Obesity is a major global health burden and a key modifiable risk factor for cardiometabolic disease, including coronary artery disease (CAD). Excess adiposity exacerbates atherogenesis, endothelial dysfunction, systemic inflammation, and metabolic dysregulation, significantly increasing cardiovascular morbidity and mortality. Conventional management strategies comprising caloric restriction, pharmacotherapy, and structured exercise recommend gradual weight reduction of 5%–10% over six months, typically through moderate caloric deficit and aerobic exercise under clinical supervision (1–3).

Although intensive lifestyle modification programs have demonstrated efficacy in improving cardiometabolic profiles, most guidelines emphasize progressive rather than aggressive approaches, particularly in patients with established CAD (4–6). Extreme caloric restriction with high protein diet and high-intensity exercise have rarely been evaluated in individuals with high-risk coronary lesions due to concerns regarding arrhythmia, myocardial ischemia, hemodynamic instability, electrolyte imbalance, and adverse metabolic adaptations (7–9). Consequently, evidence on the safety and clinical response to highly intensive weight-loss strategies in patients with obstructive coronary disease remains limited.

Here we report a case of a 43-year-old male with severe obesity (BMI 43.8 kg/m²) and significant coronary artery stenosis who declined percutaneous coronary intervention (PCI) and instead underwent a supervised program combining extreme caloric deficit with high protein diet and high-intensity physical training. The case provides insight into physiological adaptation, metabolic changes, and cardiovascular safety considerations when implementing highly intensive lifestyle interventions in a high-risk CAD population.

A 43-year-old Asian male underwent medical evaluation with shortness of breath during exercise. He denied dyspnea, palpitation and syncope. He reported lifelong obesity, sedentary lifestyle, and poorly controlled hypertension. He stated that his body condition had been similar since elementary school and denied any history of weight loss. The patient reported a long-standing struggle with weight since childhood and had attempted multiple conventional weight-loss programs in the past, including calorie-restricted diets and intermittent exercise, without sustained success. He expressed a strong personal motivation to improve his health following a family history of premature cardiovascular disease and his father's fatal myocardial infarction at age 55. The patient worked in an office-based administrative role, led a predominantly sedentary lifestyle, he denied smoking, alcohol and drug abuse. He had history of uncontrolled hypertension and take amlodipine occasionally. There was no history of diabetes, dyslipidemia diagnosis, or thyroid disease. On physical examination, the patient appeared in good condition, with a pyknic body habitus. Vital signs showed a blood pressure of 185/100 mmHg, heart rate of 98 beats per minute (strong and regular), respiratory rate of 21 breaths per minute, and body temperature of 36.8 °C. Anthropometric measurements were: height 167 cm, weight 122 kg, and waist circumference 125 cm. Body fat percentage was calculated using dual-energy x-ray absorptiometry (DXA) at 40% (Figure 1A).

Stress test showed METS 6.3, peak HR 155 bpm, BP 200/110 mmHg, no ischemia. Coronary CTA showed severe proximal LAD stenosis (70%–99%, CAD-RADS 4). Laboratories showed mild leukocytosis (11,000/µL), HDL 0.97 mmol/L, HbA1c 5.3%, normal renal & hepatic function. The patient declined PCI and consented to intensive monitored lifestyle therapy. Medications included amlodipine, rosuvastatin, clopidogrel, and allopurinol. Weekly clinical reviews were performed.

Table 1.

This case illustrates that a patient at high risk for severe coronary syndrome with comorbid obesity was able to physiologically compensate for an intensive dietary program and high-intensity exercise regimen. Serial clinical evaluations demonstrated favorable adaptation and positive outcomes throughout the intervention. Although current guidelines generally recommend initiating lifestyle interventions gradually and starting at low intensity (1), the program in this case was accelerated according to the patient's tolerance and functional capacity.

