Influenza vaccination reduces the risk of premature death in coronary patients

Influenza vaccination reduces the risk of premature death in coronary patients

OVERVIEW

  • Infection with the influenza virus creates inflammatory conditions that increase the risk of a myocardial infarction.
  • In patients who have had a heart attack, the administration of an influenza vaccine significantly reduces the risk of death within 12 months of the coronary event.
  • These results suggest that influenza vaccination should be considered an integral part of post-infarction treatment.

With the COVID-19 pandemic that has been raging for almost two years now, we sometimes forget that other respiratory viruses exist and can also have very negative impacts on health. This is particularly the case with influenza, one of the most common viral diseases, which affects 5 to 20% of the world’s population each year.

Infection of the airway cells with the influenza virus triggers a myriad of clinical symptoms, the most common being a “runny nose”, sore throat, fever and general discomfort. The human body generally has good resistance to the virus, and in the vast majority of cases healthy people manage to overcome the infection within a few days. However, influenza remains a dangerous disease for people whose immunity is not optimal (young children, the elderly or those affected by a chronic disease) because the virus can cause serious pulmonary complications (pneumonia, hemorrhagic bronchitis) and potentially fatal complications in these people.

In addition to its harmful effects on the lungs, several observations indicate that infection with the influenza virus can also affect the cardiovascular system. For example, it has long been known that the peak of the flu season is correlated with an increase in deaths associated with ischemic diseases such as myocardial infarction and stroke. Some studies have also reported that patients who are admitted to hospital with an acute infarction are significantly more likely to have been affected by a respiratory infection in the days or weeks before their admission. Likewise, other studies have shown that people who see a doctor for an acute respiratory infection or flu symptoms are at greater risk of having a serious cardiovascular event later on.

This link between influenza and cardiovascular disease is particularly well illustrated by the results of a Canadian study published in the New England Journal of Medicine. Researchers found that people who tested positive for any of the different respiratory viruses had a much higher risk of being hospitalized for an acute heart attack within 7 days of diagnosis. This increased risk is particularly high for influenza A and B viruses (5 and 10 times, respectively), but is also observed for infections with syncytial virus (RSV) as well as for other respiratory viruses (adenovirus, metapneumovirus, coronavirus, etc.) (Figure 1). It is therefore certain that these increases in the risk of serious cardiovascular events contribute to the mortality associated with respiratory infections, in particular that caused by influenza viruses.

Figure 1. The impact of different respiratory viruses on the risk of myocardial infarction. From Kwong et al. (2018).

This association between lung infections and the risk of cardiovascular events may be due to the close interaction between these two organs. During gas exchange, venous blood (poor in oxygen) is propelled from the right ventricle of the heart into the pulmonary arteries, oxygenates in the pulmonary capillaries, returns to the left atrium through the pulmonary veins to be finally expelled into the circulation through the aorta. The presence of an inflammatory focus associated with the presence of a lung infection can therefore be transmitted rapidly to the whole body. This is particularly dangerous for the heart because this pro-inflammatory climate caused by the infection causes acute inflammation of the vessel walls and an increased coagulation potential, two phenomena known to promote the rupture of atherosclerotic plaques and cause the obstruction of the coronary arteries responsible for the infarction.

The impact of vaccination
Winter is the peak of the flu season because the influenza virus is highly contagious in low temperatures and low humidity levels, two characteristics of winter weather conditions. Despite imperfect protection (around 50–70% effectiveness, in the best years), vaccination remains the best way to reduce the risk of contracting influenza and at the same time reduce the sometimes severe complications of this infection.

This is especially important for people at high risk due to a history of cardiovascular disease. Several studies have shown that influenza vaccination reduces the incidence of cardiovascular events in patients with coronary heart disease, especially those who have recently had a heart attack. The FLUVACS (FLU Vaccination Acute Coronary Syndromes) randomized study showed that in patients admitted for a heart attack or for angioplasty (placement of a stent to dilate the obstructed coronary artery), vaccination reduced the risk of death from cardiovascular causes after 6 months (75% reduction) and one year (66% reduction). Likewise, the FLUCAD randomized study has shown that vaccination of patients with coronary heart disease (as visualized by angiography) halves the risk of a heart attack in the following year.

The results of a randomized, double-blind study recently published in Circulation provide a clear picture of the benefits of influenza vaccination for people who have had a myocardial infarction. In this multicenter study, patients hospitalized for a heart attack or for revascularization (placement of stents to treat severe obstruction of the coronary arteries) were divided into two groups, a control group (placebo) and a group receiving a vaccine against influenza within 72 hours of hospitalization. To judge the effectiveness of the intervention, the primary endpoint used was a combination of infarction, thrombosis, and all-cause mortality occurring within one year of patient randomization. The incidence of heart attack, cardiovascular mortality, and all-cause mortality was also analyzed separately as secondary endpoints.

