Flu season is just around the corner, which means it is time for you to ponder whether to get a flu shot.
The skeptical cardiologist may have been on the fence about getting another COVID-19 booster vaccine at times, but he has always gotten the recommended annual flu vaccine, even when his employer didn’t mandate it.
Influenza, of course, is a huge killer that causes around 36,000 deaths per year in the United States. We adults 65 and older are particularly vulnerable to complications of influenza, and we are the ones who account for most of the more than 200,000 hospitalizations per year from the disease.
In 2019, I wrote about my decision to go with the newish “high-dose” flu vaccine, noting that:
Hospital cardiology consultations typically spike during flu season as a bad case can worsen heart failure or trigger heart attacks and arrhythmias.
Although vaccination is the most effective intervention against influenza and associated complications, older individuals mount a lower antibody response to the vaccine compared to younger individuals.
Flu Increases the Risk of Heart Attack
In addition to being at higher risk for serious illness, hospitalization and death with influenza infections, older individuals, especially those with documented cardiovascular disease, are at higher risk for heart attacks.
A range of factors occurring in patients with flu are thought to be responsible, including inflammatory release of cytokines, disruption of atherosclerotic plaques and thrombogenesis
Speculation on specific mechanisms includes:
- 1) the induction of pro-inflammatory changes in the cellular composition of atherosclerotic lesions,
- 2) the induction of a persistent pro-coagulant state, including platelet activation,
- 3) the increased metabolic needs of peripheral tissues and organs compromising arterial perfusion, and
- 4) the infection and inflammation of myocardial cells disturbing the cardiac function
Here’s a nice graphic of possible pathways sans image of heart
And here is an image with a clunky image of the heart , simplified text and large colored arrows to help drive home the point!
The best evidence for how much influenza infection increases cardiovascular risk comes from a 2018 study that showed that the frequency of hospital admissions for acute myocardial infarction was sixfold higher during the seven days after a laboratory-confirmed influenza infection than during a control period.
AHA/ACC Recommends Influenza Vaccination to Lower Major Adverse Cardiovascular Events for Secondary Prevention
In 2006, the AHA/ACC issued a “scientific advisory” recommending annual influenza vaccination as secondary prevention for individuals with coronary and other atherosclerotic vascular disease (Class I, Level B).
This recommendation was based on several observational studies and one small randomized controlled trial (RCT.)
The skeptical cardiologist remains skeptical of most observational studies. With vaccination studies, in particular, one has to be aware that “healthy vaccinee bias” in particular confounds the data and can spuriously suggest benefit when there is none.
The AHA/ACC advisory leads with the one RCT available at the time, the FLUVACS trial which came out in 2004:
The strongest evidence for a protective effect comes from a randomized, controlled trial of influenza vaccination (FLU Vaccination in Acute Coronary Syndromes [FLUVACS]) in which 301 patients hospitalized for either myocardial infarction (MI) or planned angioplasty/stenting were randomly assigned to receive influenza vaccination or remain unvaccinated. At 1 year, the relative risk of cardiovascular mortality in the vaccinated group was 0.25 (95% confidence interval [CI] 0.07 to 0.86) compared with the unvaccinated group (overall rates 2% versus 8%), and the relative risk of a composite end point (cardiovascular death, nonfatal MI, or severe ischemia) was 0.59 (95% CI 0.30 to 0.86; 11% versus 23%) (18). At 2 years, although risk reductions of similar magnitude were measured, the remaining sample size after loss to follow-up was too small to find statistical significance. Of note, the FLUVACS trial was conducted without financial support from the influenza vaccine industry.
This was a small study showing an unrealistic 75% reduction in cardiovascular mortality with vaccination at one year which had disappeared by year two. To be honest although I was aware of it and the scientific advisory, I was not convinced enough to emphasize to my patients they should get the flu shot to reduce their heart attack risk.
What Do Recent Studies Show?