To date, there remains limited high-quality evidence supporting the safety of extreme caloric restriction combined with high-intensity training in adults with elevated cardiovascular risk. Such ultra-intensive lifestyle interventions (large caloric deficits and aerobic and resistance training) have not been extensively evaluated in symptomatic coronary artery disease populations, and therefore long-term safety cannot be presumed. Potential adverse effects include increased risk of electrophysiologic disturbances and arrhythmias [rapid weight loss can alter cardiac repolarization (QT and T-wave changes), heightening arrhythmia susceptibility (Level IIb, Grade B)] (2), as well as fluid and electrolyte imbalance, and myocardial stress [rapid weight fluctuation exceeding 10%–15% over a short period has been associated with catabolic stress, electrolyte shifts, and increased cardiovascular morbidity and mortality (Level IIb, Grade B)] (3).

Current cardiovascular prevention guidelines endorse diet and exercise as first-line therapy; however, they emphasize moderate targets (e.g., a caloric deficit of 500–750 kcal/day and ≥150 min of moderate-intensity aerobic activity weekly) aimed at a 5%–10% reduction in body weight (4, 5). Accordingly, strict supervision by a multidisciplinary team (internist, cardiologist, nutritionist, and sports medicine specialist) is essential in such intensive approaches. Several reports suggest that aggressive weight reduction can be performed safely, provided that close monitoring is implemented (electrolytes, ECG, renal function, and cardiovascular biomarkers) (2). Extreme diet and exercise protocols may be feasible in carefully selected patients under highly controlled settings; however, they should not be considered universally safe for high-risk populations. For this group, guideline-directed moderate-intensity intervention remains preferable, with gradual escalation to high intensity based on clinical tolerance and structured monitoring (2, 4, 5) (Table 9).

In this case, physiologic parameters and weight reduction were closely monitored throughout the intervention. Extreme weight loss induces several metabolic and systemic adaptations, including reductions in basal metabolic rate (metabolic adaptation), hormonal shifts [characterized by decreased leptin, insulin, and thyroid hormone (T3) levels, alongside increases in ghrelin and cortisol which promote appetite and energy conservation], and hemodynamic changes such as reduced blood volume and lower ventricular filling pressures. These alterations may influence cardiovascular physiology by reducing cardiac workload, decreasing peripheral vascular resistance, and improving endothelial function, ultimately contributing to enhanced cardiorespiratory capacity. Additionally, substantial weight loss triggers adaptive thermogenesis as a compensatory mechanism to maintain energy balance (6, 7). Weight reduction exceeding 10% has been consistently associated with significant improvements in cardiovascular risk factors, particularly serum lipid profiles and blood pressure, across multiple observational studies (8).

Based on the patient's laboratory findings, there was an increase in HDL cholesterol and a reduction in HbA1c. However, elevations in LDL cholesterol and total cholesterol were also observed. Extreme weight loss can trigger substantial mobilization of adipose tissue fat stores, increasing the flux of free fatty acids to the liver and stimulating lipoprotein production, which may result in a transient rise in LDL or total cholesterol (lipid rebound effect). Rapid fat loss mobilizes large triglyceride reserves from adipose tissue, thereby increasing hepatic delivery of free fatty acids and subsequently promoting VLDL production and its conversion to LDL. Following a period of severe caloric restriction, caloric reintroduction may amplify hepatic lipogenesis and impair lipoprotein clearance, contributing to elevations in LDL and total cholesterol. Hormonal changes involving adipokines (e.g., leptin, adiponectin) and thyroid hormones further influence hepatic lipoprotein synthesis, while residual low-grade inflammation may modify lipid metabolism (6). Although LDL increased during the period of rapid weight loss, this finding should be interpreted cautiously. Potential contributors include diet composition, negative energy balance, altered hepatic cholesterol flux, and inter-individual variation in response to statin therapy. However, there were absence of ApoB and LDL particle data, making remain speculative and requires cautious interpretation. Further mechanistic work is required to clarify whether such LDL elevations reflect unfavorable atherogenic changes or benign transitional physiology during major weight reduction. In the context of obstructive CAD, this rise is clinically relevant and reinforces the need for close lipid monitoring and optimization of lipid-lowering therapy rather than being considered a benign or expected phenomenon (17, 18, 20, 21).

