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.