Bedtime may be the best time for taking antihypertensive medication

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.

 

 

Hypertension and hypercholesterolemia in young adults increase cardiovascular risk after the age of 40

Hypertension and hypercholesterolemia in young adults increase cardiovascular risk after the age of 40

Numerous epidemiological studies carried out over the last decades have shown a link between exposure to cardiovascular risk factors early in life and cardiovascular events at a later age. High blood pressure and high cholesterol are important modifiable risk factors for cardiovascular disease (CVD) and major components of risk prediction algorithms.

In prospective studies, childhood obesity, which subsides in adulthood, appears to cause only a slight increase in the risk of developing cardiovascular disease (CVD) over the course of life. Similarly, a few years after quitting smoking, the cardiovascular risk associated with smoking seems very low, even if smoking is stopped in adulthood. The same is not true for hypertension and hypercholesterolemia. Treatment of hypertension with medication does not reverse the damage done earlier in life, mainly to the heart, blood vessels and kidneys. For example, people who are hypertensive, but whose blood pressure is normalized by medication, have an increased risk of CVD after age 40. Treatment of familial hypercholesterolemia by statins significantly reduces the risk of CVD in young adults, but these people have more atherosclerotic CVD.

Until recently, we did not know whether exposure to these risk factors in early adulthood independently contributed to the risk of CVD, i.e. regardless of exposure to these same risk factors later in life. A study on the long-term effects of hypercholesterolemia and hypertension experienced at a young age, including a large amount of data and therefore of great statistical power, was recently published in the Journal of the American College of Cardiology (JACC). The data included in this study came from 6 U.S. cohorts, including 36,030 participants, who were followed for an average of 17 years.

The study found a strong association between having high blood pressure (BP) or high LDL-cholesterol at a young age (18–39 years), and the development of cardiovascular disease later in life (≥40 years). Specifically, young adults with LDL-cholesterol> 2.6 mmol/L had a 64% higher risk of coronary heart disease than those with a level of <2.6 mmol/L, regardless of cholesterol-LDL levels later in life. Similarly, young adults with systolic BP ≥130 mmHg had a 37% higher risk of heart failure than those with systolic BP <120 mmHg, and young adults with diastolic BP ≥80 mmHg had a 21% higher risk of heart failure than those with diastolic BP <80 mmHg. With respect to the risk of stroke after age 40, they are not affected by elevated cholesterol levels or increased systolic or diastolic BP at a younger age (18–39 years).

Even slightly elevated LDL-cholesterol levels of 2.6-3.3 mmol/L during early adulthood significantly increase the risk of coronary heart disease (28%) compared to <2.6 mmol / L. However, LDL cholesterol levels of 2.6-3.3 mmol/L are generally considered acceptable for healthy individuals who have no known CVD or other cardiovascular risk factors.

In an editorial published in the same journal, Gidding and Robinson suggest that the impacts of high cholesterol and hypertension in young people on cardiovascular risks later in life could be underestimated since: 1) the data from this study come from old cohorts, and we know that today’s young adults are more likely to be obese and have diabetes at a younger age; 2) there is probably a “survivor bias” in this type of study, i.e. it is possible that some young adults with particularly high blood pressure or cholesterol may have had a cardiovascular accident (an exclusion criteria) or that they have died before reaching the age at which the participants in these studies are recruited.

The increase in cardiovascular accidents before the age of 65 and the results of the study described above make it urgentto take action on prevention. Young adults, particularly women and non-Caucasians, did not benefit from the overall reduction of cardiovascular disease rates in the general population. This is probably due to three factors: the epidemic of obesity and diabetes; the lack of treatment for young adults who would benefit; the lack of clinical trials focusing on this age group, which would lead to better guidelines.

Drs. Gidding and Robinson believe that the first response of the medical community to the results of the study recently published in JACC and other similar analyses should be to become aware and recognize that there is a prevention deficit among young adults. In the United States, less than one third of adults under the age of 50 who should be treated for hypertension according to the guidelines receive treatment, and less than half of the participants in the NHANES study (National Health and Nutrition Examination Survey) who had a diagnostic criterion for familial hypercholesterolemia were treated with a statin.

The current trend is to treat hypercholesterolemia at a later age when the burden of the disease is already high and only a modest reduction in cardiovascular risk has been demonstrated. However, by lowering cholesterol earlier in life, mainly through a change in lifestyle, it is possible to avoid cardiovascular events in old age. By focusing more on young adults with less advanced disease and therefore more likely to be treated successfully, prevention and future clinical trials will reduce the burden of cardiovascular disease for future generations.

Dark chocolate is good for the heart!

Dark chocolate is good for the heart!

Updated on February 11, 2019

Not only are plants important sources of vitamins, fibres and minerals but they also contain phytochemicals such as polyphenols that play a very important role in the positive effects of these foods on cardiovascular health. Among the thousands of distinct polyphenols found in nature, the family of flavonoids has received special attention in recent years because of its presence in a large number of plants (fruits, vegetables, nuts, legumes) and beverages (tea, coffee, red wine) that are part of our daily diet. The impact of these molecules on health appears to be particularly important, as population studies indicate that people with the highest flavonoid intake have a lower risk of stroke or coronary artery disease, effects that are accompanied by a decrease in cardiovascular mortality and overall mortality.

