The importance of properly controlling your blood pressure

The importance of properly controlling your blood pressure

OVERVIEW

  • Hypertension is the main risk factor for cardiovascular disease and is responsible for 20% of deaths worldwide.
  • Early hypertension, before the age of 45, is associated with an increased risk of cardiovascular disease, cognitive decline and premature mortality.
  • Adopting an overall healthy lifestyle (normal weight, not smoking, regular physical activity, moderate alcohol consumption, and a good diet including sodium reduction) remains the best way to maintain adequate blood pressure.

According to the latest data from the Global Burden of Disease Study 2019, excessively high blood pressure was responsible for 10.8 million deaths worldwide in 2019, or 19.2% of all deaths recorded. This devastating impact is a direct consequence of the enormous damage caused by hypertension on the cardiovascular system. Indeed, a very large number of studies have clearly shown that excessive blood pressure, above 130/80 mm Hg (see box for a better understanding of blood pressure values), is closely linked to a significant increased risk of coronary heart disease and stroke.

 

Systolic and diastolic

It is important to remember that blood pressure is always expressed in the form of two values, namely systolic pressure and diastolic pressure. Systolic pressure is the pressure of the blood ejected by the left ventricle during the contraction of the heart (systole), while diastolic pressure is that measured between two beats, during the filling of the heart (diastole). To measure both pressures, the arterial circulation in the arm is completely blocked using an inflatable cuff, then the cuff pressure is allowed to gradually decrease until blood begins to flow back into the artery. This is the systolic pressure. By continuing to decrease the swelling of the cuff, we then arrive at a pressure from which there is no longer any obstacle to the passage of blood in the artery, even when the heart is filling. This is the diastolic pressure. A blood pressure value of 120/80 mm Hg, for example, therefore represents the ratio of systolic (120 mm Hg) and diastolic (80 mm Hg) pressures.

As shown in Figure 1, this risk of dying prematurely from coronary heart disease is moderate up to a systolic pressure of 130 mm Hg or a diastolic pressure of 90 mm Hg, but increases rapidly thereafter to almost 4 times for pressures equal to or greater than 150/98 mm Hg. This impact of hypertension is even more pronounced for stroke, with an 8 times higher risk of mortality for people with systolic pressure above 150 mm Hg and 4 times higher for a diastolic pressure greater than 98 mm Hg (Figure 1, bottom graph). Consequently, high blood pressure is by far the main risk factor for stroke, being responsible for about half of the mortality associated with this disease.


Figure 1. Association between blood pressure levels and the risk of death from coronary heart disease or stroke. From Stamler et al. (1993).

Early hypertension
Blood pressure tends to increase with aging as blood vessels become thicker and less elastic over time (blood circulates less easily and creates greater mechanical stress on the vessel wall). On the other hand, age is not the only risk factor for high blood pressure: sedentary lifestyle, poor diet (too much sodium intake, in particular), and excess body weight are all lifestyle factors that promote the development of hypertension, including in younger people.

In industrialized countries, these poor lifestyle habits are very common and contribute to a fairly high prevalence of hypertensive people, even among young adults. In Canada, for example, as many as 15% of adults aged 20–39 and 39% of those aged 40–59 have blood pressure above 130/80 mm Hg (Figure 2).


Figure 2. Prevalence of hypertension in the Canadian population. Hypertension is defined as systolic pressure ≥ 130 mm Hg or diastolic pressure ≥ 80 mm Hg, according to the 2017 criteria of the American College of Cardiology and the American Heart Association. The data are from Statistics Canada.

This proportion of young adults with hypertension is lower than that observed in older people (three in four people aged 70 and over have hypertension), but it can nevertheless have major repercussions on the health of these people in the longer term. Several recent studies indicate that it is not only hypertension per se that represents a risk factor for cardiovascular disease, but also the length of time a person is exposed to these high blood pressures. For example, a recent study reported that onset of hypertension before the age of 45 doubles the risk of cardiovascular disease and premature death, while onset of hypertension later in life (55 years and older) has a much less pronounced impact (Figure 3). These findings are consistent with studies showing that early hypertension is associated with an increased risk of cardiovascular mortality and damage to target organs (heart, kidneys, brain). In the case of the brain, high blood pressure in young adults has been reported to be associated with an increased risk of cognitive decline at older ages. Conversely, a recent meta-analysis suggests that a reduction in blood pressure with the help of antihypertensive drugs is associated with a lower risk of dementia or reduced cognitive function.

Figure 3. Change in risk of cardiovascular disease (red) or death from all causes (blue) depending on the age at which hypertension begins. Adapted from Wang et al. (2020).

Early hypertension should therefore be considered an important risk factor, and young adults can benefit from managingtheir blood pressure as early as possible, before this excessively high blood pressure causes irreparable damage.

The study of barbershops
In African-American culture, barbershops are gathering places that play a very important role in community cohesion. For health professionals, frequent attendance at these barbershops also represents a golden opportunity to regularly meet Black men to raise their awareness of certain health problems that disproportionately affect them. This is particularly the case with hypertension: African American men 20 years and older have one of the highest prevalence of high blood pressure in the world, with as many as 59% of them being hypertensive. Also, compared to whites, Black men develop high blood pressure earlier in their lives and this pressure is on average much higher.

