Childhood obesity, a ticking time bomb for cardiometabolic diseases

Childhood obesity, a ticking time bomb for cardiometabolic diseases

OVERVIEW

  • Obesity rates among Canadian children and teens have more than tripled over the past 40 years.
  • Childhood obesity is associated with a marked increase in the risk of type 2 diabetes and cardiovascular disease in adulthood, which can significantly reduce healthy life expectancy.
  • Policies to improve the diet of young people are key to reversing this trend and preventing an epidemic ofcardiometabolic diseases affecting young adults in the coming years.

One of the most dramatic changes to have occurred in recent years is undoubtedly the marked increase in the number of overweight children. For example, obesity rates among Canadian children and adolescents have more than tripled over the past 40 years. Whereas in 1975, obesity was a fairly rare problem affecting less than 3% of children aged 5–19, the prevalence of obesity has made a gigantic leap since that time, affecting nearly 14% of boys and 10% of girls in 2016 (Figure 1). If data on overweight is added to these figures, then approximately 25% of young Canadians are overweight (a similar trend is observed in Quebec). This prevalence of obesity appears to have plateaued in recent years, but recent US surveys suggest that the COVID-19 pandemic may have caused an upsurge in the number of overweight young people, particularly among 5-11-year-olds.

Figure 1. Increase in the prevalence of obesity among Canadian children over the past 40 years. From NCD Risk Factor Collaboration (2017).

Measuring childhood obesity
Although not perfect, the most common measure used to determine the presence of overweight in young people under the age of 19 is the body mass index (BMI), calculated by dividing the weight by the square of height (kg/m²). However, the values obtained must be adjusted according to age and sex to take into account changes in body composition during growth, as shown in Figure 2.

Figure 2. WHO growth standards for boys aged 5–19 living in Canada. Data comes from WHO (2007).

Note that a wide range of BMI on either side of the median (50th percentile) is considered normal. Overweight children have a BMI higher than that of 85–95% of the population of the same age (85th-95th percentile), while the BMI of obese children is higher than that of 97% of the population of the same age (97th percentile and above). Using z-scores is another way to visualize childhood overweight and obesity. This measurement expresses the deviation of the BMI from the mean value, in standard deviation. For example, a z-score of 1 means that the BMI is one standard deviation above normal (corresponding to overweight), while z-scores of 2 and 3 indicate, respectively, the presence of obesity and severe obesity.

This marked increase in the proportion of overweight children, and particularly obese children, is a worrying trend that bodes very badly for the health of future generations of adults. On the one hand, it is well established that obesity during childhood (and especially during adolescence) represents a very high risk factor for obesity in adulthood, with more than 80% of obese adults who were already obese during their childhood. This obesity in adulthood is associated with an increased risk of a host of health problems, both from a cardiovascular point of view (hypertension, dyslipidemia, ischemic diseases) and the development of metabolic abnormalities (hyperglycemia, resistance to insulin, type 2 diabetes) and certain types of cancer. Obesity can also cause discrimination and social stigma and therefore have devastating consequences on the quality of life, both physically and mentally.

Another very damaging aspect of childhood obesity, which is rarely mentioned, is the dramatic acceleration of the development of all the diseases associated with overweight. In other words, obese children are not only at higher risk of suffering from the various pathologies caused by obesity in adulthood, but these diseases can also affect them at an early age, sometimes even before reaching adulthood, and thus considerably reduce their healthy life expectancy. These early impacts of childhood obesity on the development of diseases associated with overweight are well illustrated by the results of several recent studies on type 2 diabetes and cardiovascular disease.

Early diabetes
Traditionally, type 2 diabetes was an extremely rare disease among young people (it was even called “adult diabetes” at one time), but its incidence has increased dramatically with the rise in the proportion of obese young people. For example, recent US statistics show that the prevalence of type 2 diabetes in children aged 10–19 has increased from 0.34 per 1000 children in 2001 to 0.67 in 2017, an increase of almost 100% since the beginning of the millennium.

The main risk factors for early diabetes are obesity, especially severe obesity (BMI greater than 35) or when the excess fat is mainly located in the abdomen, a family history of the disease, and belonging to certain ethnic groups. However, obesity remains the main risk factor for type 2 diabetes: in obese children (4–10 years) and adolescents (11–18 years), glucose intolerance is frequently observed during induced hyperglycemia tests, a phenomenon caused by the early development of insulin resistance. A characteristic of type 2 diabetes in young people is its rapid development. Whereas in adults, the transition from a prediabetic state to clearly defined diabetes is generally a gradual process, occurring over a period of 5–10 years, this transition can occur very quickly in young people, in less than 2 years. This means that the disease is much more aggressive in young people than in older people and can cause the early onset of various complications, particularly at the cardiovascular level.

A recent study, published in the prestigious New England Journal of Medicine, clearly illustrates the dangers that arise from early-onset type 2 diabetes, appearing during childhood or adolescence. In this study, the researchers recruited extremely obese children (BMI ≥ 35) who had been diagnosed with type 2 diabetes in adolescence and subsequently examined for ten years the evolution of different risk factors and pathologies associated with this disease.

