Myocardial infarction (MI) has been associated with natural influenza infection, and stroke has been associated with natural varicella infection, albeit both very rarely. Thus, influenza vaccine prevents MI and varicella vaccine prevents stroke by protecting against natural infection. Vaccines currently routinely recommended to the general population in the U.S.* have not been shown to cause myocardial infarction or stroke.
The 2012 report by the Institute of Medicine (IOM), now called the National Academy of Medicine (NAM), described one study with sufficient validity and precision that reported a decreased risk of both MI and stroke within the first month after influenza vaccine . The report also described one study assessing stroke and varicella vaccine (Varivax) , but this study did not provide convincing evidence due to a lack of validity and precision .
A matched case-control study of 78,706 persons published since the 2012 IOM report found that receipt of seasonal influenza vaccine within the previous year was significantly associated with lower odds of MI (adjusted odds ratio [OR] 0.81, 95% confidence interval [CI] 0.77-0.85) and receipt of pneumococcal vaccine was not associated with a change in odds of MI in adults . Another matched case-control study of 94,022 persons found that receipt of seasonal influenza vaccine within-season was significantly associated with lower odds of stroke (adjusted odds ratio [OR] 0.76, 95% confidence interval [CI] 0.72-0.80) and receipt of pneumococcal vaccine was not associated with a change in odds of stroke . In both of these studies, early seasonal influenza vaccination (before mid-November) was much more beneficial than later seasonal influenza vaccination. A self-controlled case series found a decreased incidence of MI up to 60 days after seasonal influenza vaccination, ranging from a 32% reduction within the first 14 days (incidence rate ratio [IRR] 0.68, 95% CI 0.60-0.78) to a 18% reduction within 29-59 days (IRR 0.82, 95% CI 0.75-0.90) . A case-control study of 559 Australian patients also found decreased odds of MI after influenza vaccination (OR 0.55, 95% CI 0.35-0.85) . Pooled data from several studies examining adults with recent ischemic stroke found no association between influenza vaccination and MI or stroke . A matched case-control study of Taiwanese patients over 65 years of age found decreased odds of stroke after influenza vaccination . Prospective cohorts of older adults found that receipt of pneumococcal polysaccharide vaccine was either not associated with MI or stroke [10, 11] or associated with a decreased risk of acute coronary syndrome events in general . A prospective cohort of 27,204 Spanish individuals initially found a decreased risk of stroke in individuals receiving 23-valent pneumococcal polysaccharide vaccine ; however, this association was later refuted by the authors . This study did show that influenza vaccine was associated with reduced risk of death from stroke , and that pneumococcal vaccine was not associated with MI . A study in 193,083 adults over 50 years of age found no association between varicella zoster vaccine and MI using both case-centered and self-controlled case series analyses . Two large Vaccine Safety Datalink studies found no association between stroke and receipt of quadrivalent HPV vaccine (Gardasil®) in females age 9 to 26  or receipt of the DTaP-IPV combination vaccine (Kinrix®) in children age 4 to 6 , respectively. Herpes zoster vaccine was not associated with an increased risk of stroke or cardiovascular events in numerous safety studies .
Potential mechanisms for MI include viral infection and alterations in the coagulation cascade . MI has been associated with natural influenza infection, albeit very rarely . Potential mechanisms for stroke include direct viral infection, viral reactivation, and alterations in the coagulation cascade . Stroke has been associated with natural varicella infection, at an incidence of about 1 in 15,000 cases .
The IOM concluded that the only mechanistic evidence for an association between MI and live attenuated influenza vaccine or between stroke and varicella vaccine was knowledge about the natural infections. The IOM also concluded that there was no mechanistic evidence for an association between stroke and influenza vaccine or between MI and inactivated influenza vaccine, as the publications reviewed provided little evidence beyond a temporal association .
1. Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute infection or vaccination. The New England journal of medicine 2004;351:2611-8.
2. Donahue JG, Kieke BA, Yih WK, et al. Varicella vaccination and ischemic stroke in children: is there an association? Pediatrics 2009;123:e228-34.
3. Institute of Medicine. In: Stratton K, Ford A, Rusch E, Clayton EW, eds. Adverse Effects of Vaccines: Evidence and Causality. Washington (DC): National Academies Press (US); 2012.