High-intensity exercise can enhance lipolysis and fat mobilization; however, in the setting of increased caloric intake or metabolic adaptive transition, compensatory lipogenesis may occur. Without precise synchronization of energy deficit and metabolic demands, a “lipid metabolism overshoot” may develop. Additionally, elevated intake of saturated fats or cholesterol, or substantial shifts in macronutrient composition (e.g., very low-carbohydrate diets), may increase LDL levels. Extreme carbohydrate restriction and macronutrient alterations have been shown to modify lipoprotein patterns, including increases in LDL-cholesterol and LDL particle size (Level Ia, Grade A recommendations) (9, 17).

Intensive lifestyle modification programs incorporating structured exercise can induce favorable adaptations in endothelial function, autonomic balance, inflammatory tone, and metabolic efficiency in patients with coronary artery disease. Vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) act synergistically to enhance endothelial progenitor cell (EPC) proliferation, migration, and differentiation while reducing apoptosis, whereas these effects are not extended to vascular smooth muscle cells. The findings highlight the interplay between angiogenic and chemokine signaling in vascular repair processes and suggest potential therapeutic strategies to support revascularization and inhibit vascular stenosis during exercise. Emerging pharmacologic and physiologic research demonstrates that structured exercise acts as a potent disease-modifying stimulus, interacting with signaling pathways related to vascular tone, lipid metabolism, mitochondrial function, and oxidative stress (22, 23). Our findings are consistent with this broader body of work, illustrating concordant improvements in blood pressure, functional capacity, and anthropometric parameters despite severe proximal coronary stenosis.

The use of cardiovascular medications in this patient, including antihypertensives, statins, and antiplatelet therapy (aspirin/clopidogrel), aligns with primary and secondary prevention guidelines, integrating pharmacotherapy with lifestyle modification. Pharmacologic management was tailored according to the patient's cardiovascular risk classification, consistent with the 2025 ESC recommendations. The prescription of antihypertensives, high-intensity statin therapy, and antiplatelet agents was appropriate for a high-risk profile, in accordance with Class Ia, Grade A recommendations (18).

The patient also received allopurinol therapy. Beyond its urate-lowering effect, allopurinol reduces production of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, which may confer benefit in mitigating oxidative stress associated with intensive physical training. However, allopurinol administration in this case was intermittent and closely supervised by a clinician, consistent with Class Ib, Grade A recommendations (19).

Recent guidelines additionally emphasize that pharmacologic therapy for obesity (such as GLP-1 receptor agonists) may be considered earlier in the treatment course, particularly in individuals at high cardiovascular risk, as an adjunct to lifestyle-based interventions (Class Ib, Grade A recommendations) (20).

The nutritional strategy in this case represented a modified approach compared with existing guidelines. While current obesity management guidelines typically recommend a 5%–10% reduction in body weight over six months (24), this patient achieved a 24.6% weight reduction, accompanied by favorable cardiovascular adaptation. Extreme macronutrient distribution (e.g., 10% carbohydrates and 50% protein) combined with high-intensity, high-volume exercise has not been extensively evaluated in high-risk cardiovascular populations. Notably, despite being classified as CAD-RADS 4 and falling into a high-risk category according to the 2025 ESC guidelines, the patient demonstrated excellent tolerance to both intensive exercise and a highly restrictive diet (18).

This favorable response was likely facilitated by close clinical supervision and targeted supplementation (e.g., vitamin K2, omega-3 fatty acids), administered with careful consideration of dosing, interactions, and evidence-based benefit (Class Ia, Grade A recommendations). However, such comprehensive multimodal therapy is not universally required for all patients and should be reserved for carefully selected individuals (25, 26). Although vitamin D supplementation has not consistently demonstrated cardiovascular benefit in patients with established coronary artery disease (Class Ia, Grade A recommendations) (27, 28), it was used in this case to maintain adequate baseline vitamin D status.

