Allostatic Load: a Useful Concept for Advancing Nursing Research

DISCURSIVE PAPER Allostatic load: a useful concept for advancing nursing research

Marie-Anne S. Rosemberg , Yang Li and Julia Seng

Aims and objectives. To elucidate the historical development of the allostatic load concept, alongside its use in nursing research, and to explore how allostatic load What does this paper contribute has been investigated among two stress-vulnerable populations. to the wider global clinical Background. ‘Stress’ is a prominent term in understanding the development of community? disease. Allostatic load is among several approaches undertaken to quantify the • Nurse researchers and clinicians magnitude of stress and understand how stress can affect health. working with stress-vulnerable Method. We explored the advent of allostatic load including its antecedents, and populations need clear points of intervention and ability to deter- consequences. We used an exemplar case to apply the concept. We reviewed stud- mine impact of the interventions ies that used allostatic load among workers and women of childbearing age. in the short term. Results. There remains a need to consolidate a common definition and opera- • The concept of allostatic load is tionalisation of allostatic load. Despite this need for further work, allostatic load useful at broader levels, includ- is a good fit for nursing science which focuses on the client, environment and ing further developing measure- health. Only 12 studies explored allostatic load among workers (n = 6) and ment of multiple levels of stress that could take structural women of childbearing age (n = 6). In some studies, allostatic load was used as a inequalities, toxic and traumatic predictor while in others it was used as an outcome. None of the studies consid- stress into account as predictors ered it as a mediator. in all studies. This concept is Conclusions. The concept of allostatic load holds promise for nursing researchers also useful in advocating for to operationalise a holistic view of multiple stressors and to quantify their effects policies that decrease stress and allostatic load as a way to build on health. Studies are needed to affirm the role of allostatic load as a potential a culture of health and decrease mediator between multiple stressors and outcomes. Longitudinal studies are also burden, morbidity and costs of needed to demonstrate a causal pathway from stressor exposure to tertiary out- stress-related disease. comes such as chronic conditions and morbidity. • In the future, nursing is well Relevance to clinical practice. Allostatic load is a useful concept for nurses work- positioned to place the concept ing with stress-vulnerable populations. With the use of an interpretable allostatic of allostatic support within the theoretical framework and oper- load index, nurses will be able to intervene at various stages of the allostasis– ationalise it – in research and in adaptation process (stress-response) and adjust interventions accordingly. practice.

Key words: allostatic load, biomarkers, concept analysis, nursing research, stress, vulnerable populations, women of childbearing age, workers

Accepted for publication: 20 January 2017

Authors: Marie-Anne S. Rosemberg, PhD, MN, RN, Assistant Leadership, University of Michigan, School of Nursing, Ann Professor, Department of Systems, Populations and Leadership, Arbor, MI, USA University of Michigan, School of Nursing, Ann Arbor, MI; Correspondence: Marie-Anne S. Rosemberg, Assistant Professor, Yang Li, RN, PhD Candidate, School of Nursing, University of 400 North Ingalls, Room 3175, Ann Arbor, MI 48109, USA. Tele- Michigan, Ann Arbor, MI; Julia Seng, PhD, RN CNM, phone: +1 (734) 647 0146. FAAN, Professor, Department of Systems, Populations and E-mail: [email protected]

