Quitting smoking in favour of e-cigarettes leads to rapid improvement in cardiovascular health

Quitting smoking in favour of e-cigarettes leads to rapid improvement in 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.26 November 2019

OVERVIEW

  • 141 regular smokers were subjected to three different treatments: 1) tobacco cigarette (control group), 2) e-cigarette containing nicotine, and 3) e-cigarette containing no nicotine.
  • A month later, researchers measured arterial stiffness and dysfunction of blood vessels, two major risk factors for cardiovascular disease.
  • The results show that the transition to e-cigarettes rapidly improves the function of blood vessels, regardless of its nicotine content, confirming the usefulness of these devices for reducing cardiovascular damage caused by tobacco.

A study recently published in the Journal of the American College of Cardiology confirms the enormous potential of e-cigarettes to reduce cardiovascular damage caused by combustible tobacco. In this randomized clinical study, researchers recruited 141 regular smokers (15 or more cigarettes per day for at least two years) and randomly separated them into 3 distinct groups: 1) a control group, in which participants continued to smoke tobacco cigarettes; 2) a group where participants replaced tobacco cigarettes with e-cigarettes containing nicotine (16 mg); and 3) a group where participants replaced tobacco cigarettes with e-cigarettes not containing nicotine. To measure the impact of different treatments on cardiovascular health, the researchers measured, at the start of the study and 1 month later, arterial stiffness and dysfunction of blood vessels, two important risk factors for cardiovascular disease.

This approach measured 5 major positive changes associated with the substitution of tobacco cigarettes by e-cigarettes:

1) The transition to e-cigarettes quickly improves the function of blood vessels. The function of the endothelium (the thin layer of cells lining the inside of blood vessels) was assessed by flow-mediated dilatation, a technique that measures the ability of these vessels to dilate. An increase in vasodilation allows a better supply of oxygen to peripheral tissues and is considered an excellent marker of the health of blood vessels.

The researchers observed that flow-mediated vasodilation is increased significantly only 1 month after the substitution of tobacco cigarettes by e-cigarettes, independently of the presence of nicotine (Figure 1). The increase observed (about 1.5%) may seem minimal at first glance, but several studies have shown that an increase of only 1% in flow-mediated vasodilation is associated with a 13% decrease in the risk of cardiovascular events. According to the authors, the observed vasodilation values are even close to those of healthy non-smokers, which shows how quickly the transition to e-cigarettes had beneficial effects on the cardiovascular health of smokers.

Figure 1. Change in mean flow-mediated dilatation among tobacco cigarette smokers and e-cigarette users.

2) Arterial stiffness is reduced as a result of the transition to e-cigarettes. Arterial stiffness was assessed using pulse wave velocity, a technique that measures the speed at which the pulse travels along the arteries. The stiffer the arteries, the less ability they have to contract and expand as a result of changes in blood volume and therefore the higher the speed of pulse wave propagation. A reduction in velocity should thus be considered as a sign of improved vessel health.

This is what has been observed in smokers who have smoked the equivalent of a pack of 20 cigarettes per day for less than 20 years (20 packs-years): the measurement of pulse wave velocity in these people indicates a significant decrease in artery stiffness following the transition to e-cigarettes (with or without nicotine). However, this phenomenon is not observed in smokers who have been smoking longer (>20 pack-years), which could suggest that in these people, the damage caused by tobacco to the elasticity of the arteries is more pronounced and could not be mitigated in just one month of intervention.

3) Women can particularly benefit from the transition to e-cigarettes. An analysis of the results by sex of smokers indicates that the improvement in vasodilation mediated by the flow obtained following the adoption of e-cigarettes appears to be more pronounced among women smokers than men smokers. This is very important because women who smoke are much more at risk of developing smoking-related health problems than men, with almost 3 times more risk of developing lung cancer and 2 times more risk of having a myocardial infarction. With approximately 200 million women currently smoking cigarettes worldwide, the potential for harm reduction by e-cigarettes in this population is therefore considerable.

