Ambulatory blood pressure variation: Allostasis and adaptation

Ambulatory blood pressure variation: Allostasis and adaptation

Autonomic Neuroscience: Basic and Clinical 177 (2013) 87–94 Contents lists available at ScienceDirect Autonomic Neuroscience: Basic and Clinical jou...

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Autonomic Neuroscience: Basic and Clinical 177 (2013) 87–94

Contents lists available at ScienceDirect

Autonomic Neuroscience: Basic and Clinical journal homepage: www.elsevier.com/locate/autneu

Review

Ambulatory blood pressure variation: Allostasis and adaptation Gary D. James ⁎ Decker School of Nursing, Department of Anthropology, Department of Bioengineering, Binghamton University, Binghamton, NY 13902-6000, USA

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Article history: Received 7 September 2012 Received in revised form 13 March 2013 Accepted 28 March 2013 Keywords: Ambulatory blood pressure Allostasis Job strain Appraisal

a b s t r a c t Allostasis is defined as achieving stability through change and was originally coined as a term to describe the adaptive variability of blood pressure. While there have been a growing number of studies using ambulatory blood pressure monitors that have examined the sources of blood pressure variation in everyday life, these studies have largely not conceptualized that variation in allostatic terms. This brief overview evaluates ambulatory blood pressure variability and its sources in the context of allostasis and adaptation. The effects of job strain and the impact of evolutionary aspects of population biology on blood pressure variation are also discussed. © 2013 Elsevier B.V. All rights reserved.

Contents 1. 2. 3. 4.

Introduction . . . . . . . . . . . . . . . . . . . . . . . Ambulatory blood pressure measurements . . . . . . . . Modeling the sources of blood pressure variation . . . . . Quantifying sources of momentary blood pressure variation 4.1. Situation of measurement . . . . . . . . . . . . . 4.2. Posture and physical activity . . . . . . . . . . . . 4.3. Emotional state . . . . . . . . . . . . . . . . . . 5. Job strain appraisal and ambulatory blood pressure variation 6. Population biology and blood pressure variation . . . . . . 7. Summary and conclusions . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . .

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1. Introduction In 1628, William Harvey published An Anatomical Treatise on the Motion of the Heart and Blood in Animals in which he proved that the heart was muscular, that its most important movement was contraction and not dilation, and that it was the beat of the heart that produced a continuous circular motion of blood in the body (Magner, 1992). In 1733, more than 100 years later, Stephen Hales made the first measure of systemic blood pressure in a horse, where he also found that the pressure was not fixed, but variable (Pickering, 1991). Over the next 170 years, methods for blood pressure assessment were slowly refined and the specific relationships between the cardiac rhythm and arterial pressure were discovered (O'Rourke, 1990; Paskalev et al., 2005). However, a ⁎ Tel.: +1 607 777 6086; fax: +1 607 777 6162. E-mail address: [email protected]. 1566-0702/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.autneu.2013.03.012

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simple and reproducible blood pressure measurement that described both the maximum and minimum pressures of the pulsatile blood flow as it left the heart remained elusive. Finally, in 1905, Nikolai Korotkoff using the arterial occlusion method of Riva-Rocci discovered the auscultatory technique of blood pressure measurement, reporting on the sounds that bear his name in a paper presented to the Imperial Military Medical Academy in St. Petersburg, Russia (Paskalev et al., 2005). Since that time, other methods of assessment have been added, including oscillometric and ultrasound techniques (Pickering, 1991), but the quantitation of blood pressure as a ratio of the maximum (systolic) and minimum (diastolic) of the pressure pulse wave that is based on Korotkoff sounds remains the standard for describing blood pressure. Throughout the 20th century and into the 21st, ausculted blood pressures taken by Korotkoff's technique have been used as an indicator of cardiovascular health, and a condition, hypertension, has been defined as seated systolic/diastolic blood pressure that exceeded 140/90 mm Hg