A recent study indicates that barbershops may raise awareness among African Americans about the importance of controlling their blood pressure and promoting the treatment of hypertension. In this study, researchers recruited 319 African Americans aged 35 to 79 who were hypertensive (average blood pressure approximately 153 mm Hg) and who were regular barbershop customers. Participants were randomly assigned to two groups: 1) an intervention group, in which clients were encouraged to see, in the barbershops, pharmacists specially trained to diagnose and treat hypertension and 2) a control group, in which barbers suggested that clients make lifestyle changes and seek medical attention. In the intervention group, pharmacists met regularly with clients during their barbershop visits, prescribed antihypertensive drugs, and monitored their blood pressure.

After only 6 months, the results obtained were nothing short of spectacular: the blood pressure of the intervention group fell by 27 mm Hg (to reach 125.8 mm Hg on average), compared to only 9.3 mm Hg (to reach 145 mm Hg on average) for the control group. Normal blood pressure (less than 130/80 mm Hg) was achieved in 64% of participants in the intervention group, while only 12% of those in the control group were successful. A recent update of the study showed that the beneficial effects of the intervention were long-lasting, with continued pressure reductions still observed one year after the start of the study.

These reductions in blood pressure obtained in the intervention group are of great importance, as several studies have clearly shown that pharmacological treatment of hypertension causes a significant reduction in the risk of cardiovascular diseases, including coronary heart disease and stroke, as well as kidney failure. This study therefore shows how important it is to know your blood pressure and, if it is above normal, to normalize it with medication or through lifestyle changes.

The importance of lifestyle
This last point is particularly important for the many people who have blood pressure slightly above normal, but without reaching values ​​as high as those of the participants of the study mentioned above (150/90 mm Hg and above). In these people, an increase in the level of physical activity, a reduction in sodium intake, and body weight loss can lower blood pressure enough to allow it to reach normal levels. For example, obesity is a major risk factor for hypertension and a weight loss of 10 kg is associated with a reduction in systolic pressure from 5 mm to 10 mm Hg. This positive influence of lifestyle is observed even in people who have certain genetic variants that predispose them to high blood pressure. For example, adopting an overall healthy lifestyle (normal weight, not smoking, regular physical activity, moderate alcohol consumption, and a good diet including sodium reduction) has been shown to be associated with blood pressure approximately 3 mm Hg lower and a 30% reduction in the risk of cardiovascular disease, regardless of the genetic risk. Conversely, an unhealthy lifestyle increases blood pressure and the risk of cardiovascular disease, even in those who are genetically less at risk of hypertension.

In short, taking your blood pressure regularly, even at a young age, can literally save your life. The easiest way to regularly check your blood pressure is to purchase one of the many models of blood pressure monitors available in pharmacies or specialty stores. Take the measurement in a seated position, legs uncrossed and with the arm resting on a table so that the middle of the arm is at the level of the heart. Two measurements in the morning before having breakfast and drinking coffee and two more measurements in the evening before bedtime (wait at least 2 hours after the end of the meal) generally give an accurate picture of blood pressure, which should be below 135/85 mm Hg on average according to Hypertension Canada.

Electronic cigarettes drastically reduce exposure to toxic substances from tobacco

Electronic cigarettes drastically reduce exposure to toxic substances from tobacco

OVERVIEW

  • Cigarette smoke contains more than 7,000 chemical compounds, of which at least 250 are well-characterized toxic substances and 70 are established carcinogens.
  • By allowing the absorption of nicotine without the combustion of tobacco, e-cigarettes are therefore an alternative to reduce exposure to these toxic compounds.
  • According to an analysis by the Institut Pasteur, this reduction is very significant since the aerosols generated by electronic cigarettes contain less than 1% of the toxic compounds found in cigarette smoke.

There is nothing worse than smoking for heart and blood vessel health (and health in general), and quitting smoking is by far the best decision a person can make to lower their risk of developing cardiovascular disease. However, quitting smoking is very difficult for many smokers, and, for several years, I have recommended that my patients who are unable to quit by conventional means (patches, gum, etc.) use electronic cigarettes.

In an e-cigarette, a solution of nicotine is heated to around 80°C using an atomizer, which generates an aerosol that allows vapers to inhale a small amount of nicotine (like smokers) to satisfy their addiction, but which does not contain the multiple toxic molecules that are generated during the combustion of tobacco (at around 900°C). This last point is the most important: contrary to what many think (including the majority of doctors), it is the combustion products of tobacco cigarettes that cause health problems, not nicotine. The latter is a drug that creates tobacco addiction and encourages people to smoke, but it has no major health effects and is especially not responsible for cardiovascular disease or lung cancer that result from smoking. The advantage of the electronic cigarette is therefore that it allows smokers who are highly dependent on nicotine to considerably reduce their exposure to the many toxic substances of cigarette smoke. This is a classic example of what is called harm reduction.

In addition, not only is the e-cigarette less toxic than tobacco, but a randomized clinical study recently published in the prestigious New England Journal of Medicine shows that it can be very useful for smoking cessation, with twice the effectiveness of traditional approaches based on nicotine substitutes. These devices therefore represent a very interesting technological innovation that adds a new dimension to the fight against tobacco.

