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 .
* These conclusions do not necessarily consider vaccines recommended only for special populations in the United States such as Yellow Fever vaccine (international travelers) or Smallpox vaccine (military personnel).
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