Chronic obstructive pulmonary disease (COPD) is increasingly recognized to be closely linked to cardiovascular-kidney-metabolic (CKM) conditions. As the population ages, patients with multiple comorbidities, including CKM syndrome and COPD, are commonly encountered in clinical practice across multiple specialties. A more coordinated effort and enhanced awareness are required for better management and outcome. At a symposium organized by the Federation of Medical Societies of Hong Kong (FMSHK) chaired by Dr Samuel Ka-Shun Fung, Executive Committee Member of FMSHK, Dr Ka-Chun Leung, Specialist in Nephrology of Tuen Mun Hospital, Dr Emmanuel Chun-Ka Wong of the Division of Cardiology, University of Hong Kong, and Dr Fanny Wai-San Ko of the Division of Respiratory Medicine, the Chinese University of Hong Kong, discussed how evolving multiorgan dysfunction, overlapping clinical presentations, and sequential treatment decisions shape diagnosis and management of these conditions. A case discussion of progression from chronic kidney disease (CKD) to worsening COPD and, subsequently, heart failure (HF) highlighted diagnostic and therapeutic complexities, and provided practice insights.
CKD: Key driver of CKM syndrome progression
CKM syndrome is a systemic condition characterized by complex interactions between metabolic risk factors, CKD, and the cardiovascular (CV) system that contribute to progressive multiorgan dysfunction and increased CV and kidney risk. Within this continuum, CKD is both a consequence of metabolic dysfunction and a key driver of disease progression. Declining kidney function is associated with persistent inflammation and other interconnected pathophysiological processes that promote vascular injury, accelerate CV disease, and further impair kidney function. Therefore, early identification and management of CKD are critical to slowing disease progression, reducing CV risk, and improving long-term outcomes. (Figure 1) [Circulation 2023;148:1606-1635; Clin J Am Soc Nephrol 2026;doi:10.2215/ CJN.0000001054]
COPD interacts closely with CKM syndrome
COPD is increasingly recognized as closely interacting with CKM syndrome through shared risk factors and interconnected pathophysiological mechanisms, including systemic inflammation. These processes contribute to both CV and pulmonary pathology, including atherosclerosis and airway inflammation that increase the risk of myocardial infarction (MI) and COPD exacerbations, respectively. Persistent inflammation and progressive tissue remodelling over time may contribute to cumulative multiorgan dysfunction, including HF and respiratory failure. (Figure 2) [J Clin Med 2019;8:69; Int J Chron Obstruct Pulmon Dis 2024;19:2259-2271]
Acute exacerbations of COPD further amplify CV risk, especially in the weeks immediately following the exacerbation. A meta-analysis of the EXACOS-CV observational studies demonstrated that the risk of a severe CV event or all-cause death was approximately 20-fold higher during the first week after a severe COPD exacerbation; this risk remained elevated for up to 1 year. Similarly, a population-based study reported that, within the first 14 days after a COPD exacerbation, patients experienced an approximately twofold increased risk of acute coronary syndrome, a threefold increased risk of arrhythmia or HF, and a 1.5-fold increased risk of ischaemic stroke vs patients who did not experience an exacerbation. [Eur J Intern Med 2025;135:74-82; Pollack M, et al, ATS 2024, poster 159; Am J Respir Crit Care Med 2024;209:960-972]
Navigating evolving multimorbidity: Case discussion & practice insights
January 2024: Abnormal lab results in an older man with multimorbidity
A 70-year-old man presented in the clinic with abnormal laboratory results. (Table 1) Urinalysis showed 1+ proteinuria without haematuria, and urine microscopy was unremarkable. Findings were consistent with CKD stage G3aA1 with mild hyperkalaemia.
History included hypertension, hyperlipidaemia, type 2 diabetes (T2D) (10-year duration), and COPD (diagnosed in 2019). He was a former smoker (40 pack-years, quit 6 months earlier). Vaccinations were up to date. Medications included losartan, rosuvastatin, metformin, olodaterol/ tiotropium, salbutamol, and intermittent ibuprofen.