As shown in Figure 2, the results of the study are quite dramatic overall. For example, the incidence of the primary endpoint (infarction, thrombosis, and all-cause mortality) was reduced by almost half in vaccinated patients (5.3% vs. 7.2% for placebo). Similar decreases were also observed for secondary endpoints such as all-cause mortality (2.9% vs. 4.9%) and cardiovascular mortality (2.7% vs. 4.5%). Only the decrease in the incidence of myocardial infarction was not significantly changed in the vaccinated patients (2.0% vs. 2.4%). Overall, the results of the study confirm that influenza vaccination of patients who have suffered a heart attack or who are at a very high risk of coronary heart attacks (revascularization) significantly reduces the risk of premature death in the year following hospitalization. These observations are in agreement with a recent meta-analysis, involving nearly 240,000 patients with cardiovascular disease, which showed that influenza vaccination was associated with a reduction in the risk of cardiovascular and all-cause mortality, but not in the incidence of myocardial infarction.

Figure 2. Kaplan-Meier curves of events following the administration of the placebo (red lines) or influenza vaccine (blue lines). The cumulative incidence of events is presented for the primary outcome of the study (a combination of myocardial infarction, thrombosis, and all-cause mortality) (A) and secondary outcomes such as all-cause mortality (B), cardiovascular mortality (C), and myocardial infarction (D). From Fröbert et al. (2021).

It should also be noted that influenza vaccination also appears to be beneficial in primary prevention, as a study carried out on 80,363 people aged 65 and over showed that vaccination reduced the incidence of myocardial infarction by 25% over a period of 13 years. Whether you are healthy or have cardiovascular disease, there are only advantages to getting the influenza vaccine.

Effects of cold on cardiovascular health

Effects of cold on cardiovascular health

OVERVIEW

  • Exposure to cold causes a contraction of blood vessels as well as an increase in blood pressure, heart rate, and the work of the heart muscle.
  • The combination of cold and exercise further increases stress on the cardiovascular system.
  • Cold temperatures are associated with increased cardiac symptoms (angina, arrhythmias) and an increased incidence of myocardial infarction and sudden cardiac death.
  • Patients with coronary artery disease should limit exposure to cold and dress warmly and cover their face when exercising.

Can the sometimes biting cold of our winters affect our overall health and our cardiovascular health in particular? For an exhaustive review of the literature on the effects of cold on health in general, see the summary report (in French only) recently published by the Institut national de santé publique du Québec (INSPQ). In this article, we will focus on the main effects of cold on the cardiovascular system and more specifically on the health of people with cardiovascular disease.

Brief and prolonged exposure to cold both affect the cardiovascular system, and exercise in cold weather further increases stress on the heart and arteries. Numerous epidemiological studies have shown that cardiovascular disease and mortality increase when the ambient temperature is cold and during cold spells. The winter season is associated with a greater number of cardiac symptoms (angina, arrhythmias) and cardiovascular events such as hypertensive crisis, deep venous thrombosis, pulmonary embolism, aortic ruptures and dissections, stroke, intracerebral hemorrhage, heart failure, atrial fibrillation, ventricular arrhythmia, angina pectoris, acute myocardial infarction, and sudden cardiac death.

Mortality from cold
Globally, more temperature-related deaths were caused by cold (7.29%) than heat (0.42%). For Canada, 4.46% of deaths were attributable to cold (2.54% for Montreal), and 0.54% to heat (0.68% for Montreal).

Intuition may lead us to believe that it is during periods of extreme cold that more adverse health effects occur, but the reality is quite different. According to a study that analyzed 74,225,200 deaths that occurred between 1985 and 2012 in 13 large countries on 5 continents, extreme temperatures (cold or hot) accounted for only 0.86% of all deaths, while the majority of cold-related deaths occurred at moderately cold temperatures (6.66%).

Acute effects of cold on the cardiovascular system of healthy people

Blood pressure. The drop in skin temperature upon exposure to cold is detected by skin thermoreceptors that stimulate the sympathetic nervous system and induce a vasoconstriction reflex (decrease in the diameter of the blood vessels). This peripheral vasoconstriction prevents heat loss from the surface of the body and has the effect of increasing systolic (5–30 mmHg) and diastolic (5–15 mmHg) blood pressure.

Heart rate. It is not greatly affected by exposure of the body to cold air, but it increases rapidly when, for example, the hand is dipped in ice water (“cold test” used to make certain diagnoses, such as Raynaud’s disease) or when very cold air is inhaled. Cold air usually causes a slight increase in heart rate in the range of 5 to 10 beats per minute.