Large-scale misinformation
That being said, one of the most disconcerting aspects of the media coverage surrounding anything related to e-cigarettes is the negative, often even alarmist, tone that is used to report the latest research developments on these devices. Any study that claims to show a negative impact of e-cigarettes on health makes headlines, even those that are low-quality and published in second-rate journals, while studies that instead report a positive effect are simply ignored, even when they are very scientifically sound and published in prestigious medical journals. This imbalance means that the population is informed only of the potential risks associated with e-cigarettes, without knowing that there is also a whole body of literature showing that these devices have positive effects on the health of smokers.

Perhaps one of the best examples of this media bias is the coverage of a study claiming to show an increased risk of heart attack in vapers, a study that was widely circulated in the media around the world when it was published. However, a critical examination of the results revealed that the majority of the 38 patients in the study had suffered a heart attack on average 10 years BEFORE they started vaping and therefore that these heart attacks could not have been due to e-cigarettes. Since vapers are almost always ex-smokers, the increase in heart attacks observed in vapers is simply due to the fact that these people gave up smoking after being sick and now use e-cigarettes to avoid a recurrence. This is a blatant case of scientific misconduct that resulted in the retraction of the article, but the withdrawal of this fraudulent study was not reported by most media. It should be noted that the main author of this retracted article, Stanton Glantz, is one of the most committed researchers against the use of e-cigarettes.

This is all the more unfortunate because a randomized clinical study, which was very well done, showed that it is exactly the opposite phenomenon that occurs, i.e. that the transition of smokers to e-cigarettes is positive because it is accompanied by a rapid improvement (in only one month) in the health of the blood vessels. However, this important study has not been reported by the media, and the public therefore does not know that, far from being harmful to the heart, e-cigarettes are instead associated with concrete health benefits for smokers.

The immediate consequence of this misinformation is that fewer and fewer people see e-cigarettes as a less harmful alternative to tobacco, including smokers, and there is a risk that the number of smokers who make the leap to e-cigarettes will decrease. I see it already in my practice: patients who weaned themselves off tobacco through vaping have resumed smoking, while others are reluctant to try e-cigarettes to quit smoking. In both cases, the reason given is the same: if vaping is as bad as smoking, why make the switch? This shows that disinformation campaigns can have real consequences for people’s lives and even literally make the difference between life and death for some of them.

Toxics reduction
Yet no one can seriously argue that e-cigarettes are as bad for your health as cigarettes. Cigarette smoke contains more than 7,000 chemical compounds, of which at least 250 are well-characterized toxic substances and 70 are established carcinogens. Repeated exposure to these toxic emissions is directly responsible for 8 million deaths each year worldwide, making smoking the leading cause of preventable deaths, especially those caused by cancer (30% of all cancers are caused by tobacco) and cardiovascular and respiratory diseases.

Analyses by Public Health England, the American National Academies of Sciences, Engineering, and Medicine and the British Committee on Toxicity of Chemicals in Food, Consumer Products, and the Environment all show that aerosols from e-cigarettes contain a much smaller number and amount of toxic substances than cigarette smoke and are therefore less harmful to health than smoked tobacco. It is for this reason that organizations such as Public Health England and France’s Académie nationale de médecine strongly recommend that smokers do not hesitate and make the transition to vaping.

This does not mean that e-cigarettes are completely safe, but they are undeniably much less harmful than the product they replace (which is the principle of harm reduction). By focusing only on identifying the potential harmful effects of vaping, we come to forget that the basic principle of vaping is to reduce the harms of smoking in smokers who are repeatedly exposed to toxic substances from tobacco.

A recent study by the Institut Pasteur provides a clear view of this potential for harm reduction. In this study, scientists compared the presence of two major classes of toxics (carbonyl compounds and aromatic hydrocarbons) in aerosols from smoked cigarettes, heated tobacco products (IQOS) and e-cigarettes. The results are really impressive: for the 19 carbonyls and 23 aromatic hydrocarbons tested, the e-cigarette chosen for the study (high-capacity tank device, used at maximum power) reduces these toxic compounds by 99.8 and 98.9% compared to tobacco cigarettes (Figure 1). IQOS (heated tobacco product) is also less toxic than cigarettes, with reductions of 85% and 96% in the concentration of these toxic compounds, but these reductions nevertheless remain lower than those observed with e-cigarettes, in line with previous studies.

Figure 1. Content of carbonyl compounds (A) and polycyclic aromatic hydrocarbons (PAHs) (B) in aerosols produced by a cigarette, a heated tobacco product and an e-cigarette. Note the drastic reduction of these two classes of toxics in e-cigarette vapour compared to tobacco smoke. From Dusautoir et al. (2020).

The researchers then compared the toxicity of different types of cigarettes by measuring the viability of bronchial epithelial cells following repeated exposure to aerosol puffs generated by cigarettes, heated tobacco products and e-cigarettes. As shown in Figure 2, exposing the cells to only 2 puffs from a cigarette is enough to kill half of the cells, and no residual cells are detectable after coming into contact with 10 puffs of smoke. Heated tobacco products significantly reduce this toxicity (40 puffs are necessary to kill half of the cells and a hundred to eliminate them completely), but it is here again that e-cigarettes are by far the least toxic, with all cells remaining alive even after exposure to 120 puffs of aerosols.