From a caloric standpoint, the patient's intake during Phase 1 (initiation; 1,500 kcal/day) and Phase 2 (transition; 2,000 kcal/day), falls within the range of a high deficit calorie diet or even maintenance intake in certain contexts (24, 29). This regimen was subsequently followed by Phase 3 (maintenance; 2,000–2,500 kcal/day). The relatively high caloric intake in later phases (despite substantial weight loss) reflects the patient's markedly elevated total daily energy expenditure (TDEE), driven by a large body mass and sustained high-intensity physical activity (six sessions per week). As such, a caloric deficit was still achieved (30).

According to current guidelines, a balanced dietary pattern typically consists of approximately 45%–50% carbohydrates, 15%–20% protein, and the remainder from fats (29). In this case, however, the macronutrient composition represented a modified high-protein, low-carbohydrate strategy, incorporating elements similar to the Dukan diet (31). This was most apparent during Phase 2, in which the dietary pattern became highly restrictive, with carbohydrate intake reduced to 10% and protein increased to 50% to preserve lean body mass and enhance satiety (24). Intermittent fasting play a roll in effective dietary intervention for slowing cardiometabolic aging process. Its related to the influences key for cardiometabolic risk factors like insulin sensitivity, inflammation and lipid metabolism (32).

Furthermore, the elimination of processed foods, sugars, and flour paralleled core principles of Mediterranean (DASH) dietary frameworks, emphasizing whole foods and supporting cardiovascular risk reduction (24). However, the markedly elevated protein proportion (50%) during Phase 2 may elicit metabolic responses such as increases in urea and uric acid levels, which represent physiological consequences of elevated protein turnover and treating with allopurinol medications (Table 7) (19, 29).

Patients undergoing this intensive lifestyle modification program must have preserved organ function (cardiac, renal, and hepatic), absence of decompensated comorbidities or arrhythmias, high adherence, close clinical supervision, meticulous monitoring of electrolytes and cardiovascular status. Ideal candidates include individuals in early middle adulthood, without unstable cardiovascular disease or severe metabolic derangements (e.g., renal failure, fluid overload), with adequate psychosocial support, and involvement of a multidisciplinary care team. Patients at high risk of complications (e.g., advanced cardiac disease, ventricular dysfunction) should be excluded or monitored with extreme vigilance. In obesity research, intensive interventions demonstrate greater effectiveness among individuals with severe obesity (BMI >35–40 kg/m²), substantial metabolic risk, and who are not elderly or burdened by advanced comorbidities (33).

In this case, the patient demonstrated improved cardiovascular performance during the stress test. Enhanced exercise tolerance (reflected by improved vital sign responses, reduced dyspnea during exertion, and higher METS) indicated robust cardiovascular compensation following the intervention program. These improvements can be attributed to reduced cardiac workload secondary to weight loss, enhanced endothelial and vascular function, decreased peripheral resistance, improved skeletal muscle oxidative capacity (including mitochondrial efficiency), and reductions in oxidative stress and inflammation, all of which facilitate greater VO₂ and METS achievement. Lower blood pressure and coronary arterial resistance improved myocardial perfusion during exertion. Both aerobic and resistance training contributed to superior cardiorespiratory reserve and cardiac–muscle efficiency. Reduced body mass decreased baseline oxygen demand and improved blood-flow distribution to active muscle groups. Concurrently, exercise enhanced mitochondrial function and muscular oxidative capacity, improving oxygen extraction. Endothelial improvements (via nitric oxide–mediated vasodilation) and reduced vascular resistance further optimized systemic and coronary perfusion under stress. Decreases in arterial pressure, insulin resistance, and metabolic load likely reduced functional coronary stenosis, enabling improved oxygen delivery. Accordingly, aerobic and resistance training has been shown to lower coronary artery disease risk by approximately 30%–40% in primary prevention settings, while participation in structured exercise-based cardiac rehabilitation programs reduces all-cause and cardiovascular mortality by 20%–25% in secondary prevention (Level Ia, Grade A) (34).