The results are very worrying, because the vast majority of patients in the study developed one or more complications during follow-up that significantly increased their risk of developing serious health problems (Figure 3). Of particular note is the high incidence of hypertension, dyslipidemia (LDL-cholesterol and triglyceride levels too high), and kidney (nephropathies) and nerve damage (neuropathies) in this population, which, it should be remembered, is only 26 years on average. Worse still, almost a third of these young adults had 2 or more complications, which obviously increases the risk of deterioration of their health even more. Moreover, it should be noted that 17 serious cardiovascular accidents (infarction, heart failure, stroke) occurred during the follow-up period, which is abnormally high given the young age of the patients and the relatively small number of people who participated in the study (500 patients).

Figure 3. Incidence of different complications associated with type 2 diabetes in adolescents. From TODAY Study Group (2021).

It should also be noted that these complications occurred despite the fact that the majority of these patients were treated with antidiabetic drugs such as metformin or insulin. This is consistent with several studies showing that type 2 diabetes is much harder to control in young people than in middle-aged people. The mechanisms responsible for this difference are still poorly understood, but it seems that the development of insulin resistance and the deterioration of the pancreatic cells that produce this hormone progress much faster in young people than in older people, which complicates blood sugar control and increases the risk of complications.

This difficulty in effectively treating early type 2 diabetes means that young diabetics are much more at risk of dying prematurely than non-diabetics (Figure 4). For example, young people who develop early diabetes, before the age of 30, have a mortality rate 3 times higher than the population of the same age who is not diabetic. This increase remains significant, although less pronounced, until about age 50, while cases of diabetes that appear at older ages (60 years and over) do not have a major impact on mortality compared to the general population. It should be noted that this increase in mortality affecting the youngest diabetics is particularly pronounced at a young age, around 40 years of age.

These results therefore show how early type 2 diabetes can lead to a rapid deterioration in health and take decades off life, including years that are often considered the most productive of life (forties and fifties). For all these reasons, type 2 diabetes must be considered one of the main collateral damages of childhood obesity.

Figure 4. Age-standardized mortality rates for diagnosis of type 2 diabetes. Standardized mortality rates represent the ratio of mortality observed in individuals with diabetes to anticipated mortality for each age group. From Al-Saeed et al. (2016).

Cardiovascular disease
In recent years, there has been an upsurge in the incidence of cardiovascular disease in young adults. This new trend is surprising given that mortality from cardiovascular diseases has been in constant decline for several years in the general population (thanks in particular to a reduction in the number of smokers and improved treatments), and one might have expected that young people would also benefit from these positive developments.

The data collected so far strongly suggests that the increase in the prevalence of obesity among young people contributes to this upsurge of premature cardiovascular diseases, before the age of 55. On the one hand, it has been shown that a genetic predisposition to develop overweight during childhood is associated with an increased risk of coronary heart disease (and type 2 diabetes) in adulthood. On the other hand, this increased risk has also been observed in long-term studies examining the association between the weight of individuals during childhood and the incidence of cardiovascular events once they have reached adulthood. For example, a large Danish study of over 275,000 school-aged children (7–13 years old) showed that each one-unit increase in BMI z-score at these ages (see legend to Figure 2 for the definition of the z-score) was associated with an increased risk of cardiovascular disease in adulthood, after 25 years (Figure 5).

This increased risk is directly proportional to the age at which children are overweight, i.e., the more a high BMI is present at older ages, the greater the risk of suffering a cardiovascular event later in adulthood. For example, an increase of 1 in the z -score of 13-year-old children is associated with twice as much of an increase in risk in adulthood as a similar increase in a 7-year-old child (Figure 5). Similar results are observed for girls, but the increased risk of cardiovascular disease is lower than for boys.


Figure 5. Relationship between body mass index in childhood and the risk of cardiovascular disease in adulthood. The values represent the risks associated with a 1-unit increase in BMI z-score at each age. From Baker et al. (2007).

Early atherosclerosis
Several studies suggest that the increased risk of cardiovascular disease in adulthood observed in overweight children is a consequence of the early development of several risk factors that accelerate the process of atherosclerosis. Autopsy studies of obese adolescents who died of non-cardiovascular causes (e.g., accidents) revealed that fibrous atherosclerotic plaques were already present in the aorta and coronary arteries, indicating an abnormally rapid progression of atherosclerosis.

As mentioned earlier, type 2 diabetes is certainly the worst risk factor that can generate this premature progression, because the vast majority of diabetic children and adolescents very quickly develop several abnormalities that considerably increase the risk of serious damage to blood vessels (Figure 3). But even without the presence of early diabetes, studies show that several risk factors for cardiovascular disease are already present in overweight children, such as hypertension, dyslipidemia, chronic inflammation, glucose intolerance or even vascular abnormalities (thickening of the internal wall of the carotid artery, for example). Exposure to these factors that begins in childhood therefore creates favourable conditions for the premature development of atherosclerosis, thereby increasing the risk of cardiovascular events in adulthood.

