Hypertension Archives - Observatoire de la prévention

Harmful health effects of exposure to “Forever Chemicals”

Dr Martin Juneau, M.D., FRCPCardiologue 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.8 July 2022

OVERVIEW

Per- and polyfluoroalkyl substances (PFAS) are added to a variety of products (e.g., cosmetics, food packaging, non-adhesive cookware) to make them resistant to heat, water, oil and corrosion.
These “Forever Chemicals” are found in tap water, bottled water and in the blood of almost everyone in the West.
The presence of PFAS in the blood has been associated with higher risks of developing hypertension and type 2 diabetes in women.
PFAS are possibly associated with several health problems, including preeclampsia, impaired liver enzymes, increased blood lipids, decreased response to vaccines, and low birth weight.

Per- and polyfluoroalkyl substances (PFAS) are widely used in industrial and everyday consumer products, such as cosmetics, food packaging, non-adhesive cookware and floor coverings. PFAS contain extremely stable chemical bonds between fluorine and carbon atoms (F–C bonds), hence their pun-like nickname “Forever Chemicals” (see Figure 1). PFAS should not be confused with phthalates, another class of industrial products potentially harmful to health (see our article on the subject). It should be noted that another class of “Forever Chemicals” related to PFAS, hydrofluorocarbons or HFCs, are used to replace CFCs in refrigerants since they do not affect the ozone layer, but they are now being gradually withdrawn from the market since they are still greenhouse gases.

Figure 1. Structure of 3 per- and polyfluoroalkylated substances (PFAS) used in everyday consumer products.

PFAS are added to a host of products to make them resistant to heat, water, oil and corrosion. For example, the wrappers in which burgers, pizzas, salads, and other take-out food are wrapped contain PFAS, which helps prevent oil or dressing leaks. PFAS can migrate into food, especially when it contains a lot of fat and salts. In addition, the packaging is ultimately buried in landfills where there is the possibility of contaminating the soil and groundwater or, if they are incinerated, they can end up in the air. Consumer Reports tested more than 100 packaging products used in US restaurants and supermarkets and found PFAS in several products such as wrapping paper for french fries, hamburgers, disposable plates, and moulded fibre salad bowls. Further testing by Consumer Reports found that PFAS are present in tap water and bottled water in the United States. PFAS were detected in the blood of 98% of Americans tested.

During the first 60 years of PFAS production, many believed that the potential adverse effects only affected workers exposed to these products at an industrial level and not the general population. That was until in 1998 a farmer in Virginia in the United States started sounding the alarm about the effects of pollution produced by a DuPont factory on the health of his cows. Perfluorooctanoic acid (PFOA, also known as “C8”) may have affected approximately 70,000 people who got their water from the same contaminated source, according to the ensuing class action lawsuit in US courts. A committee set up to examine the dangerousness of PFOA subsequently established probable links between exposure to this product and several diseases, including thyroid disease, hypercholesterolemia, kidney and testicular cancer, pregnancy-induced hypertension, and ulcerative colitis.

Three PFAS (PFOS, PFOA and LC-PFCAs) are now banned in Canada because of the risk they pose to human health and the environment. It appears that the new PFAS that are being used today as replacements for the banned PFAS could also be harmful to human health and the environment. Therefore, the Government of Canada is considering regulating the use of all PFAS. PFAS are associated with several health problems, including preeclampsia, impaired liver enzymes, increased blood lipids, decreased response to vaccines, and low birth weight (see profile report of PFAS by the US Agency for Toxic Substances and Disease Registry).

