UNSW: Flu Vaccine Provides Significant Protection Against Heart Attacks

Photo Credit - CDC PHIL

 

# 10,471

Roughly 18 years ago, a study looked at the rate of heart attacks in the United States, and found that Acute Myocardial Infarctions (AMIs) run as much 53% higher during the winter months than than during the summer.

 

While numerous theories have been offered (holiday stress, cold weather, over-indulgence during the holidays, etc.), a growing number of studies have suggested that  Influenza - and other acute respiratory infections - can act as a trigger for heart attacks (see Study: Influenza And Heart Attacks).  

 

Assuming that flu is a major trigger for heart attacks, then it stands to reason that the flu vaccine ought to provide some measurable level of protection against them.  And over the years we’ve looked at a number of studies that have attempted to quantify that number.

• In 2010 we saw a study in the CMAJ: Flu Vaccinations Reduce Heart Attack Risk that found that those over the age of 40 who get a seasonal flu vaccine each year may reduce their risk of a heart attack by as much as 19%. Questions were raised over the way this study was conducted (see Vaccine/Heart Attack Study Questioned), and so the results are in dispute.
• In August of 2013 (see Study: Flu Vaccine May Reduce Heart Attack Risk), we looked at study out of Australia – published in the BMJ Journal Heart, that found compelling – but not exactly conclusive – evidence that flu shots may reduce the risk of heart attacks as much as 45%.
• In October of 2013 (see JAMA: Flu Vaccine and Cardiovascular Outcomes) we looked at a meta analysis that found among patients who had previously had a heart attack, the receipt of a flu vaccine was linked to a 55% reduction in having another major cardiac event in the next few months.

Complicating matters, those who are most likely have cardiac events (> 65) are also the cohort least likely to derive optimal protection from the flu vaccine (see NFID: The Challenges Of Influenza In Older Adults).  There is some evidence, however, that even when it doesn’t prevent infection, the flu vaccine may reduce the severity of illness (CDC: Flu Shots Reduce Hospitalizations In The Elderly).

 

Building on the 2013 Australian BMJ study mentioned above, researchers at the University of New South Wales have put together a new meta analysis which further supports the link between getting the flu jab, and reducing the risks of having a heart attack.

 

First the link to the study, and a press release, after which I’ll return with a bit more.

Acute myocardial infarction and influenza: a meta-analysis of case–control studies

Michelle Barnes, Anita E Heywood, Abela Mahimbo, Bayzid Rahman, Anthony T Newall, C Raina Macintyre

Published Online First 26 August 2015

Abstract

Objective Acute myocardial infarction (AMI) is the leading cause of death and disability globally. There is increasing evidence from observational studies that influenza infection is associated with AMI. In patients with known coronary disease, influenza vaccination is associated with a lower risk of cardiovascular events. However, the effect of influenza vaccination on incident AMI across the entire population is less well established.

Method The purpose of our systematic review of case–control studies is twofold: (1) to estimate the association between influenza infection and AMI and (2) to estimate the association between influenza vaccination and AMI. Cases included those conducted with first-time AMI or any AMI cases. Studies were appraised for quality and meta-analyses using random effects models for the influenza exposures of infection, and vaccination were conducted.

Results 16 studies (8 on influenza vaccination, 10 on influenza infection and AMI) met the eligibility criteria, and were included in the review and meta-analysis. Recent influenza infection, influenza-like illness or respiratory tract infection was significantly more likely in AMI cases, with a pooled OR 2.01 (95% CI 1.47 to 2.76). Influenza vaccination was significantly associated with AMI, with a pooled OR of 0.71 (95% CI 0.56 to 0.91), equating to an estimated vaccine effectiveness of 29% (95% CI 9% to 44%) against AMI.

Conclusions Our meta-analysis of case–control studies found a significant association between recent respiratory infection and AMI. The estimated vaccine effectiveness against AMI was comparable with the efficacy of currently accepted therapies for secondary prevention of AMI from clinical trial data. A large-scale randomised controlled trial is needed to provide robust evidence of the protective effect of influenza vaccination on AMI, including as primary prevention.

 

Some excerpts from the UNSW press release follow:

 

UNSW study finds flu jab provides significant protection against heart attacks

27 Aug 2015

Dan Wheelahan

If you’re over 50 and get the flu jab, you’ll not only help to keep the dreaded lurgy at bay but you could also reduce your risk of a heart attack.

That is the advice of UNSW researchers after their study estimated a vaccine effectiveness of 29% in preventing heart attacks which is on par with other heart attack preventative measures.

Previous studies have estimated the effectiveness of statins for the secondary prevention of heart attacks at 25%, anti-hypertensives (15-18%) and smoking cessation interventions (26%).

Researchers in the School of Public Health and Community Medicine (SPHCM) conducted a systematic review and meta-analysis of 16 international case control studies to estimate the association of influenza and vaccination with heart attacks.

They found significant associations between influenza infection and heart attacks, with heart attack patients twice as likely to have recently had the flu. Their review also confirmed existing evidence, including their own 2013 study, which found that the flu vaccination could lower the risk of a heart attack by 45%.

The study was published today in the journal Heart.

(Continue . . . )

 

Although the `street creds’ of the flu vaccine took a major hit last winter after the late arrival of a `mismatched’ H3N2 virus (see CDC: Updated Estimated Seasonal Flu Vaccine Effectiveness), most years the flu vaccine provides a `moderate’ level of protection.  Something on the order of 40%-60% Vaccine Effectiveness (VE).

 

As we’ve discussed before, there is a pressing need for better flu vaccines (see CIDRAP: The Need For `Game Changing’ Flu Vaccines).While far from perfect - the flu shots we have remain the best preventative action you can take against the flu.

And while not conclusive (more research is needed),  the evidence suggests it may also be one of the best preventative actions you can take against having a heart attack as well.  

 

Which is more than enough reason that I’ll be rolling up my sleeve again this year for the flu shot.

JAMA: Flu Vaccine and Cardiovascular Outcomes

 

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One of the problems with determining the true burden of influenza on the public’s health is that influenza is rarely listed as the primary cause of death when a patient dies with a history of other co-morbidities like coronary artery disease, Asthma, Diabetes, or COPD.   Yet we know that during the winter months, when influenza and other respiratory viruses are at their height – overall mortality goes up. 