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in the clinical setting. Data from numerous clinical and epidemiological studies show that hypertension is a risk factor for cardiovascular diseases and stroke (e.g. JNC VII, 2003), and because of this association, the pharmaceutical industry has produced a cornucopia of vasoactive agents designed to lower blood pressure as a means of lessening the burden of cardiovascular morbidity and mortality (JNC VII, 2003). While the level of ausculted blood pressure has been the focus of medical attention for over 100 years, the diurnal variability of blood pressure, until relatively recently, has been of minimal interest. The increasing use of automated ambulatory blood pressure monitors in medical practice over the past 30 years has demonstrated that there is enormous intraday variability in blood pressure (James, 2007a). By employing these monitors, white coat hypertension (Pickering et al., 1988; Ohkubo et al., 2005) and masked hypertension (Ohkubo et al., 2005; Pickering et al., 2007; Angeli et al., 2010), conditions defined by the difference in blood pressure between the clinic and daily life and which likely also differentially influence cardiovascular morbidity risk (e.g. Konstantopoulou et al., 2010) have been identified. Furthermore, other aspects of the diurnal variation in blood pressure, such as the waking–sleep difference in blood pressure (dipping) (Fagard et al., 2009; Cuspidi et al., 2010; Hansen et al., 2011) and the surge in pressure upon awakening (Kario, 2010; Yano and Kario, 2012) have also been shown to predict cardiovascular morbidity and mortality. These studies suggest that blood pressure variability is perhaps as important as the mean level of blood pressure when it comes to defining cardiovascular health. Although the literature on blood pressure is dominated by its role as an indicator of cardiovascular health, the fundamental nature of blood pressure as a biological phenomenon has also come into sharper focus. In the 1980s, Sterling and Eyer (1988) introduced the concept of “allostasis” defined as “achieving stability through change” using blood pressure as an exemplar of the process. Blood pressure changes dramatically and continuously to adapt individuals to their changing daily circumstances (James, 1991). Because it continuously changes, the individual does not have a single “homeostatic” blood pressure state, but rather has many stable blood pressure states that are related to their ever-changing internal and external environments (Ice and James, 2012). Sterling and Eyer (1988) have argued that in the process of allostasis, the brain coordinates multiple systems of local control in an integrated fashion which allows for anticipation of change in systemic demand. Thus, allostatic regulation (such as with blood pressure) has two components: the parameter variation and anticipated demand from that variation. Sterling (2004) has further suggested that allostasis can be used to explain the connections between social conditions, behavior, and health, such that poor social conditions can place an individual in a state of constant arousal and encourage negative health behaviors leading to the development of disease. From this perspective, essential hypertension (high blood pressure) can be seen as arising from sustained neural input that emerges from “unsatisfactory social interactions” (Sterling, 2004). Thus, how people appraise their social circumstances is a key element of allostatic regulation (Ice and James, 2012). Adverse appraisal might necessarily lead to a continued enhanced allostatic response which in turn could create an allostatic load resulting in metabolic failure (McEwen, 2004). Several studies have shown that appraisal of common life phenomena, such as job strain has a significant effect on blood pressure variation which may also lead to hypertension (Schnall et al., 1990; Landesbergis et al., 2003). In the discussions of allostasis, there is also an implication that it is a process that acts in a similar fashion in all people. This may not be the case. Missing from most discussions of allostasis and blood pressure is an evaluation across populations; specifically the impact that evolution has had on allostatic variation in blood pressure among diverse populations living in contrasting ecologies. Several studies have found that there are significant physiological differences between populations that are related to climatic factors (James, 2010). These

