Could Hypertension Be a Consequence of the 24/7 Society? The Effects of Sleep Deprivation and Shift Work

Sleep has been much in the news lately as a contributor to cardiovascular disease, and a good case could be made for including obstructive sleep apnea as one of the components of the metabolic syndrome. The mechanism by which sleep apnea leads to hypertension and other adverse cardiovascular effects is thought to be increased activity of the sympathetic nervous system, which is triggered by the apneic episodes during the night and for some unknown reason carries over into the day, leading to a sustained increase of blood pressure (BP) throughout the day and night. ¹ Sleep apnea is thus a facet of the epidemic of obesity which, in turn, is attributed to the predominant lifestyle of the 21st century—too much food, and too little exercise.

Another aspect of contemporary life, which has received much less attention for its effects on health, is the “24/7” society. More and more people are doing shift work or working two jobs in an effort to maintain their standard of living and commuting further and further to work. A survey of Long Island Rail Road commuters found that more than half reported sleep problems, and 70% reported napping while on the train. ² The National Sleep Foundation recommends 8 hours of sleep a night to maintain optimal health in adults, but it has been estimated that the average duration of sleep in Western societies has decreased from 9 hours in 1910 to 7.5 hours today. ³ People who do shift work often report getting 5 hours of sleep or less. ⁴ According to the National Sleep Poll conducted in 2006, ⁵ the number of adults who get ≥8 hours of sleep a night has decreased from 35% in 1998 to 26% in 2005, and the number who get <6 hours has increased from 12% to 16%. The reasons for this include the need to get more work done (45% of respondents) and watching television or using the Internet (43%). It is not only adults who are affected by this trend, however. The same poll found that only 20% of adolescents get 9 hours of sleep a night (the recommended amount), and that nearly half get <8 hours on weekday nights. More than half reported feeling tired or sleepy during the day.

SLEEP DEPRIVATION

What are the implications of these trends for those of us interested in hypertension and cardiovascular disease? The evidence that chronic sleep deprivation has adverse consequences on the cardiovascular system is at present fragmentary but suggestive. A survey of approximately one million male and female volunteers of the American Cancer Society ⁶ found a U‐shaped relationship between self‐reported hours of sleep and mortality, with the bottom of the U (lowest mortality) being at 7 hours. The odds ratio for those reporting only 3 hours of sleep was 1.3. How this relationship is mediated is far from clear, but there are some clues. There is evidence that short sleep increases the risk of coronary heart disease: in the Nurses' Health Study, ⁷ sleeping ≤5 hours was associated with a 39% increased risk of coronary heart disease after adjusting for obesity and diabetes.

It is well established that short sleep is related to obesity. A recent review ⁸ was able to identify 14 studies, 7 cross‐sectional and 7 prospective, all of which found that people who reported short sleep times were more likely to be, or to become, obese. The relationship has been identified in children as young as 5 years ⁸ and appears to be stronger in younger than older adults. Self‐reported sleep duration has also been shown to predict diabetes: in a 14‐year follow‐up study (the Massachusetts Male Aging Study), ⁹ there was a hazard ratio of 1.95 for the onset of diabetes in men sleeping <6 hours. In a cohort of the Nurses' Health Study, ¹⁰ 70,026 nurses were followed for 10 years, and it was reported that there was a 57% increased risk of diabetes for short sleep (<5 hours) and a 47% increased risk of diabetes in women who slept >9 hours. After adjustment for body mass index (BMI) and other confounders, the relationship with short sleep was no longer significant, but the relationship with long sleep persisted. In women who developed more severe, symptomatic diabetes there was still a weak relationship between short sleep and diabetes that was independent of BMI. The authors concluded that the relationship between short sleep and diabetes was largely mediated through weight gain. We have obtained very similar results in analyses of the National Health and Nutrition Examination Survey (NHANES), where there was a U‐shaped relationship between the probability of developing diabetes and hours of sleep, again with a lowest value at 7 hours (Richards et al ¹¹ and Gangwisch et al, ²⁰ unpublished data, 2006). For men aged 32–59 years, the hazard ratio for becoming diabetic over an 8–10‐year follow‐up was about 1.5.

Hypertension, type 2 diabetes, and obesity go hand in hand, and our analysis of the same NHANES data showed that people who reported <5 hours of sleep were also at increased risk for developing hypertension. ¹² The risk ratio was 1.7 after controlling for predictors of hypertension, and decreased only to 1.6 after controlling for diabetes and obesity. So far, this is the only study to look at the relationship between short sleep and hypertension, although the Long Island Rail Road survey ² found that people with the longest commutes were more likely to report being hypertensive.