 

Roughly 15 years ago, a study looked at the rate of heart attacks in the United States, and found that Acute Myocardial Infarctions (AMIs) run as much 53% higher during the winter months than than during the summer. While cold weather combined with strenuous physical activity (like clearing snow from sidewalks) have often been blamed for this spike, even in balmy Southern California, studies have shown a 33% increase in heart attacks over the holidays (cite).

 

Although not the first to do so, a year ago  in Study: Influenza And Heart Attacks, we looked at research that appeared in the Journal of Infectious Diseases that suggested Influenza - and other acute respiratory infections - can act as a trigger for heart attacks.  

Despite often disappointing vaccine effectiveness (VE) numbers for those over the age of 65 (see NFID: The Challenges Of Influenza In Older Adults), in recent years we’ve seen a series of studies that have suggested that the flu vaccine may be partially protective against heart attacks. 

 

In 2010 we saw a study in the CMAJ: Flu Vaccinations Reduce Heart Attack Risk that found that those over the age of 40 who get a seasonal flu vaccine each year may reduce their risk of a heart attack by as much as 19%. Almost immediately questions were raised over the way this study was conducted (see Vaccine/Heart Attack Study Questioned). The primary concern was these researchers only looked at heart attacks during `flu season’, without the control of looking at AMI risks year-round.

 

Just last August (see Study: Flu Vaccine May Reduce Heart Attack Risk), we looked at a new study out of Australia – published in the BMJ Journal Heart, that found compelling – but not exactly conclusive – evidence that flu shots may reduce the risk of heart attacks.

 

Today, another study, which appears in JAMA, that performed a meta-analysis of  5 published and 1 unpublished randomized clinical trials involving  6735 patients - some of whom received a flu shot while others received a placebo - and calculated the number of cardiac events each group suffered in the months that followed. 

 

Among those who had previously had a heart attack, the receipt of a flu vaccine was linked to a 55% reduction in having another major cardiac event in the next few months.

 

First a link to the JAMA study, and then some excerpts from the press release from  Women's College Hospital at the University of Toronto:

 

Association Between Influenza Vaccination and Cardiovascular Outcomes in High-Risk Patients

A Meta-analysis

FREE

Jacob A. Udell, MD, MPH, FRCPC¹; Rami Zawi, MD²; Deepak L. Bhatt, MD, MPH^3,4; Maryam Keshtkar-Jahromi, MD, MPH^5,6; Fiona Gaughran, MD^7,8; Arintaya Phrommintikul, MD⁹; Andrzej Ciszewski, MD¹⁰; Hossein Vakili, MD¹¹; Elaine B. Hoffman, PhD⁴; Michael E. Farkouh, MD, MSc, FRCPC¹²; Christopher P. Cannon, MD⁴

Results Five published and 1 unpublished randomized clinical trials of 6735 patients (mean age, 67 years; 51.3% women; 36.2% with a cardiac history; mean follow-up time, 7.9 months) were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%; RR, 0.64 [95% CI, 0.48-0.86], P = .003) in published trials. A treatment interaction was detected between patients with (RR, 0.45 [95% CI, 0.32-0.63]) and without (RR, 0.94 [95% CI, 0.55-1.61]) recent ACS (P for interaction = .02). Results were similar with the addition of unpublished data.

Conclusions and Relevance In a meta-analysis of RCTs, the use of influenza vaccine was associated with a lower risk of major adverse cardiovascular events. The greatest treatment effect was seen among the highest-risk patients with more active coronary disease. A large, adequately powered, multicenter trial is warranted to address these findings and assess individual cardiovascular end points.

 

 

From the press release:

Flu shot halves risk of heart attack or stroke in people with history of heart attack, study finds

TORONTO, ON, October 22, 2013 — The flu vaccine may not only ward off serious complications from influenza, it may also reduce the risk of heart attack or stroke by more than 50 per cent among those who have had a heart attack, according to new research led by Dr. Jacob Udell, a cardiologist at Women's College Hospital and clinician-scientist at the University of Toronto. What's more, the vaccine's heart protective effects may be even greater among those who receive a more potent vaccine.

"Our study provides solid evidence that the flu shot helps prevent heart disease in vulnerable patients —with the best protection in the highest risk patients," Dr. Udell said. "These findings are extraordinary given the potential for this vaccine to serve as yearly preventative therapy for patients with heart disease, the leading cause of death among men and women in North America."

Published today in the Journal of the American Medical Association, the study reviewed six clinical trials on heart health in people who received the flu vaccine. The studies included more than 6,700 patients with a history of heart disease. The researchers found people who received the flu shot:

• Had a 36 percent lower risk of a major cardiac event (heart attack, stroke, heart failure, or death from cardiac–related causes) one year later
• Had a 55 percent lower risk of a major cardiac event if they had a recent heart attack
• Were less likely to die from cardiac-related and other causes, and
• Were less likely to have a major cardiac event with a more potent vaccine compared with the standard seasonal vaccine

(Continue . . .)

 

While not a slam dunk (larger, more robust more studies are needed), this latest report adds to the body of evidence suggesting that influenza contributes significantly to cardiovascular events, and that flu vaccines may be useful in reducing cardiac mortality rates. 

I’m fully cognizant of the limitations of today’s flu vaccines, and try not to `oversell’  them in this blog. Nevertheless, I get one every year and urge that others do the same.

 

Not because they are 100% protective.  They aren’t. But they do offer moderate levels of protection (see CIDRAP: A Comprehensive Flu Vaccine Effectiveness Meta-Analysis), and have an excellent safety profile. 

 

We take sensible precautions every day – like buckling up when we drive, or wearing a helmet when we bike. None of these provide a 100% guarantee of avoiding injury, but they make sense because they increase our odds of walking away from an accident.   

 

I view getting a yearly flu shot in much the same way. 

CPR As A Basic Holiday Survival Skill

 

# 10,745

 

While some may call it a `Christmas Coronary’ or a Hanukkah Heart Attack’ , the winter holiday season usually heralds a spike in myocardial infarctions, which may be brought on by a variety of factors.  Seventeen years ago, a study looked at the rate of heart attacks in the United States, and found that Acute Myocardial Infarctions (AMIs) run as much 53% higher during the winter months than than during the summer.