CKD: Early identification and cardiorenal protection
CKD screening should include both eGFR and UACR, which independently predict CV and kidney outcomes. Risk stratification tools (eg, KDIGO heatmap, PREVENT equations) integrate renal and metabolic markers to estimate CV risk. CKD is recognized as a Stage A HF risk state, underscoring the need for proactive cardiorenal risk management. (Figure 3) [Kidney Int 2024;105:S117-S314; J Am Soc Nephrol 2013;24:302-308; J Am Soc Nephrol 2009;20:1813-1821; Kidney Int 2026;109:1095-1113; Circulation 2023;148:1982-2004]
Guideline-directed Tx for CKD & practical considerations
The patient was managed according to Kidney Disease: Improving Global Outcomes (KDIGO) guidance, with:
- Initiation of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) (dapagliflozin 10 mg QD) – recommended in eligible CKD patients, in combination with renin-angiotensin-aldosterone system inhibitors (RAASis), to provide cardiorenal protection beyond glucose lowering;
- Addition of potassium-lowering therapy (eg, sodium zirconium cyclosilicate) to support continued RAASi use;
- Optimization of RAASi therapy (losartan dose increased from 50 to 100 mg QD once potassium level was normalized); and
- Discontinuation of ibuprofen to reduce nephrotoxic risk. [Kidney Int 2024;105:S117-S314]
To maintain guideline-directed RAASi therapy, hyperkalaemia should be managed proactively through medication review, dietary potassium management, and potassium-lowering therapies. A modest early decline in eGFR following SGLT2i initiation is expected and generally does not warrant treatment discontinuation. This initial eGFR dip reflects favourable haemodynamic changes and is associated with slower CKD progression over time. [J Am Soc Nephrol 2023;34(11S):379; Kidney Int 2024;105:S117-S314; Mayo Clin Proc 2026:S0025-6196(26)04334-X]
Before initiating SGLT2i, patient counselling should be provided to minimize the risk of adverse effects and optimize treatment adherence. Hypovolaemia can be managed by reducing or discontinuing diuretics, when appropriate, and encouraging adequate fluid intake. The risk of genital mycotic infections can be reduced through patient education on genitourinary hygiene, with prompt antifungal treatment if infection occurs. The risk of euglycaemic diabetic ketoacidosis can be minimized by avoiding ketogenic diets and reinforcing sick-day guidance, including temporary discontinuation of SGLT2i during acute illness or before major surgery. Patients should also be monitored for symptomatic hypotension and hypoglycaemia, particularly when receiving concomitant glucose-lowering or antihypertensive therapies, with treatment adjusted as needed. [Nephrology (Carlton) 2023;28:415-424]
December 2024: Hospitalization due to COPD exacerbation
The patient was hospitalized due to worsening dyspnoea, cough, sputum production, and wheeze. He reported a 6-month history of progressive dyspnoea, reduced exercise tolerance, and an accident and emergency (A&E) department visit 2 months earlier, which was treated with oral corticosteroids and antibiotics. Examination and imaging supported a diagnosis of COPD exacerbation, with no evidence of infection or acute cardiac abnormalities. (Table 2) His metabolic profile and cardiac markers were normal. Symptom burden was high (Modified Medical Research Council Dyspnoea Scale [mMRC] grade 3, COPD Assessment Test [CAT] score, 20). Maintenance therapy prior to admission included olodaterol/tiotropium and salbutamol.
COPD: Tx optimization, exacerbation risk and comorbidities
Discharge after a COPD exacerbation is a key opportunity to optimize long-term management and reduce future risk. Before discharge, optimize maintenance therapy, review inhaler technique, and complete acute treatments (eg, corticosteroids and antibiotics) when appropriate. Assess CV risk and manage identified comorbidities with GDMT, including cardio-selective β-blockers and statins when indicated. Early follow-up is important to reassess symptoms and optimize maintenance therapy.