Aims A recent systematic review by a nurse researcher exploring the concept of AL among 58 studies indicated the lack of Nursing’s meta-paradigm defines the basis of nursing’s homogeneity in the operationalisation and measurement of work as focused on the person, environment, health and AL (Beckie 2012). Beckie (2012) also noted inconsistencies nursing (Fawcett 1984). Stressors are a ubiquitous aspect of in the study results. For example, some studies were able to ‘environment’. Types of stressors that must be taken into show a strong relationship between socio-economic status account include those at each eco-social level which are (SES) and AL biomarkers (Seeman et al. 2004), while cumulating and interacting, including social determinants, others did not (Dowd & Goldman 2006). There were also marginalised identities, socio-economics and interpersonal variations in the selection and number of indicators used in and intrapersonal factors (Juster et al. 2010). The literature operationalising the concept, which usually are added is replete with evidence supporting a strong relationship together into an AL index (Juster et al. 2010). There’s also between socio-environmental stressors and health outcomes a lack of consensus about how best to score the AL index (National Center for Health Statistics 2012, Cohen et al. (Beckie 2012). Thus, work remains to advance this promis- 2013). Nursing care includes health promotion and risk ing concept into one that can be broadly and consistently reduction interventions that address this stress diathesis. used for health research. These are necessarily complex because the stressors and adverse effects are complex while the clients are diverse. Nursing research could be enhanced by a theory that eluci- Design and method dates a mechanism for assessment of the near-term impact In this discursive paper, we extend Beckie’s (2012) work. of our interventions (i.e. have a valid proxy endpoint) with- Having selected a concept and determined the aim, we will out having to await the long-term endpoint of morbidity or follow the rest of the steps outlined by Walker and Avant mortality. The theory of allostasis, and the core concept of (2005). The work to identify uses of the concept and deter- allostatic load are excellent candidates for this purpose. mine defining attributes has been accomplished by others The aim of this discursive paper was to provide a concept (McEwen & Seeman 1999), but we will summarise. We analysis of ‘allostatic load’ to advance its use in nursing will identify antecedents and consequences. The concept research. has already been situated in a theoretical framework (Beckie 2012), but we will illustrate this with a model case. We will discuss issues related to empirical referents. Finally, Background we will extend focus on cases by looking at two small sets McEwen (1998) proposed the concept of allostatic load (AL) of studies that used AL to research stress effects on health to explicate how chronic life stressors, including toxic and of workers and childbearing women. traumatic stress, impact individuals’ health via the physiological responses to such chronic stressors. The concept of AL Evolution of the concept has been applied in research across various disciplines and findings have generally confirmed that cumulative effects of Homeostasis social and environmental stressors increase the risks for phys- In 1932, Cannon introduced the term homeostasis to iological dysregulation and ill-mental and physical health, describe the tight regulation of physiological and biochemi- especially among vulnerable groups (Seeman et al. 1997, cal function (Cannon 1932). Homeostasis involves the 2014, McEwen 2000, 2004, Read & Grundy 2012). The maintenance of balance within the bodily systems. With clinical value of this concept is that it could serve as a signal self-correcting negative feedback actions, it could reduce of health risk early enough (i.e. when the physiological dys- variability and maintain constancy from those systems regulation is still subclinical) to lead to interventions that where invariability is a characteristic of a healthy system may prevent further deterioration of health and thus prevent (Sterling & Eyer 1988). Those physiological systems work future associated morbidity and mortality. For research pur- in concert to re-establish the body’s initial conditions when- poses, it could also serve as a near-term proxy outcome or ever one or more of the systems exhibited perturbation. As endpoint in clinical health promotion and risk reduction such, homeostatic systems are those where a narrow physi- studies (Juster et al. 2010). Despite its promise, AL remains ological range is indicative of health and deviance from this underused in nursing research. range is an indication of pathology [e.g. an elevated body There may be several reasons for underuse of this con- temperature (Carlson & Chamberlain 2005)]. However, the cept (McEwen & Wingfield 2010, Read & Grundy 2012). homeostasis concept of stable states and feedback loops is

© 2017 John Wiley & Sons Ltd 5192 Journal of Clinical Nursing, 26, 5191–5205 Discursive paper Allostatic load and nursing research insufficient to capture the complexity of physiological sys- factors (e.g. low socio-economic status, stressful life events tems or account for the variability of integrative networks including trauma) and individual factors (e.g. post-trau- of adaptation to environmental stressors (Goldberger et al. matic stress, isolation or maladaptive coping). These can be 2002). Hence, the theory of allostasis was developed. thought of as occurring at all eco-social levels (Bronfen- brenner & Morris 2006) and so would include structural Allostasis inequalities and time-specific stressors, such as exposure to Allostasis refers to the mechanisms through which physio- a disaster, war or famine. logical systems adapt to a changing environment or to A variety of types of stressors have been considered as stressful challenges (Sterling & Eyer 1988, Karlamangla antecedents. For example, in the National Health and Nutri- et al. 2002, McEwen 2002). The resting points change tion Examination Surveys, the antecedent, race, was associ- according to dynamic biological processes. Variability is a ated with AL. Blacks had higher AL index scores than did healthy adaptive mechanism in response to environmental Whites at all ages (Geronimus et al. 2006). The differences in demands, which is in contrast to homeostasis which sup- AL index scores increased with age. Black women, in particu- ports stability (Carlson & Chamberlain 2005). Sterling and lar, had higher AL index scores compared with either Black Eyer (1988) proposed allostasis as the process of achieving men or White women. Lower SES (lower education, occupa- stability through change. tional status, income) and greater social challenges (recent widowhood, high demands) have been reported to be highly AL and allostatic overload correlated with higher AL (Weinstein et al. 2003). A study in McEwen and Stellar (1993) elucidated the concept of AL as a Alzheimer patients’ caregivers showed a greater number of multisystemic approach to understand the cumulative effects negative life events related to higher AL (von Kanel et al. of stress on health as the body responds to stressors that are 2003). Among the older, ties with close friends and/or neigh- chronic or severe enough to force adaptation. This central bours have been reported in relation to lower AL for both concept, AL, refers to the accumulation of wear and tear on men and women (Seeman et al. 2004). Type A personality interacting physiological systems from the adaptation process traits were associated with higher AL in a large sample (Sun (McEwen & Seeman 1999). This physiological wear and tear et al. 2007). Inactivity and poor diet have also been reported is a natural consequence or the price paid for the adaptation. in relation to higher AL (Juster et al. 2010). Variation in AL among individuals may reflect individual dif- Consequences refer to the events that result from the ferences in exposure to stressors and/or the ability to adapt occurrence of a concept (Walker & Avant 2005). Conse- to environments and challenges (Lipowicz et al. 2014). It quences that could occur as a result of AL include the lead- may also reflect allostatic supports they find or receive, which ing causes of death for vulnerable populations whose stress can be multiple and synergistic (Friedman & McEwen 2004). levels are higher by definition. Consequences of AL include In essence, given stressors and physiological responses to negative health outcomes such as cardio- and cerebrovascu- them, if the allostatic load is not too high and adaptation lar disease, cognitive deficits, weaker physical performance, occurs, health is likely to be maintained. If the allostatic load depression and premature mortality (Seplaki et al. 2004, is too high (i.e. if there is allostatic overload), the price paid Szanton et al. 2009). In the MacArthur Studies of Success- is dysregulation across multiple systems which leads to dis- ful Aging, AL index score explained 35% of socio-eco- ease development. Read and Grundy (2012) defined (high) nomic variation in mortality (Seeman et al. 2004). AL as ‘a sub-clinical dysregulation state, resulting from the body’s response to stress’ (p.1). Allostatic overload is a more Theoretical framework and model case extreme form of AL. Allostatic overload, which is AL at the pathological level, can result from sustained, severe or The British Economic and Social Research Council’s repeated stress, the failure to habituate to repeated challenge, National Centre for Research Methods Working Paper the inability to shut off allostatic responses and inadequate elaborated a conceptual framework with three stages in the allostatic responses (McEwen & Wingfield 2010). allostasis–adaptation process (Read & Grundy 2012, p. 3). The primary mediators between stress and outcomes are neuroendocrine responses (i.e. stress regulation hormones Antecedents and consequences such as cortisol, oxytocin or catecholamines). Secondary Antecedents refer to the events or attributes that must pre- outcomes are (potentially still subclinical) dysregulations cede the occurrence of a concept (Walker & Avant 2005). that can be seen in immune, metabolic, cardiovascular and Antecedents that occur prior to AL include psychosocial anthropometric indicators (i.e. C-reactive protein, glucose,