 

Seasonal distribution of acute myocardial infarction in the second National Registry of Myocardial Infarction.

Spencer FA, Goldberg RJ, Becker RC, Gore JM.

 

Although cold weather combined with strenuous physical activity (like clearing snow from sidewalks) has often been blamed for this increase, even in balmy Southern California, studies have shown a 33% increase in heart attacks over the holidays (see below).

 

When Throughout the Year Is Coronary Death Most Likely to Occur?

A 12-Year Population-Based Analysis of More Than 220 000 Cases

Robert A. Kloner, MD, PhD; W. Kenneth Poole, PhD; Rebecca L. Perritt, MS

 

Non-climate related factors – like over indulgence in food and alcohol, diminished activity levels, forgetting to take prescription medicines, and combined holiday stressors like shopping, running up debt, traveling, meal preparation, and the angst that comes from dysfunctional family gatherings are likely contributors to this yearly spike. 

 

But increasingly influenza and other respiratory infections have been linked to this seasonal increase in heart attacks as well.

Which helps to explain why we’ve seen a spate of studies – like last Augusts'  UNSW: Flu Vaccine Provides Significant Protection Against Heart Attacks – linking flu vaccination to a lower risk of sudden cardiac death.

Others include:

• In 2010 we saw a study in the CMAJ: Flu Vaccinations Reduce Heart Attack Risk that found that those over the age of 40 who get a seasonal flu vaccine each year may reduce their risk of a heart attack by as much as 19%. Questions were raised over the way this study was conducted (see Vaccine/Heart Attack Study Questioned), and so the results are in dispute.
• In August of 2013 (see Study: Flu Vaccine May Reduce Heart Attack Risk), we looked at study out of Australia – published in the BMJ Journal Heart, that found compelling – but not exactly conclusive – evidence that flu shots may reduce the risk of heart attacks as much as 45%.
• In October of 2013 (see JAMA: Flu Vaccine and Cardiovascular Outcomes) we looked at a meta analysis that found among patients who had previously had a heart attack, the receipt of a flu vaccine was linked to a 55% reduction in having another major cardiac event in the next few months.

 

Although the reputation of the flu vaccine took a major hit last winter after the late arrival of a `mismatched’ H3N2 virus (see CDC: Updated Estimated Seasonal Flu Vaccine Effectiveness), this year appears to be a better match and should provide something on the order of 40%-60% Vaccine Effectiveness (VE).

While it takes a couple of weeks for the vaccine to reach maximum effectiveness, it is not too late to get this year’s flu vaccine, as flu season is just getting started.

 

Regardless of the effectiveness of this year’s flu vaccine, or the severity of this year’s flu season, even on an `average day’ roughly 1,000 people suffer a Sudden Cardiac Arrest (SCA) in the United States alone. While the rate is higher in the winter than in the summer, having basic CPR skills can be a lifesaver year round.

 

This from the Heart Rhythm Association:

• Sudden Cardiac Arrest (SCA) is a leading cause of death in the United States, claiming more than 350,000 lives each year.
• Approximately 92% of those who experience sudden cardiac arrest do not survive.
• SCA kills more than 1,000 people a day, or one person every 90 seconds

 

What the people who witness these events do in the first few minutes can mean the difference between life and death for the stricken individual. Luckily, hands-only CPR (cardio-pulmonary resuscitation) is easier to do than ever before, and there are thousands of AEDs (automated external defibrillators) stationed in public venues across the nation.

 

With a little bit of training, you have the potential to save someone’s life.

 

While it won’t take the place of an actual class, you can watch how it is done on in this brief instructional video from the American Heart Association.  To learn how to use an AED, you can use this online training module  I wrote about in CPR Skills & AED Simulator.  A  CPR class only takes a few hours, can be fun, and is well worth the effort.  

 

To find a local CPR course contact your local chapter of the American Red Cross, the American Heart Association, or (usually) your local fire department or EMS can steer you to a class.

Of course, despite your best efforts, many SCA victims will not survive. It isn’t at all like on TV, where 75% of  recipients of CPR survive.  Even when cardiac arrests occur inside a hospital, the survival to discharge rate is less than 40%. Outside the hospital, the odds of seeing a good outcome are lower.

 

While there are no guarantee of success, early and coordinated action taken by bystanders (calling 911, starting CPR, using AED if available) can substantially improve the SCA’s chances of survival. 

 

For more on heart attacks, and CPR, you may wish to visit some of these earlier blogs.

Deadlier Than For The Male

Survivability Of Non-Shockable Rhythms With New CPR Guidelines

Fear Of Trying

NPM11: Early CPR Saves Lives

AHA: Study Shows Flu Shots Reduce Deaths From Heart Failure

#13,729


With the medicines and treatments available today, many people live for years after receiving a diagnosis of heart failure, although it remains one of major causes of death in the United States (cite).

But, as we've discussed often in the past (see list below), influenza and other respiratory infections are known to have a greater health impact on people with certain chronic health conditions, including coronary artery disease.

NFID: Chronic Health Problems & The Flu

Eur. Resp.J.: Influenza & Pneumonia Infections Increase Risk Of Heart Attack and Stroke

NEJM: Acute Myocardial Infarction After Laboratory-Confirmed Influenza Infection

‘Tis The Cardiac Season

Int. Med. J.: Triggering Of Acute M.I. By Respiratory Infection

It follows then, that if you can reduce the incidence (or at least the  severity) of influenza infection in the general population using the flu vaccine, you ought to be able to reduce the number of deaths among high risk individuals.

Proving that, however, hasn't been easy:

• In 2010 we saw a study in the CMAJ: Flu Vaccinations Reduce Heart Attack Risk that found that those over the age of 40 who get a seasonal flu vaccine each year may reduce their risk of a heart attack by as much as 19%. Questions were raised over the way this study was conducted (see Vaccine/Heart Attack Study Questioned), and so the results are in dispute.
• In August of 2013 (see Study: Flu Vaccine May Reduce Heart Attack Risk), we looked at study out of Australia – published in the BMJ Journal Heart, that found compelling – but not exactly conclusive – evidence that flu shots may reduce the risk of heart attacks as much as 45%.
• In October of 2013 (see JAMA: Flu Vaccine and Cardiovascular Outcomes) we looked at a meta analysis that found among patients who had previously had a heart attack, the receipt of a flu vaccine was linked to a 55% reduction in having another major cardiac event in the next few months. 