Cosmetics
PFAS have been found in the ingredient list of several dozen cosmetic products sold in Europe and Asia, where they are added to make foundations, mascaras and liquid lipsticks more durable, waterproof and easier to spread. In a recent study, where more than 231 North American cosmetic products (including 21 from Canada) were analyzed, 52 products had a high fluorine content, indicating the presence of PFAS in high concentration. The presence of PFAS was confirmed in 29 products by mass spectrometry. Most of these cosmetic products, however, did not mention PFAS in the list of ingredients on the label. PFAS have been found particularly in products advertised as “long-lasting” or “wear-resistant”. Specifically, high levels of fluorine (from PFAS) were detected in 82% of water-resistant mascaras, 58% of other eye cosmetics (eye shadows and creams, eyeliner), 63% of foundations, and 62% of lipsticks. Among the 17 Canadian cosmetic products considered in the study, only one indicated the presence of PFAS in the list of ingredients.

Why are PFAS found in cosmetic products when they are not included in the list of ingredients? Some basic ingredients such as mica and talc can be treated with PFAS to improve their durability. Other ingredients such as acrylates, methicone, and other silicone polymers can be purchased in a form containing PFAS. It therefore seems that some cosmetic manufacturers use ingredients containing PFAS, yet don’t include them in the list of ingredients. It is best to avoid as much as possible using cosmetic products containing PFAS as they can be harmful to health and the probability of absorption through the skin is very high. The results of the study show that there are cosmetic products containing very little or no fluoride (and therefore PFAS), but they are difficult to identify since PFAS are not included in the ingredient lists of most cosmetic products. It is recommended to avoid using products advertised as “water-resistant”, “long-lasting” or “wear-resistant” which are likely to contain PFAS.

Hypertension
A prospective study found an unfavourable association between blood PFAS concentration and the risk of hypertension. The data comes from the Study of Women’s Health Across the Nation-Multi-Pollutant Study (SWAN-MPS) with 1058 middle-aged, normotensive women at baseline, who were followed from 1999 to 2017. During these years, 470 women became hypertensive (systolic pressure ≥140 mmHg or diastolic pressure ≥90 mmHg). Women who had the highest concentrations of PFOS, PFOA and EtFOSAA (a precursor to PFOS) in their blood had 42%, 47% and 42% higher risks, respectively, of developing hypertension compared to those who had the lowest concentrations of these PFAS. Women who had the highest concentrations of total PFAS had a 71% higher risk of developing hypertension. No significant association was observed for the following PFAS: perfluorononanoic acid (PFNA) and perfluorohexanesulfonic acid (PFHxS).

Type 2 diabetes
The same research group that conducted the study on the association between PFAS and the risk of hypertension also evaluated the association with the incidence of type 2 diabetes. The prospective study was conducted among 1237 women in the SWAN-MPS cohort who were 45-56 years old and nondiabetic at the start of the study (1999). During the study period (18 years), 102 women became diabetic. The latter had higher blood concentrations of PFAS than the non-diabetic women. Women who had high levels of PFAS in their blood were more likely to be black, to smoke or have smoked cigarettes, to be menopausal, or to have a higher body mass index (BMI). However, the data were adjusted to take into account several confounding factors, including race/ethnicity, place of residence, level of education, smoking, alcohol consumption, total energy intake, physical activity, menopause, and BMI.

Women who had the highest concentrations of n-PFOA, PFHxS, sm-PFOS and MeFOSAA in the blood had 67%, 58%, 36% and 85% higher risks, respectively, of developing type 2 diabetes compared to those with the lowest concentrations of these PFAS. Women who had the highest concentrations of four common PFAS (n-PFOA, PFNA, PFHxS and total PFOS) had a 64% higher risk of developing type 2 diabetes.

How to reduce exposure to PFAS?
PFAS have many important applications and eliminating them completely seems out of the question. The most problematic PFAS (PFOA, PFOS and LC-PFCAs) are no longer used in Canada. PFOA was used, among other things, for the manufacture of kitchen accessories with Teflon coating. The major problem with accessories containing Teflon is not that they release PFOA during use (very low level), but that their manufacture can release this “Forever Chemical” into the environment. Ceramic coatings and anodized aluminum are good alternatives. If the demand for kitchen accessories containing PFAS decreases, production will decrease and less of these substances will end up in the environment. Fast food wrapped in waterproof packaging or containers, cosmetics and body care products that contain PFAS should be avoided as much as possible, especially “water-resistant” or “wear-resistant” cosmetics. These are simple actions that can reduce exposure to these products that are potentially harmful to health.