For patients with exacerbation history, particularly those with elevated blood eosinophil counts, consider escalation to triple therapy with inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA) and long-acting β-agonist (LABA), consistent with Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations, to reduce future exacerbation risk. Given the associated increase in CV risk, preventing future COPD exacerbations remains a key management goal. [GOLD Pocket Guide to COPD Diagnosis, Management, and Prevention, 2026]
Benefits of early triple therapy in COPD
In patients with frequent COPD exacerbations, triple inhaled therapy reduces exacerbations and may lower cardiopulmonary risk vs dual bronchodilator therapy. Single-inhaler triple therapy (SITT) is preferred over multiple-inhaler triple therapy (MITT), as it reduces medication errors and is associated with improved treatment effectiveness. Early initiation of SITT (≤30 days) after an exacerbation is associated with lower rates of subsequent exacerbations and cardiopulmonary events vs delayed initiation. [BMC Pulm Med 2025;25:345; Am J Med 2025;138:650- 659.e10; Am J Respir Crit Care Med 2025;211:A7383]
July 2025: Progressive lower-extremity oedema
The patient presented to an A&E department with progressive lower-extremity oedema and exertional dyspnoea with orthopnoea and paroxysmal nocturnal dyspnoea (PND). COPD was stable.
Physical examination revealed elevated jugular venous pressure, bibasilar crackles, and pitting oedema to the mid-shin. Electrocardiography demonstrated sinus tachycardia with left ventricular hypertrophy pattern. Chest X-ray showed pulmonary congestion. Echocardiography demonstrated reduced left ventricular ejection fraction and hypokinesia over the left anterior descending (LAD) territory. (Table 3)
Findings were consistent with HF with reduced ejection fraction (HFrEF), with features suggestive of possible ischaemic cardiomyopathy. Further evaluation to exclude prior MI was arranged.
Differential diagnosis: HF vs COPD exacerbation
In patients with dyspnoea and lower-extremity oedema, distinguishing HF from COPD exacerbation or cor pulmonale can be challenging. NT-proBNP testing and echocardiography are key investigations, with clinical examination (eg, auscultation) and chest X-ray providing additional diagnostic clues.
HF: Early GDMT initiation & practical considerations
Following HF diagnosis, management focuses on relieving congestion, initiating GDMT, and addressing contributing comorbidities. Volume overload can be managed with diuretics such as furosemide, with close monitoring of urine output, fluid status, renal function and electrolytes. GDMT should be introduced early during hospitalization and optimized as tolerated, including the four foundational therapies for HFrEF: angiotensin receptor–neprilysin inhibitor (ARNI)/angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonist (MRA), and SGLT2i. [Eur Heart J 2021;42:3599-3726]
Therapy selection should consider the broader clinical context and multimorbidity. When transitioning from an ACEi to an ARNI, a 36-hour washout period is required to minimize the risk of angioedema. In patients with COPD, cardioselective β-blockers can still be considered, as COPD alone is not an absolute contraindication. Maintaining optimal COPD control alongside HF therapy is an important aspect of comprehensive management in patients with coexisting HF and COPD. [Eur Heart J 2021;42:3599-3726]
January 2026: Outcomes after optimization
By January 2026, symptoms and biomarkers improved with stable renal function (stage G3aA1) and HF (New York Heart Association functional class II) control. COPD symptoms persisted (mMRC, 3; CAT, 14), but there had been no hospitalizations or A&E department visits in the preceding year. HbA1c improved to 6.6–6.8 percent. NT-proBNP decreased to 200 pg/mL and blood eosinophils remained stable at about 330 cells/μL. Spirometry demonstrated moderate airflow limitation. Coronary assessment and management were arranged.
At this stage, the patient’s regimen included cardiorenal therapies (losartan, dapagliflozin, bisoprolol, and spironolactone), metabolic and CV risk management (aspirin, metformin and rosuvastatin), and optimized COPD maintenance therapy (MITT with olodaterol/tiotropium plus beclomethasone switched to SITT with budesonide/glycopyrronium/formoterol). Salbutamol was continued as needed for symptom relief.
Conclusion
CKD, COPD and HF form a multisystem continuum. Isolated management may miss opportunities for earlier intervention.
COPD exacerbations increase CV risk and should prompt evaluation of cardiac comorbidities. NT-proBNP testing and echocardiography can be considered to distinguish HF from COPD-related dyspnoea. Early initiation and optimization of GDMT are essential for slowing disease progression, preventing end-organ damage and improving outcomes.
The above content is for medical education purpose supported by AstraZeneca (Hong Kong) Limited.
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