Figure 2. Viability of bronchial epithelial cells after repeated exposure to aerosols from a regular cigarette, a heated tobacco product or an e-cigarette. Note the high toxicity of cigarettes, which cause 50% mortality after cells are exposed to just 2 puffs of smoke, while cells remain viable even after being in contact with 120 puffs of aerosols from an e-cigarette. From Dusautoir et al. (2020).

Another study shows that this very significant reduction in toxicity is also observed for Juul, the e-cigarette which has recently captured the majority of the e-cigarette market (see our article on this subject). Compared to traditional cigarettes, the vapour generated by Juul contains almost 100% less carbon monoxide and carbonyl compounds like acetaldehyde, formaldehyde, and acrolein (a major irritant in cigarette smoke) (Table 1). Similar results were also reported in another study. These data are important because Juul is particularly popular among young vapers. Contrary to what we often hear, the vast majority of young people (> 99%) who regularly vape are occasional or regular smokers and these people can therefore substantially reduce their exposure to tobacco toxins by vaping. In addition, recent data indicates that nicotine absorbed through e-cigarettes is less addictive than when it comes from burning tobacco, which decreases the risk of developing longer-term dependence.

Table 1. Concentration of certain toxic compounds present in cigarette smoke or in the vapour generated by the Juul e-cigarette. From Son et al. (2020).

It is worth remembering that the ultimate goal of tobacco control is to reduce the incidence of smoking-related diseases, especially cardiovascular disease and lung cancer. To achieve this, total abstinence is desirable, but the large number of people who are unable to quit smoking on their own or by using current cessation tools and therefore remain at risk of dying prematurely must be taken into account. In my clinical experience over the past ten years, the electronic cigarette is the most popular nicotine replacement for smokers and for many of them represents the only approach that allows them to successfully quit smoking. Instead of constantly seeking to discredit these devices, as is currently the case, they should instead be seen as a technological innovation that can greatly contribute to the fight against diseases caused by smoking, and we need to clearly inform smokers of the benefits associated with the transition to vaping.

The cardiovascular benefits of soy

The cardiovascular benefits of soy

OVERVIEW

  • Asians have a much lower incidence of cardiovascular disease than North Americans, a difference that has been attributed, at least in part, to their high consumption of soybeans.
  • This protection is due to soy’s high content of isoflavones, a class of polyphenols that have several positive effects on the cardiovascular system.
  • A recent study carried out among 210,700 Americans (168,474 women and 42,226 men) has just confirmed this reduction in the risk of coronary heart disease associated with the consumption of soybeans, illustrating how this legume is an attractive alternative to meat as a source of protein.

It has been known for several years that people in Asian countries have a much lower incidence of cardiovascular disease than in the West. The study of migrant populations has shown that this difference is not due to genetic factors. For example, an analysis carried out in the 1970s revealed that the Japanese who had emigrated to California had twice the incidence of coronary heart disease than that of their compatriots who remained in Japan. It should be mentioned that these Asia-America differences are also observed for several types of cancer, in particular breast cancer. Asian women (China, Japan, Korea) have one of the lowest incidences of breast cancer in the world, but this cancer can become up to 4 times more common as a result of their migration to America, and its incidence even becomes similar to that of third generation Americans. The rapid rise in cardiovascular disease or cancer following migration to the West therefore suggests that abandoning the traditional lifestyle of Asians for the one in vogue in North America greatly favours the development of these diseases.

One of the differences between the Asian and North American lifestyles that has long interested researchers is the huge gap in soy consumption. While an average of 20 to 30 g of soy protein is consumed daily in Japan and Korea, this consumption barely reaches 1 g per day in the United States (Figure 1). It is proposed that this difference could contribute to the higher incidence of cardiovascular disease in the West for two main reasons:

  • Like all members of the legume family (lentils, peas, etc.), soy is an excellent source of fibre, vitamins, minerals, and polyunsaturated fats, nutrients known to be beneficial to heart and vessel health;
  • Soybeans are an exceptional source of isoflavones, a class of polyphenols found almost exclusively in this legume. The main isoflavones in soybeans are genistein, daidzein and glycitein (Figure 2), these molecules being present in varying amounts depending on the degree of processing of soybeans.

Figure 1. Comparison of the amounts of soybeans consumed daily by people in different countries. From Pabich and Materska (2019).

 


Figure 2. Molecular structures of the main isoflavones.
Note that equol is not present in soy products, but is rather generated by the gut microbiome following their ingestion.

The highest concentrations of isoflavones are found in the starting beans (edamame) and foods derived from fermented beans (natto, tempeh, miso), while foods from the pressing of beans (tofu, soy milk) contain slightly less (Table 1). These foods are commonly consumed by Asians and allow them to obtain isoflavone intakes varying from 8 to 50 mg per day, depending on the region, quantities clearly greater than those of the inhabitants of Europe and America (less than 1 mg per day). It should be noted, however, that soy is gradually becoming more and more popular in the West as an alternative to meat and that isoflavone intake can reach levels similar to Asians (18–21 mg per day) in certain groups of health-conscious people.


Table 1. The isoflavone content of various foods.
Source: United States Department of Agriculture, Nutrient Data Laboratory.