© 2017 John Wiley & Sons Ltd Journal of Clinical Nursing, 26, 5191–5205 5193 M-AS Rosemberg et al. blood pressure, hip–waist ratio). Tertiary outcomes are the adaptation to motherhood is not fulfilling to her, and she clinical manifestations that develop as dysregulations accu- chooses not to risk having any additional children, especially mulate [i.e. poor subjective health, cognitive decline, disease given depression and early ill health. It would have been pos- states and premature death (Read & Grundy 2012)]. The sible, however, to have allostasis and adaptation be the result premise and promise of AL is that a cumulative index that without adverse outcomes. Imagine an alternative scenario in captures levels of multiple biomarker or anthropometric which her stress had been reduced with a regular Spanish indicators can signal overload in time to provide a clinical interpreter in the NICU, ability to Skype with her mother in response and prevent adverse outcomes. Mexico, adequate insurance to prevent worry, maternity A model case scenario can illustrate this allostasis–adap- leave to accommodate the slow recovery from surgery and tation process (see Fig. 1). Imagine first, a scenario where the need to be with the infant, as well as nursing home visit- overload occurs. A 22-year-old Latina immigrant hotel ing to support her maternal development, monitor her low housekeeper gave birth by Caesarean to an infant with a mood and provide health promotion interventions to support genetic anomaly who was admitted to the NICU. The stres- her in regaining healthy sleep and diet until her blood glucose sors are young age, immigration status, non-native English and blood pressure normalise. Her adaptation to mothering speaker, low wages, surgical delivery and separation from a child with chronic health needs becomes a source of pride, the infant. Primary mediators involve elevated cortisol and and she channels some of her healthy energy into becoming dysregulated oxytocin. Secondary outcomes appear as sleep an interpreter in the hospital’s NICU. alterations with changes in insulin levels, altered immune and inflammatory responses and mildly elevated blood pres- Empirical referents sure. The tertiary outcomes manifest as near- and long-term outcomes. In the near term, she experiences fatigue, weight Empirical referents are the measurable ways to validate the gain, delayed bonding and slow Caesarean wound healing. occurrence of a concept (Walker & Avant 2005). To opera- In the longer term, she develops type 2 diabetes, depression, tionalise AL, measurement of biomarker and anthropometric chronic pain from adhesions and hypertension. Her indicators chosen to represent the primary mediator response

Stressors Primary Mediators Secondary Tertiary Outcomes • Young Age • Elevated cortisol Outcomes • Low SES • Dysregulated • Sleep alteration • Low wage oxytocin • Change in insulin Long Term Near Term • Language barrier levels • Type 2 diabetes • Slow healing of • Immigration • Dysregulation in • Depression Caesarean scar status immunologic & • Chronic pain and adhesion • Discrimination inflammation from adhesion formation • Surgical delivery responses • • Fatigue • Hypertension • Separation from Elevated blood • Weight gain infant pressure • Delayed bonding

Nursing care providing allostatic support at any of these points

• Spanish-speaking interpreter in NICU • Nursing home visits to monitor successful recovery • Health promotion intervention to help regain sleep and effective everyday life functioning • Access to resources (i.e. health insurance; maternity leave) • Counselling

Figure 1 Model Case Illustrating Read and Grundy’s (2012) Allostasis–Adaptation Process.