differences can influence how blood pressure is regulated (James and Baker, 1995; James, 2010). While blood pressure allostasis has been discussed theoretically, there has been little discussion of its operationalization based on real life data. The purposes of this brief overview are 1) to evaluate ambulatory blood pressure variability, both in terms of how it is measured and the factors that drive it, 2) to assess the impact of the appraisal of common life phenomenon (specifically job strain) on diurnal blood pressure variation and allostasis, and 3) to summarize the possible impact of evolutionary aspects of population biology on allostatic blood pressure variation. 2. Ambulatory blood pressure measurements Ambulatory blood pressure monitors continue to use a cuff occlusion method to take blood pressures; they either have a microphone attached to the cuff that is placed above the brachial artery to detect Korotkoff sounds, or employ an oscillometric method using a manufacturer proprietary algorithm to calculate the pressures (James, 2007a). Typically when blood pressure variation is studied, pressures are examined for their variability over the course of one 24-hour period, although it should be noted that in making this evaluation, pressures may be measured over the course of several days (e.g. Kamarck et al., 2002) and there has also been interest in determining whether blood pressure variability differs across different types of days (e.g. a weekend non-work day vs. a mid-week workday) (e.g. Pieper et al., 1993). Since each heart beat generates a systolic and diastolic pressure (defined as the maximum and minimum of the pulse wave of blood that is produced when the heart ejects blood into the aorta as it contracts), depending upon the heart rate, upwards of 100,000 blood pressures occur over 24 h (James, 2007a). Monitors can be programmed to take a blood pressure as often as every 5 min, but for the purpose of diurnal variation studies, monitors are programmed to take pressures between 15 and 30 min while awake and every 30 to 60 min while sleeping (James, 2007a). Thus, diurnal studies of blood pressure variation have evaluated samples of blood pressures in the range of 40 to 80 measurements per subject per day, a relative few considering how many are actually generated daily. 3. Modeling the sources of blood pressure variation To understand why blood pressure varies, it is critical to have information regarding the conditions of measurement. That is, if blood pressure is responding to ambient conditions during everyday life, in order to show the relationship, there needs to be a means of defining the conditions. While direct observation of subjects wearing the monitor has been used (e.g. Ice et al., 2003), for most studies of diurnal blood pressure variation, subjects have self-reported the ambient conditions of each blood pressure measurement in a diary, which have taken on a variety of forms, from pencil and paper to hand held computers (James, 2007b). Most studies of blood pressure variation have not been conducted with a focus toward allostasis, or even understanding cardiovascular adaptation for that matter. Rather the interest has either been in simply understanding the sources of diurnal blood pressure variation, or evaluating whether people with specific characteristics differ in their responses to similar stimuli (Gerin and James, 2010; Ice and James, 2012). To assess the sources of diurnal ambulatory blood pressure variation two general approaches have been used (James, 2007b). The first employs what might be termed a “natural experimental” approach in which there are a priori design elements that define predictable dynamically changing behaviors or situations that occur during a typical day (James, 2007b). This approach has its roots in the study of blood pressure reactivity in the laboratory, where blood pressure change to various “stressful” tasks has been evaluated (see for example, Pickering

