Flu vaccinations may reduce mortality risk in patients with hypertension

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Influenza vaccination in patients with high blood pressure is associated with an 18% reduced risk of death during flu season, according to research presented at ESC Congress 2019 together with the World Congress of Cardiology. “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.

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, 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.”

Abstract
Background: Influenza infection is associated with an increased risk of acute myocardial infarction (AMI) and stroke. It is currently unknown whether influenza vaccination may reduce mortality in patients with hypertension.
Purpose: To determine whether influenza vaccination is associated with lower risks of death in hypertensive patients without significant cardiovascular or other chronic disease.
Methods: Using nationwide registers, we identified all patients with hypertension in Denmark during 9 consecutive influenza seasons in the period 2007-2016 who were treated with at least 2 different classes of antihypertensive medication (beta-blockers, diuretics, calcium antagonists or renin-angiotensin system inhibitors). Patients who were not 18-100 years old or had ischemic heart disease, heart failure, chronic obstructive lung disease, cancer or cerebrovascular disease were excluded. Prior to each influenza season we assessed the exposure to influenza vaccination. End-points were death from all causes, from AMI or stroke, or cardiovascular death. For each season, patients were followed from December 1 until April 1 the next year, spanning the period of high influenza activity in Denmark.
Results: A total of 608,452 Patients were followed for a median of 5 seasons (interquartile-range: 2-8 seasons), with total follow-up time of 975,902 person-years. The vaccine coverage during study seasons ranged from 26% to 36%. During follow-up, 21,571 patients died of all-causes (3.5%), 12,270 patients died of cardiovascular causes (2.0%) and 3,846 patients died of AMI/stroke (0.6%). Vaccination was associated with older age, Diabetes Mellitus, atrial fibrillation, lower educational level, lower income and higher medication use. In unadjusted analysis considering all seasons, vaccination was significantly associated with increased risk of all-cause death, cardiovascular death and death from AMI/stroke. However, following adjustment for season, age, sex, comorbidities, medications, income, education, and more, vaccination was significantly associated with reduced risks of all-cause death, cardiovascular death and death from AMI/stroke (Figure).
Conclusion: In a nationwide study spanning 9 consecutive influenza seasons including more than 600,000 hypertensive patients without significant cardiovascular disease identified through medication use, influenza vaccination was significantly associated with a reduced risk of death from all-causes, cardiovascular causes and AMI/stroke. Influenza vaccination may improve patient outcome in hypertension.

Authors
D Modin, B Claggett, ME Joergensen, L Koeber, T Benfield, M Schou, JU Jensen, S Solomon, R Trebbien, M Fralick, O Vardeny, MA Pfeffer, C Torp-Pedersen, G Gislason, T Biering-Soerensen

European Society of Cardiology material
ESC Congress 2019 abstract


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