4. Siriwardena AN, Gwini SM, Coupland CA. Influenza vaccination, pneumococcal vaccination and risk of acute myocardial infarction: matched case-control study. CMAJ 2010;182:1617-23.
5. Siriwardena AN, Asghar Z, Coupland CC. Influenza and pneumococcal vaccination and risk of stroke or transient ischaemic attack-matched case control study. Vaccine 2014;32:1354-61.
6. Gwini SM, Coupland CA, Siriwardena AN. The effect of influenza vaccination on risk of acute myocardial infarction: self-controlled case-series study. Vaccine 2011;29:1145-9.
7. Macintyre CR, Heywood AE, Kovoor P, et al. Ischaemic heart disease, influenza and influenza vaccination: a prospective case control study. Heart 2013;99:1843-8.
8. Lavallee PC, Labreuche J, Fox KM, et al. Influenza vaccination and cardiovascular risk in patients with recent TIA and stroke. Neurology 2014;82:1905-13.
9. Lin HC, Chiu HF, Ho SC, Yang CY. Association of influenza vaccination and reduced risk of stroke hospitalization among the elderly: a population-based case-control study. International journal of environmental research and public health 2014;11:3639-49.
10. Tseng HF, Slezak JM, Quinn VP, Sy LS, Van den Eeden SK, Jacobsen SJ. Pneumococcal vaccination and risk of acute myocardial infarction and stroke in men. Jama 2010;303:1699-706.
11. Hedlund J, Christenson B, Lundbergh P, Ortqvist A. Effects of a large-scale intervention with influenza and 23-valent pneumococcal vaccines in elderly people: a 1-year follow-up. Vaccine 2003;21:3906-11.
12. Eurich DT, Johnstone JJ, Minhas-Sandhu JK, Marrie TJ, Majumdar SR. Pneumococcal vaccination and risk of acute coronary syndromes in patients with pneumonia: population-based cohort study. Heart 2012;98:1072-7.
13. Vila-Corcoles A, Ochoa-Gondar O, Rodriguez-Blanco T, et al. Clinical effectiveness of pneumococcal vaccination against acute myocardial infarction and stroke in people over 60 years: the CAPAMIS study, one-year follow-up. BMC Public Health 2012;12:222.
14. Vila-Corcoles A, Ochoa-Gondar O, Rodriguez-Blanco T, de Diego C, Satue E. Ineffectiveness of pneumococcal vaccination in cardiovascular prevention: the CAPAMIS study. JAMA Intern Med 2013;173:1918-20.
15. Vila-Corcoles A, Ochoa-Gondar O, Rodriguez-Blanco T, et al. Evaluating clinical effectiveness of pneumococcal vaccination in preventing stroke: the CAPAMIS Study, 3-year follow-up. J Stroke Cerebrovasc Dis 2014;23:1577-84.
16. Ochoa-Gondar O, Vila-Corcoles A, Rodriguez-Blanco T, de Diego-Cabanes C, Hospital-Guardiola I, Jariod-Pamies M. Evaluating the clinical effectiveness of pneumococcal vaccination in preventing myocardial infarction: The CAPAMIS study, three-year follow-up. Vaccine 2014;32:252-7.
17. Tseng HF, Liu A, Sy L, et al. Safety of zoster vaccine in adults from a large managed-care cohort: a Vaccine Safety Datalink study. J Intern Med 2012;271:510-20.
18. Gee J, Naleway A, Shui I, et al. Monitoring the safety of quadrivalent human papillomavirus vaccine: findings from the Vaccine Safety Datalink. Vaccine 2011;29:8279-84.
19. Daley MF, Yih WK, Glanz JM, et al. Safety of diphtheria, tetanus, acellular pertussis and inactivated poliovirus (DTaP-IPV) vaccine. Vaccine 2014;32:3019-24.
20. Keating GM. Shingles (herpes zoster) vaccine (zostavax((R))): a review of its use in the prevention of herpes zoster and postherpetic neuralgia in adults aged >/=50 years. Drugs 2013;73:1227-44.
21. Estabragh ZR, Mamas MA. The cardiovascular manifestations of influenza: a systematic review. Int J Cardiol 2013;167:2397-403.
22. Nagel MA, Mahalingam R, Cohrs RJ, Gilden D. Virus vasculopathy and stroke: an under-recognized cause and treatment target. Infect Disord Drug Targets 2010;10:105-11.