FoodIsoflavone content
(mg/100 g)
Natto82.3
Tempeh
60.6
Soybeans (edamame)49.0
Miso41.5
Tofu22.1
Soy milk10.7

The importance of a high intake of isoflavones comes from the multiple biological properties of this class of molecules. In addition to their antioxidant and anti-inflammatory activities, common to many polyphenols, a unique feature of isoflavones is their structural resemblance to estrogens, the female sex hormones, and it is for this reason that these molecules are often referred to as phytoestrogens. This estrogenic action has so far been mainly studied in relation to the development of hormone-dependent breast cancers. Since the growth of these cancers is stimulated by estrogens, the presence of phytoestrogens creates a competition that attenuates the biological effects associated with these hormones, especially the excessive growth of breast tissue (this mode of action is comparable to that of tamoxifen, a drug prescribed for several years against breast cancer). It is also important to note that, contrary to a very widespread misconception, the consumption of soybeans should not be discouraged for women who have survived breast cancer. On the contrary, many studies conducted in recent years clearly show that regular soy consumption by these women is absolutely safe and is even associated with a significant decrease in the risk of recurrence and mortality from this disease. It should be mentioned that despite the similarity of isoflavones to estrogens, studies indicate that soy does not interfere with the effectiveness of tamoxifen or anastrozole, two drugs frequently used to treat hormone-dependent breast cancers. Consequently, for people who have been affected by breast cancer, there are only benefits to incorporating soy into their diet.

Several data suggest that the positive effect of isoflavones on health is not limited to their anticancer action, and that the combination of the antioxidant, anti-inflammatory and estrogenic activities of these molecules may also contribute to the cardiovascular benefits of soy (Table 2).


Table 2. Main properties of isoflavones involved in reducing the risk of cardiovascular disease associated with soy consumption.

Cardiovascular effectsProposed mechanisms
Vasodilation of blood vesselsIsoflavones interact with a subtype of estrogen receptor present in the coronary arteries (Erβ), leading to the production of nitrous oxide (NO), a gas that induces vasodilation of blood vessels.
Lower cholesterol levels
Accelerated elimination of LDL and VLDL in the liver.
Isoflavones reduce LDL-cholesterol oxidation in diabetic patients.
AntioxydantEquol, a metabolite of daidzein formed by the intestinal microbiome, has a strong antioxidant activity.
Anti-inflammatoryIsoflavones promote the establishment of an intestinal microbiome enriched with bacteria that produce anti-inflammatory molecules (Bifidobacterium spp., for example).

A cardioprotective effect associated with soy consumption is also suggested by the results of an epidemiological study recently published in Circulation. By examining the eating habits of 210,700 Americans (168,474 women and 42,226 men), the researchers found that people with the highest isoflavone intake (about 2 mg per day on average) had a risk of coronary heart disease decreased by 13% compared to those with minimal intake (0.15 mg per day on average). A protective effect is also observed for tofu, with an 18% reduction in the risk of coronary heart disease for people who consume it once or more per week compared to those who ate it very rarely (less than once per month). Regular consumption of soy milk (once or more per week) is also associated with a slight decrease in risk, but this decrease is not statistically significant.

These reductions may seem modest, but it should be noted that the amounts of soybeans consumed by participants in this study are relatively small, well below what is commonly measured in Japan. For example, in a Japanese study that reported a 45% decrease in the risk of myocardial infarction in women who consumed the most soy, the isoflavone intake of these people was on average around 40 mg/day, i.e. 20 times more than in the American study (2 mg/day). It is therefore likely that the reductions in the risk of coronary heart disease observed in the United States represent a minimum and could probably be greater as a result of higher soy intake.

An interesting aspect of the decreased risk of coronary heart disease associated with tofu is that it is observed as much in younger women before menopause as in postmenopausal women, but only if they are not using hormone therapy (Figure 3). According to the authors, it is possible that after menopause, the estrogenic action of isoflavones compensates for the drop in estrogen levels and may mimic the cardioprotective effect of these hormones. In the presence of synthetic hormones, on the other hand, isoflavones are “masked” by excess hormones and therefore cannot exert their beneficial effects. For younger women, it is likely that the higher expression of the estrogen receptor before menopause promotes a greater interaction with isoflavones and allows these molecules to positively influence the function of blood vessels.

Figure 3. Association between risk of coronary heart disease and tofu consumption by hormonal status.
From Ma et al. (2020).

Taken together, these observations suggest that soy products have a positive effect on cardiovascular health and therefore represent an excellent alternative to meat as a source of protein. A recent study reports that these cardiovascular benefits can be even more pronounced following the consumption of fermented soy products such as natto, which is very rich in isoflavones, but given its texture (sticky, gooey), its strong smell (reminiscent of a well-made cheese), and its low availability in grocery stores, this food is foreign to our food culture and unlikely to be adopted by the North American population. Tofu is probably the most accessible soy-derived food given its neutral taste that allows it to be used in a wide variety of dishes, Asian-style or not. Soy milk is a less attractive alternative, not only because its consumption is not associated with a significant decrease in the risk of coronary heart disease, but also because these products often contain significant amounts of sugar.