I asked two of my favorite AI-powered medical search platforms, OpenEvidence and Vera Health “Does flu vaccine lower cardiovascular events?” and they both answered with an unequivocal “yes, especially in patients with established cardiovascular disease.”
Vera Health provided me with this nice summary chart
The second study in that chart is a 2022 JAMA Net Open meta-analysis of 6 RCTS which found a 45% reduction in major adverse cardiovascular events (MACE1), in patients with a recent (within one year) acute coronary syndrome (ACS2). Patients without recent vaccination received no benefit. Overall mortality was not different between the groups with or without vaccination.
Despite using the term ACS 24 times the 2022 meta-analysis does not define ACS2 but I would assume this is mostly patients with heart attacks and patients who had undergone stenting or bypass for an unstable coronary presentation.
Several studies have pointed out that the benefit seen with the flu shot is in the same ballpark as the big 3 ASCVD risk reducers (smoking cessation, statins, and antihypertensive drugs).
Does the flu vaccine Work in Primary Prevention of Cardiovascular Disease?
Although observational studies suggest a benefit from flu vaccination in lowering heart attack and cardiovascular death those with no prior heart attack, stent, or bypass surgery, given the absence of benefit demonstrated in RCTs in this population, I feel it is an overreach to conclude flu vaccine cardiovascular benefits extend to primary prevention.
A recent review of this topic in the journal Vaccines came to the same conclusion:
the current data are insufficient to establish the definitive role of influenza vaccination in the primary prevention of MACE in the general population. Further research is needed to clarify its potential benefits in low-risk individuals
However, like many articles on this topic, the authors managed to conflate primary and secondary prevention in their conclusions:
“The magnitude of benefit observed underscores the need to reposition influenza vaccination as not merely a preventive measure against respiratory infection but as a cardioprotective strategy equivalent in importance to pharmacologic therapies in both primary and secondary prevention settings…”
I don’t think the flu shot will reduce cardiovascular death or heart attacks in low-risk heart disease patients.
As we’ve pointed out repeatedly, however, there are many individuals walking around with subclinical coronary atherosclerosis whose risk of heart attack and sudden cardiac death is much higher than patients who have had a heart attack and are post-coronary stenting and on optimal medical therapy.
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Final Recommendations
If you’ve had a heart attack or other ACS presentation in the last year, I strongly advise you to get the influenza vaccination this fall to reduce your risk of cardiovascular events. The evidence is quite strong that this procedure will cut your risk by 45%.
If you have had a stent, coronary bypass or heart attack over a year ago and have no symptoms, and are taking your cardiac medications regularly and are not smoking, the evidence of benefit strictly on CV disease is weak.
It is still probably a good idea to get the flu vaccine if you are older or have other diseases that increase your risk of respiratory complications.
For those who have never had documented clinical cardiovascular disease but have very advanced subclinical atherosclerosis. Hopefully, you have been started on the right medications to lower your cardiovascular risk. No studies are available to provide evidence but I would advise the flu vaccine to reduce CV events.
For those who are unclear on their cardiovascular risks, I would advise getting a good evaluation from a great preventive cardiologist to provide clarity. Of course, this is my advice to everyone, independent of flu vaccine considerations.
Skeptically Yours,
-ACP
- MACE equals a composite of major adverse cardiovascular events (ie, cardiovascular death or hospitalization for myocardial infarction, unstable angina, stroke, heart failure, or urgent coronary revascularization) within 12 months of follow-up. ↩︎
- A recent (2025) ACC/AHA Guidelines for the management of patients with ACS defines it as “a spectrum of clinical conditions caused by acute myocardial ischemia due to disruption (rupture or erosion) of an unstable atherosclerotic plaque in a coronary artery, with associated partial or complete thrombosis and/or microemboli, resulting in diminished blood flow to the myocardium and subsequent ischemia. ACS encompasses three related entities: unstable angina, non–ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). ↩︎