Over the past couple of years, the evidence has become much clearer, and there is some evidence - that even when it doesn’t prevent infection - the flu vaccine may reduce the severity of illness (CDC: Flu Shots Reduce Hospitalizations In The Elderly). 

All reasons why - despite its moderate and sometimes inconsistent record of protecting against influenza infection - I get the flu shot every year, and recommend that others do so as well. 

Adding to the list of studies on the flu vaccine reducing coronary deaths, we have the following study appearing this week in the American Heart Association's journal Circulation, which finds a substantial reduction in deaths among heart failure patients who received a yearly flu shot.

Influenza Vaccine in Heart Failure: Cumulative Number of Vaccinations, Frequency, Timing, and Survival: A Danish Nationwide Cohort Study
Daniel Modin, Mads Emil Jørgensen, Gunnar Gislason, Jan Skov Jensen, Lars Køber, Brian Claggett, Sheila M. Hegde, Scott D. Solomon, Christian Torp-Pedersen, and Tor Biering-Sørensen
Originally published10 Dec 2018Circulation. 2018;0

Abstract

Background: Influenza infection is a serious event for patients with heart failure (HF). Little knowledge exists about the association between influenza vaccination and outcome in patients with HF. This study sought to determine whether influenza vaccination is associated with improved long-term survival in patients with newly diagnosed HF.

Methods: We performed a nationwide cohort study including all patients who were >18 years of age and diagnosed with HF in Denmark in the period of January 1, 2003, to June 1, 2015 (n=134048). We collected linked data using nationwide registries. Vaccination status, number, and frequency during follow-up were treated as time-varying covariates in time-dependent Cox regression.

Results: Follow-up was 99.8% with a median follow-up time of 3.7 years (interquartile range, 1.7-6.8 years). The vaccination coverage of the study cohort ranged from 16% to 54% during the study period. In unadjusted analysis, receiving ≥1 vaccinations during follow-up was associated with a higher risk of death. After adjustment for inclusion date, comorbidities, medications, household income, and education level, receiving ≥1 vaccinations was associated with an 18% reduced risk of death (all-cause: hazard ratio, 0.82; 95% CI, 0.81-0.84; P < 0.001; cardiovascular causes: hazard ratio, 0.82; 95% CI, 0.81-0.84; P < 0.001). Annual vaccination, vaccination early in the year (September to October), and greater cumulative number of vaccinations were associated with larger reductions in the risk of death compared with intermittent vaccination.

Conclusions: In patients with HF, influenza vaccination was associated with a reduced risk of both all-cause and cardiovascular death after extensive adjustment for confounders. Frequent vaccination and vaccination earlier in the year were associated with larger reductions in the risk of death compared with intermittent and late vaccination.

 From the accompanying press release, we get the following summary:

Regular flu shots may save heart failure patients' lives
Circulation Journal report
American Heart Association

(Excerpt)

In this study, researchers analyzed data on 134,048 patients with newly diagnosed heart failure over a 12-year period. Flu vaccination rates ranged from 16 percent in 2003 to 52 percent in 2015 with a peak of 54 percent in 2009. Among the researchers' findings:

• Flu vaccination was associated with an 18 percent reduced risk of premature death, even after accounting for other factors such as medications, other health conditions, income and education.
• Annual flu vaccination following a heart failure diagnosis was associated with a 19 percent reduction in both all-cause and cardiovascular death when compared with no vaccination.
•  Flu vaccination frequency mattered; getting a flu shot less than once per year but more than not at all was associated with a 13 percent reduced risk of all-cause death and an 8 percent reduced risk of cardiovascular death.
• Timing mattered; there was a greater reduction in cardiovascular and all-cause death when vaccination occurred earlier in the flu season during September and October versus in November and December.
  

Lead study author Daniel Modin, an investigator from the University of Copenhagen in Denmark, said that while this research only looked at patients with newly-diagnosed heart failure, the protection from a flu shot likely benefits any patient with heart failure.

(Continue . . . )

While there is an obvious need for better flu vaccines (see CIDRAP: The Need For `Game Changing’ Flu Vaccines), we've seen some significant improvements over the past few years (quadrivalent vaccines, high-dose vaccines, cell based vaccines, etc.), and most years the flu vaccine provides a moderate (40%-60%) degree of protection.

Unless and until something better comes along, getting the yearly flu shot, and practicing good flu hygiene (covering coughs, washing hands, staying home when sick, etc.) remain your best bets for avoiding the flu and its complications each winter.

2019 ESC Congress: Flu Vaccination Linked To Lower Mortality For Patients With High BP

From NFID Report

 #14,281



Two decades ago, a study looked at the rate of heart attacks in the United States, and found that Acute Myocardial Infarctions (AMIs) run as much 53% higher during the winter months than than during the summer.

Seasonal distribution of acute myocardial infarction in the second National Registry of Myocardial Infarction.

Spencer FA, Goldberg RJ, Becker RC, Gore JM. 

Cold weather combined with strenuous physical activity (like clearing snow from sidewalks) has often been blamed for this increase, but even in balmy Southern California, studies have shown a 33% increase in heart attacks over the holidays (see below). 

When Throughout the Year Is Coronary Death Most Likely to Occur?

A 12-Year Population-Based Analysis of More Than 220 000 Cases

Robert A. Kloner, MD, PhD; W. Kenneth Poole, PhD; Rebecca L. Perritt, MS

There are likely many factors involved, such as over-indulgence in food and alcohol, diminished activity levels, forgetting to take prescription medicines, and combined holiday stressors like shopping, running up debt, traveling, meal preparation, and the angst that comes from dysfunctional family gatherings are all likely contributors to this yearly spike.

But increasingly influenza and other respiratory infections have been linked to a significant seasonal increase in heart attacks and strokes.

• Just last week, in PLoS One: Transient Depression of Myocardial Function After Influenza Virus Infection, we looked at a study that foundtransient myocardial function changes among a small group of influenza patients studied.

• In 2018's NEJM: Acute Myocardial Infarction After Laboratory-Confirmed Influenza Infection, we saw a study that found a `significant association ' between recent (lab confirmed) influenza infection and Myocardial Infarction.  

