Health Psychology 2015, Vol. 34, No. 7, 765–774

© 2014 American Psychological Association 0278-6133/15/$12.00 http://dx.doi.org/10.1037/hea0000194

Stressful Life Events and Orthostatic Blood Pressure Recovery in Older Adults Joanne Feeney and Cara Dooley

Ciarán Finucane

Trinity College

Trinity College and St. James’s Hospital, Dublin, Ireland

Rose Anne Kenny This document is copyrighted by the American Psychological Association or one of its allied publishers. This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.

Trinity College Objective: The majority of the literature on stress and blood pressure (BP) concerns the increased risk of cardiovascular morbidity and mortality from high BP. Because the sympathetic nervous system is critical to the maintenance of orthostatic BP, it was hypothesized that older adults who have experienced more stressful life events (SLEs) would be more likely to show impaired recovery of BP in response to orthostatic stress. Method: A total of 3,765 participants (Mage ⫽ 61.6 years, SD ⫽ 8.2; 54% female) from the first wave of The Irish Longitudinal Study on Ageing (TILDA) were included in the current analysis. Exposure to lifetime SLEs was ascertained by self-completion questionnaire, and beat-to-beat orthostatic BP measurement was carried out. Individuals who failed to recover at least 95% of their baseline BP by 60 s post stand were characterized as having impaired orthostatic BP recovery. Results: An independent, dose-response relationship between the number of SLEs reported and the odds of impaired systolic BP recovery was observed after adjustment for covariates (1 event: odds ratio [OR] ⫽ 1.19, 95% confidence interval [CI] [0.98, 1.45], p ⫽ .078; 2 events: OR ⫽ 1.33, 95% CI [1.03, 1.73], p ⫽ .031; 3 or more events: OR ⫽ 1.56, 95% CI [1.12, 1.73], p ⫽ .009). This relationship was not evident for diastolic BP recovery. Conclusion: The reporting of a higher number of SLEs is associated with greater risk of impaired systolic BP recovery from orthostatic stress. Potential clinical implications include an increased risk of cerebral hypoperfusion, which predisposes older adults to falls, faints, and changes in cognitive status. Keywords: stress, life events, blood pressure, orthostatic stress, ageing Supplemental materials: http://dx.doi.org/10.1037/hea0000194.supp

Thomas, Nelesen, Ziegler, Bardwell, and Dimsdale (2004) found that individuals experiencing high job strain have a greater BP response to a sympathetic agonist than those with lower levels of job-related stress. Furthermore, those individuals with lower reported levels of perceived control exhibited evidence of blunted baroreflex sensitivity. The “reactivity hypothesis” posits that individuals with high prior stress exposure or those currently experiencing high levels of stress are more likely to exhibit an increase in physiological parameters such as BP and heart rate, in response to a mental or psychosocial stress task, than those with no such prior exposure (Roy, Steptoe, & Kirschbaum, 1998). Increased BP reactivity to laboratory stressors has also been associated with an increase in ambulatory BP over time (Carroll, Ring, Hunt, Ford, & Macintyre, 2003; Light et al., 1999). However, a growing number of studies examining the effects of exposure to stressful life events (SLEs) on cardiovascular reactivity have found the converse; that is, that high stress exposure is associated with a blunting of the BP response to subsequent stressors (Boyce & Chesterman, 1990; Carroll, Phillips, Ring, Der, & Hunt, 2005; Lovallo, Farag, Sorocco, Cohoon, & Vincent, 2012; Matthews, Gump, & Owens, 2001). This finding of an attenuated response is likely equally reflective of underlying system dysregulation (Lovallo, 2011). Exposure to cumulative adverse events may contribute more to autonomic dysregulation than isolated events, because the system

There is a well-established association between the experience of emotional stress and the regulation of blood pressure (BP) by the autonomic nervous system (ANS). The link between stress and hypertension is widely documented, and stress has been proposed as a triggering stimulus for adverse cardiac events such as myocardial infarction and stroke (Chi & Kloner, 2003; Middlekauff et al., 1997). Experimental evidence has also demonstrated an association between stress and various indices of autonomic function.

This article was published Online First December 22, 2014. Joanne Feeney and Cara Dooley, The Irish Longitudinal Study on Ageing, Department of Medical Gerontology, Trinity College; Ciarán Finucane, The Irish Longitudinal Study on Ageing, Department of Medical Gerontology, Trinity College, and Department of Medical Physics and Bioengineering, St. James’s Hospital, Dublin, Ireland; and Rose Anne Kenny, The Irish Longitudinal Study on Ageing, Department of Medical Gerontology, Trinity College. Joanne Feeney is now at Queen’s University Belfast. Supported by the Atlantic Philanthropies, Irish Life plc, the Irish Government, and the Centre for Ageing Research & Development in Ireland (CARDI) Leadership Programme in Ageing Research. Correspondence concerning this article should be addressed to Joanne Feeney, Centre for Public Health, Queen’s University Belfast, Belfast BT12 6BA, United Kingdom. E-mail: [email protected] 765