© 2017 John Wiley & Sons Ltd 5194 Journal of Clinical Nursing, 26, 5191–5205 Discursive paper Allostatic load and nursing research and secondary outcomes are combined in a clinometric index The workplace represents a major source of stress and – an AL index score. When AL was first proposed, an AL thus can impact AL leading to poor health outcomes. First, index of 10 biomarkers was used to measure the concept. The work relates to SES, and lower SES has shown to be 10 original AL measures included systolic blood pressure strongly correlated with high AL (Szanton et al. 2005). Sec- (SBP), diastolic blood pressure (DBP), waist–hip ratio (WHR), ond, work where employees experience high demand and high-density lipoprotein (HDL), total HDL/cholesterol ratio, low control (a phenomenon known as job strain) results in total cholesterol, dehydroepiandrosterone sulphate (DHEA- high stress (Karasek & Theorell 1992). Some workers are S), urinary free cortisol, noradrenaline and adrenaline (See- therefore at risk for high stress and poor health outcomes, man et al. 1997). However, studies have since used a variety making it important to explore AL among workers. of biomarkers, some using additional biomarkers (Goldman Trauma exposure and sequelae are strongly related to gen- et al. 2006, Glei et al. 2007, Bellingrath et al. 2009) and der, and pregnancy is another stress exposure unique to others using fewer (Gersten 2008, Loucks et al. 2008, Evans females, making women another key group to study in rela- & Schamberg 2009) based on the outcomes of interest that tion to AL. McEwen and Seeman (1999) pointed out that they are trying to predict or feasibility. early traumatic events combined with ongoing life stress In measuring AL, each of the different physiological sys- could contribute to AL. In a study with a random sample of tems must be represented. However, there are inconsistencies 1442 subjects from the USA, 32Á3% of women reported in the combination of indicators included in AL index across childhood sexual abuse (CSA), which was twice as much as studies (Beckie 2012, Read & Grundy 2012). Given the vari- in men (Briere & Elliott 2003). In a review of population- ation in which indicators are included in the AL index, it is based studies, 10–69% of women reported intimate partner not surprising that there are inconsistencies in study findings. violence (Krug et al. 2002). The peak age of trauma exposure Scoring is also a source of inconsistency. A summation for women is in adolescence, so post-traumatic stress – where approach is the most often used method to calculate the re-experiencing the trauma in memory, flashbacks or night- index score. Individuals are ranked by the indicator values, mares is a hallmark of the disorder and an intrapersonal ranging between the highest and lowest risks (Seeman et al. chronic stress – is also prevalent early in the lifespan and dur- 1997). Individuals in the highest risk quartile for each indica- ing reproduction (Breslau 2002). There is growing evidence tor are ‘1’ and others are ‘0’. These are summed so that those suggesting the causal links between adverse childhood events, with the highest sum score have the highest AL and are con- adult traumatic events, traumatic stress sequelae and physical sidered at risk for poor tertiary outcomes (Read & Grundy and reproductive health outcomes (Felitti et al. 1998, Camp- 2012). Thus, AL has been operationalised as a count-based bell 2002, Groer et al. 2016). Thus, women of childbearing multisystemic index representing the sum of biomarkers and age who are experiencing traumatic stress are another prior- anthropometric indicators falling within a high-risk per- ity population among which to explore the mediating role of centile based on the sample’s distribution of values (Juster AL on the association of stress with adverse health outcomes. et al. 2010). This approach presents some unique challenges To find articles with which to explore these research ‘cases’ in that there is loss of granularity in the data reduction and to illustrate the AL model, we searched PubMed, Web of the amount of risk depends on the nature of the sample itself. Science, CINAHL, PsycInfo and Scopus databases using the Alternative scoring approaches have been considered (Karla- keywords: AL and workers and AL and women of childbear- mangla et al. 2002, Seplaki et al. 2005, Gruenewald et al. ing age. Our initial search yielded 207 articles across all the 2006) and more consensus may emerge in the near future. databases. We only included articles that were written in Eng- lish and for which full texts were provided. We then limited selection to the handful that specifically used the theory of Extending the analysis of AL concept from clinical case allostasis as their conceptual framework for the study in rela- to research examples with two vulnerable populations tion to workers (six papers, Table 1) or women of childbear- The model case scenario above was a clinical example at ing age (six papers, Table 2). how the concept of AL could function within a single individual. In the near term, it is more likely that AL’s useful- AL and workers ness in nursing will be as a concept deployed in research. Six studies were identified exploring AL among workers. The So we will extend the illustration of AL as a concept link- studies were conducted in industrialised nations, included ing stress and adverse health outcomes by exploring studies men and women, and focused primarily on industry employ- reported about two stress-vulnerable populations, workers ees. The studies took place in across several countries includ- and women of childbearing age. ing the USA, Sweden, Germany and China. There were