Risk of atheromatous plaque rupture?
Post-mortem studies have shown that rupture of atheroma plaques (deposits of lipids on the lining of the arteries) is the immediate cause of over 75% of acute myocardial infarctions. Could cold stress promote the rupture of atheromatous plaques? In a laboratory study, mice exposed to cold in a cold room (4°C) for 8 weeks saw their blood LDL cholesterol level and the number of plaques increase compared to mice in the control group (room at 30°C). Furthermore, it is known that exposure to cold induces aggregation of platelets in vitro and increases coagulation factors in vivo in patients during colder days (< 20°C) compared to warmer days (> 20°C). Combined, these cold effects could help promote plaque rupture, but to date no study has been able to demonstrate this.

Risk of cardiac arrhythmias
Arrhythmias are a common cause of sudden cardiac death. Even in healthy volunteers, the simple act of dipping a hand in cold water while holding the breath can cause cardiac arrhythmias (nodal and supraventricular tachycardias). Could cold promote sudden death in people at risk for or with heart disease? Since arrhythmias cannot be detected post-mortem, it is very difficult to prove such a hypothesis. If it turns out that exposure to cold air can promote arrhythmias, people with coronary artery disease may be vulnerable to the cold since the arrhythmia would amplify the oxygenated blood deficit that reaches the heart muscle.

Effects of cold combined with exercise
Both cold and exercise individually increase the heart’s demand for oxygen, and the combination of the two stresses has an additive effect on this demand (see these two review articles, here and here). Exercising in the cold therefore results in an increase in systolic and diastolic blood pressure as well as in the “double product” (heart rate x blood pressure), a marker of cardiac work. The increased demand for oxygen by the heart muscle caused by cold weather and exercise increases blood flow to the coronary arteries that supply the heart. The rate of coronary blood flow increases in response to cold and exercise combined compared to exercise alone, but this increase is mitigated, especially in older people. Therefore, it appears that cold causes a relative lag between the oxygen demand from the myocardium and the oxygenated blood supply during exercise.

In a study carried out by our research team, we exposed 24 coronary patients with stable angina to various experimental conditions in a cold room at – 8°C, specifically a stress test with electrocardiogram (ECG) in cold without antianginal medication and an ECG at + 20°C. We then repeated these two ECGs after taking one drug (propranolol) that slows the heart rate, and then another drug (diltiazem) that causes dilation of the coronary arteries. The results showed that the cold caused mild to moderate ischemia (lack of blood supply) to the myocardium in only 1/3 of the patients. When ECG was done with medication, this effect was completely reversed. The two drugs have been shown to be equally effective in reversing this ischemia. The conclusion: cold had only a modest effect in 1/3 of patients and antianginal drugs are as effective in cold (- 8°C) as at + 20°C.

In another study in the same type of patients, we compared the effects of an ECG at – 20°C with an ECG at + 20°C. The results showed that at this very cold temperature, all patients presented with angina and earlier ischemia.

Hypertension
The prevalence of hypertension is higher in cold regions or during winter. Cold winters increase the severity of hypertension and the risk of cardiovascular events such as myocardial infarction and stroke in people with hypertension.

Heart failure
The heart of patients with heart failure is not able to pump enough blood to maintain the blood flow necessary to meet the body’s needs. Only a few studies have looked at the effects of cold on heart failure. Patients with heart failure do not have much leeway when the heart’s workload increases in cold weather or when they need to exert sustained physical effort. Cold combined with exercise further decreases the performance of people with heart failure. For example, in a study we conducted at the Montreal Heart Institute, cold reduced exercise time by 21% in people with heart failure. In the same study, the use of beta-blocker class antihypertensive drugs (metoprolol or carvedilol) significantly increased exercise time and reduced the impact of cold exposure on the functional capacity of patients. Another of our studies indicates that treatment with an antihypertensive drug from the class of angiotensin converting enzyme inhibitors, lisinopril, also mitigates the impact of cold on the ability to exercise in patients with heart failure.

Cold, exercise and coronary heart disease
It is rather unlikely that the cold alone could cause an increase in the work of the heart muscle large enough to cause a heart attack. Cold stress increases the work of the heart muscle and therefore the blood supply to the heart in healthy people, but in coronary patients there is usually a reduction in blood flow to the coronary arteries. The combination of cold and exercise puts coronary patients at risk of cardiac ischemia (lack of oxygen to the heart) much earlier in their workout than in warm or temperate weather. For this reason, people with coronary artery disease should limit exposure to cold and wear clothes that keep them warm and cover their face (significant heat loss in this part of the body) when working out outdoors in cold weather. In addition, the exercise tolerance of people with coronary heart disease will be reduced in cold weather. It is strongly recommended that coronary heart patients do indoor warm-up exercises before going out to exercise outdoors in cold weather.