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. Influenza vaccine has been associated with a reduced risk of 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: 0.81; 95% confidence interval: 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 (aOR: 0.76; 95% CI: 0.72-0.80) and receipt of pneumococcal vaccine was not associated with a change in odds of stroke .
A self-controlled case-series study of 17,853 persons found a reduction in incidence of stroke after receipt of influenza vaccine . In all three of these studies, early seasonal influenza vaccination (before mid-November) was much more beneficial than later seasonal influenza vaccination. A 2017 meta-analysis also concluded that influenza vaccine was associated with a reduced risk of stroke (OR: 0.82; 95% CI: 0.75-0.91) . 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: 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 (aOR: 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 . Two case-control studies and one population study of Taiwanese patients over 65 years of age found decreased odds of cardiovascular events such as MI and stroke after influenza vaccination [11-13].
Prospective cohorts of older adults found that receipt of pneumococcal polysaccharide vaccine was either not associated with MI or stroke [14, 15] or associated with a decreased risk of acute coronary syndrome events in general [16, 17]. 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. A review of quadrivalent HPV vaccine safety data published between 2006 and 2015 found no increase in incidence of stroke compared to background rates . Herpes zoster vaccine was not associated with an increased risk of stroke or cardiovascular events in numerous safety studies .
A 2015 international case-control study concluded that routine vaccinations in childhood appear to be protective against stroke . A 2015 Cochrane review determined that influenza vaccination may reduce cardiovascular mortality and combined cardiovascular events among patients with cardiovascular disease, although not enough evidence was available to establish whether influenza vaccination prevented primary cardiovascular disease .
Proposed Biological Mechanism
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 .
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