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and Gerin, 1990; Kamarck et al., 2003; Linden et al., 2003). In laboratory experiments, a baseline condition is established and then the subject undertakes a series of defined “stressful” tasks. The difference between the baseline measurements and those during the tasks defines the magnitude of blood pressure reactivity. Laboratory experiments are well controlled such that there are a specific number of measurements at baseline and during each task, and all participants experience the same protocol. Moving this experimental paradigm to a “natural” setting (e.g. into real life and outside the laboratory) requires modification because no true baseline can be established. But, as I have noted (James, 1991) a “natural experiment” can be designed where blood pressure changes can be evaluated as people move from microenvironment to microenvironment (such as their work and home situations) during the course of their everyday lives. For example, a person who lives in a suburb and commutes to an urban workplace everyday likely has a structured, urban work environment where economic related activities occur, where social interactions take place with non-relative coworkers, and where a specific occupational hierarchy dictates the nature of social relationships (James, 2007a). The parameters of this environment contrast sharply with that of the suburban home, where domestic tasks and leisure activity happen in a social context where interactions are with relatives and neighbors. The allostatic variation in blood pressure required to adapt to the changes between these relatively predictable microenvironments can be assessed by comparison with the average blood pressure during overnight sleep, or more specifically, while lying quietly in a dark room acting as a pseudo-baseline (see Fig. 1) (James, 2007a). The second approach is one where each blood pressure measurement is evaluated with regard to the specific circumstances reported in a diary (often called ecological momentary data) using a variety of statistical modeling techniques (see for example James et al., 1986; Schwartz et al., 1994; Kamarck et al., 1998; Brondolo et al., 1999; Gump et al., 2001; Kamarck et al., 2002). In these models, the variation in blood pressure is partitioned among several aspects of the measurement circumstance (such as the posture of the subject and the location of the subject). The proportion of variation associated with each of these aspects is quantified, as is the number of mm Hg that alternative circumstances contribute to either increasing or decreasing the values of individual blood pressure measurements relative to some standard value (James, 2007b). In evaluating blood pressure variation this way, the choice of diary reporting alternatives is critical; that is, the factors chosen to have reported in the diary and how the diary factors are recorded will dictate how the variation in blood pressure gets partitioned (James, 2007b). Analysis of ecological momentary blood pressure data has been undertaken using raw (e.g. Schwartz et al., 1994; Brondolo et al., 1999; Kamarck et al., 2003) and standardized (e.g. James et al., 1986; Brown et al., 1998; Ice et al., 2003) data. The estimated effect sizes using these approaches vary

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considerably, not only due in part to the fact that there is no consensus as to what ought to be the standard value against which effects should be measured, but also because of the demographic and cultural diversity of the groups studied (James, 2007a). 4. Quantifying sources of momentary blood pressure variation How variable is blood pressure over a day, or more specifically, one 24-hour waking–sleep cycle? Fig. 2 depicts the data from a typical study subject whose blood pressure average was 141/86 over a 24-hour monitoring. Note that in this example, systolic pressures ranged from 93 to 164 (71 mm Hg) and diastolic pressured ranged from 46 to 107 (63 mm Hg). It is not uncommon to see a range of up to 100 mm Hg over the course of one waking–sleep cycle (Pickering et al., 1986). Blood pressure can thus be quite variable. However, it is also important to note that there is heteroscedasticity in blood pressure across people, such that there is a direct relationship between the 24-hour mean blood pressure and its variance (Pickering, 1991). Thus, people with lower 24-hour average blood pressure will tend to have a narrower range of blood pressures diurnally than those with higher average pressures. This heteroscedasticity is probably related to underlying arterial structural differences such as stiffness (Pickering, 1991) and/or differences in vasoactive hormone receptor density or sensitivity (see Van BergeLandry et al., 2008). So what environmental and cognitive factors affect blood pressure variation and how big are the effects? The following is a summary of some effects that have been assessed from ambient circumstances reported in diaries. 4.1. Situation of measurement The first studies of ambulatory blood pressure variation using automatic monitors (e.g. Harshfield et al., 1982; Pickering et al., 1982) found that the situation of measurement had a profound effect on blood pressure. Subsequent studies, whether conducted in a “natural experiment” context or as an evaluation of ecological momentary factors, consistently show that location, or situation of measurement is among the most important sources of diurnal blood pressure variation. Studies evaluating people employed outside their home have found that blood pressures measured at the place of employment tend to be the highest during the day, while that measured during sleep is the lowest (see James, 2007a for review). Interestingly, the elevation in pressure needed to meet the predictable demands of work appears to be independent of the time of day, as several researchers have shown that the average ambulatory work pressure is highest when compared to other daily situations, even among night-shift workers (Sundburg et al., 1988; Baumgart et al., 1989; Yamasaki et al., 1998).

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Fig. 2. An example of diurnal (24-hour) blood pressure variation, where a pressure was taken every 15 min from about 8:45 AM to 10 PM and every 30 min from 10 PM to about 6:30 AM the next morning. The x-axis is labeled on a 24-hour clock beginning on the day the monitor was applied; thus, hours labeled 28 and 32 refer to 4 AM and 8 AM the following day.