It should be noted, however, that the negative impact of childhood obesity on health in adulthood is not irreversible. Indeed, studies show that people who were overweight or obese during childhood, but who had a normal weight in adulthood, have a risk of cardiovascular disease similar to that of people who have been thin all their lives. However, obesity is extremely difficult to treat, both in childhood and in adulthood, and the best way to avoid prolonged chronic exposure to excess fat and damage to cardiovascular health (and health in general) which results from it is obviously to prevent the problem at the source by modifying lifestyle factors, which are closely associated with an increased risk of developing overweight, in particular the nature of the diet and physical activity (psychosocial stress may also play a role). Given the catastrophic effects of childhood obesity on health, cardiovascular health in particular, the potential for this early preventive approach (called “primordial prevention”) is immense and could help halt the current rise in diabetes and premature mortality affecting young adults.

Ideal cardiovascular health
A recent study shows how this primordial prevention approach can have an extraordinary impact on cardiovascular health. In this study, researchers determined the ideal cardiovascular health score, as defined by the American Heart Association (Table 1), of more than 3 million South Koreans with an average age of 20–39 years. Excess weight is a very important element of this score because of its influence on other risk factors also used in the score such as hypertension, fasting hyperglycemia and cholesterol.

Participants were followed for a period of approximately 16 years, and the incidence of premature cardiovascular disease (before age 55) was assessed using as the primary endpoint a combination of hospitalization for infarction, stroke, cardiac insufficiency, or sudden cardiac death.

Table 1. Parameters used to define the ideal cardiovascular health score. Since there is 1 point for each target reached, a score of 6 reflects optimal cardiovascular health. Adapted from Lloyd-Jones et al. (2010), excluding dietary factors that were not assessed in the Korean study.

As shown in Figure 6, cardiovascular health in early adulthood has a decisive influence on the risk of cardiovascular events that occur prematurely, before the age of 55. Compared to participants in very poor cardiovascular health at the start (score of 0), each additional target reached reduces the risk of cardiovascular events, with maximum protection of approximately 85% in people whose lifestyle allows achieving 5 or more ideal heart health targets (scores of 5 and 6). Similar results were obtained in the United States and show how early health, from childhood through young adulthood, plays a key role in preventing the development of cardiovascular disease during aging.

Figure 6. Influence of cardiovascular health in young adults on the risk of premature cardiovascular events. From Lee et al. (2021).

Yet our society remains strangely passive in the face of the rise in childhood obesity, as if the increase in body weight of children and adolescents has become the norm and that nothing can be done to reverse this trend. This lack of interest is really difficult to understand, because the current situation is a ticking time bomb that risks causing a tsunami of premature chronic diseases in the near future, affecting young adults. This is an extremely worrying scenario if we consider that our healthcare system, in addition to having to contend with diseases that affect an aging population (1 out of 4 Quebecers will be over 65 in 2030), will also have to deal with younger patients suffering from cardiometabolic diseases caused by overweight. Needless to say, this will be a significant burden on healthcare systems.

This situation is not inevitable, however, as governments have concrete legislative means that can be used to try to reverse this trend. Several policies aimed at improving diet quality to prevent disease can be quickly implemented:

  • Taxing sugary drinks. A simple and straightforward approach that has been adopted by several countries is to introduce a tax on industrial food products, especially soft drinks. The principle is the same as for all taxes affecting other products harmful to health such as alcohol and tobacco, i.e., an increase in prices is generally associated with a reduction in consumption. Studies that have examined the impact of this approach for soft drinks indicate that this is indeed the case, with reductions in consumption observed (among others) in Mexico, Berkeley (California) and Barbados. This approach therefore represents a promising tool, especially if the amounts collected are reinvested in order to improve the diet of the population (subsidies for the purchase of fruit and vegetables, for example).
  • Requiring clear nutrition labels on packaging. We can help consumers make informed choices by clearly indicating on the front of the product whether it is high in sugar, fat or salt, as is the case in Chile (see our article on this subject).
  • Eliminating the marketing of unhealthy foods for children. The example of Chile also shows that severe restrictions can be imposed on the marketing of junk food products by prohibiting the advertising of these products in programs or websites aimed at young people as well as by prohibiting their sale in schools. The United Kingdom plans to take such an approach very soon by eliminating all advertising online and on television of products high in sugar, salt and fat before 9 p.m., while Mexico has gone even further by banning all sales of junk food products to children.

There is no reason Canada should not adopt such approaches to protect the health of young people.

Chile, an example of aggressive state intervention to combat the obesity epidemic

Chile, an example of aggressive state intervention to combat the obesity epidemic

OVERVIEW

  • Chile, like most countries in Latin America, has seen the incidence of obesity in its population skyrocket over the past 20 years.
  • This rise in overweight is directly correlated with overconsumption of ultra-processed industrial foods, especially sugary drinks.
  • To reverse this situation, a law severely restricting the promotion, sale and labelling of these products was introduced in 2016, and this tough approach seems to be starting to bear fruit.

