] These observations suggest that insufficient physical activity may play a more pivotal role in CRF improvement than the presence or number of risk factors.

Taken together, our findings underscore the role of physical activity in CVD management, particularly for patients recovering from medical or surgical interventions, supporting initiatives such as the World Health Organization (WHO) campaign against physical inactivity. Clinically, the results highlight the need for universal referral to structured phase II CR for all post-CABG patients. Individualized and intensive exercise, particularly for those with obesity, may optimize CRF outcomes. Policymakers should integrate personalized CR pathways into standard care to improve long-term cardiovascular health.

Nonetheless, this study has certain limitations. Its single-center, retrospective, cross-sectional design may introduce recall and selection bias and limit generalizability. This design was chosen for feasibility in using routinely collected CR data, enabling inclusion of a real-world post- CABG cohort while minimizing time and resource demands. To reduce recall bias, all data were extracted from standardized electronic records completed by trained staff. However, potential selection bias and unmeasured confounders still remain. The small sample size may have reduced statistical power to detect associations between risk factors and CRF improvement. Baseline functional capacity served as a surrogate for pre-rehabilitation activity, but no direct measurement was performed, possibly affecting results. Inclusion of the patients without conventional risk factors may have diluted associations, although it reflects real-world practice and improves external validity. Future studies should employ prospective, multi-center designs with larger, more diverse populations, objective activity measurements, and biomarker assessments to clarify CRF improvement mechanisms. Longterm follow-up for cardiovascular events, mortality, and cost-effectiveness of tailored CR strategies is warranted.

In conclusion, phase II cardiac rehabilitation significantly improved cardiorespiratory fitness in post-coronary artery bypass grafting patients across all risk factor profiles, with obesity linked to greater gains, while other risk factors and total risk factor burden showed no significant effect. These findings support structured cardiac rehabilitation as standard care, with tailored interventions for patients with obesity, and provide rare regional data from Southeast Asia. Future research should use prospective, stratified designs with objective assessments, biomarker evaluations, and long-term outcome analysis to guide personalized, resource-efficient cardiac rehabilitation models.

Data Sharing Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Author Contributions: Idea/concept, design, control/ supervision, data collection and processing, analysis and interpretation, literature review, writing the article, critical review, references and funding, materials: A.N.; Idea/concept, design, data collection and processing, analysis and interpretation, writing the article, references and funding, materials: B.C.; Control/supervision, data collection and processing, literature review, critical review: B.B.T.; Control/supervision, literature review, critical review: N.S., J.W.M.

Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding: The authors received no financial support for the research and/or authorship of this article.

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