Influenza vaccination and cardiovascular and respiratory outcomes in high-risk populations: an umbrella review of systematic reviews and meta-analyzes

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Background: Influenza infection is an important trigger of acute cardiovascular events and respiratory decompensation in vulnerable populations. Although influenza vaccination may reduce cardiopulmonary morbidity and mortality, the overall certainty and methodological reliability of the evidence remain unclear. Objective: To synthesize and critically evaluate published systematic reviews and meta-analyses on the effectiveness and safety of influenza vaccination in populations at high risk of cardiovascular and respiratory complications. Methods: We conducted an umbrella review of systematic reviews and meta-analyses identified through PubMed, Embase, and the Cochrane Library from inception to December 1, 2025. Methodological quality was assessed using AMSTAR-2, evidence certainty using GRADE, and overlap of primary studies using citation matrices and corrected covered area (CCA). Given heterogeneity and review overlap, we performed a narrative synthesis and applied predefined rules to prioritize representative reviews. Results: Fourteen systematic reviews and meta-analyses were included. The strongest evidence supported an association between influenza vaccination and reduced major cardiovascular risk, particularly major adverse cardiovascular events in patients with ischemic heart disease and acute coronary syndrome. Vaccination was also associated with reduced cardiovascular mortality and all-cause mortality in some high-risk populations. In respiratory high-risk populations, vaccination was associated with fewer COPD exacerbations and lower laboratory-confirmed influenza incidence among older adults. Across an evidence base covering more than 230 million participants, no clear increase in serious adverse events was observed. The highest-certainty evidence was concentrated in selected cardiovascular and influenza-related outcomes, whereas stroke and several respiratory outcomes remained moderate to low in certainty because of heterogeneity and mixed study designs. Conclusion: Influenza vaccination appears to be a safe and clinically meaningful preventive strategy in populations at high risk of cardiopulmonary complications. The strongest current evidence supports selected cardiovascular endpoints and influenza-related outcomes. This umbrella review provides an integrated synthesis of cardiovascular, respiratory, and safety outcomes while explicitly addressing review quality, overlap of primary studies, and certainty of evidence. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251267371.

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