Table 1 Allostatic load and workers al. et

Role of AL Reference Sample (workers (mediator or (author/year) vs. women) Study Purpose AL Deﬁnition AL Component Scoring Method predictor) Study Findings Notes

de Castro N = 30 male Latino This was a pilot study The physiological SBP, DBP, salivary The sum of the Outcome Average age was Suggested need for et al. (2010) day labourers in – cross-sectional effects of chronic cortisol, WHR, number of biological (dependent 46 years and the studies to explore AL Seattle Washington, design. stress CRP and BMI measures on which variable) average length of as a mediator USA To evaluate the each participant residency in the USA between stressors and feasibility of scored in the top was 12 years. 47% clinical health conducting a research quartile of risk for were married and the outcomes. Used the project focused on the total sample majority (97%) spoke ﬁnger prick and stressors (work Spanish and were sterile lancet to related, economic, from Mexico (77%). collect the blood for social) and AL among Workers who reported the CRP. day labourers more stressors (work, Trust and economic, social) had collaboration higher AL physically between researchers and mentally. and community They found no partners are very statistical signiﬁcance important. between the groups They calculated AL compared with those score by summing the with low AL who number of parameters have been working as in which levels were day labourers for just in the highest quartile under 5 years (at or above the 75% ora fCiia Nursing Clinical of Journal quartile) and the parameters in the lowest quartile. AL scores can range from

07Jh ie osLtd Sons & Wiley John 2017 were then further dichotomised into two categories low and high , 26 5191–5205 , ora fCiia Nursing Clinical of Journal © icriepaper Discursive 07Jh ie osLtd Sons & Wiley John 2017

Table 1 (continued)

Role of AL Reference Sample (workers (mediator or (author/year) vs. women) Study Purpose AL Deﬁnition AL Component Scoring Method predictor) Study Findings Notes

, von Thiele N 241 healthy This was a secondary A multisystems SBP, DBP, HR, The sum of the Outcome No significant Insufficient recovery 26 et al. (2006) women working in data analysis. approach describes HDL, LDL, LDL/ number of biological differences in the from work stress may 5191–5205 , two public healthcare To investigate the how daily stress HDL ratio, TC, measures on which demographic result in high AL. organisations in relationships between relates to health and TG, serum each participant characteristics of Acknowledged that the Stockholm, Sweden self-rated recovery disease DHEA-S, glucose, scored in the top study participants. operationalisation of from work stress and HbA1c, prolactin quartile of risk for The fatigued women AL differs between biological and WHR. the total sample had an increased risk studies depending on dysregulation in (except for HDL and for high AL. In the type and number terms of AL and DHEA-S, where contrast, there was of biomarkers individual inclusion into the no significant available biomarkers, lowest quartile difference in respectively, in constitutes risk) individual biomarkers healthy women between recovered within the public and nonrecovered healthcare sector women Sun et al. N = 1219 healthy This was a cross- 1. The accumulation of FIB, CRP, cortisol, The sum of the Outcome The average age was 38. Excluded people (2007) Chinese employees sectional study wear and tear on adnephrin, BMI, number of biological About 70% had a already diagnosed including both men design. physiological systems WHR, SBP, DBP, measures on which college level education. with conditions (50%) and women To determine the from the process of HbA1c, IGR, TC/ each participant High job strain had such as hypertension (50%) from five relationship between adaptation to chronic HDL, HDL and scored in the top higher AL compared to and diabetes or industries in China job strain and AL stress. TG quartile of risk for low job strain. Positive taking medication for 2. A possible the total sample association between these conditions; also biological warning (except for HDL in AL and age (r = .203, measured type A system for health the lowest quartile) p < 0Á001), and behaviour which outcomes. positive relationship showed to be 3. The cumulative between AL and associated with physiological toll that education level (lower higher job strain. may be exacted on education yielded to They also assessed for lottcla n usn research nursing and load Allostatic the body through its higher job strain) behavioural responses attempts to adapt to (r = À0.122, associated with stress life’s demands P < 0Á001) such as smoking, alcohol intake, diet and exercise 5197 5198 Table 1 (continued) Rosemberg M-AS

Role of AL Reference Sample (workers (mediator or (author/year) vs. women) Study Purpose AL Deﬁnition AL Component Scoring Method predictor) Study Findings Notes

Schnorpfeil N = 324 employees This was a cross- A biological warning BMI, WHR, SBP, The sum of the Outcome Older individuals and tal. et et al. (2003) from an airplane sectional study system DBP, CRP, TNF- number of biological men had higher AL manufacturing plant design. a, HDL, measures on which scores than younger in Germany To evaluate the cholesterol, each participant participants and relationship between DHEA-S, HbA1c, scored in the top women. Job demand objective health urinary cortisol, quartile of risk for related signiﬁcantly status and work adrenaline, the total sample to AL characteristics in the noradrenaline and (except for HDL, workers albumin DHEA-S and cholesterol in the lowest quartile) Hasson Female employees To investigate how A multisystems SBP, DBP, HR, The sum of the Outcome A poor self-rated et al. (2009) from the healthcare biological approach describes HDL, LDL, LDL/ number of biological health, along with sector (n = 241) and dysregulation, in how daily stress HDL ratio, TC, measures on which occupational sector, IT/media sector terms of AL, relates relates to health and TG, serum each participant age and education, (n = 98), Stockholm, to self-rated health disease. DHEA-S, glucose, scored in the top were signiﬁcantly Sweden (SRH) in women HbA1c, prolactin quartile of risk for associated with a and WHR the total sample high AL, particularly (except for HDL and for those working DHEA-S in the within the healthcare lowest quartile) sector. Li et al. (2007) N-504 industrial To evaluate the The price of allostasis BMI, WHR, The sum of the Outcome 50% were male. Most employees, China relationship between HbA1c, B-cell number of biological were married (78%). job stress and function, TC, TG, measures on which About 70% had a glycolipid metabolic HDL, LDL, each participant college level change in healthy adiponectin and scored in the top education. industrial employees visfatin quartile of risk for High job stress was in China the total sample extremely correlated ora fCiia Nursing Clinical of Journal (except for HDL, with increased adiponectin and B- glycolipid AL score. cell function in the Low job control lowest quartile) showed to be the

