Acute Exacerbation of Chronic Obstructive Pulmonary Disease as a Short-Term Cardiopulmonary Risk Window: A Time-Stratified Systematic Review and Meta-analysis

Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are often managed as discrete respiratory events, but patients may enter a short period of systemic cardiopulmonary vulnerability during recovery. We performed a systematic review and meta-analysis to define the timing and magnitude of serious cardiovascular risk after COPD exacerbation.

Methods: PubMed, Embase, Scopus, and Web of Science were searched from database inception to April 2026. The review was registered in PROSPERO (CRD420261384390) and followed PRISMA guidance. Eligible studies evaluated cardiovascular outcomes after acute COPD exacerbation using time-defined follow-up windows. Adjusted hazard ratios (HRs) were prioritized for quantitative synthesis. Random-effects meta-analysis used restricted maximum likelihood with Hartung-Knapp adjustment, prediction intervals, time-windowed analyses, and leave-one-study-out sensitivity analyses. Biomarker-only, diagnostic-only, conference-only, and studies without a post-exacerbation cardiovascular outcome were excluded from the primary clinical synthesis. Risk of bias was assessed independently by two reviewers using Newcastle-Ottawa Scale domains.

Results: Forty-three studies met inclusion criteria, and 9 studies contributed to the primary 30-day synthesis. COPD exacerbation was associated with increased serious cardiovascular risk within 30 days (pooled HR 2.38, 95% confidence interval [CI] 1.68-3.39). The highest relative risk was observed during the first week after exacerbation (HR 12.53, 95% CI 4.93-31.85; k=5), and the 30-day signal persisted after excluding first-week-only estimates (HR 2.13, 95% CI 1.57-2.88; k=8). Leave-one-study-out analyses did not eliminate the association, although heterogeneity and prediction intervals were substantial. The evidence was predominantly observational or post hoc, and very early estimates were also susceptible to diagnostic overlap. A single aggregate participant count was not calculated because several structurally related cohorts could overlap.

Conclusions: Acute COPD exacerbation appears to mark a time-dependent cardiopulmonary risk window rather than an isolated respiratory event. Recent exacerbation should be considered a pragmatic trigger for short-term cardiovascular risk review, particularly after severe or hospitalized exacerbations, while current evidence does not support uniform pharmacologic escalation for all patients. PROSPERO registration: CRD420261384390. Funding: None.