• And in May 2017, in Int. Med. J.: Triggering Of Acute M.I. By Respiratory Infection we looked at research  from the University of Sydney that found the risk of a heart attack is increased 17-fold in the week following a respiratory infection such as influenza or pneumonia.

While influenza A and B infections aren't the only viral triggers of heart attacks and strokes, it stands to reason if you can reduce their incidence by yearly vaccination, you could reduce the number of related cardiovascular events.

Despite some less-than-stellar influenza Vaccine Efficiency (VE) numbers - particularly among those in the highest risk groups (65+) - we've seen some evidence that vaccination does reduce complications like heart attacks and strokes.  

• In August of 2013 (see Study: Flu Vaccine May Reduce Heart Attack Risk), we looked at study out of Australia – published in the BMJ Journal Heart, that found compelling – but not exactly conclusive – evidence that flu shots may reduce the risk of heart attacks as much as 45%.
   
• In October of 2013 (see JAMA: Flu Vaccine and Cardiovascular Outcomes) we looked at a meta analysis that found among patients who had previously had a heart attack, the receipt of a flu vaccine was linked to a 55% reduction in having another major cardiac event in the next few months.

• In 2015, in UNSW: Flu Vaccine Provides Significant Protection Against Heart Attacks, we saw another study that found that if you are over 50 - getting the flu vaccine can cut your risk of a heart attack by up to 45%.

• Last year, a study appearing  the American Heart Association's journal Circulation, found a substantial reduction in deaths among heart failure patients who received a yearly flu shot (see AHA: Study Shows Flu Shots Reduce Deaths From Heart Failure).

• Last January, in Chest: Flu Vaccine Reduces Severe Outcomes Among Hospitalized Patients With COPD, researchers found a lower mortality rate, less critical illness, and a 38% reduction in influenza-related hospitalizations in vaccinated vs unvaccinated individuals. 

• Three weeks ago, in Flu Vaccine May Lower Stroke Risk in Elderly ICU Patients, we saw a study that found influenza vaccinated ICU survivors had a lower 1-year risk of stroke and a lower 1-year risk of death than unvaccinated survivors.

To this growing body of evidence we can add a presentation - given this past weekend at the 2019 European Society of Cardiology Congress - that links flu vaccination with an 18% lower risk of death among patients with high blood pressure.

Flu vaccination linked with lower risk of death in patients with high blood pressure

01 Sep 2019
Topic(s): Hypertension Epidemiology

Paris, France – 1 Sept 2019: Influenza vaccination in patients with high blood pressure is associated with an 18% reduced risk of death during flu season, according to research presented today at ESC Congress 2019 together with the World Congress of Cardiology. (1)

“Given these results, it is my belief that all patients with high blood pressure should have an annual flu vaccination,” said first author Daniel Modin research associate of the University of Copenhagen, Denmark. “Vaccination is safe, cheap, readily available, and decreases influenza infection. On top of that, our study suggests that it could also protect against fatal heart attacks and strokes, and deaths from other causes.”

According to previous research, the stress flu infection puts on the body may trigger heart attacks and strokes. Patients with hypertension (high blood pressure) are at raised risk of heart attack and stroke. By stopping flu infection, vaccination could also protect against cardiovascular events, but until now this had not been investigated.

The study used Danish nationwide healthcare registers to identify 608,452 patients aged 18 to 100 years with hypertension during nine consecutive influenza seasons (2007 to 2016). The researchers determined how many patients had received a flu vaccine prior to each season. They then followed patients over each season and tracked how many died. In particular, they recorded death from all causes, death from any cardiovascular cause, and death from heart attack or stroke.

Finally, they analysed the association between receiving a vaccine prior to flu season and the risk of death during flu season. The analysis controlled for patient characteristics that could impact the likelihood of dying such as age, comorbidities, medications, and socioeconomic status.

After adjusting for patient differences, in a given influenza season, vaccination was associated with an 18% relative reduction in the risk of dying from all causes, a 16% relative reduction in the risk of dying from any cardiovascular cause, and a 10% relative reduction in the risk of dying from heart attack or stroke.

Mr Modin said: “We show that influenza vaccination may improve cardiovascular outcomes in patients with hypertension. During the nine flu seasons we studied, vaccine coverage ranged from 26% to 36%, meaning that many patients with high blood pressure were not vaccinated. If you have high blood pressure, it would be worth discussing vaccination with your doctor.”

Regarding how flu and cardiovascular disease might be connected, Mr Modin noted that when the influenza virus infects the body it triggers a strong immune reaction and subsequent inflammation. These responses fight the infection and clear the virus from the body but may increase the risk of having a heart attack or stroke.

He said: “Heart attacks and strokes are caused by the rupture of atherosclerotic plaques in the arteries leading to the heart or the brain. After a rupture, a blood clot forms and cuts off the blood supply. It is thought that the high levels of acute inflammation induced by influenza infection reduce the stability of plaques and make them more likely to rupture.”

ENDS

Individually, these studies may not constitute a slam dunk, but when taken together there make a good case that the flu shot can do more than just prevent a nasty respiratory infection. 

And even when it doesn't prevent flu infection, it may help reduce the severity of one's illness (see CMAJ Research: Repeated Flu Vaccinations Reduce Severity of Illness In Elderly).

I view getting a yearly flu shot like always wearing a seat belt in an automobile. It doesn't guarantee a good outcome in a wreck, but it sure increases your odds of walking away. 

And despite the anti-vaccine rhetoric on the internet, flu vaccines have an excellent (albeit, not perfect) safety record.

All reasons why I'll be rolling up my sleeve again this fall, and I urge others to look at the evidence, and hopefully decide to do the same.

JAHA: Another Study Linking ILI To Increased Risk Of Heart Attack & Stroke

#15,495

Ask just about anyone in emergency medicine and they will tell you that the incidence of heart attacks and strokes goes up in the winter months. More than twenty years ago, a study looked at the rate of heart attacks in the United States, and found that Acute Myocardial Infarctions (AMIs) run as much 53% higher during the winter months than than during the summer.

Seasonal distribution of acute myocardial infarction in the second National Registry of Myocardial Infarction.

Spencer FA, Goldberg RJ, Becker RC, Gore JM.

While cold weather combined with strenuous physical activity (like clearing snow from sidewalks) has often been blamed for this spike, even in balmy Southern California, studies have shown a 33% increase in heart attacks over the holidays (see below).