07Jh ie osLtd Sons & Wiley John 2017 impacting health outcomes in the participants

AL, allostatic load; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; DHEA-S, dehydroepiandrosterone sulphate; HDL, high-density lipoprotein; ,

26 LDL, low-density lipoprotein; TC, total cholesterol; TG, triglyceride; FIB, ﬁbrinogen; IGR, insulin–glucose ratio; HbA1c, glycosylated haemoglobin; HR, heart rate; WHR, waist–hip 5191–5205 , ratio; CRP, C-reactive protein; TNF-a, tumour necrosis factor alpha. ora fCiia Nursing Clinical of Journal © icriepaper Discursive 07Jh ie osLtd Sons & Wiley John 2017

Table 2 Allostatic load and women

Sample Role of AL Reference (workers vs. (mediator or

, (author/year) women) Study Purpose AL Deﬁnition AL Component Scoring Method predictor) Study Findings Notes 26 5191–5205 , Lindfors N = 200 women To investigate The dysregulation in Resting SBP and DBP, The sum of the Predictor All women were et al. with no previously how physiological multiple bodily HDL, TC, HbA1c, WHR number of biological 43 years old. 77Á5% (2006) diagnosed dysregulation, in systems in response and PEF measures on which were married or pathology in terms of AL and to stress challenges each participant living with a partner. Sweden clinical risk, over the life course scored in the top 94Á5% had children. respectively, relates quartile of risk for 51Á5% had a lower to sense of the total sample education. coherence (SOC) (except for HDL and AL was found to in women with no PEF in the lowest predict future SOC, previously diagnosed quartile) whereas clinical risk pathology did not Gustafsson N = 394 women To examine whether The cumulative SBP, DBP, BMI, waist The sum of the Outcome All women were et al. (2012) in Sweden social and material dysregulations which circumference, fasting number of biological 43 years of age. adversity over the life eventually develop glucose, TC, HDL, TG, measures which was Social adversity course is related to across multiple apolipoprotein A1 and B, divided into tertiles accumulated over the AL in mid-adulthood interconnected CRP and diurnal salivary (coded 0, 1, 2), life course was physiological systems cortisol AUC except for cortisol related to AL, as a result of (coded symmetrically independently of frequently repeated or with sextile: 1 and cumulative socio- chronic activation 6 = 2, 2 and 5 = 1, 3 economic over the life course and 4 = 0) and HDL disadvantage. (coded inversely: 2, 1, Moreover, social 0) adversity in adolescence was related to AL,

independently of research nursing and load Allostatic cumulative socioeconomic disadvantage and also of later adversity exposure during adulthood 5199 5200 -SRosemberg M-AS

Table 2 (continued)

Sample Role of AL al. et Reference (workers vs. (mediator or (author/year) women) Study Purpose AL Deﬁnition AL Component Scoring Method predictor) Study Findings Notes

Morrison N = 6131 To determine whether The cumulative wear SBP, DBP, 60-second pulse The sum of the Outcome Women were aged 15– et al. pregnant women AL can be measured and tear on the body rate, homocysteine, CRP, number of biological 44 years. Among (2013) (n = 1138) and in a meaningful way resulting from serum albumin, HbA1c, measures on which pregnant women, nonpregnant during pregnancy exposure to chronic HDL, TC and creatinine each participant 56Á4% were non- (n = 4993) stress scored in the top Hispanic White, women in the quartile of risk for 14Á2% were non- USA the total sample Hispanic Black, (except for HDL and 16Á1% were Mexican serum albumin in the American, and 13Á2% lowest quartile) were other races; Among nonpregnant women, 66Á1% were non-Hispanic White, 12Á6% were non- Hispanic Black, 9Á4% were Mexican American, and 11Á9% were other races. The distribution of each AL-related biomarker differed signiﬁcantly between pregnant and nonpregnant women. ora fCiia Nursing Clinical of Journal Among nonpregnant women, higher AL was found in women who are Black, are

, women 26 5191–5205 , ora fCiia Nursing Clinical of Journal © icriepaper Discursive 07Jh ie osLtd Sons & Wiley John 2017

Table 2 (continued)

Sample Role of AL Reference (workers vs. (mediator or (author/year) women) Study Purpose AL Deﬁnition AL Component Scoring Method predictor) Study Findings Notes