Cocoa and its by-products, especially dark chocolate, are exceptional sources of polyphenols (Table 1), in particular flavonoids, suggesting that regular consumption of cocoa products could be very positive for cardiovascular health.

Table 1. Polyphenol content of some foods and beverages. Adapted from Pérez-Jiménez et al. (2010).

FoodPolyphenol content
(mg/100 g or 100 mL)
Cocoa powder3448
Dark chocolate1664
Flax seeds1528
Blueberries836
Black olives569
Pecans493
Coffee (filter)214
Red wine101
Green tea89
Tofu42

The first clue to this positive effect comes from Marjorie McCullough’s observations on the Kuna Indians of the San Blass Islands, an archipelago off Panama. These people are very large consumers of cocoa, which they use to prepare a beverage according to the traditional method of pre-Colombian civilizations. The Kuna drink about five cups of cocoa a day, which translates into a polyphenol intake of around 1800 mg per day, almost 10 times more than North Americans. These people are also distinguished for their very low blood pressure  (110/70 mmHg even at over 60 years old), despite a very high salt diet, and their low incidence of myocardial infarction and stroke. These characteristics are not of genetic origin, because the individuals who have left the island to live on the mainland see their blood pressure quickly increase. Among the lifestyle factors that may explain this difference, the most plausible is the drastic decrease in continental cocoa consumption, which is 10 times lower than among islanders. Therefore, it seems that cocoa polyphenols can have a real impact on cardiovascular health by lowering blood pressure and, at the same time, the risk of ischemic events such as heart attack or stroke that result from hypertension.

Several epidemiological studies have confirmed that high cocoa intake is indeed associated with a decrease in blood pressure and a reduction in the risk of cardiovascular disease and premature mortality. For example, a 15-year Dutch study of 500 people over the age of 65 found that those who consumed the most cocoa-based products had an average systolic pressure of 3.7 mm Hg and a marked reduction (50%) in the risk of cardiovascular mortality. These results have been confirmed by several randomized clinical trials where the consumption of dark chocolate, cocoa or cocoa-derived polyphenols is associated with a decrease in blood pressure and an improvement in endothelial function and insulin sensitivity. These vascular effects are largely due to an increase in the formation of nitric oxide (NO), a powerful vasodilator, by some cocoa flavonoids. A beneficial effect of cocoa consumption on the lipid profile (triglycerides, LDL and HDL cholesterol) and on the reduction of chronic inflammation has also been reported and could contribute to the benefits of dark chocolate for cardiovascular health.

These beneficial effects are also suggested by the results of a meta-analysis of 14 prospective studies conducted with a total of 508,705 participants, followed for a period of 5 to 16 years. The authors observed that people who consumed the most cocoa had a lower risk of coronary heart disease (10% decrease), stroke (16% decrease), and diabetes (18% decrease).

The most recent meta-analysis, which included 23 prospective studies with 405,304 participants, indicates that chocolate consumption is associated with a reduced risk of cardiovascular disease (CVD), if consumption is limited to less than 100 g/week. Those who consumed more chocolate had a 12% lower risk of CVD in general (stroke: -16.3%, myocardial infarction: -16.2%) than those who consumed little. However, the dose-response analysis (Figure 1) shows that at more than 100 g/week there is no longer any protective effect and that the risk of CVD increases at higher doses, which could be attributable to the harmful effect of consuming too much sugar. According to the authors of this meta-analysis, the best dose of chocolate to reduce the risk of CVD is 45 g/week (about half of a 100 g chocolate bar, a common size sold in grocery stores).

Figure 1. Dose-effect association between the consumption of chocolate and the risks of cardiovascular events. From Ren et al., Heart, 2019.

It is now clearly established that several risk factors for cardiovascular disease (hypertension, inflammation, insulin resistance, metabolic syndrome) also increase the risk of cognitive decline and dementia. Conversely, recognized factors to protect cardiovascular health, such as physical exercise or the Mediterranean diet, are associated with a significant decrease in the risk of cognitive disorders. In other words, what is good for the heart is also good for the brain, which raises the interesting possibility that the regular consumption of cocoa-based products can also result in benefits for cognitive function. Studies conducted to date support this, as a high intake of flavonoid-rich foods such as tea, red wine and chocolate is associated with reduced risk of cognitive decline and improved brain performance. In a study of people aged 65 to 82 who showed clinical signs of early cognitive decline, daily consumption of a beverage made with chocolate high in polyphenols was associated with significant improvement of cognitive functions.

More recently, a randomized clinical study showed that dark chocolate consumption was associated with a significant improvement in visual acuity and contrast sensitivity a few hours after intake, a positive impact possibly related to an improvement in blood circulation in the richly vascularized retina. Milk chocolate, which contains less polyphenols, has no effect, suggesting that flavonoids in cocoa are responsible for this improvement in vision.