4) The more complete the transition to e-cigarettes, the better its impact on the health of blood vessels. An easy test to determine if a person has recently smoked a tobacco cigarette is to measure the level of expired carbon monoxide (CO). The authors observed that participants with the lowest CO levels also had the strongest improvements in blood vessel function, suggesting that the positive effects observed in the study would have been even more pronounced if all smokers had used e-cigarettes exclusively. Nevertheless, the significant improvement in vessel health, even among those who “cheat” from time to time, indicates that any reduction in tobacco use, even if not total, is positive for health.

5) The presence of nicotine has no influence on the benefits of e-cigarettes. No difference in cardiovascular benefits could be observed between e-cigarettes containing nicotine or not, which is consistent with several observations showing that it is tobacco combustion products, not nicotine, that are responsible for the negative effects of smoking. Of course, nicotine is the drug that creates tobacco addiction and encourages people to smoke, but it has no major health effects and is not responsible for cardiovascular disease or lung cancer that results from smoking.

Overall, this study, which stands out from many others, must be commended for its scientific rigour and its clinical relevance. Recently, there have been many reports in the media about studies that claim to show that the vapour generated by electronic cigarettes has harmful health effects, with some going as far as to say that they are as harmful as cigarettes. What the media reports do not say, however, is that these studies often have serious methodological flaws that completely invalidate their conclusions. For example, a few days before the publication of the article described here, a summary presented at the American Heart Association’s annual conference reported that e-cigarettes had an adverse effect on blood vessel function, i.e. they decreased flow-mediated vasodilation. However, these parameters were measured immediatelyafter the inhalation of the vapour, which makes no such conclusions possible: just about anything that is stimulating (coffee, sex, alcohol or even certain foods) elicits this type of acute response in the short term, but this effect is transient and has no longer-term impact. It is only when abnormalities in blood vessel function occur over long periods of time (as in the study described earlier) that they can serve as a marker of risk of future cardiovascular events.

Another good example of disinformation about the effects of e-cigarettes is a study that claims to show an increased risk of heart attack in vapers: a close examination of the data indicates that the majority of the infarctions reported in the study occurred before the adoption of vaping by participants and therefore cannot be due to e-cigarettes! Since vapers are generally ex-smokers, the increase in infarction observed among vapers is simply due to the fact that these people have given up smoking after being sick and are now using e-cigarettes to avoid a recurrence.   It is therefore appalling that this type of study, which does not even respect the basic rules of the scientific approach, is currently being used as a pretext to claim that e-cigarettes are as dangerous as tobacco cigarettes, and at the same time create a climate of mistrust towards these devices.

The main danger of the current anti-vaping climate is to reduce the number of smokers who make the leap to e-cigarettes. I can already see it in my practice: patients who had quit smoking thanks to vaping have started smoking again, while others are reluctant to try e-cigarettes. In both cases, the reason given is the same: if vaping is as bad as smoking, why make the transition? So, we can see 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.

It is worth remembering that the ultimate goal of tobacco control is to reduce the incidence of smoking-related diseases, particularly cardiovascular disease and lung cancer. Although in theory total abstinence is desirable to achieve this goal (one cannot be against virtue), the reality remains that many people are unable to quit using current smoking cessation tools and therefore remain at risk of dying prematurely. The value of e-cigarettes is that they allow these people to considerably reduce their exposure to the many toxic substances of cigarette smoke, with immediate positive effects on their health. Moreover, not only are e-cigarettes less toxic than tobacco, but a randomized clinical study recently published in the prestigious New England Journal of Medicine shows that they can be very useful for smoking cessation, with twice the effectiveness of traditional nicotine substitute approaches. Instead of trying by all means to “demonize” e-cigarettes, these devices should instead be seen as a very interesting technological innovation that adds a new dimension to the fight against tobacco.

We must therefore hope that serious studies, such as the one described here, will succeed in putting an end to current disinformation campaigns and remind smokers that e-cigarettes are much less harmful than tobacco and can greatly help them quit smoking definitively.

I want to make it clear that I do not receive any compensation from companies and shops that sell e-cigarettes. I also do not receive fees as a speaker or consultant from pharmaceutical companies, especially those that make products to quit smoking, unlike many doctors and scientists who are very critical of e-cigarettes.