To prevent cardiovascular disease, medication should not be a substitute for improved lifestyle

To prevent cardiovascular disease, medication should not be a substitute for improved lifestyle

OVERVIEW

  • Cardiovascular disease dramatically increases the risk of developing serious complications from COVID-19, again highlighting the importance of preventing these diseases in order to live long and healthy lives.
  • And it is possible! Numerous studies clearly show that more than 80% of cardiovascular diseases can be prevented by simply adopting 5 lifestyle habits (not smoking, maintaining a normal weight, eating a lot of vegetables, exercising regularly, and drinking alcohol moderately).

The current COVID-19 pandemic has exposed two major vulnerabilities in our society. The first is, of course, the fragility of our health care system, in particular everything related to the care of the elderly with a loss of autonomy. The pandemic has highlighted serious deficiencies in the way this care is delivered in several facilities, which has directly contributed to the high number of elderly people who have died from the disease. Hopefully, this deplorable situation will have a positive impact on the ways of treating this population in the future.

A second vulnerability highlighted by the pandemic, but much less talked about, is that COVID-19 preferentially affects people who present pre-existing conditions at the time of infection, in particular cardiovascular disease, obesity and type 2 diabetes. These comorbidities have a devastating impact on the course of the disease, with increases in the death rate of 5 to 10 times compared to people without pre-existing conditions. In other words, not only does poor metabolic health have a disastrous impact on healthy life expectancy, it is also a significant risk factor for complications from infectious diseases such as COVID-19. We are therefore not as helpless as we might think in the face of infectious agents such as the SARS-CoV-2 coronavirus: by adopting a healthy lifestyle that prevents the development of chronic diseases and their complications, we simultaneously greatly improve the probability of effectively fighting infection with this type of virus.

Preventing cardiovascular disease
Cardiovascular disease is one of the main comorbidities associated with severe forms of COVID-19, so prevention of these diseases can therefore greatly reduce the impact of this infectious disease on mortality. It is now well established that high blood pressure and high blood cholesterol are two important risk factors for cardiovascular disease. As a result, the standard medical approach to preventing these diseases is usually to lower blood pressure and blood cholesterol levels with the help of drugs, such as antihypertensive drugs and cholesterol-lowering drugs (statins). These medications are particularly important in secondary prevention, i.e. to reduce the risk of heart attack in patients with a history of cardiovascular disease, but they are also very frequently used in primary prevention, to reduce the risk of cardiovascular events in the general population.

The drugs actually manage to normalize cholesterol and blood pressure in the majority of patients, which can lead people to believe that the situation is under control and that they no longer need to “pay attention” to what they eat or be physically active on a regular basis. This false sense of security associated with taking medication is well illustrated by the results of a recent study, conducted among 41,225 Finns aged 40 and over. By examining the lifestyle of this cohort, the researchers observed that people who started medication with statins or antihypertensive drugs gained more weight over the next 13 years, an excess weight associated with an 82% increased risk of obesity compared to people who did not take medication. At the same time, people on medication reported a slight decrease in their level of daily physical activity, with an increased risk of physical inactivity of 8%.

These findings are consistent with previous studies showing that statin users eat more calories, have a higher body mass index than those who do not take this class of drugs, and do less physical activity (possibly due to the negative impact of statins on muscles in some people). My personal clinical experience points in the same direction; I have lost count of the occasions when patients tell me that they no longer have to worry about what they eat or exercise regularly because their levels of LDL cholesterol have become normal since they began taking a statin. These patients somehow feel “protected” by the medication and mistakenly believe that they are no longer at risk of developing cardiovascular disease. This is unfortunately not the case: maintaining normal cholesterol levels is, of course, important, but other factors such as smoking, being overweight, sedentary lifestyle, and family history also play a role in the risk of cardiovascular disease. Several studies have shown that between one third and one half of heart attacks occur in people with LDL-cholesterol levels considered normal. The same goes for hypertension as patients treated with antihypertensive drugs are still 2.5 times more likely to have a heart attack than people who are naturally normotensive (whose blood pressure is normal without any pharmacological treatment) and who have the same blood pressure.

In other words, although antihypertensive and cholesterol-lowering drugs are very useful, especially for patients at high risk of cardiovascular events, one must be aware of their limitations and avoid seeing them as the only way to reduce the risk of cardiovascular events.

Superiority of lifestyle
In terms of prevention, much more can be done by addressing the root causes of cardiovascular disease, which in the vast majority of cases are directly linked to lifestyle. Indeed, a very large number of studies have clearly shown that making only five lifestyle changes can very significantly reduce the risk of developing these diseases (see Table below).

The effectiveness of these lifestyle habits in preventing myocardial infarction is quite remarkable, with an absolute risk drop to around 85% (Figure 1). This protection is seen both in people with adequate cholesterol levels and normal blood pressure and in those who are at higher risk for cardiovascular disease due to high cholesterol and hypertension.

Figure 1. Decreased incidence of myocardial infarction in men combining one or more protective factors related to lifestyle. The comparison of the incidences of infarction was carried out in men who did not have cholesterol or blood pressure abnormalities (upper figure, in blue) and in men with high cholesterol levels and hypertension (lower figure, in orange). Note the drastic drop in the incidence of heart attacks in men who adopted all 5 protective lifestyle factors, even in those who were hypertensive and hypercholesterolemic. Adapted from Åkesson (2014).