From a medical point of view, one of the greatest upheavals of the 20th century was certainly the dramatic increase in the body weight of the world population. Globally, recent estimates indicate that about 2 billion adults are overweight (BMI between 25 and 30), including 650 million who are obese (BMI> 30), about three times more than in 1975. This very rapid increase in the proportion of overweight people has several consequences on the health of the population because overweight and obesity are associated with significant increases in the incidence of several chronic diseases, including cardiovascular disease, type 2 diabetes and several types of cancer, that reduce healthy life expectancy. In addition to these chronic diseases, the COVID-19 pandemic has also shown that obesity is associated with an increased risk of developing serious complications of the disease and of dying from it. The increase in the number of overweight people is therefore one of the main public health problems of our time and is in the process of erasing the gains achieved as a result of the sharp decline in smoking in recent years.

From undernutrition to overnutrition
This rapid increase in the incidence of obesity is observed globally, but has been particularly noticeable in low- and middle-income countries. Until the late 1970s, the main nutritional problem faced by these countries was the high food insecurity of their populations and the high proportion of children suffering from malnutrition. With the globalization of trade that began in the 1980s, the standard of living of these populations began to resemble more and more that of richer countries, both for some of its positive aspects (access to safe drinking water, hygiene, reduction of infectious diseases and infant mortality, education) as well as for its negative ones (sedentary lifestyle, diet based on ultra-processed foods and fast food).

The result is that all countries, without exception, that have adopted these new eating habits and the Western way of life now have to deal with a greater proportion of obese individuals. In poorer countries, this “nutritional transition” has been so rapid that the increase in the body weight of the population can also coexist with malnutrition. For poor people, the high availability and low cost of ultra-processed foods provide for their energy needs, but the lack of nutrients in these foods means that the excess of calories ingested is paradoxically accompanied by a nutritional deficiency. While this may seem surprising at first glance, overnutrition and undernutrition can therefore occur simultaneously in a population, sometimes within the same family.

Latin America hit hard
Latin America is probably one of the best examples of the impact of these dietary changes on the incidence of obesity and the diseases associated with being overweight. Mexico, for example, was the country that experienced the largest increase in obesity globally between 1990 and 2010, and in 2014, more than 300 million adults living in Latin America were overweight, including 100 million who were obese. The situation may even worsen over the next few years due to the high incidence of childhood obesity, which reaches, for example, 12% in Chile and 11% in Mexico (a percentage similar to that of Canadian children, among the highest in the world).

The economic growth of the 1990s led to a rush for typical North American products such as fast food, televisions and cars, leading to increased calorie intake and a parallel decrease in physical activity levels. The very high consumption of ultra-processed foods, in particular sugary drinks, is certainly one of the new eating habits that contribute to the increase in overweight of the inhabitants of these regions. Globally, three of the four countries consuming the highest number of calories in the form of sugary drinks are in Latin America, with Chile and Mexico in first and second place, followed by Argentina in fourth place just behind the United States (Figure 1).


Figure 1. Comparison of the number of calories from sugary drinks sold in different countries in 2014. Note the very high consumption of these drinks in Chile (red asterisk), more than twice as high as in Canada (black asterisk). From Popkin (2016).

Several studies indicate that this overconsumption of added sugars is generally associated with a poor quality diet (low in nutrients) and significantly contributes to the development of obesity, type 2 diabetes and cardiovascular disease. This is especially true in Latin America, as some studies indicate that in the presence of a high sugar intake, some people of Hispanic descent are genetically predisposed to develop nonalcoholic fatty liver disease, an abnormal buildup of fat in the liver that is closely related to the development of type 2 diabetes and metabolic syndrome.

Government response
The close link between the consumption of ultra-processed foods and the increased risk of obesity illustrates the chasm between the financial interests of the multinational food companies that manufacture these products and the health of the population. The goal of these companies is obviously not to make people sick, but it is undeniable that their primary goal remains to generate profits, without worrying too much about whether the consumption of their products can lead to the development of a large number of chronic diseases.

Governments do not have this luxury, however, as they have to deal directly with the enormous pressures that diseasesassociated with being overweight place on health systems. A simple and straightforward approach that has been adopted by several countries is to introduce a tax on these industrial food products, in particular soft drinks. The principle is the same as for all taxes on other unhealthy products such as alcohol and tobacco, i.e. higher prices are generally associated with lower consumption. Studies that have examined the impact of this approach for soft drinks indicate that this is indeed the case, with decreases in consumption observed (among others) in Mexico, Berkeley (California) and Barbados. Despite the legendary reluctance of politicians to impose new taxes, there is no doubt that this approach represents a promising tool, especially if the amounts collected are reinvested in order to improve the diet of the population (subsidies for the purchase of fruits and vegetables, for example).

Another, even more promising, approach is to help consumers make an informed choice by informing them of the sugar, fat, salt and calorie content of products. This information currently exists, but in the form of nutritional labels that are quite difficult to interpret. The amounts of sugar, saturated fat, sodium and calories are indeed indicated on these labels, but refer to percentages of the recommended daily intake. For most people, seeing that the sugar content of a particular food is, for example, “15% of the recommended intake” is a rather abstract concept that does not specify whether this amount is low, adequate or too high. A simpler and more straightforward way is to clearly indicate on the front of the product whether it is high in sugar, fat or salt, as is the case in Chile. In response to the rampant rise in obesity in its population, the country’s Ministry of Health has introduced a labelling system, featured on the front of the package, which allows consumers to immediately see whether a product contains high amounts of sugar, saturated fat, sodium and calories (Figure 2).Figure 2. Labels produced by the Chilean Ministry of Health (Ministerio de Salud) and affixed to the packaging of products sold in stores. The labels indicate a high content (alto) in sugar (azúcares), saturated fat (grasas saturadas), salt (sodio) or calories (calorías). From Kanter et al. (2019).