Bedtime may be the best time for taking antihypertensive medication

Bedtime may be the best time for taking antihypertensive medication

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.18 November 2019

OVERVIEW

  • 19,084 hypertensive patients were randomly assigned to take their antihypertensive medication in a single dose daily, either at bedtime or upon waking up.
  • For six years, researchers measured the ambulatory blood pressure of each participant annually over 48 hours. 1,752 patients experienced a cardiovascular event during this period.
  • Compared to patients who took their hypertension medication when they woke up, those who took it at bedtime had a 45% lower risk of having a cardiovascular event.

A Spanish research group recently conducted a study (Hygia Chronotherapy Trial) to test whether or not it is advantageous to take medication for hypertension before going to bed rather than upon waking up. This is the largest study published to date on this issue, with 19,084 hypertensive patients randomly assigned to take their antihypertensive medication in a single daily dose, either at bedtime or upon awakening. A 48-hour ambulatory blood pressure (BP) monitoring was performed for each patient at least once a year during the study with an average duration of 6.3 years. During these years, 1,752 patients underwent a cardiovascular event (composite criteria including cardiovascular mortality, myocardial infarction, coronary revascularization, heart failure and stroke).

Compared to patients who took their hypertension medication when they woke up, those who took it at bedtime had a 45% lower risk of having a cardiovascular event (composite criteria including myocardial infarction, stroke, heart failure, coronary revascularization and cardiovascular mortality). These results were adjusted for several factors, including age, sex, type 2 diabetes, chronic kidney disease, smoking, high cholesterol and a previous cardiovascular event.

In particular, the risks were reduced by 56% for cardiovascular mortality, 34% for myocardial infarction, 40% for coronary revascularization (intervention to unblock coronary arteries), 42% for heart failure, and 49% for stroke. All of these differences were statistically highly significant (P<0.001).

Current guidelines for the treatment of hypertension do not recommend taking medication at any particular time of day. Many doctors recommend that their hypertensive patients take their medication when they wake up, in order to reduce BP, which suddenly increases in the morning (morning surge). However, it is well established that BP during sleep is intimately associated with cardiovascular events and organ damage in hypertensive patients.

Previous studies, including a study by the Spanish group Hygia Project published in 2018, have reported that average systolic BP during sleep is the most significant and independent factor in cardiovascular disease risk, regardless of BP values during the waking period or during physician consultation. The Hygia Project consists of a network of 40 primary health care centres located in northern Spain in which 292 doctors are involved. Between 2008 and 2015, 18,078 normotensive or hypertensive people were recruited. The participants’ ambulatory BP was measured for 48 hours at the time of inclusion in the study and at least once a year thereafter. During the median follow-up of 5.1 years, 1,209 participants underwent a fatal or nonfatal cardiovascular event.

Participants with high nocturnal BP had a 2-fold higher risk of having a cardiovascular event than those who had normal BP during sleep, regardless of BP during the waking period (see Figure 2 of the original article). Nocturnal systolic BP was the most significant risk factor for cardiovascular events, with an exponential increase in risk as a function of nocturnal systolic BP (see Figure 4C of the original article).

Nocturnal hypertension
Current guidelines for treating hypertension focus on controlling BP during the waking period. However, even after controlling for daytime BP there is still a risk: uncontrolled and masked nocturnal hypertension. BP follows a circadian rhythm (Figure 1), characterized by a 10–20% drop at night in healthy people (dipper pattern) and a sudden increase upon awakening (morning surge). The nighttime BP drop profiles are categorized into 4 groups: dipper, non-dipper, riser, and extreme dipper (see this review article). People with high blood pressure who do not have organ damage also have a dipper-type drop during the night, but those with organ damage tend to have a lower BP drop during the night (non-dipper pattern). In addition, BP may vary abruptly upon rising (morning surge), due to physical or psychological stress during the day, or at night, due to obstructive sleep apnea, sexual arousal, REM sleep and nocturia (need to urinate at night).


Figure 1. Characteristics and determinants of nocturnal hypertension.  From Kario, Hypertension, 2018.