Even people who have had a heart attack in the past and are being treated with medication can benefit from a healthy lifestyle. For example, a study conducted by Canadian cardiologist Salim Yusuf’s group showed that patients who modify their diet and adhere to a regular physical activity program after a heart attack have their risk of heart attack, stroke and mortality reduced by half compared to those who do not change their habits (Figure 2). Since all of these patients were treated with all of the usual medications (beta blockers, statins, aspirin, etc.), these results illustrate how lifestyle can influence the risk of recurrence.

Figure 2. Effect of diet and exercise on the risk of heart attack, stroke, and death in patients with previous coronary artery disease. Adapted from Chow et al. (2010).

In short, more than three quarters of cardiovascular diseases can be prevented by adopting a healthy lifestyle, a protection that far exceeds that provided by drugs. These medications must therefore be seen as supplements and not substitutes for lifestyle. The development of atherosclerosis is a phenomenon of great complexity, which involves a large number of distinct phenomena (especially chronic inflammation), and no drug, however effective, will ever offer protection comparable to that provided by a healthy diet, regular physical activity, and maintenance of a normal body weight.

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

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

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.

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

COVID-19 and cardiovascular disease

OVERVIEW

  • People with cardiovascular disease are more likely to develop the more severe forms of COVID-19, which significantly increases the mortality rate of this disease.
  • In addition to being an important risk factor for COVID-19, cardiovascular disease can also be a consequence of SARS-CoV-2 coronavirus infection.
  • Patients with severe COVID-19 frequently have heart damage, which increases the severity of the infection and is life threatening.

COVID-19 is a respiratory disease caused by a new virus, the SARS-CoV-2 coronavirus. The COVID-19 epidemic began in December 2019 in Wuhan, Hubei Province, China, and has spread rapidly worldwide with more than 1,360,000 people affected and 75,973 deaths as of April 7, 2020. Although most patients infected with the virus do not have major symptoms, about 15% of them develop a much more severe form of the disease, including severe acute respiratory syndrome that requires mechanical ventilation. This severe form of COVID-19 is particularly dangerous for the elderly: while the mortality rate is around 1% among those aged 50 and under, it rises to 3.6% in those aged 60, to 8% for those aged 70 and up, and to 14.8% for those 80 years and older.

An aggravating factor: Chronic diseases
Data from previous outbreaks caused by coronaviruses similar to SARS-CoV-2 have shown that a large proportion of infected patients are affected by underlying chronic conditions. For example, during the 2002 severe acute respiratory syndrome (SARS) epidemic, the prevalence of type 2 diabetes and preexisting cardiovascular disease was 11 and 8%, respectively, and the presence of either of these chronic conditions was associated with a very large increase (almost 10 times) in the mortality rate. Similarly, in patients infected with Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 and presenting with severe symptoms, 50% suffered from hypertension and diabetes and up to 30% from heart disease.

The presence of these comorbidities (coexistence in the same patient of two or more diseases) is also observed during the current COVID-19 epidemic. In all the studies carried out to date, a significant proportion of patients were affected by a preexisting chronic condition, the most common being hypertension, type 2 diabetes and cardiovascular disease (Table 1).

PopulationComorbiditiesSource
99 infected patients
(Wuhan, China)
Cardiovascular disease (40 %)
Diabetes (12 %)
Chen et al. (2020)
191 infected patients
(Wuhan, China)
Hypertension (30 %)
Diabetes (19 %)
Cardiovascular disease (8 %)
Zhou et al. (2020)
138 infected patients
(Wuhan, China)
Hypertension (31 %)
Diabetes (10 %)
Cardiovascular disease (15 %)
Wang et al. (2020)
1099 infected patients
(China)
Hypertension (15 %)
Diabetes (7.4 %)
Cardiovascular disease (2.5 %)
Guan et al. (2020)
46,248 infected patients
(China, meta-analysis)
Hypertension (17 %)
Diabetes (8 %)
Cardiovascular disease (5 %)
Yang et al. (2020)
355 deceased patients
(Italy)
Hypertension (76 %)
Diabetes (36%)
Cardiovascular disease (33 %)
Atrial fibrillation (25 %)
Cancer (20 %)
Instituto Superiore di Sanita (2020)

In all cases, these chronic conditions are more frequently observed in patients with the more severe forms of COVID-19. For example, a study carried out in Wuhan showed that the proportion of patients with hypertension, type diabetes 2 and cardiovascular disease is almost twice as high in those who have developed a severe form of COVID-19. This contribution of chronic diseases to the burden imposed by COVID-19 seems particularly important in Italy, one of the countries hardest hit by COVID-19: data collected by the country’s health authorities show that 99% of people who have died from the disease had at least one chronic condition such as hypertension (76%), type 2 diabetes (36%), coronary heart disease (33%), atrial fibrillation (25%) or cancer (20%).

The impact of these chronic diseases is considerable, with the mortality rate of COVID-19 increasing by 5 to 10 times compared to people who do not have preexisting conditions (Figure 1).

Figure 1. Influence of preexisting chronic conditions on the COVID-19 mortality rate. From: The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team (2020).

People with a chronic condition, including cardiovascular disease, are therefore at much higher risk of developing a severe form of COVID-19, especially if they are older. Consequently, this population must be extra vigilant and avoid interacting with people who may have been in contact with the virus.