= – , Wallace N 886 women To examine more The dysregulation SBP, DBP, TC, HDL, LDL, The sum of the Predictor Women were aged 13 26 et al. from the Bogalusa closely the across the body’s TG, glucose, insulin and number of biological 41 years. 59Á4% of 5191–5205 , (2013) Heart Study in relationships between multiple physiological waist circumference measures on which women are White, the USA AL, race and adverse systems responsible each participant and 40Á6% of women birth outcomes within for maintaining scored in the top are African American. the context of equilibrium when quartile of risk for African American neighbourhood-level faced with physical the total sample women resided in poverty or social challenges (except for HDL in more impoverished the lowest quartile) neighbourhoods and had higher AL scores compared with Whites; however, AL was not associated with preterm birth or low birthweight. Wallace and N = 123 women To identify The wear and tear on Cholesterol, cortisol, The sum of z-scores Predictor Women were aged 20– Harville at 26-28 weeks associations between the body that arises DHEA-S, HbA1c and for all ﬁve biological 35 years. All are (2013) gestation in the AL and birth from chronic, SBP measures White or African USA outcomes and to prolonged or American. assess differences in persistent activation Black women had a AL and its relation to of allostatic effectors lower AL index than birth outcomes and a breakdown of White women. between White and the regulatory Gestational age was Black women feedback mechanisms associated with AL. A signiﬁcant interaction with age indicated that the

effect wasn’t as research nursing and load Allostatic strong at higher maternal ages. There was no racial difference in the effect of AL on birth outcomes 5201 M-AS Rosemberg et al.

signiﬁcant variations in the operationalisation of AL across the studies. The number of indicators used in the AL index ranged from 6–14 (Table 3). All the studies included primary

was poorly designed, it is difﬁcult to determine whether differences in AL occur prior to or after pregnancy as a result of the adverse outcomes and secondary indicators in the AL index, and all the studies As the study reviewed used the high-risk scoring approach (e.g. highest – quartile for BMI or glucose, lowest quartile for HDL cholesterol or DHEA-S). In all of the studies, AL was used as a 4% are Á 1% are Á dependent variable (an outcome). None of the studies used

HDL, high-density lipoprotein; AL as a mediator or an independent variable (a predictor). 9% are Black, and Á 6% are other races.

Á All of the studies found a positive relationship between the 35 years. 62 White, 20 Latino/Hispanic, 14 2 of small for gestational age or preterm birth had higher AL than did those with normal birthweight outcomes Women with history stressors (i.e. job strain, recovery from work stress) and AL index score. None of the studies explored tertiary outcomes

hip ratio; CRP, C-reactive protein; AUC, area such as chronic diseases, quality of life or mortality. – Role of AL (mediator or predictor)Predictor Study Findings Women were aged 17 Notes AL and women of childbearing age Two of the articles focused on pregnant women to examine the relationships between AL and adverse birth outcomes. All six studies included women of childbearing age, with the age ranging from 13–44 years. Four studies used primary and secondary outcome indicators in the AL index (Table 3). All of number of biological measures on which each participant scored in the top quartile of risk for the total sample (except for HDL and serum albumin in the lowest quartile) The sum of the the studies except one used the upper and lower quartile scoring approach to AL. Wallace and Harville (2013) used the sum of the z-scores for the biomarkers. Again these six studies mod- elled either the contributing factors of AL (as a dependent variable) or adverse outcomes of AL (AL as a predictor). The predictors of AL included PTSD, age, race, ethnicity, chronic work, ﬁnancial and caregiving stress, lifestyle factors (e.g. exer- serum albumin, HbA1c, HDL, TC and creatinine

SBP, DBP, BMI, CRP, cise, alcohol consumption and smoking), social adversity (e.g. parental illness or loss, residential instability, exposure to threat/violence) and occupational social class. Adverse outcomes of AL included sense of coherence (Lindfors et al. 2006) and adverse birth outcomes [e.g. preterm birth, low birthweight (Wallace & Harville 2013)]. of chronic physiological and psychological stress The cumulative burden Conclusions

We aimed to extend analysis of the concept of AL to advance its use in nursing research as it is a concept well suited to the nursing meta-paradigm and to health promotion and risk reduction intervention science. Important papers have past history of having had a pregnancy with low birthweight outcome is associated with higher AL To determine whether recently reviewed and clearly delineated the theory (Read & Grundy 2012) and systematically reviewed AL research (Beckie 2012), and these reviews highlighted areas for further methodological work. It is apparent that we need more con-

877 women sistent operationalisation in terms of indicators to include = in the USA Sample (workers vs. women) Study Purpose AL Deﬁnition AL Component Scoring Method N and scoring methods to apply. From examining these two sets of study reports on different populations to serve as (continued) research cases to illustrate the concept in use, we see mostly

et al. affirmation for the proposition that stress leads to higher AL (2014) under the curve; PEF, peak expiratory flow. Table 2 Reference (author/year) AL, allostatic load; BMI,LDL, body low-density lipoprotein; mass TC, index; total SBP, cholesterol; systolic TG, blood triglyceride; pressure; FIB, DBP, fibrinogen; diastolic HbA1c, blood glycosylated pressure; haemoglobin; WHR, DHEA-S, waist dehydroepiandrosterone sulphate; Hux and for the proposition that higher AL leads to adverse