Organ damage that can be caused by nocturnal hypertension includes silent neurovascular diseases that can be detected by magnetic resonance imaging of the brain: silent cerebral infarction, microbleeding, vascular disease affecting the white matter of the brain. Nocturnal hypertension and nocturnal “non-dipper/riser” BP profiles predispose to neurocognitive dysfunctions (cognitive dysfunctions, apathy, falls, sedentary lifestyle, stroke), left ventricle hypertrophy, vascular damage and chronic kidney failure.

New studies will need to be carried out elsewhere in the world on other populations that use different antihypertensive medications to confirm the results of the Spanish study. It is very important to consult your doctor and pharmacist before changing the time you take antihypertensive medications. Indeed, it is possible for doctors to prescribe their patients take the medication in the morning or in the evening for specific reasons.

 

 

How much exercise to live longer?

How much exercise to live longer?

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.12 November 2019

OVERVIEW

  • A meta-analysis published in October 2019 confirms that exercising reduces the risk of all-cause or cardiovascular mortality.
  • The decrease in risk is directly proportional to the amount of exercise up to about 2 hours of running per week. More than 4 hours of running per week or the equivalent do little to reduce the risk further.
  • Very high amounts of exercise (up to 8 times the amount of exercise recommended in public guidelines) do not reduce longevity, contrary to what some previous studies have suggested.

Exercise to live longer
Physical activity has many and varied beneficial effects on cardiovascular risk factors, including lower blood pressure and resting heart rate, improved blood sugar and lipidemia, normalizing body mass index, improved sleep and reduced stress. According to several long-term epidemiological studies, regular physical activity is one of the most effective lifestyle habits to increase life expectancy, up to 6 years.

Can too much exercise be detrimental to longevity?
This is an issue that is the subject of debate due to the conflicting data published to date. A meta-analysis published in October 2019 concludes that high amounts of exercise (up to 8 times the amount of exercise recommended by public guidelines) do not reduce longevity. This meta-analysis included 48 prospective studies, one of which included 6 distinct cohorts and another 9 distinct cohorts. Compared to the recommended level of physical activity (150 minutes of moderate to intense exercise per week), the mortality risk was lower for people who exercised more, at least up to 10 hours of running per week (Figure 1). This applies to all-cause mortality, and even more so to mortality from cardiovascular disease, including coronary heart disease. It should be noted that the reduction in mortality risk appears to be directly proportional to the amount of exercise up to about 2 hours of running per week and that more than 4 hours of running or the equivalent does little to reduce the risk further.

Figure 1. Dose-effect relationship between the amount of exercise and mortality from all causes, or mortality from cardiovascular disease, or mortality from coronary heart disease. The amount of exercise recommended in the public guidelines was used as a reference. Adapted from Blond et al., Br. J. Sports Med. 2019.

Some studies have suggested that a very large amount of exercise can decrease longevity. For example, a 15-year study of 55,137 participants (including 13,016 joggers) indicated that running reduced the risk of death from all causes by about 30% and the risk of cardiovascular mortality by 45%, with an increase in life expectancy of 3 years. A more detailed analysis of the results was made by the authors in an attempt to answer the question, “Is more exercise better for life expectancy?” The results show a so-called U-shaped curve (Figure 2) where hard runners (>49 MET-h/wk) appeared to have less benefit than light or moderate runners, but this difference was not statistically significant (P>0.05). One MET (Metabolic Equivalent of Task) corresponds to the amount of energy expended at rest, for walking it is 3.5 MET and for running it is approximately 7–8 MET.

Figure 2. Risk of mortality depending on the amount of running.
Adapted from Lee et al., Mayo Clinic Proc, 2016.

It should be noted that this is a single study, that the people who did >49 MET-h/wk represented only 1.6% of the study participants, and that the variation in the data collected was high. In contrast, the study described above, where very large amounts of exercise had no adverse effect on longevity, is a meta-analysis of 48 studies with a much higher total number of participants. This example illustrates why meta-analyses are so useful in epidemiology: they provide more accurate results (greater statistical power) and make it possible to draw global conclusions from a large number of studies and data.

