Effects of cold on cardiovascular health

Effects of cold on cardiovascular health

Cardiologue et Directeur de la prévention, Institut de Cardiologie de Montréal. Professeur titulaire de clinique, Faculté de médecine de l'Université de Montréal. / Cardiologist and Director of Prevention, Montreal Heart Institute. Clinical Professor, Faculty of Medicine, University of Montreal.16 February 2021

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.

Hydroxychloroquine and COVID-19: A potentially harmful effect on the heart

Hydroxychloroquine and COVID-19: A potentially harmful effect on the heart

Cardiologue et Directeur de la prévention, Institut de Cardiologie de Montréal. Professeur titulaire de clinique, Faculté de médecine de l'Université de Montréal. / Cardiologist and Director of Prevention, Montreal Heart Institute. Clinical Professor, Faculty of Medicine, University of Montreal.19 May 2020

Updated June 8, 2020

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 coronavirus strain that primarily, but not exclusively, affects the respiratory system. While in the majority of infected people the symptoms of the disease are relatively mild or moderate (cough, fever, dyspnea or difficulty breathing, digestive disorders, temporary loss of taste and smell, hives, vascular lesions on the fingertips and toes), they may worsen in some people who have one or more risk factors (diabetes, hypertension, obesity, cardiovascular disease, advanced age) into acute respiratory distress syndrome that requires hospitalization in an intensive care unit and can lead to death.

There is no vaccine or effective drug available to reduce the mortality associated with COVID-19. The use of an antiviral drug, remdesivir, which was urgently approved by the FDA on May 1, 2020, reduces the number of days in hospital in people with COVID-19, but does not significantly reduce mortality. As of May 15, 2020, more than 1,500 studies on various aspects of COVID-19 have been registered on ClinicalTrials.gov, including more than 885 intervention studies and randomized controlled studies, with 176 on the use of hydroxychloroquine.

Hydroxychloroquine
One of the first candidates tested for treating COVID-19 was hydroxychloroquine, a drug used for its anti-inflammatory properties in the treatment of rheumatoid arthritis and systemic lupus erythematosus. Prior to the current COVID-19 pandemic, it was already known that chloroquine and its derivatives, including hydroxychloroquine, have non-specific antiviral activity against several types of enveloped viruses (HIV, hepatitis C, dengue, influenza, Ebola, SARS, MERS) in vitro. Two recent studies (see here and here) have shown that hydroxychloroquine also inhibits infection with the SARS-CoV-2 virus in vitro, i.e. in cultured epithelial cells. Hydroxychloroquine, which has a better safety profile than chloroquine, has been shown to be a more potent SARS-CoV-2 inhibitor in vitro.

The results obtained in vitro do not necessarily imply that chloroquine and its derivatives have antiviral activity in humans. Indeed, studies have shown that in vivo chloroquine and/or hydroxychloroquine have no effect on viral replication or increase viral replication and the severity of illness caused by infection by influenza, dengue, Simliki forest virus, encephalomyocarditis virus, Nipah and Hendra viruses, Chikungunya virus, and Ebola virus (references here).

Initial results from studies on the use of hydroxychloroquine to treat COVID-19 are unclear. Chinese researchers have reported treating over 100 patients with beneficial effects, but have not released any data. French microbiologist Didier Raoult and his collaborators published two articles (see here and here) on the use of hydroxychloroquine (in combination with the antibiotic azithromycin) for the treatment of COVID-19, in which they concluded that this drug lowers viral load in nasal swabs. However, these studies were not randomized and they do not report essential clinical data, such as the number of deaths among participants. In addition, two other French groups (see here and here) report having found no evidence of antiviral activity of hydroxychloroquine/azithromycin or of clinical benefit in hospitalized patients with a severe form of COVID-19.