These labels help consumers make better choices and can encourage the industry to reformulate their products to escape this labelling and become more attractive. It should be noted that Health Canada has also developed a labelling project of the same type, but the adoption of this practice is still pending, more than two years after the end of public consultations. Mexico, meanwhile, has recently moved forward with a system similar to that of Chile, as have Peru, Uruguay and Israel.

The Chilean approach is part of a comprehensive plan to fight obesity, largely based on changing a food culture that is far too focused on ultra-processed products. In addition to the new labelling system, Chile’s Law of Food Labelling and Advertising introduced in 2016 prohibits the sale of caloric products (ice cream, soft drinks, chips, etc.) in schools, imposes severe restrictions on the marketing of industrial products (elimination of characters loved by children on cereal boxes, ban on sales of candy containing toys, e.g., Kinder), prohibits the advertising of these products on programs or websites aimed at young people, and imposes an 18% tax on sugary drinks, one of the highest in the world. This strong government intervention seems to be paying off: a recent study shows that the consumption of sugary drinks fell 25% within 18 months of the law’s implementation, while that of bottled water increased by 5%. The authorities are now considering expanding the scope of the law by introducing an additional tax on all junk food products.

In North America, we remain extremely passive in the face of the dramatic increase in the number of overweight people in our society. Yet the burden of overweight-related illnesses weighs heavily on our health care system here too, and as mentioned earlier, the future looks bleak as we are now among the world leaders in childhood obesity. The example of Chile shows that governments have concrete legislative means that can be used to try to reverse this trend. Faced with an industry that refuses to self-discipline, the authorities must take a much more aggressive approach to protect the population from the health problems associated with the overconsumption of ultra-processed foods, especially among young people. The risk of obesity is established very early in life, since half of children and adolescents who become obese are already overweight when they enter kindergarten.

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.

Obesity and heart function

Obesity and heart function

OVERVIEW

  • Obesity is normally associated with a decrease in the heart’s energy metabolism, but it is not clear how the heart adapts to cope with this energy deficit.
  • Study participants who were obese had an average 14% lower phosphocreatine/ATP ratio than non-obese participants, but the total energy supply (ATP) delivered to the heart muscle was preserved by a compensatory mechanism that involves the acceleration of the enzymatic reaction catalyzed by creatine kinase.
  • This adaptation mechanism has negative consequences for obese participants in situations where the workload of the heart increases.
  • Obese participants who successfully lost weight (-11% on average) following a 6-month nutritional intervention saw their myocardial energy parameters return to values ​​similar to those measured in non-obese participants.

Obesity is a major public health problem, which is growing so rapidly in our societies that it is now referred to as an “obesity epidemic” (see this article on the subject). Obesity is a significant risk factor for many cardiovascular diseases, including heart failure (HF) and especially heart failure with preserved ejection fraction (HFpEF). Heart failure is the inability of the heart to supply enough blood to deliver oxygen to tissues while maintaining normal filling pressures. People with HFpEF account for about half of people with heart failure, with the other half living with heart failure with reduced ejection fraction (HFrEF). In the United States, more than 80% of patients with HFpEF are overweight (BMI between 25 and 30) or obese (BMI > 30), twice as many as the general population. Obesity is now a risk factor for HFpEF almost as significant as hypertension. Yet hypertension has received much more attention to date than obesity as a cause of HFpEF.

The mechanisms by which obesity leads to HFpEF are multiple: cardiac overload, systemic inflammation, renal retention, insulin resistance, and alterations in cellular metabolism. The direct effects of obesity on heart muscle cells have recently become the subject of interesting studies. Studies published to date suggest that the accumulation of lipids in the heart has toxic effects that promote cardiac dysfunction in obese people. Obesity is normally associated with a decrease in the heart’s energy metabolism, but it is not clear how the heart adapts to cope with this energy deficit.

A study published in 2020 in the journal Circulation makes an important contribution to our understanding of the relationship between obesity and cardiac energy metabolism. The researchers recruited 80 volunteers who had no known cardiovascular disease, including 35 non-obese people (BMI: 24 ± 3 kg/m2) and 45 obese people (BMI: 35 ± 5 kg/m2). All participants were subjected to a battery of tests before and after the nutritional intervention with obese participants only, which aimed to make them lose weight. Among the various tests performed, nuclear magnetic resonance imaging (NMR) was used to assess cardiac function, abdominal visceral fat volume and in the liver, conventional phosphorus (31P) NMR spectroscopy was used to measure phosphocreatine and ATP (energy sources) at rest, and a more sophisticated variant of phosphorus NMR spectroscopy, called “31P saturation transfer”, was used to evaluate the enzymatic kinetics of creatine kinase, the enzyme that allows the rapid formation of ATP from phosphocreatine in muscle cells (ADP + phosphocreatine + H+ → ATP + creatine).