4.2. Posture and physical activity As in laboratory studies, posture has been found to also have a substantial effect on diurnally assessed ambulatory blood pressure variability. Analyses of ecological momentary blood pressure data consistently show that pressures taken while standing are substantially higher during the day than pressures while sitting or reclining (James, 2007a), although pressures taken while sleeping and reclining are lower than pressures taken while awake and reclining (James et al., 2001). The effects of posture will often co-vary with physical activity, as most diary reportable activities tend to occur in a single posture; thus in most studies that evaluate the effect of posture, the effects of activity are not estimated. Researchers who have assessed the effects of changing daily activities find that physical activities (from walking to doing household chores) elevate pressures the most, whereas activities such as reading or writing, which require mental effort, or other activities such as eating, watching TV, or talking have less effect (see James, 2007a for review). It should be noted that the estimates of the more physically active activities are probably underestimates, as a person must stop moving and remain still for the entire cycle of an ambulatory blood pressure measurement (usually 30 to 40 s) (James, 2007b). Fig. 3 presents some estimated effects of various activities on ambulatory blood pressures (from James and Pickering, 1991). Finally, other studies have assessed the effects of physical activity using actigraphy. From this work it has been estimated that about one-third of the variance among intermittently sampled ambulatory pressures is related to the constant change in motion during the day (Gretler et al., 1993; Kario et al., 2001). 4.3. Emotional state The initial studies regarding the ecological momentary effects of mood on automatic ambulatory blood pressure measurements showed that reported happiness, anger and anxiety increased blood pressure to differing degrees and that the effects varied with mood intensity (e.g. James et al., 1986). Subsequent studies have generally confirmed this finding (see James, 2007a for review). However, a number of studies have found that the size of the effect of emotion on blood pressure

depends on the situation, and other factors such as gender and season of the year can also moderate the effects (see James, 2007a). Fig. 4 presents an example of estimated mood effects in conjunction with posture and location of measurement on the blood pressures of a sample of women (from James et al., 1988). The effect sizes shown are based on standardized measurements, and represent the number of mm Hg from the 24-hour mean of a person who had a 24-hour standard deviation of 10. It should be recognized that the effect sizes will increase or decrease as the 24-hour standard deviation varies. As indicated in the figure, the size of the estimated blood pressure adjustments associated with the mix of ecological momentary factors varies considerably. A closer examination of the effects of posture, location, and emotional state shows that they are more or less additive with regard to blood pressure variation. However, each set of factor alternatives defines a momentary state typically experienced by a person. By simple subtraction, it is easy to calculate that the allostatic change in pressure from one state to another can be substantial. Because a change in habitus from sitting to standing, or a mood change from happy to angry could happen almost instantly, it is clear that the process of allostasis is also instantaneous, and that people move across blood pressure states very quickly. 5. Job strain appraisal and ambulatory blood pressure variation Job strain, a measure of how an individual appraises their work situation and has been extensively studied with regard to interindividual variation in ambulatory blood pressure averages calculated from measurements taken during a 4–8-hour time frame while individuals are at work (Gerin and James, 2010). An individual's appraisal of job strain is determined from elevated scores on two orthogonal subscales of the Job Content Survey: “psychological job demands,” which measures the psychological workload of the job, and “decision latitude,” which describes the degree of control that subjects perceive they have over their job (Karasek et al., 1981; Pickering et al., 1991). Those with high demands and low decision latitude at their job have job strain. Job strain is an adverse appraisal of working condition and is not good. Researchers who have studied it hypothesize that it should increase blood pressure, both in the short and long terms. Investigations into job strain and ambulatory blood pressure began in

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Fig. 3. Exemplar effects of various reported activities on daily blood pressure. (Data from James and Pickering, 1991). Defined as mm Hg from the 24-hour mean, and is based on the assumption that the measure of dispersion around the 24-hour mean (standard deviation) is 10.