When Throughout the Year Is Coronary Death Most Likely to Occur?

A 12-Year Population-Based Analysis of More Than 220 000 Cases

Robert A. Kloner, MD, PhD; W. Kenneth Poole, PhD; Rebecca L. Perritt, MS

Non-climate related factors – like over indulgence in food and alcohol, diminished activity levels, forgetting to take prescription medicines, and combined holiday stressors like shopping, running up debt, traveling, meal preparation, and the angst that comes from dysfunctional family gatherings are all likely contributors to this yearly spike.

But over the past decade we've seen mounting evidence linking ILIs (Influenza-like-illnesses) to an increased risk of heart attack or stroke.  A few relatively recent studies include:

• In September 2019, in PLoS One: Transient Depression of Myocardial Function After Influenza Virus Infection, we looked at a study that found transient myocardial function changes among a small group of influenza patients studied.

• In 2018's NEJM: Acute Myocardial Infarction After Laboratory-Confirmed Influenza Infection, we saw a study that found a `significant association ' between recent (lab confirmed) influenza infection and Myocardial Infarction.  

• Also in 2018, in Eur. Resp.J.: Influenza & Pneumonia Infections Increase Risk Of Heart Attack and Stroke, researchers reported `substantially increased MI rates in the week after S.pneumoniae and influenza' while the risks of stroke was elevated for as much as 28 days.
• And in May 2017, in Int. Med. J.: Triggering Of Acute M.I. By Respiratory Infection we looked at research  from the University of Sydney that found the risk of a heart attack is increased 17-fold in the week following a respiratory infection such as influenza or pneumonia.

To this growing list of studies we can add a new statistical analysis published in JAHA - the Journal of the American Heart Association - that finds that heart attacks and strokes rise (with differing lag periods) during times of elevated ILI activity.   

Of note: This study found the same 7-day window for heart attacks, and 28 window for strokes, as have previous studies.

Due to the length and complexity of the analysis, we'll begin by drawing some basic information from an AHA press release.

AHA News: Strokes and Heart Attacks Increase When Flu-Like Illnesses Rise 

Published: October 8, 2020

Heart attack risk increases quickly after a flu-like illness, while stroke risk rises slower, according to new research.

The study, published Thursday in the Journal of the American Heart Association, examined the relationship between the flu, heart attacks and strokes, which all occur more frequently during winter months.

Researchers looked at New York state public health data from 2004 to 2015 and focused on adults who were hospitalized or came to the emergency department for stroke, heart attack or "flu-like illnesses." Study author Amelia Boehme said pinpointing people with the flu from administrative records is difficult. Instead, her study relied on an algorithm developed by the Centers for Disease Control and Prevention to identify influenza and influenza-like symptoms through billing codes.

The study found that strokes and heart attacks increase during times of high flu-like illness rates, with a "time lag" occurring only for strokes.

"We found that if someone's going to have a heart attack, it's going to occur within seven days of the flu-like illness, during the acute phase," said Boehme, assistant professor of epidemiology in the department of neurology at Columbia University in New York City. "With stroke, we see an increased risk seven to 15 days after, similar to heart attacks. But with stroke, there is an additional higher-risk period after 30 days."

(SNIP)

The researchers didn't have information on whether people included in the study had received a flu vaccine. But they did find that "in the years where the vaccine effectiveness was higher, overall, the number of people who had influenza-like illness and the number of people who subsequently had strokes and heart attacks after influenza-like illness was lower."

Past studies have shown that those who skip a flu shot are six times more likely to experience a heart attack.

         

(Continue . . . )

It should be noted that while `Influenza-like-illness' encompasses influenza A & B, it also includes non-influenza respiratory infections like rhinovirus, coronavirus, adenovirus, and parainfluenza which are not covered by the influenza vaccine - and when combined - generally exceed the number of flu infections. 

The full open-access study is available at the link below. I'll have a postscript when you return.

Seasonality of Influenza‐Like‐Illness and Acute Cardiovascular Events Are Related Regardless of Vaccine Effectiveness 

Erin R. Kulick, Michelle Canning, Neal S. Parikh, Mitchell S. V. Elkind, and Amelia K. Boehme
Originally published8 Oct 2020 https://doi.org/10.1161/JAHA.120.016213

Journal of the American Heart Association.  

Abstract

Background

Influenza has been identified as a trigger for stroke and myocardial infarction (MI) with prior studies demonstrating that influenza vaccination may decrease risk of stroke and MI.

(SNIP)

Conclusions

We identified that seasonality of cardiovascular events may be associated with seasonality in ILI, though VE did not modify this relationship.

          (Continue . . . )

The design of this study, and the lack of vaccination data for patients, makes it impossible to link receipt of the  flu vaccine with a lowered risk of stroke of heart attack, even though those rates did decline slightly during years with a high VE (Vaccine Effectiveness). 

In the discussion section, the authors wrote:

In years with increased VE we did see overall reductions in the absolute risk of ILI, and small decreases in subsequent stroke and MI, but the overall association between ILI and stroke or MI was not significantly influenced by VE

(SNIP)

Future work incorporating vaccination information is needed to elucidate the role of the influenza vaccine in reducing stroke or MI risk.

But we do have other, recent studies that suggest flu vaccines appear reduce the risk having a heart attack or stroke, and may even reduce the risk of dementia. 

CDC: Another Study Linking Severe Influenza To Heart Damage

(AAIC®) 2020 Presentation : Flu & Pneumonia Shots Appear To Reduce Dementia Risk In Elderly

Flu Vaccine May Lower Stroke Risk in Elderly ICU Patients

While the current flu vaccine is nowhere near as effective as we'd like it to be, and the promise of a universal flu vaccine remains elusive (see  J.I.D.: NIAID's Strategic Plan To Develop A Universal Flu Vaccine), there is evidence to suggest the benefits of vaccination may extend beyond preventing influenza infection. 

I view getting a yearly flu shot like always wearing a seat belt in an automobile. It doesn't guarantee a good outcome in a wreck, but it sure increases your odds of walking away. 

And for me - now that I've entered that dreaded `elderly' demographic - that is an extra bit of insurance worth having.

Study: Flu Vaccine May Reduce Heart Attack Risk

 

 

# 7592

 

In a perfect world, the conclusions drawn from medical research would always be unequivocal and we would be able to automatically accept their results as being the final word on the subject.

