OBJECTIVE Recent influenza infection is associated with an increased risk of atherothrombotic events, including acute myocardial infarction (AMI) and stroke. Little is known about the association between influenza vaccination and cardiovascular outcomes in patients with diabetes. RESEARCH DESIGN AND METHODS We used nationwide register data to identify patients with diabetes in Denmark during nine consecutive influenza seasons in the period 2007–2016. Diabetes was defined as use of glucose-lowering medication. Patients who were not 18–100 years old or had ischemic heart disease, heart failure, chronic obstructive lung disease, cancer, or cerebrovascular disease were excluded. Patient exposure to influenza vaccination was assessed before each influenza season. We considered the outcomes of death from all causes, death from cardiovascular causes, and death from AMI or stroke. For each season, patients were monitored from December 1untilApril1thenextyear. RESULTS A total of 241,551 patients were monitored for a median of four seasons (interquartile range two to eight seasons) for a total follow-up of 425,318 person-years. The vaccine coverage during study seasons ranged from 24% to 36%. During follow-up, 8,207 patients died of all causes (3.4%), 4,127 patients died of cardiovascular causes (1.7%), and 1,439 patients died of AMI/stroke (0.6%). After adjustment for confounders, vaccination was significantly associated with reduced risks of all-cause death (hazard ratio [HR] 0.83, P < 0.001), cardiovascular death (HR 0.84, P < 0.001), and death from AMI or stroke (HR 0.85, P = 0.028) and a reduced risk of being admitted to hospital with acute complications associated with diabetes (diabetic ketoacidosis, hypoglycemia, or coma) (HR 0.89, P = 0.006). CONCLUSIONS In patients with diabetes, influenza vaccination was associated with a reduced risk of all-cause death, cardiovascular death, and death from AMI or stroke. Influenza vaccination may improve outcome in patients with diabetes.
Bibliographical noteFunding Information:
The sponsors had no role in the study design, data collection, data analysis, data interpretation, or writing of the article. Duality of Interest. S.D.S. has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol-Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, Novartis, Sanofi Pasteur, and Theracos and has consulted for Akros, Alnylam, Amgen, Arena, AstraZeneca,Bayer,Bristol-MyersSquibb,Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GlaxoSmithKline, Ironwood, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AOBiome, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Di-naqor, and Tremeau. S.D.N. has received research grants and traveling grants from Gilead. No other potential conflicts of interest relevant to this article were reported. Author Contributions. D.M. researched the data and wrote the manuscript. D.M. and T.B.-S. conceived the study. B.C. provided statistical insight, contributed to discussion, and reviewed and edited the manuscript. L.K., M.S., J.U.S.J., S.D.S., O.V., F.K.K., S.D.N., M.F., C.T.-P., and G.G. provided specialist knowledge, input, and suggestions for the final plan of analysis, contributed with intellectual discussion, and reviewed and edited the manuscript for intellectual content. C.T.-P., G.G., and T.B.-S. provided data access. D.M. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Funding. D.M. was supported by the Novo Nordisk Foundation (grant number NNF18OC0052966), by the Else og Mogens Wedell Wedellsborgs Fond, by the Fru Asta Florida Bolding Født Andersens Mindelegat Fond, and by the Snedkermester Sophus Jacobsen og Hustru Astrid Jacobsens Fond during the preparation of this manuscript. S.D.S. has received support from National Institutes of Health/National Heart, Lung, and Blood Institute. S.D.N. has received research grants from the Novo Nordisk Foundation.
D.M. was supported by the Novo Nordisk Foundation (grant number NNF18OC0052966), by the Else og Mogens Wedell Wedellsborgs Fond, by the Fru Asta Florida Bolding F?dt Andersens Mindelegat Fond, and by the Snedkermester Sophus Jacobsen og Hustru Astrid Jacobsens Fond during the preparation of this manuscript. S.D.S. has received support from National Institutes of Health/National Heart, Lung, and Blood Institute. S.D.N. has received research grants from the Novo Nordisk Foundation.