The study showed that obese participants had on average a phosphocreatine/ATP ratio 14% lower than non-obese participants, but that the total ATP supply delivered to the heart muscle was preserved by a compensatory mechanism that involves acceleration of the enzymatic reaction catalyzed by creatine kinase. Indeed, the resting creatine kinase catalytic constant, kfCKrest was 33% higher in obese participants than in non-obese participants.

The researchers suspected that this adaptation mechanism could have negative consequences in situations where the workload of the heart increases. To test this hypothesis, they induced an increase in cardiac output from the heart by administering dobutamine by infusion to the participants, while doing the imaging and NMR spectroscopy tests described above. In non-obese participants, both ATP delivery and kfCK  increased in response to dobutamine infusion, by 80% and 86%, respectively. In contrast, there was no significant increase in ATP delivery and kfCK in obese participants under the same stress conditions imposed on the heart. In addition, the systolic increase caused by the increased heart workload was lower in obese participants (+16%) than in non-obese participants (+21%).

Impacts of weight loss
Of the 45 obese participants, 36 agreed to participate in a 6-month weight loss nutritional intervention, and of these 27 successfully lost weight (-11% of body weight and -23% of body fat, on average). This weight loss was associated with an improvement in several parameters, including a 13% decrease in blood cholesterol, a 9% decrease in fasting glucose, and a 41% reduction in insulin resistance. Weight loss has also been associated with reduced left ventricular end diastolic mass and volume, improved diastolic function, and increased ability to exercise. Weight loss in obese participants was associated with increased phosphocreatine/ATP ratio and decreased kfCkrest and ATP delivery. In fact, obese participants who were successful in losing weight saw their myocardial energy parameters return to values ​​similar to those measured in non-obese participants.

These findings shed light on the likely cause of the exhaustion symptoms after an effort that are present in the majority of obese people. Fortunately, the decrease in cardiac energy capacity induced by obesity is reversible by weight loss, which represents new avenues for the treatment of cardiomyopathies associated with obesity.

 

Toward a consensus on the effects of dietary fat on health

Toward a consensus on the effects of dietary fat on health

The role of dietary fat in the development of obesity, cardiovascular disease and type 2 diabetes has been the subject of vigorous scientific debate for several years. In an article recently published in the prestigious Science, four experts on dietary fat and carbohydrate with very different perspectives on the issue (David Ludwig, Jeff Volek, Walter Willett, and Marian Neuhouser) identified 5 basic principles widely accepted in the scientific community and that can be of great help for non-specialists trying to navigate this issue.

This summary is important as the public is constantly bombarded with contradictory claims about the benefits and harmful effects of dietary fat. Two great, but diametrically opposed currents have emerged over the last few decades:

  • The classic low-fat position, i.e., reducing fat intake, adopted since the 1980s by most governments and medical organizations. This approach is based on the fact that fats are twice as caloric as carbohydrates (and therefore more obesigenic) and that saturated fats increase LDL cholesterol levels, a major risk factor for cardiovascular disease. As a result, the main goal of healthy eating should be to reduce the total fat intake (especially saturated fat) and replace it with carbohydrate sources (vegetables, bread, cereals, rice and pasta). An argument in favour of this type of diet is that many cultures that have a low-fat diet (Okinawa’s inhabitants, for example) have exceptional longevity.
  • The low-carb position, currently very popular as evidenced by the ketogenic diet, advocates exactly the opposite, i.e., reducing carbohydrate intake and increasing fat intake. This approach is based on several observations showing that increased carbohydrate consumption in recent years coincides with a phenomenal increase in the incidence of obesity in North America, suggesting that it is sugars and not fats that are responsible for excess weight and the resulting chronic diseases (cardiovascular disease, type 2 diabetes, some cancers). One argument in favour of this position is that an increase in insulin in response to carbohydrate consumption can actually promote fat accumulation and that low-carb diets are generally more effective at promoting weight loss, at least in the short term.

Reaching a consensus from two such extreme positions is not easy! Nevertheless, when we look at different forms of carbohydrates and fat in our diet, the reality is much more nuanced, and it becomes possible to see that a number of points are common to both approaches. By critically analyzing the data currently available, the authors have managed to identify at least five major principles they all agree on:

1) Eating unprocessed foods of good nutritional quality helps to stay healthy without having to worry about the amount of fat or carbohydrate consumed.
A common point of the low-fat and low-carb approaches is that each one is convinced it represents the optimal diet for health. In fact, a simple observation of food traditions around the world shows that there are several food combinations that allow you to live longer and be healthy. For example, Japan, France and Israel are the industrialized countries with the two lowest mortality rates from cardiovascular disease (110, 126 and 132 deaths per 100,000, respectively) despite considerable differences in the proportion of carbohydrates and fat from their diet.

It is the massive influx of ultra-processed industrial foods high in fat, sugar and salt that is the major cause of the obesity epidemic currently affecting the world’s population. All countries, without exception, that have shifted their traditional consumption of natural foods to processed foods have seen the incidence of obesity, type 2 diabetes, and cardiovascular disease affecting their population increase dramatically. The first step in combating diet-related chronic diseases is therefore not so much to count the amount of carbohydrate or fat consumed, but rather to eat “real” unprocessed foods. The best way to do this is simply to focus on plant-based foods such as fruits, vegetables, legumes and whole-grain cereals, while reducing those of animal origin and minimizing processed industrial foods such as deli meats, sugary drinks, and other junk food products.