the 1990s when its effects on ambulatory blood pressure averaged at work, home and during sleep were examined in a case control study of men employed in various businesses in New York City (Schnall et al., 1990; Schnall et al., 1992). In this seminal study, men who

appraised themselves as having job strain had work systolic pressure that was 7 mm Hg higher and work diastolic pressure 3 mm Hg higher than men who appraised themselves as not having job strain (Schnall et al., 1992). A later follow-up study of this cohort of men

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Fig. 4. Exemplar effects of posture (sitting, standing), location (work, home, elsewhere) and emotional state (happy, angry, anxious) on daily blood pressure. (Data from James et al., 1988). Defined as mm Hg from the 24-hour mean, and is based on the assumption that the measure of dispersion around the 24-hour mean (standard deviation) is 10.

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found that over the long term, the systolic blood pressure of men employed for 25 or more years who had appraised job strain for at least half of their work life was about 5 mm Hg higher at work and 8 mm Hg higher at home than that of men with no past job strain (Landesbergis et al., 2003). Since the initial study, the effects of job strain on situationally-measured ambulatory blood pressures of men working in a variety of occupations have been explored in other population groups and samples from Western industrialized nations, including the United States (Van Egeren, 1992; Curtis et al., 1997; Brown and James, 2000; Brown et al., 2003, 2006; Landesbergis et al., 2003), Canada (Brisson et al., 1999; Laflamme et al., 1998; Tobe et al., 2005, 2007), the United Kingdom (Steptoe et al., 1995, 1999), Italy (Cesana et al., 2003), the Netherlands (Riese et al., 2004), Belgium (Clays et al., 2007), and Sweden (Theorell et al., 1993) (see Gerin and James, 2010 for review). These studies have examined people employed in a wide variety of occupations and have found similar effects on adult male ambulatory blood pressures. From the perspective of allostasis, these studies suggest that if men perceive job strain at work, the blood pressure increase needed to adjust to the work situation is accentuated, and possibly blood pressure responses to other daily situations (such as being at home or during sleep) as well. This increase, when sustained, appears to also lead to a perpetually higher daily pressure (Landesbergis et al., 2003). Interestingly, the impact of job strain on the blood pressures of women differs from that of men, with many of the studies showing that it often has no effect. Other factors such as their means of coping with stress (see also Light et al., 1995), familial responsibilities (Brisson et al., 1999) and domestic stress (see James et al., 1996) appear to have greater moderating effects on their situational blood pressure averages (see also Gerin and James, 2010; Ice and James, 2012 for review and discussion). The fact that men and women differ on average in their blood pressure response to job strain intimates that differences in appraisal have profound effects on allostatic processes. Finally, in examining the impact of psychological appraisals on blood pressures averaged in differing situations, it is difficult to know whether the appraisal itself directly affects blood pressure or whether the higher or lower average situational blood pressure happens as a result of the effects of particular emotional states, postures, activities, and/or their interactions that occurred during the situation. That is, it is possible that the appraisal is dictated by the frequency and intensity of emotional arousals or long periods of standing or the result of some other ecological momentary factor during the time spent in the situation, so that job strain, for example, may be perceived because of emotional difficulties or excessive activity that occurred during the work situation. Regardless of how the effects are manifest, when someone appraises a situation adversely, blood pressure responses can be accentuated, beyond what is necessary for simply adapting to the situation and perhaps even sustaining the increased response in a way that leads in the long-term to pathology (e.g. allostatic load model, see McEwen, 2004 for discussion). 6. Population biology and blood pressure variation Several studies have shown that ambient temperature has an effect on ambulatory blood pressure variation, changing pressures by as much as 5 mm Hg as the weather changes (e.g. Jehn et al., 2002; Modesti et al., 2006; Morabito et al., 2008). However, while ambient temperature is part of the immediate environment to which an individual must adapt, there have also been physiological changes driven by climate in various population (ethnic) groups that have occurred through natural selection that also affect blood pressure variation (James and Baker, 1995; Young et al., 2005; James, 2010). The influences of these changes are reflected in populational differences in blood pressure responses to environmental stressors such as dietary salt and prolonged cold temperature.