To minimize potential adverse effects associated with this intensive program, several precautionary measures must be implemented. Long-term extreme caloric deficits should be avoided, and adequate micronutrient intake (including electrolytes, vitamins, and minerals) must be ensured. Exercise intensity should be progressively increased rather than initiated at moderate to high intensity, with close attention to the patient's physiological compensation. Periodic assessment for refeeding or metabolic rebound phenomena is essential, and weight reduction should follow a gradual, controlled trajectory (≤0.5–1 kg/week) to reduce metabolic adaptation and adverse outcomes (Level Ia, Grade A) (35).

Routine monitoring of electrolytes, renal function, ECG parameters, and cardiac biomarkers (e.g., troponin and NT-proBNP when indicated) is recommended. Adequate protein consumption (≥1.2 g/kg ideal body weight/day) should be maintained to minimize loss of lean body mass (Level III, Grade B) (36). Furthermore, careful evaluation of potential interactions between medications and supplements is required, particularly in patients with cardiovascular disease (e.g., statins and antiplatelet agents). Consideration should also be given to the risk of micronutrient deficiency and the possibility of acute cardiometabolic disturbances (1, 4, 6, 37).

Following completion of the intensive intervention (initial and transition phases), the patient entered a maintenance phase. This phase included sustaining a structured exercise regimen with moderate-intensity aerobic and resistance training while maintaining a high overall training volume. Dietary adjustments emphasized either mild caloric deficit or energy balance to support weight maintenance.

A combined aerobic–resistance program was continued to optimize cardiometabolic benefits, and strategies to minimize metabolic adaptation such as periodic diet breaks, training load variation, and enhancement of non-exercise activity thermogenesis (NEAT) were incorporated. Longitudinal monitoring of metabolic markers (lipid profile, glucose, and relevant hormones) was performed to guide individualized adjustment of dietary and exercise interventions in the event of weight regain or unfavorable metabolic shifts. Importantly, energy restriction during this phase was maintained at a mild, physiologically sustainable level rather than reverting to extreme caloric deficits, alongside continued cardiovascular assessment to ensure safety and clinical stability (20, 38).

Based on the considerations and analyses, the patient completed a ten months intensive lifestyle program, achieving a total weight loss of 50 kg (41% from baseline). This was accompanied by marked improvements in lipid and glycemic parameters, including a substantial increase in HDL-cholesterol (from 0.97 mmol/L to 1.63 mmol/L) and a reduction in HbA1c (from 5.3% to 4.9%). Functional capacity also improved meaningfully, as demonstrated by enhanced exercise stress testing performance, including improved heart rate and blood-pressure responses and a notable increase in MET capacity (from 6.30 to 11.50), reflecting substantial cardiovascular and cardiorespiratory adaptation.

Despite these favorable metabolic and functional changes, a rise in LDL-cholesterol (from 1.51 mmol/L to 3.44 mmol/L) and total cholesterol (from 3.32 mmol/L to 5.47 mmol/L) was observed. This paradoxical lipid elevation likely represents compensatory lipid-metabolism regulation related to rapid weight reduction and mobilization of adipose tissue stores, a phenomenon previously reported in intensive weight-loss interventions (9, 17). Nonetheless, given the patient's coronary risk profile, these changes warrant careful longitudinal evaluation and, if necessary, adjunctive lipid-lowering therapy to mitigate residual atherosclerotic risk (1, 5, 20).

The safety of structured exercise training in patients with coronary artery disease is highly dependent on rigorous patient selection, individualized intensity prescription, and appropriate monitoring. Contemporary evidence emphasizes that hemodynamic surveillance, symptom-guided workload adjustment, and attention to pharmacologic interactions can reduce adverse events during intensive exercise in cardiometabolic disease. As well as TGF-β1-induced cardiac fibroblast proliferation, differentiation, and collagen overproduction by modulating the PTEN/Akt/mTOR signaling pathway during exercise. PTEN/Akt/mTOR modulation in cardiometabolic disease is central to its antifibrotic activity (39). Consistent with these recommendations, our program incorporated ECG telemetry during early sessions, predefined blood pressure and ischemia-related termination thresholds, and intensity targets based on percentage heart rate reserve and Borg RPE. The present case therefore supports the concept that appropriately supervised and carefully titrated intensive exercise can be implemented safely even in anatomically severe CAD, although broader generalization requires caution.