Cardiorespiratory capacity and mortality risk
A recent study evaluated the association between cardiorespiratory capacity and all-cause mortality. The study population consisted of 122,007 patients who were followed for 8.4 years on average, during which time 13,637 patients died. At the beginning of the study, all patients did a treadmill stress test (limited by symptoms) to assess their cardiorespiratory capacity (CRC). For the analysis, participants were divided into 5 groups, according to the level of their CRC: low (<25th percentile), below average (25th–49th percentile), above average (50th–74th percentile), high (75th–97.6th percentile) and “Elite” (≥97.7th percentile). The results (Figure 3) clearly indicate that a greater CRC is associated with a decrease in mortality and that patients with very high CRC (Elite group) had the lowest risk of mortality.

Figure 3. Risk of all-cause mortality as a function of cardiorespiratory capacity.
Adapted from Mandsager et al., JAMA Network Open, 2018.

There is no U-curve in this study, but it must be noted that patients in the “Elite” group are not athletes and that it is not known whether or not they exercised regularly. The maximum cardiorespiratory capacity of the “Elite” group averaged 13.8 MET, which is considered excellent functional capacity, but slightly below the level of elite athletes (marathon runners, triathletes, cyclists) whose maximum cardiorespiratory capacity is about 17 to 20 MET. The fact remains thatcardiorespiratory capacity is a modifiable indicator of long-term mortality and that health care professionals should encourage their patients to achieve and maintain a high level of physical fitness.

Running a marathon puts a significant strain on the hearts of amateur runners
According to a Spanish study published in Circulation, amateur runners who complete a marathon event (42.2 km) see their levels of cardiac damage markers increase significantly. Cardiac markers are proteins that are released into the blood when the heart muscle is damaged. In contrast, in half-marathon runners (21.1 km) and 10 km races there was no significant increase in markers of heart damage. A sudden increase in cardiac markers after exercise is generally considered benign because the normal values of these markers are restored after a few days. The authors of the study note that although the release of cardiac troponins into the blood is not an indicator of heart malfunction, higher concentrations after a marathon reflect greater cardiac stress than for shorter runs. The incidence of cardiac arrest during marathons is a fairly rare phenomenon, i.e. 1 in 50,000 runners who complete the race, but these accidents are highly publicized. Cardiorespiratory arrests during marathons occur especially in men aged 35 and over and are caused by coronary artery disease (obstruction of one of the coronary arteries that irrigates the heart muscle). When cardiorespiratory arrest occurs in a young person under the age of 35, the cause is usually congenital heart disease. Given the growing popularity of marathons and the lack of experience and adequate preparation of some amateur runners, this study suggests that shorter races (e.g. half marathons) would be more suited to reduce the stress placed on the hearts of these runners.

No U-curves for light to moderate intensity exercise
The Copenhagen City Heart Study recently reported that leisure time physical activity reduces both all-cause mortality and mortality from coronary heart disease. Compared to sedentary participants, the gains in life expectancy were: 2.8 years for those who did light physical activity, 4.5 years for moderate-intensity physical activity, and 5.5 years for high-intensity physical activity. There is no U-curve in this study, but it should be noted that participants who exercised intensely (4 hours per week or several hours per week of a competitive sport) in this study still did less than those of the other studies cited above. In several other studies of light to moderate intensity exercise during leisure time, a U-shaped relationship was not observed. In other words, it does not seem possible to do too much light to moderate physical activity, such as walking, housework, gardening, baseball or softball, bowling, volleyball, golf, doubles tennis (and other racket sports) and dance.

Humans have adapted to do a lot of physical activity during life. A recent study of the Hazda hunter-gatherer modern tribe in northern Tanzania shows that, on average, these people do 14 times more light-to-moderate physical activity than North Americans. Members of the Hazda tribe have few cardiovascular risk factors (low prevalence of hypertension throughout life, optimal levels for cardiovascular health biomarkers). The Chimanes, an indigenous people in the Bolivian Amazon who have a subsistence lifestyle based on hunting, fishing, gathering, and farming, also has excellent cardiovascular health. Chimanes are very active, travelling up to 18 km per day and it is estimated that less than 10% of waking hours are spent on sedentary activities, compared to more than 60% in North America.

On the contrary, North American adults today sit an average of about 10 hours a day out of 16 waking hours. Physical exercise on a regular basis is therefore necessary to maintain good cardiorespiratory capacity as well as good cardiovascular health and to be able to live longer in good health.