2) Replace saturated fat with unsaturated fat.
The Seven Countries Study showed that the incidence of cardiovascular disease was closely correlated with saturated fat intake (mainly found in foods of animal origin such as meats and dairy products). A large number of studies have shown that replacing these saturated fats with unsaturated fats (e.g., vegetable oils) is associated with a significant reduction in the risk of cardiovascular events and premature mortality. A reduction in saturated fat intake, combined with an increased intake of high quality unsaturated fat (particularly monounsaturated and omega-3 polyunsaturated), is the optimal combination to prevent cardiovascular disease and reduce the risk of premature mortality.

These benefits can be explained by the many negative effects of an excess of saturated fat on health. In addition to increasing LDL cholesterol levels, an important risk factor for cardiovascular disease, a high intake of saturated fat causes an increase in the production of inflammatory molecules, an alteration of the function of the mitochondria (the power plants of the cell), and a disturbance of the normal composition of the intestinal microbiome. Not to mention that the organoleptic properties of a diet rich in saturated fats reduce the feeling of satiety and encourage overconsumption of food and accumulation of excess fat, a major risk factor for cardiovascular disease, type 2 diabetes and some cancers.

3) Replace refined carbohydrates with complex carbohydrates.
The big mistake of the “anti-fat crusade” of the ’80s and ’90s was to believe that any carbohydrate source, even the sugars found in processed industrial foods (refined flours, added sugars), was preferable to saturated fats. This belief was unjustified, as subsequent studies have demonstrated beyond a doubt that these refined sugars promote atherosclerosis and can even triple the risk of cardiovascular mortality when consumed in large quantities. In other words, any benefit that can come from reducing saturated fat intake is immediately countered by the negative effect of refined sugars on the cardiovascular system. On the other hand, when saturated fats are replaced by complex carbohydrates (whole grains, for example), there is actually a significant decrease in the risk of cardiovascular events.

Another reason to avoid foods containing refined or added sugars is that they have low nutritional value and cause significant variations in blood glucose and insulin secretion. These metabolic disturbances promote excess weight and the development of insulin resistance and dyslipidemia, conditions that significantly increase the risk of cardiovascular events. Conversely, increased intake of complex carbohydrates in whole-grain cereals, legumes, and other vegetables helps keep blood glucose and insulin levels stable. In addition, unrefined plant foods represent an exceptional source of vitamins, minerals and antioxidant phytochemicals essential for maintaining health. Their high fibre content also allows the establishment of a diverse intestinal microbiome, whose fermentation activity generates short-chain fatty acids with anti-inflammatory and anticancer properties.

4) A high-fat low-carb diet may be beneficial for people who have disorders of carbohydrate metabolism.
In recent years, research has shown that people who have normal sugar metabolism may tolerate a higher proportion of carbohydrates, while those with glucose intolerance or insulin resistance may benefit from adopting a low-carb diet richer in fat. This seems particularly true for people with diabetes and prediabetes. For example, an Italian study of people with type 2 diabetes showed that a diet high in monounsaturated fat (42% of total calories) was more effective in reducing the accumulation of fat in the liver (a major contributor to the development of type 2 diabetes) than a diet low in fat (28% of total calories).

These benefits seem even more pronounced for the ketogenic diet, in which the consumption of carbohydrates is reduced to a minimum (<50 g per day). Studies show that in people with a metabolic syndrome, this type of diet can generate a fat loss (total and abdominal) greater than a hypocaloric diet low in fat, as well as a higher reduction of blood triglycerides and several markers of inflammation. In people with type 2 diabetes, a recent study shows that in the majority of patients, the ketogenic diet is able to reduce the levels of glycated haemoglobin (a marker of chronic hyperglycaemia) to a normal level, and this without drugs other than metformin. Even people with type 1 diabetes can benefit considerably from a ketogenic diet: a study of 316 children and adults with this disease shows that the adoption of a ketogenic diet allows an exceptional control of glycemia and the maintenance of excellent metabolic health over a 2-year period.

5) A low-carb or ketogenic diet does not require a high intake of proteins and fats of animal origin.
Several forms of low carbohydrate or ketogenic diets recommend a high intake of animal foods (butter, meat, charcuteries, etc.) high in saturated fats. As mentioned above, these saturated fats have several negative effects (increase of LDL, inflammation, etc.), and one can therefore question the long-term impact of this type of low-carb diet on the risk of cardiovascular disease. Moreover, a study recently published in The Lancet indicates that people who consume little carbohydrates (<40% of calories), but a lot of fat and protein of animal origin, have a significantly increased risk of premature death. For those wishing to adopt a ketogenic diet, it is therefore important to realize that it is quite possible to reduce the proportion of carbohydrates in the diet by substituting cereals and other carbohydrate sources with foods rich in unsaturated fats like vegetable oils, vegetables rich in fat (nuts, seeds, avocado, olives) as well as fatty fish.