Recent scientific bulletins stress that lifestyle-centered therapy should not be considered merely adjunctive, but rather an integral therapeutic strategy across the continuum of cardiometabolic disease, including patients with angiographically significant CAD. The present case aligns with these updated perspectives, illustrating that high-adherence, multidisciplinary lifestyle intervention may yield marked functional improvement even in advanced anatomical disease, although decisions regarding revascularization should remain individualized. Accumulating evidence highlights the role of immunometabolic pathways linking obesity, inflammation, and atherosclerosis and fibrosis progression (40). Intensive exercise and weight reduction likely act in part through modulation of these immune-metabolic networks. Although we did not measure cytokines or immune markers, the observed clinical improvements are compatible with favorable alterations in systemic inflammatory activity suggested in prior immunologic research (39, 40).

A high-intensity exercise approach combined with extreme dietary modification may result in substantial weight reduction and significant improvement in functional capacity. However, current evidence does not yet support the long-term safety and efficacy of such an approach in patients with coronary artery disease (CAD).

Gradual, moderate, and structured interventions aligned with established international guidelines (AHA, ESC, ACC) remain the preferred strategy, supported by robust evidence (Level Ia, Grade A recommendations). Intensive programs of this nature should only be considered in carefully selected patients with adequate clinical stability, under comprehensive multidisciplinary supervision and rigorous monitoring of clinical status and biomarkers.

Furthermore, appropriate pharmacotherapy in accordance with guideline recommendations and evidence-based supplementation are essential to ensure safety and optimize therapeutic benefit. Ongoing evaluation is required to notice the immunometabolic respon on cardiovascular, and pharmacology and nutritional side effects during the intervention process.

Extreme lifestyle therapy is not routine in CAD but may be possible in carefully selected patients.

Close cardiovascular monitoring is essential to avoid ischemia and arrhythmia.

Rapid weight loss may temporarily raise LDL due to fat mobilization.

Guideline-based moderate lifestyle therapy remains first-line; extreme programs belong only in supervised settings.

This is a single patient observation without control group. Therefore causality cannot be inferred. The protocol applied in this case is not guideline standard and should not be interpreted as evidence for routine use in CAD patients. Hormonal and advanced lipid testing (apo-B, lipoprotein subfractions) were not performed. In this study, cardiopulmonary exercise testing was not available, therefore VO₂ peak and ventilatory efficiency variables could not be obtained and physiologic adaptations were inferred from exercise treadmill test performance. Physiologic adaptation was inferred from ETT parameters. Imaging follow-up of coronary anatomy was not repeated, so plaque regression or progression cannot be determined. Diet composition, statin adherence variability, and genetic lipid responsiveness confound the interpretation of LDL changes. Therefore, generalizability is limited and findings should be interpreted cautiously.

When I first learned about the severity of my coronary artery condition, I felt anxious but determined to avoid surgery if possible. I declined the PCI procedure because the risk of lifelong anticoagulant use after PCI and the surgery cost. I wanted to prove to myself that I could change my lifestyle and take control of my health. I decided to pursue a non-procedural approach and committed fully to the intensive program recommended by my clinical team.

The early phase was very challenging. Adjusting to strict nutrition changes and high-intensity exercise was physically exhausting and mentally demanding. There were moments when I felt weak and doubted whether I could continue. However, the gradual improvements in my breathing, stamina, blood pressure, and overall energy motivated me to stay consistent.

Progress did not happen overnight. It required discipline, patience, and continuous monitoring by my doctors. As my body changed, I felt lighter, more confident, and capable of activities I had not imagined doing before. This journey taught me that extreme programs require careful supervision and personal commitment. The most important lesson for me is that meaningful improvement is possible with the right guidance, consistent discipline, and strong support from healthcare professionals.

Now, I feel proud of my progress and more aware of maintaining my health long-term. I am grateful for the multidisciplinary team that guided me safely through this journey.