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.

The benefits of extra virgin olive oil on cardiovascular health

OVERVIEW

In addition to being an excellent source of monounsaturated fat, olive oil is the only vegetable oil that contains a significant amount of phenolic compounds with antioxidant and anti-inflammatory properties.
These molecules are found in much larger quantities in extra virgin quality oils compared to refined olive oils.
Several studies indicate that the presence of these phenolic compounds contributes to the many positive effects of extra virgin olive oil on cardiovascular health.

The traditional Mediterranean diet has several positive effects on cardiovascular health by improving the lipid profile (cholesterol, triglycerides) and by reducing chronic inflammation, blood pressure, blood sugar and the risk of diabetes. Several studies have clearly established that these effects result in a significant reduction in the risk of cardiovascular disease.

The Mediterranean diet is characterized by the abundant consumption of plant-based foods (fruits, vegetables, whole-grain cereals, legumes, nuts, herbs), a moderate intake of fermented dairy products (yogurt, cheese), fish, seafood and red wine as well as a low consumption of red meat and added sugars. It is therefore an exemplary diet, in which complex plant sugars are the main sources of carbohydrates and where the proteins come mainly from fish and legumes instead of red meat.

Another important feature of the Mediterranean diet is the daily use of large amounts (60–80 mL) of olive oil as the main source of fat for cooking. Several studies have reported that countries that are heavy consumers of olive oil have a much lower incidence of cardiovascular disease than those that consume mainly animal fats, suggesting a positive role of olive oil in this protective effect. Traditionally, these beneficial properties of olive oil have been attributed to its very high content (around 80%) of oleic acid, a monounsaturated fatty acid that contributes to its antioxidant properties. However, and unlike most vegetable oils, olive oil also contains a host of minor compounds (1–3% of the oil) that also play very important roles in its positive effects on cardiovascular health (see below). This is particularly the case for several phenolic compounds found exclusively in olive oil, including phenolic alcohols such as hydroxytyrosol and tyrosol and polyphenols of the secoiridoid family such as oleuropein, ligstroside, oleacein and oleocanthal (Figure 1).

Figure 1. Molecular structures of the main phenolic compounds of olive oil.

One fruit, several types of oils
Most vegetable oils come from seeds that have been extracted with an organic solvent (e.g. hexane) and subsequently heated to a high temperature to evaporate this solvent and remove impurities that give them an undesirable smell and flavour. These drastic procedures are not necessary for olive oil as the olives are simply pressed and the oil in the pulp is extracted by mechanical pressure, without using chemical processes or excessive heat.

Olive oils are classified according to the quality of the oil that is obtained by the pressing procedure (Figure 2). Good quality oils, i.e. those with low acidity (<2% free oleic acid) and that meet certain taste, bitterness and spiciness criteria are called “virgin” olive oils or, if their acidity is less than 0.8%, “extra virgin” olive oils. These oils contain the majority of the polyphenols in the starting olives and, after centrifugation and filtration, can be consumed as is.

On the other hand, some olive varieties give an inferior quality oil due to too high acidity (> 2%) and/or an unpleasant smell and taste that does not meet the established criteria. These oils, which are unfit for consumption, are called “lampantes” (a name which comes from their ancient use as fuel in oil lamps) and must be refined as is done for other vegetable oils, i.e. using different physicochemical procedures (neutralization with soda, high temperature bleaching and deodorization, hexane extraction, etc.). These steps remove the compounds responsible for the excess acidity and the unpleasant taste of the oil and produce a “neutral” olive oil that has lost its acidity and its flaws, but that is now devoid of the smell, flavour, colour and most of the phenolic components of the starting virgin olive oil. To stabilize these oils and improve their taste, a certain proportion (15–20%) of virgin olive oil is subsequently added and the final product, which is a mixture of refined olive oil and virgin olive oil, is what is sold in grocery stores as “pure olive oil” or simply “olive oil”.