 

But as we’ve seen often in the past (When Studies Collide & When Studies Collide (Revisited)), no research methodology is perfect, all studies are subject to limitations, and it isn’t unusual to end up with conflicting results from different research teams.

 

While we would all like medicine to be based on treatments, drugs, and procedures proved – beyond a shadow of a doubt – to be safe and effective  . . . sometimes we must accept a lower burden of proof -the preponderance of evidence – instead.

 

All of which brings us to a new study out of Australia – published yesterday in the BMJ Journal Heart, that finds compelling – but not exactly conclusive – evidence that flu shots may reduce the risk of heart attacks.

 

If all of this sounds vaguely familiar, it’s because we’ve trod this ground before.

 

In 2010 we saw a study in the CMAJ: Flu Vaccinations Reduce Heart Attack Risk that found that those over the age of 40 who get a seasonal flu vaccine each year may reduce their risk of a heart attack by as much as 19%.

 

Almost immediately questions were raised over the way this study was conducted (see Vaccine/Heart Attack Study Questioned). The primary concern was these researchers only looked at heart attacks during `flu season’, without the control of looking at AMI risks year-round.

 

Last year, in Study: Influenza And Heart Attacks, we looked at a study appearing in the Journal of Infectious Diseases that suggested Influenza - and other acute respiratory infections - can act as a trigger for heart attacks.  There was an accompanying editorial called Increasing Evidence That Influenza Is a Trigger for Cardiovascular Disease published in the same issue.

 

In February of this year, in Another Study Links Heart Attacks & Influenza, we looked at a study from the University of Iowa that appeared in the January issue of the journal of Epidemiology and Infection linking spikes in AMIs (acute myocardial infarction) to influenza during the winter months, and also finds a similar spike in AMIs during the H1N1 pandemic wave of the fall of 2009.

 

Today’s study, which looked 559 patients over three flu seasons in Sydney, Australia, finds a 45% reduction in AMI risk among those who had received a flu vaccine.

 

They also found that those who had reported a recent respiratory infection were twice as likely to have a heart attack.  But the link between Influenza infection and an AMI was more tenuous.

 

Ischaemic heart disease, influenza and influenza vaccination: a prospective case control study

C Raina MacIntyre, Anita E Heywood, Pramesh Kovoor, Iman Ridda, Holly Seale, Timothy Tan, Zhanhai Gao, Anthea L Katelaris, Ho Wai Derrick Siu, Vincent Lo, Richard Lindley, Dominic E Dwyer

Published Online First 21 August 2013

Abstract

Background Abundant, indirect epidemiological evidence indicates that influenza contributes to all-cause mortality and cardiovascular hospitalisations with studies showing increases in acute myocardial infarction (AMI) and death during the influenza season.

Objective To investigate whether influenza is a significant and unrecognised underlying precipitant of AMI.

Design Case-control study.

Setting Tertiary referral hospital in Sydney, Australia, during 2008 to 2010.

Patients Cases were inpatients with AMI and controls were outpatients without AMI at a hospital in Sydney, Australia.

Main outcome measures Primary outcome was laboratory evidence of influenza. Secondary outcome was baseline self-reported acute respiratory tract infection.

Results Of 559 participants, 34/275 (12.4%) cases and 19/284 (6.7%) controls had influenza (OR 1.97, 95% CI 1.09 to 3.54); half were vaccinated. None were recognised as having influenza during their clinical encounter. After adjustment, influenza infection was no longer a significant predictor of recent AMI. However, influenza vaccination was significantly protective (OR 0.55, 95% CI 0.35 to 0.85), with a vaccine effectiveness of 45% (95% CI 15% to 65%).

Conclusions Recent influenza infection was an unrecognised comorbidity in almost 10% of hospital patients. Influenza did not predict AMI, but vaccination was significantly protective but underused. The potential population health impact of influenza vaccination, particularly in the age group 50–64 years, who are at risk for AMI but not targeted for vaccination, should be further explored. Our data should inform vaccination policy and cardiologists should be aware of missed opportunities to vaccinate individuals with ischaemic heart disease against influenza.

 

 

While these researchers found receiving the flu vaccine to provide statistically significant protection against a heart attack, a bit counter-intuitively, they were unable to directly link influenza to an increased risk of AMI.

 

They write:

 

While we showed a protective effect of influenza vaccination against AMI, we were unable to demonstrate a direct effect of influenza infection on AMI. This could reflect low statistical power, with laboratory-confirmed influenza being a much rarer event than vaccination, which showed significant association. Furthermore, the high vaccination rate in our participants likely reduced the risk of influenza and our ability to detect a difference between groups.

 

 

Teasing out the details of this study we have a report today in the Australian Academic & research news publication The Conversation, that includes the following reaction from other researchers.

 

2 August 2013, 9.04am AEST

Flu jab may halve heart attack risk: study

(EXCERPT)

Minimising risk

Julie Redfern, Senior Research Fellow, Cardiovascular Division at George Institute for Global Health welcomed the finding.

 

“Prevention of heart attacks and cardiovascular disease is a national health priority. Improving risk factors and implementing other simple measures aimed at preventing heart attacks and reducing the burden of disease are of great importance,” said Dr Redfern, who was not involved in the study.

 

“The potential of this study, after further research, that found a benefit of the flu vaccination on heart disease risk is important and could be one strategy that help minimise future heart risk.”

 

Garry Jennings, Director and CEO, Cardiologist at Baker IDI Heart and Diabetes Institute said the researchers had made a very interesting finding.

 

“It is not possible to say whether the flu vaccination was protective or whether people who have flu injections have other characteristics that lower their risk of heart attack. There is some support for the latter in that flu itself did not seem to increase the risk but people who had flu vaccination had lower risk,” said Dr Jennings, who was also not involved in the study.

 

“As the authors point out, this is cause for further investigation, particularly as there are some theoretical links related to inflammation that might have a role in the timing of a heart attack.”

 

 

While this study delivers something less than 100% proof that flu vaccines provide some protection against heart attacks, it does add incrementally to previous studies which have found links between respiratory infections, heart attacks, and `excess winter mortality’.

 

And if this link is valid, it makes sense that if you reduce the incidence of influenza (vaccines are usually about 50% effective) among those with coronary artery disease, you ought to reduce their rate of heart attacks.