Heart damage
In addition to being an important risk factor for COVID-19, cardiovascular disease can also be a consequence of SARS-CoV-2 coronavirus infection. Studies carried out at the beginning of the pandemic observed clinical signs of cardiac injury (elevated blood level of cardiac Troponin I [hs-cTnI], abnormalities of electrocardiograms or cardiac ultrasounds) in 7.2% of infected patients, a proportion that reaches 22% in those affected by severe forms of COVID-19 and who required hospitalization in intensive care. In another study of 138 patients with COVID-19 in Wuhan, 36 patients with severe symptoms treated in intensive care units had significantly higher levels of myocardial injury markers than those not treated in intensive care units. Severe cases of COVID-19 therefore often present complications involving an acute myocardial injury, which seriously complicates the treatment of these patients. It is very likely that these cardiac injuries contribute to the mortality caused by COVID-19, since a study observed hs-cTnI values higher than the 99th percentile (which indicates a myocardial injury) in 46% of patients who had died from the disease, compared to only 1% of survivors. In addition, two recent studies (here and here) have found that the death rate of patients with cardiac injury is much higher than among those without, an increase that can be as high as 10 times in people with a history of cardiovascular disease (Figure 2).


Figure 2. Differences in mortality of patients with COVID-19 depending on the presence of preexisting cardiovascular disease and/or cardiac injury caused by infection. From Guo et al. (2020).

The mechanisms responsible for these heart lesions are very complex and involve several phenomena. On the one hand, poor functioning of the lungs can cause oxygen levels to become insufficient to keep the heart muscle working. This oxygen deficiency is all the more dangerous because the fever caused by the infection increases the body’s metabolism, which increases the workload of the heart. This imbalance between oxygen supply and demand therefore increases the risk of arrhythmia and heart damage.

Another factor involved in heart damage caused by respiratory viruses is what is known as a “cytokine storm”, a phenomenon characterized by an exaggerated inflammatory response following viral infection. The immune system goes berserk and indiscriminately attacks everything in the vicinity, including our own cells, which damages organ function and can increase susceptibility to bacterial infections. The heart is particularly sensitive to this uncontrolled inflammation given its close interaction with the lungs; the oxygenated blood from the lungs reaching the heart has been in direct contact with the foci of infection and therefore necessarily contains a greater concentration of the molecules produced by excess inflammation. When this blood is expelled from the left ventricle to the aorta, a portion of this oxygenated blood is immediately passed to the myocardium to feed the heart cells, with the result that these cells are exposed to abnormally high amounts of inflammatory molecules. An excess of inflammatory molecules can also cause thrombosis (clot formation), which blocks the flow of blood to the heart and causes a heart attack. Indeed, a recent study has shown that high levels of D-dimers, a marker of thrombosis, were associated with a very large increase (18 times) in the risk of mortality from COVID-19.

A clinical study led by Dr. Jean-Claude Tardif, Director of the MHI Research Center, has just been launched to determine whether a reduction in inflammation from viral infection with colchicine, an inexpensive and generally well tolerated anti-inflammatory medication, can prevent the excessive immune response and improve the course of the disease.

It should also be mentioned that in some rare cases, it seems that the heart is the first target of the SARS-CoV-2 virus and that cardiovascular symptoms are the first signs of infection. For example, although the first clinical signs of COVID-19 are usually fever and cough, the National Health Commission of China (NHC) reported that some patients first sought medical attention for heart palpitations and chest tightness rather than respiratory symptoms, but were subsequentlydiagnosed with COVID-19. Recent cases of acute myocarditis caused by COVID-19 in patients with no history of cardiovascular disease have also been recently reported, a phenomenon that had previously been observed for other coronaviruses, including MERS-CoV. A common feature of these viruses is to enter human cells by interacting with the surface protein ACE2 (angiotensin-converting enzyme 2), which is present in large quantities in the lungs, heart and cells of blood vessels. It is therefore possible that the virus uses this receptor to penetrate directly into the cells of the myocardium and cause heart damage. In line with this, it should be noted that analysis of heart tissue from patients who died during the 2002 SARS epidemic revealed the presence of viral genetic material in 35% of the samples. SARS-CoV-2 is very similar (75% identical) to this virus, so it is possible that a similar mechanism is at work.

COVID-19 and hypertension
The interaction of SARS-CoV-2, the virus that causes COVID-19, with the angiotensin-converting enzyme (ACE2) is intriguing, as this enzyme plays a key role in the development of hypertension, and it is precisely hypertensive people who present a more severe form of the infection. Since commonly prescribed antihypertensive drugs cause an increase in the amount of ACE2 on the surface of cells, there have been several texts on social media claiming that these drugs can increase the risk and severity of SARS-CoV-2 infection and should therefore be discontinued. It is important to mention that this hypothesis has no solid scientific basis and that all of the cardiology associations in the world still recommend hypertensive patients continue taking their drugs, whether they are inhibitors of ACE2 (captopril, enalapril, etc.) or angiotensin receptor antagonists (losartan, valsartan, telmisartan, etc.). On the contrary, preclinical studies seem rather to show that antihypertensive drugs could protect against pulmonary complications in patients infected with coronaviruses.