In short, there are three main types of olive oil on the market: virgin olive oil (VOO), extra virgin olive oil (EVOO), and regular olive oil (OO).

Figure 2. The different types of olive oil. From Gorzynik-Debicka et al. (2018).

These manufacturing differences obviously have a huge impact on the amount of polyphenols present in virgin, extra virgin, and refined oils (Table 1). For OO-type olive oils (which contain refined oils), the polyphenols come exclusively from virgin olive oil that has been added to restore a minimum of taste and colour (from yellow to greenish) to the chemically treated oil. The amount of these polyphenols is therefore necessarily less than in VOO and EVOO and, as a general rule, does not exceed 25–30% of the content of these two oils. This difference is particularly striking for certain polyphenols of the secoiridoid family (oleuropein, oleocanthal, oleacein and ligstroside) whose concentrations are 3 to 6 times greater in EVOO than in OO (Table 1). It should be noted, however, that these values can vary greatly depending on the origin and cultivar of the olives; for example, some extra virgin olive oils have been found to contain up to 10 times more hydroxytyrosol and tyrosol than regular olive oils. The same goes for other polyphenols like oleocanthal: an analysis of 175 distinct extra virgin olive oils from Greece and California revealed dramatic variations between the different oils, with concentrations of the molecule ranging from 0 to 355 mg/kg.

It should also be mentioned that even if the quantities of phenolic compounds in regular olive oil are lower than those found in virgin and extra virgin oils, they nevertheless largely exceed those present in other vegetable oils (sunflower, peanut, canola, soy), which contain very little or none at all.

Family	Molecules	OO (mg/kg)	VOO (mg/kg)	EVOO (mg/kg)
Secoiridoids	oleocanthal	38.95 ± 9.29	71.47 ± 61.85	142.77 ± 73.17
	oleacein	57.37 ± 27.04	77.83 ± 256.09	251.60 ± 263.24
	oleuropein (aglycone)	10.90 ± 0.00	95.00 ± 116.01	72.20 ± 64.00
	ligstroside (aglycone)	15.20 ± 0.00	69.00 ± 69.00	38.04 ± 17.23
Phenolic alcohols	hydroxytyrosol	6.77 ± 8.26	3.53 ± 10.19	7.72 ± 8.81
	tyrosol	4.11 ± 2.24	5.34 ± 6.98	11.32 ± 8.53
Flavonoids	luteolin	1.17 ± 0.72	1.29 ± 1.93	3.60 ± 2.32
	apigenin	0.30 ± 0.17	0.97 ± 0.71	11.68 ± 12.78
Phenolic acids	p-coumaric	-	0.24 ± 0.81	0.92 ± 1.03
	ferulic	-	0.19 ± 0.50	0.19 ± 0.19
	cinnamic	-	-	0.17 ± 0.14
	caffeic	-	0.21 ± 0.63	0.19 ± 0.45
	protocatechuic	-	1.47 ± 0.56	-

Table 1. Comparison of the content of phenolic compounds in olive oil (OO), virgin olive oil (VOO) and extra virgin olive oil (EVOO). Please note that the large standard deviations of the mean values reflect the huge variations in polyphenol content depending on the region, cultivar, degree of fruit ripeness, and olive oil manufacturing process. Adapted from Lopes de Souza et al. (2017).

Anti-inflammatory spiciness
The amounts of polyphenols contained in a bottle of olive oil are not indicated on its label, but it is possible to detect their presence simply by tasting the oil. The polyphenols in olive oil are indeed essential to the organoleptic sensations so characteristic of this oil, in particular the sensation of tickling or stinging in the throat caused by good quality extra virgin oils, what connoisseurs call “ardour”. Far from being a defect, this ardour is considered by experts as a sign of a superior quality oil and, in tasting competitions, the “spiciest” oils are often those that receive the highest honours.