 

But whether it makes sense or not, more research will be needed to know for sure. For more on this story, you may want to read Jason Gale’s report in Bloomberg News.

 

Flu Vaccine May Lower Heart Attack Risk, Researchers Find

By Jason Gale - Aug 21, 2013 6:30 PM ET

Int. Med. J.: Triggering Of Acute M.I. By Respiratory Infection

 #12,460


Last November, in UK ONS: 2014-15 Excess Winter Mortality Highest Since 1999, we looked at an all too familiar statistic that showed the number of deaths rises during the winter, and that number is usually highest during years when influenza is more prevalent.

Almost 2 decades ago, a study looked at the rate of heart attacks in the United States, and found that Acute Myocardial Infarctions (AMIs) run as much 53% higher during the winter months than than during the summer.

Seasonal distribution of acute myocardial infarction in the second National Registry of Myocardial Infarction. 

Spencer FA, Goldberg RJ, Becker RC, Gore JM.

While numerous theories have been offered (holiday stress, cold weather, over-indulgence during the holidays, etc.), a growing number of studies have suggested that Influenza - and other acute respiratory infections - can act as a trigger for heart attacks (see Study: Influenza And Heart Attacks).

Not quite two years ago, in UNSW: Flu Vaccine Provides Significant Protection Against Heart Attacks, we saw a study that found that if you are over 50 - getting the flu vaccine can cut your risk of a heart attack by up to 45%.

We've another study from down under this morning that links an increased risk of heart attack to not just influenza, but any respiratory infection.

And not by just a little. They report `The relative risk (RR) for MI occurring within 1–7 days after respiratory infection symptoms was 17.0'.  A 17-fold increase.

First the Abstract from the Internal Medicine Journal, followed by excerpts from a University of Sydney new report.  Then I'll return with a brief postscript.

Triggering of acute myocardial infarction by respiratory infection

 Lorcan Ruane, Thomas Buckley, Soon Y. S. Hoo, Peter S. Hansen, Catherine McCormack, Elizabeth Shaw, Judith Fethney and Geoffrey H. Tofler

14 MAY 2017 | DOI: 10.1111/imj.13377

Background

Respiratory infection has been associated with an increased short-term risk of myocardial infarction (MI). However, previous studies have predominantly been conducted without angiographic confirmation of MI. The possibility can therefore not be excluded that raised troponin levels or electrocardiogram abnormalities that may be seen with respiratory infections are due to non-ischaemic causes.
Aims

To investigate the association between respiratory infection and angiographically confirmed MI.

Methods

Interviews were conducted within 4 days of hospitalisation in 578 patients with angiographically confirmed MI, to assess for recent exposure to respiratory infection symptoms and the usual annual frequency of these symptoms. Using case-crossover methodology, exposure to respiratory infection prior to the onset of MI was compared against the usual frequency of exposure in the past year.
Results

Symptoms of respiratory infection were reported by 100 (17%) and 123 (21%) within 7 and 35 days, respectively, prior to MI. The relative risk (RR) for MI occurring within 1–7 days after respiratory infection symptoms was 17.0 (95% confidence interval (CI) 13.2–21.8), and declined with subsequent time periods. In a subgroup analysis, the RR tended to be lower in groups taking regular cardiac medications. For those who reported milder, upper respiratory tract infection symptoms, the RR for the 1–7-day time period was 13.5 (95% CI 10.2–17.7).

Conclusion

These findings confirm that respiratory infection can trigger MI. Further study is indicated to identify treatment strategies to decrease this risk, particularly in individuals who may have increased susceptibility.

Respiratory infections can trigger a heart attack

16 May 2017

Warning for flu season

New research from University of Sydney finds the risk of a heart attack is increased 17-fold in the week following a respiratory infection such as influenza or pneumonia.

The risk of having a heart attack is 17 times higher in the seven days following a respiratory infection, University of Sydney research has found.

Published today in Internal Medicine Journal, this is the first study to report an association between respiratory infections such as pneumonia, influenza and bronchitis and increased risk of heart attack in patients confirmed by coronary angiography (a special X-Ray to detect heart artery blockages).

“Our findings confirm what has been suggested in prior studies that a respiratory infection can act as a trigger for a heart attack," said senior author Professor Geoffrey Tofler, cardiologist from University of Sydney, Royal North Shore Hospital and Heart Research Australia.

“The data showed that the increased risk of a heart attack isn't necessarily just at the beginning of respiratory symptoms, it peaks in the first 7 days and gradually reduces but remains elevated for one month.”

The study was an investigation of 578 consecutive patients with heart attack due to a coronary artery blockage, who provided information on recent and usual occurrence of symptoms of respiratory infection.

Seventeen per cent of patients reported symptoms of respiratory infection within 7 days of the heart attack, and 21 per cent within 31 days.

Patients were interviewed about their activities before the onset of their heart attack, including if they experienced a recent “flu-like illness with fever and sore throat”. They were considered affected if they reported sore throat, cough, fever, sinus pain, flu-like symptoms, or if they reported a diagnosis of pneumonia or bronchitis.

A second analysis was among those with symptoms restricted to the upper respiratory tract, which included the common cold, pharyngitis, rhinitis and sinusitis.

Lead author Dr Lorcan Ruane, who conducted the work at University of Sydney said: “For those participants who reported milder upper respiratory tract infection symptoms the risk increase was less, but was still elevated by 13 fold.”

(Continue . . . )

Although the `street creds’ of the flu vaccine took a major hit in 2014 after the late arrival of a `mismatched’ H3N2 virus (see CDC: Updated Estimated Seasonal Flu Vaccine Effectiveness), most years the flu vaccine provides a `moderate’ level of protection.

Anywhere from 30%-70%, depending upon the strain and the age and immune response of the recipient. 

While influenza isn't the only respiratory infection that might trigger cardiac events, it imposes a heavy disease burden most years, and likely contributes heavily to the excess winter mortality rate.

  
While the vaccine can’t promise 100% protection, it – along with practicing good flu hygiene (washing hands, covering coughs, & staying home if sick) – remains your best strategy for avoiding the flu and staying healthy this winter.

And maybe, just maybe . . .  for those of us of a certain age . . .  avoiding a heart attack as well.