In an observational study conducted in New York City hospitals, hydroxychloroquine was administered to 811 patients out of a total of 1376 patients, with a follow-up lasting an average of 22.5 days after admission to the hospital. Analysis of the results indicates that among this large number of patients admitted to hospital with a severe form of COVID-19, the risk of having to be intubated or dying was not significantly higher or lower in patients who received hydroxychloroquine than in those who did not. The authors conclude that the results obtained do not support the use of hydroxychloroquine in the current context, except in randomized controlled trials, which remain the best way to establish the efficacy of a therapeutic intervention.

Cardiovascular risk: Prolongation of the QT interval
Although hydroxychloroquine and azithromycin are well-tolerated drugs, both can cause prolongation of the QT segment on the electrocardiogram (figure below). For this reason, cardiologists are concerned about the use of these two drugs in a growing number of clinical trials for the treatment of COVID-19 (see here, here, here and here). It should be noted that the prolongation of the corrected QT interval (QTc) is a recognized marker of an increased risk of fatal arrhythmias.

Figure. Normal and abnormal (long) QT interval on the electrocardiogram.

Hospital researchers in the United States assessed the risk of QTc prolongation in 90 patients who received hydroxychloroquine, 53 of whom were concomitantly given the antibiotic azithromycin. The most common comorbidities among these patients were hypertension (53%) and type 2 diabetes (29%). The use of hydroxychloroquine alone or in combination with azithromycin was associated with QTc prolongation. Patients who received the two drugs in combination had significantly greater QTc prolongation than those who received hydroxychloroquine alone. Seven patients (19%) who received hydroxychloroquine monotherapy saw their QTc increase to 500 milliseconds (ms) or more, and three patients (8%) saw their QTc increase by 60 ms or more. Among the patients who received hydroxychloroquine and azithromycin in combination, 11 (21%) saw their QTc increase to 500 milliseconds (ms) or more, and 7 (13%) saw their QTc increase by 60 ms or more. Treatment with hydroxychloroquine had to be stopped promptly in 10 patients, due to iatrogenic drug events (adverse reactions), including nausea, hypoglycemia and 1 case of torsades de pointes. The authors conclude that physicians treating their patients with COVID-19 should carefully weigh the risks and benefits of treatment with hydroxychloroquine and azithromycin, and monitor QTc closely if patients are receiving these drugs.

French doctors have also published the results of a study on the effects of hydroxychloroquine treatment on the QT interval in 40 patients with COVID-19. Eighteen patients were treated with hydroxychloroquine (HCQ) and 22 received hydroxychloroquine in combination with the antibiotic azithromycin (AZM). An increase in the QTc interval was observed in 37 patients (93%) after treatment with antiviral therapy (HCQ alone or HCQ + AZM). QTc prolongation was observed in 14 patients (36%), including 7 with a QTc ≥ 500 milliseconds, 2 to 5 days after the start of antiviral therapy. Of these 7 patients, 6 had been treated with HCQ + AZM and one patient with hydroxychloroquine only, a significant difference. The authors conclude that treatment with hydroxychloroquine, particularly in combination with azithromycin, is of concern and should not be generalized when patients with COVID-19 cannot be adequately monitored (continuous monitoring of the QTc interval, daily electrocardiogram, laboratory tests).

Update June 8, 2020
A randomized, placebo-controlled study suggests that hydroxychloroquine is not effective in preventing the development of COVID-19 in people who have been exposed to the SARS-CoV-2 virus. The study, conducted in the United States and Canada, was published in the New England Journal of Medicine. Of 821 participants, 107 developed COVID-19 during the 14-day follow-up. Among people who received hydroxychloroquine less than four days after being exposed, 11.8% developed the disease compared to 14.3% in the group who received the placebo, a non-significant difference (P = 0.35). Side effects (nausea, abdominal discomfort) were more common in participants who received hydroxychloroquine than in those who received a placebo (40% vs. 17%), but no serious side effects, including cardiac arrhythmia, were reported. Clinical trials are underway to verify whether hydroxychloroquine can be effective in pre-exposure prophylaxis.