In short, the current debate about the merits of low-fat and low-carb diets is not really relevant: for the vast majority of the population, several combinations of fat and carbohydrate make it possible to remain in good health and at low risk of chronic diseases, provided that these fats and carbohydrates come from foods of good nutritional quality. It is the overconsumption of ultra-processed foods, high in fat and refined sugars, which is responsible for the dramatic rise in food-related diseases, particularly obesity and type 2 diabetes. Restricting the consumption of these industrial foods and replacing them with “natural” foods, especially those of plant origin, remains the best way to reduce the risk of developing these diseases. On the other hand, for overweight individuals with metabolic syndrome or type 2 diabetes, currently available scientific evidence suggests that a reduction in carbohydrate intake by adopting low-carb and ketogenic diets could be beneficial.

Insulin resistance: A dangerous consequence of being overweight

Insulin resistance: A dangerous consequence of being overweight

The recent death of eminent American researcher Gerald Reaven, nicknamed the “father of insulin resistance,” is a good opportunity to recall the leading role this metabolic disorder plays in the development of type 2 diabetes and cardiovascular disease.

What is insulin resistance?
After a meal, insulin is secreted by the pancreas to signal to the body that circulating sugar levels need to be lowered, either by capturing it in the muscles and adipose tissue, or by promoting its storage in the liver. Under normal conditions, this mechanism is highly accurate and helps to keep the blood sugar level at an adequate level.

In people who are overweight, and especially those whose excess fat is located at the abdominal level, this insulin action is often disrupted and organs are no longer able to capture and store sugar effectively; they are said to be “insulin-resistant”. In its early stages, this insulin resistance often goes unnoticed because the pancreas is able to produce larger amounts of the hormone to compensate for this loss of effectiveness and thus allows organs to continue to collect and store enough sugar (see left portion of the figure). This compensatory hyperinsulinemia makes it possible to maintain blood glucose at approximately normal levels, but it unfortunately causes several metabolic abnormalities that can lead to the development of certain serious diseases. For example, excess insulin stimulates the production of triglycerides by the liver, which promotes the accumulation of fat and can result in the development of hepatic steatosis (fatty liver). Increased secretion of these fats into the bloodstream causes dyslipidemia, characterized by high triglycerides, an increase in LDL cholesterol, and a decrease in HDL cholesterol. Meanwhile, hyperinsulinemia increases sodium retention in the kidneys, contributing to the increased incidence of hypertension seen in insulin-resistant individuals.

All of these factors (dyslipidemia, hepatic steatosis, hypertension), combined with increased inflammation and a change in the properties of the endothelial cells lining the blood vessels (inflammation, procoagulant properties), make insulin resistance an important risk factor for cardiovascular disease.

Type 2 diabetes
In the longer term, overproduction of insulin can lead to pancreas depletion, which ultimately leads to the cessation of hormone production and the onset of type 2 diabetes, i.e., a state of chronic hyperglycaemia (see the right portion of the figure). This excess of blood sugar is very harmful to the blood vessels and significantly increases the risk of cardiovascular disease (heart attack and stroke) as well as damage to tissues whose function depends on the small blood vessels such as the retina, kidneys or nerves. Insulin resistance can be considered as a prediabetic state, the harbinger of diabetes developing insidiously.

“Excess abdominal fat should be considered as the first clinical sign of insulin resistance.”

Stay alert
One problem with insulin resistance is that it is often difficult to diagnose at an early stage, not only because it does not cause clinical symptoms but also because blood glucose is normal. As mentioned earlier, in the early stages of resistance, the pancreas offsets the loss of insulin efficiency by secreting larger amounts of the hormone, which is sufficient to maintain blood sugar at normal levels. Patients (just like their doctors) then have the false impression that they are in perfect health, even if in fact they are prediabetic and will become diabetic in the coming years if nothing is done. Overall, the studies suggest that a slight elevation of glycated haemoglobin (Hb1Ac 5.5% and above), a marker of chronic hyperglycaemia, may be a better approach for early detection of insulin resistance than tests that are used to measure blood glucose (fasting glucose, glucose tolerance). For example, it has recently been shown that people with normal fasting glucose but a HbA1c greater than 5.9% were eight times more likely to develop diabetes in the next four years than those whose HbA1c was less than 5.7%.

In short, it is important to remain vigilant and realize that excess fat, although somehow becoming the norm in our society (more than 60% of Canadians are overweight), is far from  harmless. In practice, excess abdominal fat (waist circumference greater than 102 cm for men and 88 cm for women) should be considered as the first clinical sign of insulin resistance and an increased risk of developing type 2 diabetes, with disastrous consequences for cardiovascular health.

Fortunately, insulin resistance is not an irreversible phenomenon: several studies show that people with glucose metabolism disorders can reverse the situation by simply changing their lifestyle. For example, a recent study reports that the adoption of a diet consisting primarily of low-fat plant foods is associated with a significant improvement in insulin sensitivity in overweight individuals. Being more active also seems beneficial: a study of 44,828 Chinese adults (20–80 years old) with above-average fasting blood glucose showed that people who were the most physically active were 25% less likely to develop type 2 diabetes.