It is interesting to note that it is by tasting different olive oils that a scientist succeeded, by coincidence, in identifying the molecule responsible for the sensation of spiciness caused by extra virgin olive oil (see box).

Plant ibuprofen

Chance often plays a role in scientific discoveries, and this is especially true when it comes to the discovery of the molecule responsible for the typical irritation caused by olive oil. On a trip to Sicily (Italy) to attend a conference on the organoleptic properties of different foods, Dr. Gary Beauchamp and his colleagues were invited by the organizers of the event to a meal where guests were encouraged to taste extra virgin olive oil from olive trees cultivated on their estate. Even though it was the first time he had tasted this type of olive oil, Dr. Beauchamp was immediately struck by the tingling sensation in his throat, which was similar in every way to that caused by ibuprofen, and that he had experienced multiple times as part of his work to replace acetaminophen (paracetamol) with ibuprofen in cough syrups. Suspecting that olive oil contained a similar anti-inflammatory drug, Dr. Beauchamp and his team subsequently managed to isolate the molecule responsible for this irritation, a polyphenol they called “oleocanthal”. They subsequently discovered that oleocanthal had, like ibuprofen, a powerful anti-inflammatory action and that regular consumption of extra virgin olive oil, rich in oleocanthal, provided an intake equivalent to about 10 mg of ibuprofen and therefore may contribute to the well-documented anti-inflammatory effects of the Mediterranean diet.

But why is the stinging sensation of olive oil only felt in the throat? According to work carried out by the same group, this exclusive localization is due to a specific interaction of oleocanthal (and ibuprofen, for that matter) with a subtype of heat-sensitive receptor (TRPA1). Unlike other types of heat receptors, which are evenly distributed throughout the oral cavity (the TRPV1 receptor activated by the capsaicin of chili peppers, for example, and which causes the burning sensation of some particularly hot dishes), the TRPA1 receptor is located only in the pharynx and its activation by oleocanthal causes a nerve impulse signalling the presence of an irritant only in this region. In short, the more an olive oil stings in the back of the throat, the more oleocanthal it contains and the more anti-inflammatory properties it has. As a general rule, extra virgin olive oils contain more oleocanthal (and polyphenols in general) than virgin olive oils (see Table 1) and are therefore considered superior, both in terms of taste and their positive effects on health.

The superiority of extra virgin olive oil
Several studies have shown that the higher polyphenol content in extra virgin olive oil is correlated with a greater positive effect on several parameters of cardiovascular health than that observed for regular olive oil (see Table 2). For example, epidemiological studies carried out in Spain have reported a decrease of about 10–14% in the risk of cardiovascular disease among regular consumers of extra virgin olive oil, while regular consumption of olive oil had no significant effect. A role of phenolic compounds is also suggested by the EUROLIVE study where the effect of daily ingestion, over a period of 3 weeks, of 25 mL of olive oils containing small (2.7 mg/kg), medium (164 mg/kg), or high (366 mg/kg) amounts of polyphenols was compared. The results show that an increased intake of polyphenols is associated with an improvement in two important risk factors for cardiovascular disease: an increase in the concentration of HDL cholesterol and a decrease in oxidized LDL cholesterol levels. Collectively, the data gathered from the intervention studies indicate that the polyphenols found in extra virgin olive oil play an extremely important role in olive oil’s positive effects on cardiovascular health.