Current evidence suggests that all modern human populations are descended from tropical “heat adapted” ancestors from Africa, some 100,000 to 200,000 years ago (Smith, 2010), and it is also true that modern sub-Saharan African populations retain that heat adapted physiology, or more precisely a physiology adapted to a mostly hot, wet environment (Hanna and Brown, 1979; Young et al., 2005; James, 2010). Two important aspects of that physiology are the ability to copiously sweat and the ability to retain salt (sodium) as there is limited salt availability in hot, tropical environments (James and Baker, 1995; Young et al., 2005; James, 2010). Young et al. (2005) have reported a geographic cline from the equator to the poles of “heat adapted” allelic variants from 5 functional genetic sites that affect salt retention and blood vessel tone. Their data suggest that native populations living within 10° of the equator have an average 74% “heat adapted” allelic variants, while populations within 10° of the arctic having only 43% “heat adapted” variants. After comparing 53 populations geographically dispersed from the equator to the poles, they have hypothesized that the frequency of “heat adapted” alleles declined as our African ancestors colonized environments that were cooler and salt rich and then rose again among groups that migrated from those areas back to more salt poor tropical climates (Young et al., 2005; James, 2010). Furthermore, since the “heat adapted” alleles help to retain salt and excessive dietary salt intake is a major risk factor for hypertension, they have proposed that populations with “heat adapted” alleles are more susceptible to hypertension, particularly if they have migrated in more recent times to cooler salt rich environments or who have had salt substantially increased in their diets (Young et al., 2005). Their genetic findings may partially explain the higher prevalence of hypertension and cardiovascular morbidity in African-American populations, at least as it may relate to variation of salt in the diet (James, 2010). In addition, when cold or freezing conditions are experienced in unprotected humans, there is a sympathetically driven immediate constriction of peripheral arteries, which conserves body heat by cutting down the peripheral flow of blood, and which, if left unchecked, will lead to tissue damage and frostbite (James and Baker, 1995). To combat tissue damage, ancestral human populations who migrated out of Africa to temperate and cold climates evolved a peripheral cold induced vasodilatory (CIVD) response through natural selection, which is a periodic release of the arterial constriction allowing tissue rewarming that protects the hands and feet from frostbite (James and Baker, 1995). What this means is that another aspect of our ancestral African “heat adapted” physiology was that it was characterized by an inadequate CIVD response since such a response was unnecessary in tropical climates (James and Baker, 1995). Numerous studies have found that African-American populations who largely retain a heat adapted physiology show a generally more intense vasoconstrictive response to cold stress, with either inadequate or no CIVD (James and Baker, 1995). Importantly, while the enhanced cold pressor response among AfricanAmericans is most often noted in studies of hand emersion in freezing water, subsequent research has found first, that cold to the face also elicits the accentuated pressor response among African-Americans (Anderson et al., 1988; Treiber et al., 1990) and second, that AfricanAmericans exhibit heightened myocardial and vasoconstrictive reactivity during passive exposure to ambient temperatures from 8 to 10 degrees centigrade (Kelsey et al., 2000). What these findings mean practically, is that the typical outside exposure of the face during the cold of winter is probably sufficient to elicit the enhanced pressor and vasoconstrictive responses among African-Americans. Why this is significant from a cardiovascular perspective is that peripheral cold stress that induces sympathetically driven vasoconstriction also increases blood pressure due to the increase in peripheral resistance (Pickering and Gerin, 1990), and chronic vasoconstriction can lead to sustained hypertension (Kaplan, 1978). It is thus possible that African Americans living in the temperate and freezing climates of North America experience chronic cold stress through the winter months, potentially experiencing more chronic vasoconstriction due the their enhanced cold pressor

