Excerpt
Cardiovascular diseases (CVD) still represent the leading cause of mortality and morbidity in Western countries despite the increasing availability of highly effective strategies to control traditional risk factors in the last years [
1]. Therefore, the persistence of other under-recognized risk factors has been hypothesized. Among these, since the beginning of the 1900 the association between seasonal influenza epidemics and major cardiovascular events (MACE) has been repeatedly confirmed [
2]. Globally, the World Health Organization estimates that influenza kills almost 650,000 people annually, being a leading cause of death among people of all ages, especially those with comorbidities like CVD [
3]. Cardiovascular manifestations associated with influenza include acute coronary syndromes [
4‐
6]. There is indeed a wealth of retrospective and prospective studies showing a temporal relationship with influenza respiratory illnesses preceding acute myocardial infarction (AMI) by a variable time, with the strongest association occurring in the first three days but lasting for months [
7]. Indeed, the influenza virus may contribute to prompt acute cardiovascular events by stimulating a potent acute inflammatory response which is a known trigger of acute plaque rupture [
8‐
10]. Moreover, especially in patients at higher cardiovascular risk, influenza virus might destabilize patients through increased metabolic demand, exacerbate underlying CVD through activation of the sympathetic nervous system, inadequate coronary artery blood flow with fever and tachycardia [
11]. Furthermore, influenza infection might predispose patients to develop opportunistic infections like bacterial pneumonia, which are associated with increased cardiovascular risk [
12,
13]. Other cardiovascular manifestations of influenza include myocarditis, pericarditis, worsening of heart failure (HF) and sudden cardiac death [
14]. Influenza-related complications and deaths are much more frequent in patients already suffering from chronic CVD [
15]. Therefore, looking at the other side of the coin, it has been suggested that cardiovascular events might be prevented by influenza vaccination [
6]. First evidence in this regard came from observational trials showing a general beneficial effect of influenza vaccine on cardiovascular health in patients at high cardiovascular risk [
16‐
19]. After conflicting results of early randomized controlled trials (RCT), in 2013, Udell et al. [
20] conducted a meta-analysis of 6 RCT assessing the benefits of influenza vaccine in reducing cardiovascular events within trials of influenza vaccine. The primary outcome was a composite of MACE, including cardiovascular death, hospitalization for acute coronary syndromes (ACS), stroke, HF, or urgent coronary revascularization. The authors found that influenza vaccination was associated with a lower risk of composite cardiovascular events than placebo (in the blinded studies) or standard care without vaccination (among open-label trials). In particular, vaccination was associated with a lower risk of MACE among participants with recent ACS, suggesting that acute cardiovascular patients may benefit the most from the annual influenza vaccine. Later, in 2017 a meta-analysis including 5 RTC showed that influenza vaccination of subjects with chronic CVD reduced mortality and MACE by almost 50% compared to controls [
21]. …