Measured parameter	Results	Sources
Incidence of cardiovascular disease	10% reduction in risk for every 10 g/day of EVOO. No effect of regular OO.	Guasch-Ferré et al. (2014)
	14% reduction in risk for each 10 g/day of EVOO. No effect of regular OO.	Buckland et al. (2012)
Lipid profile	Linear increase in HDL cholesterol as a function of the amount of polyphenols.	Covas et al. (2006)
	Increase in HDL cholesterol only observed with EVOO.	Estruch et al. (2006)
Blood glucose	EVOO improves postprandial glycemic profile (decrease in glucose levels and increased insulin).	Violo et al. (2015)
	Polyphenol-rich EVOO reduces fasting blood glucose and glycated hemoglobin (HbA1c) levels in diabetic patients.	Santagelo et al. (2016)
Inflammation	EVOO, but not OO, induces a decrease in inflammatory markers (TXB(2) and LTB(4)).	Bogani et al. (2017)
	EVOO, but not OO, induces a decrease in IL-6 and CRP.	Fitó et al. (2007)
	EVOO, but not OO, decreases the expression of several inflammatory genes.	Camargo et al. (2010)
	EVOO, but not OO, decreases levels of inflammatory markers sICAM-1 and sVCAM-1.	Pacheco et al. (2007)
Oxidative stress	Strong in vitro antioxidant activity of phenolic compounds of olive oil.	Owen et al. (2000)
	Linear decrease in oxidized LDL levels as a function of the amount of polyphenols.	Covas et al. (2006)
	Lower levels of oxidized LDL after ingestion of EVOO compared to OO.	Ramirez-Tortosa et al. (1999)
	EVOO phenolic compounds bind to LDL particles and protect them from oxidation.	de la Torre-Carbot et al. (2010)
	EVOO induces the production of neutralizing antibodies against oxidized LDL.	Castañer et al. (2011)
	EVOO decreases urinary levels of 8-isoprostane, a marker of oxidative stress.	Visioli et al. (2000)
	EVOO positively influences the oxidative/antioxidant status of blood plasma.	Weinbrenner et al. (2004)
Blood pressure	EVOO causes a decrease in systolic and diastolic pressures in hypertensive women.	Ruíz-Gutiérrez et al. (1996)
	EVOO, but not OO, causes a decrease in systolic pressure in hypertensive coronary patients.	Fitó et al. (2005)
	EVOO improves postprandial endothelial dilation.	Ruano et al. (2005)
	EVOO increases the NO vasodilator and decreases systolic and diastolic pressures.	Medina-Remón et al. (2015)
	EVOO, but not OO, improves vessel dilation in pre-diabetic patients.	Njike et al. (2021)
	EVOO, but not OO, decreases systolic pressure by 2.5 mmHg in healthy volunteers.	Sarapis et al. (2020)

Table 2. Examples of studies comparing the effect of EVOO and OO on several cardiovascular health parameters.

In addition to its multiple direct actions on the heart and vessels, it should also be noted that extra virgin olive oil could also exert an indirect beneficial effect, by blocking the formation of the metabolite trimethylamine N-oxide (TMAO) by intestinal bacteria. Several studies have shown that TMAO accelerates the development of atherosclerosis in animal models and is associated with an increased risk of cardiovascular events in clinical studies. Extra virgin olive oils (but not regular olive oils) contain 3,3-dimethyl-1-butanol (DMB), a molecule that blocks a key enzyme involved in TMAO production and prevents development of atherosclerosis in animal models fed a diet rich in animal protein. Taken together, these observations show that there are only advantages to favouring the use of extra virgin olive oil, both for its superior taste and its positive effects on cardiovascular health.

Some people may dislike the slightly peppery taste that extra virgin olive oil leaves in the back of the throat, but interestingly, this irritation is greatly reduced when the oil is mixed with other foods. According to a recent study, this attenuation of the pungent taste is due to the interaction of the polyphenols in the oil with the proteins in food, which blocks the activation of the heat receptors that are normally activated by these polyphenols. People who hesitate to use extra virgin olive oil because of its irritant side can therefore get around this problem and still enjoy the benefits of these oils simply by using it as the main fat when preparing a meal.

The importance of properly controlling your blood pressure

OVERVIEW

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

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

Systolic and diastolic

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

Bedtime may be the best time for taking antihypertensive medication

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.

Harmful health effects of exposure to “Forever Chemicals”

Childhood obesity, a ticking time bomb for cardiometabolic diseases

The benefits of extra virgin olive oil on cardiovascular health

The importance of properly controlling your blood pressure

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

Bedtime may be the best time for taking antihypertensive medication

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