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response and inadequate CIVD which could then make them more susceptible to the development of hypertension (James and Baker, 1995). This possibility is supported by recent studies which suggest that sympathetic hormone receptors among African Americans appear to be more sensitive than those of European Americans (Mills et al., 1995), and that the diurnal variation in blood pressure of African Americans is more accentuated than that of European-Americans in relation to diurnal changes in epinephrine (van Berge-Landry et al., 2008). The point of mentioning these evolutionarily developed differences in salt and fluid retention and peripheral cold responses is that they undoubtedly influence allostatic blood pressure responses. However, in a broader context, what these population differences in physiology suggest is that the extent to which blood pressure may vary, or move to presumptively adaptive states in response to challenges depends upon how natural selection has shaped an individual's physiology. That is, the same stressor may lead to completely different states in different individuals because of the fact that their physiologies differ as a consequence of natural selective processes that occurred in their ancestral populations. These underlying physiological differences should thus be considered when evaluating allostatic blood pressure variation across groups.

7. Summary and conclusions Blood pressure is an archetypal allostatic trait. Over the past 30 years, studies employing ambulatory blood pressure monitors have found that the extent of intra-individual blood pressure variation is substantial. The quantification of that variation is a function of the manner in which blood pressure is measured. Blood flow is continuous but pulsatile, and its pressure is estimated from a single point maximum (systolic) and minimum (diastolic) that is determined when the flow is interrupted and then re-established. Given that each pulse has a maximum and minimum, there are as many measurable pressures as there are pulses, which are determined by the rate at which the heart beats. Blood flow (and consequently pressure) will increase or decrease depending upon anticipated physiological needs. Assessments of ecological momentary factors (the determined conditions at measurement) show that the blood pressure responses to actions such as postural change or changes in emotional state are rapid and can be large. Given that these types of factors are inherent in day to day living, the changes in pressure associated with them can be seen as the adaptive response to everyday living and an exemplar of the normative process of allostasis. Having said that, actually estimating the normative response is difficult because there is no absolute way to best describe the rapidly changing circumstances of everyday life, nor is there a best way to model the circumstantial effects with regard to blood pressure variation as there is heteroscedasticity in the measure of blood pressure (e.g. a relationship between diurnal mean and variance) (Pickering, 1991). The heteroscedasticity is a likely outcome of arterial stiffness (Pickering, 1991); thus, if stiffness increases in the individual through the development of atherosclerosis with aging, the increased variability although initiated as an adaptive response to everyday living, could lead the individual to unsustainable high blood pressure states that could in turn initiate cardiovascular system failure. Numerous studies also show that the extent of ambulatory blood pressure responses to daily situations is moderated by the cognitive appraisal of the social conditions which can accentuate the responses. In particular, the appraisal of job strain at work by men has been shown to elevate their pressures in the work situation acutely as well as over the long term, although the effects of job strain are not as clear cut in women. Nonetheless, the increased blood pressure responses that are measured in adversely appraised situations such as the elevation in work blood pressures with job strain can potentially

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lead to pathology such as hypertension, particularly if the adverse conditions persist over time. Finally, while blood pressure allostasis can be described as a uniform physiological process, its manifestation across individuals is unlikely to be constant due to genetically based physiological variation that has arisen as a consequence of natural selection. This physiological variation was precipitated by divergent climatic conditions that affected ancestral human populations as they migrated out of Africa. This variation is also likely to have an effect on the magnitude of blood pressure responses that occur not only during adversely appraised social interactions but also with normative adaptive responses as well. References Anderson, N.B., Lane, L.D., Muranaka, M., Williams Jr., R.B., Houseworth, S.J., 1988. Racial differences in blood pressure and forearm vascular responses to the cold face stimulus. Psychosom. Med. 50, 57–63. Angeli, F., Reboldi, G., Verdecchia, P., 2010. 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