Experimental studies of the effects of sleep deprivation lend support to the concept that short sleep could be causally related to the development of obesity, diabetes, and hypertension. Lusardi et al ¹³ investigated the effects on 24‐hour BP of curtailing sleep from 8 to 4 hours in hypertensive patients. As expected, the decrease in BP at night was shortened in the patients who slept for 4 hours, but of more interest was the finding that after waking, the BP remained higher for the next 8 hours than in patients who were allowed 8 hours of sleep. Similar effects were seen on heart rate, suggesting that activation of the sympathetic nervous system was a probable mediator. Support for this idea comes from another study in which it was found that sleep deprivation leads to a shift in the pattern of heart rate variability during the following day, characterized by an increased low frequency/high frequency ratio, ¹⁴ a pattern that is generally accepted as indicating a relative increase of sympathetic over vagal activity.

The metabolic effects of sleep deprivation have also been studied. When healthy men had their sleep restricted to 4 hours a night for 6 nights their glucose tolerance was impaired. This was accompanied by increased sympathovagal balance of heart rate variability and increased evening cortisol levels. ³ The same group of investigators found that sleep deprivation produced an 18% decrease in plasma leptin and a 28% increase in plasma ghrelin. ¹⁵ Leptin is a hormone that suppresses appetite, and ghrelin stimulates it, so it came as no surprise that when the subjects were sleep deprived they reported increased hunger. In a large cross‐sectional study of 1024 volunteers who had polysomnography performed in a sleep laboratory, blood was taken immediately on waking. ¹⁶ There was again a U‐shaped relationship between self‐reported average sleep duration and BMI, such that a duration of <7.7 hours was related to an increased BMI. There were also approximately linear relationships between sleep duration and morning blood levels of both leptin and ghrelin, although they went in opposite directions—short sleep was associated with low leptin and high ghrelin. ¹⁶

SHIFT WORK

In a study of nurses working 1 of 3 shifts (day, evening, or night) we found that the self‐reported sleep duration was least in the night‐shift workers (5.6 hours as opposed to 6.8 for those working the day shift, and 6.5 for the evening shift). ¹⁷ The night‐shift workers also showed an altered pattern of BP, with less dipping, and a higher BP during the hours when they reported being asleep, when compared with the day‐shift workers. The normal pattern of diurnal variation of catecholamine excretion was also disrupted. These findings are consistent with impaired sleep in the shift workers, since other studies have shown that BP follows the cycle of rest and activity very closely. ¹⁸ A study that effectively eliminated the exogenous influences on the diurnal rhythm of BP by keeping subjects awake and immobile for 24 hours, with hourly feeding, found that the diurnal rhythm of BP was also eliminated but the rhythm of heart rate persisted, suggesting that the latter was more dependent on the endogenous biological clock. ¹⁹ In an Italian study of workers on either the day or night shift, the night‐shift workers had higher BMI, higher BP, and more glucose intolerance. ²⁰ A prospective study of 6495 Japanese workers ²¹ found that those on the night shift had a 23% higher risk of developing severe hypertension over 10 years than those working the day shift. Another Japanese study ²² found that over a 10‐year period shift workers had a 35% increased risk of becoming diabetic as compared with day workers, and in a cohort of the Nurses' Heath Study ²³ that followed 79,109 women for 4 years, women who reported having done shift work had an increased risk of 1.38 (odds ratio) of experiencing cardiovascular events after controlling for other known risk factors. A Swedish case‐control study found a 30% increased risk of myocardial infarction in both men and women who reported doing shift work. ²⁴ Another analysis from Sweden found that women doing shift work were at increased risk for mortality, although this did not apply to men. ²⁵

COMPARISON OF THE EFFECTS OF SLEEP DEPRIVATION AND SHIFT WORK

As shown in the Table, the evidence discussed above suggests that sleep deprivation and shift work have many similar effects that could contribute to cardiovascular disease.

A schema describing these relationships and their possible mechanisms is shown in the Figure. Two consequences of modern society are sleep deprivation and shift work, both of which result in disruption of the diurnal rhythm of sleep and wakefulness. Three physiologic pathways that have been postulated to mediate the effects of these disruptions include increased sympathetic activity, activation of the hypothalamic‐pituitary axis, and decreased leptin. These lead to the cluster of hypertension, obesity, diabetes, and sleep apnea (although it should be pointed out that the last of these has not yet been implicated in the studies of short sleep). The fact that some of the epidemiologic studies have found that the 3 main outcomes so far identified—obesity, diabetes, and hypertension—are statistically independent of each other (in at least some of the studies) is consistent with there being multiple pathways that might be activated to different degrees in different individuals. Thus we would expect that hypertension might be the predominant outcome of sympathetic activation, while decreased leptin would favor the development of obesity. There is evidence that both the sympathetic nervous system and the hypothalamic‐pituitary axis are activated in patients with the metabolic syndrome. ²⁶

CONCLUSIONS

There is no debate about the importance of the epidemic of obesity and its related conditions and also no doubt that it has been brought on by changes in our lifestyle. While ultimately it has to be explained by an imbalance between calories taken in and calories burned, there are numerous intermediate factors that determine why some individuals are more susceptible to these influences than others. Disruption of the diurnal rhythm of sleep and wakefulness, by both shorter sleep times and doing shift work, is emerging as a potential contributor to this process.