Table 3 Measures of AL across each studies to determine impact of the interventions in the short term. Health promotion and risk reduction research is usually beha- Reference (Author/year) Measures of AL vioural and often depends on self-reported, near-term outcomes such as self-efficacy, intention or observation of de Castro et al. SBP, DBP, salivary cortisol, WHR, CRP and behaviour. This is because it is notoriously difficult to demon- (2010) BMI von Thiele SBP, DBP, HR, HDL, LDL, LDL/HDL strate prevention of disease in the long term. Practical consid- et al. (2006) ratio, TC, TG, serum DHEA-S, glucose, erations also foster adopting simple designs (i.e. one primary HbA1c, prolactin and WHR outcome) that cannot represent complexity that we know is Sun et al. (2007) FIB, CRP, cortisol, adnephrin, BMI, WHR, operating, and often the outcome has to be a proximal end- SBP, DBP, HbA1c, IGR, TC/HDL, HDL point (e.g. change in mean blood pressure) because follow-up and TG Schnorpfeil BMI, WHR, SBP, DBP, CRP, TNF-a, HDL, to the manifestation of disease (e.g. prevention of hyperten- et al. (2003) cholesterol, DHEA-S, HbA1c, urinary sion diagnosis) is not feasible. Clinical practice has constraints cortisol, adrenaline, noradrenaline and that are similar. Intervening early and seeing progress during albumin the sometimes extended period of care needed to achieve the Hasson et al. (2009) SBP, DBP, HR, HDL, LDL, LDL/HDL intervention goal are sustaining and reinforcing for both the ratio, TC, TG, serum DHEA-S, glucose, nurse and the client. Being able to explain the concept of AL HbA1c, prolactin and WHR Li et al. (2007) BMI, WHR, HbA1c, B-cell function, TC, to clients, being able to run a panel of tests that yield an inter- TG, HDL, LDL, adiponectin and visfatin. pretable ‘AL index’ result, and being able to adjust interven- Lindfors et al. Resting SBP and DBP, HDL, TC, HbA1c, tions in response would be useful. (2006) WHR and PEF The theory of allostasis is useful at broader levels as Gustafsson SBP, DBP, BMI, waist circumference, fasting well, including population health and policy. Further et al. (2012) glucose, TC, HDL, TG, apolipoprotein A1 and B, CRP and diurnal salivary cortisol developing measurement of multiple levels of stress could AUC take what we know about structural inequalities, as well Morrison SBP, DBP, 60-second pulse rate, as toxic and traumatic stress, into account as predictors et al. (2013) homocysteine, CRP, serum albumin, in all studies. Tailoring with additional measures for HbA1c, HDL, TC and creatinine specific populations will also be needed (e.g. measures of Wallace et al. (2013) SBP, DBP, TC, HDL, LDL, TG, glucose, job strain and work–life balance for studies of workers, insulin and waist circumference Wallace and Cholesterol, cortisol, DHEA-S, HbA1c and and measures of pregnancy-specific stress for perinatal Harville (2013) SBP studies). We could advocate for policies that decrease Hux et al. (2014) SBP, DBP, BMI, CRP, serum albumin, stress and AL as a way to build a culture of health and HbA1c, HDL, TC and creatinine decrease burden, morbidity and costs of stress-related dis- AL, allostatic load; BMI, body mass index; SBP, systolic blood pres- ease. sure; DBP, diastolic blood pressure; DHEA-S, dehydroepiandros- Finally, the concept of AL has been paired with the terone sulphate; HDL, high-density lipoprotein; LDL, low-density concept of allostatic support (Friedman & McEwen lipoprotein; TC, total cholesterol; TG, triglyceride; FIB, fibrinogen; 2004), but this twin concept has not been synthesised IGR, insulin–glucose ratio; HbA1c, glycosylated haemoglobin; HR, formally. Given the state of the science on AL, there heart rate; WHR, waist–hip ratio; CRP, C-reactive protein; TNF-a, tumour necrosis factor alpha; AUC, area under the curve. may be higher priority tasks. However, the goal of the theory is to depict not only the scenario where dysregulation from overload leads to disease but also the scenario outcomes. Further research is needed to test the entire model, where allostasis leads to adaptation for optimal health with AL as the mediator between stress and adverse out- under the circumstances. In the future, nursing is well comes – ideally with prospective designs. If such theory-test- positioned to place the concept of allostatic support ing research validates AL as a mediator, that will serve as a within the theoretical framework and operationalise it – more solid test of concept for AL to be used as a proximal in research and in practice. endpoint for clinical research. Contributions Relevance to clinical practice MAR, YL, JS contributed to the conceptualization and Nurse researchers and clinicians working with stress-vulner- development of the manuscript. MAR and YL conducted able populations need clear points of intervention and ability the literature reviews.

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