FEENEY, DOOLEY, FINUCANE, AND KENNY

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may become less responsive through repeated exposures (Taylor, Way, & Seeman, 2011), resulting over time in changes in blood behavior in response to physiological and environmental demands. Many studies have examined the impact of SLEs on the BP behavior in response to acute psychological stressors. Few, however, have examined the relationship between exposure to SLEs and BP regulation during physiological challenges, which also trigger an ANS response, such as standing suddenly from a seated or supine position (known as orthostatic stress). An exaggerated drop in blood pressure on stand— orthostatic hypotension—is more prevalent in the elderly and is associated with an increased risk of falls (Ooi, Hossain, & Lipsitz, 2000), syncope (Angaran et al., 2011), depression (O’Regan et al., 2013), and all-cause mortality (Xin, Lin, & Mi, 2014). Recently, following technological advancements, there has been increased interest in delineating beat-to-beat patterns of blood pressure recovery from orthostatic stress. Prior research has shown that delayed recovery of BP to baseline levels within the first minute after orthostatic challenge is associated with frailty (Romero-Ortuno, Cogan, O’Shea, Lawlor, & Kenny, 2011), symptoms of dizziness (known as “orthostatic intolerance”; Romero-Ortuno, Cogan, Fan, & Kenny, 2010), and lower cognitive performance (Frewen et al., 2013). Furthermore, Lagro et al. (2014) have shown that poor recovery of systolic BP (SBP) during the first minute after standing, and not the magnitude of the initial drop in BP, predicted mortality over the subsequent 5-year period among older outpatients attending a falls clinic, suggesting that impaired blood pressure recovery after orthostasis may be an independent marker of long-term health risk. The effect of the interaction between stress exposure and other potentially important factors, such as age, on the ANS also warrants investigation. Older adults may be particularly vulnerable to the adverse effects of stress as age-related physiological changes reduce the ability of the body to respond adequately to threats to homeostasis (Maruyama, 2012). Older adults are also more likely to experience more severe life events than younger adults (e.g., loss of a spouse or parent), making this an interesting group to study in the context of cumulative life events exposure. The majority of the literature on the impact of stress on ANS function and blood pressure behavior concerns how stress exposure relates to cardiovascular reactivity to laboratory stressors and an increased risk of cardiovascular events (e.g., stroke and myocardial infarction). Because the ANS is also critical to the regulation of orthostatic BP behavior and an impaired orthostatic hemodynamic profile has been independently associated with adverse health outcomes, the potential impact of prior stress exposure on this physiological response merits investigation. On the basis of the empirical evidence that higher prior stress exposure is associated with altered blood pressure regulation, it was hypothesized that older adults who were exposed to a higher number of SLEs would be more likely to show impaired recovery of BP in response to orthostatic stress.

Method

study that aims to assess the health, social, and economic characteristics of adults aged 50 years and older in Ireland. A representative sample for study was selected using the RANSAM sampling methodology (Whelan, 1979), which meant that every member of the population of Ireland aged 50 and older living at a private residential address was equally likely to be invited to participate in the study. TILDA surveyed 8,175 adults aged 50 and older at Wave 1, and the study design has been described previously (Kearney, Cronin, O’Regan, Kamiya, Savva, et al., 2011). Individuals with overt dementia were excluded at baseline. TILDA employs three complementary modes of data collection: (a) a computer-assisted personal interview (CAPI), which is carried out in the participant’s own home; (b) a self-completion questionnaire (SCQ); and (c) a comprehensive health assessment carried out by study nurses in one of two dedicated health assessment centers. Participants who refused or were unable to attend a health center assessment were offered a modified health assessment carried out in their own homes. Ethics approval was obtained by the institutional review board, and all respondents provided signed informed consent prior to participation in the study.

Measurement of Orthostatic Blood Pressure Behavior Orthostatic blood pressure was measured during the centerbased health assessment using beat-to-beat digital plethysmography (Finometer MIDI; Finapres Medical Systems, Arnhem, The Netherlands). Subjects underwent a lying-to-standing orthostatic stress test (active stand). For this test, participants lay in a supine position for at least 10 min before stand. Beat-to-beat recordings of 180 s in duration, beginning 60 s before stand and lasting 120 s after stand, were taken. Orthostatic BP analysis required a number of steps including: (a) data quality screening and artifact rejection; (b) preprocessing and filtering; and (c) BP waveform feature extraction as described previously (Soraghan et al., 2014). Custom-written Matlab, Version 13.0, was used to perform this first stage of signal processing. A 10-s moving average filter was used to smooth the beat-to-beat BP variations (van der Velde, van den Meiracker, Stricker, & van der Cammen, 2007). Baseline (supine) SBP and diastolic (DBP) blood pressure were defined as the average SBP/DBP over a period of 60 s—30 s before stand. The nadir was taken as the lowest value of SBP and DBP reached within 30 s of active stand and expressed as a percentage of baseline BP. SBP/DBP recovery was defined as the percentage of the baseline BP recovered by 20, 30, 60, 90, and 110 s after stand. Participants were then classified into groups based on their recovery by 60 s after stand, as per Lagro et al. (2014) and in line with the morphological clusters of orthostatic BP behavior identified by Romero-Ortuno, Cogan, Foran, Kenny, & Fan (2011). Participants were classed as being fully recovered if they had recovered more than 95% of their baseline SBP or DBP within 60 s. They were classed as only partially recovered if their SBP/DBP had reached between 80% and 95% of baseline levels by 60 s; and less than 80% recovery of baseline BP was defined as nonrecovery (Lagro et al., 2014).

Participants Data were collected during the first wave of The Irish Longitudinal Study on Ageing (TILDA), which took place between 2009 and 2011. TILDA is a nationally representative prospective cohort

Stressful Life Events Ten retrospectively recalled life events were used to derive a cumulative index of SLEs. Eight items were taken from a larger

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LIFE EVENTS AND ORTHOSTATIC BLOOD PRESSURE

list of SLEs (Krause, Shaw, & Cairney, 2004). The questions were included as part of the SCQ and were dichotomously scored. Participants were asked: whether they had ever been in a fire, flood, or other natural disaster; whether a partner or child had ever been addicted to alcohol or drugs; whether they had experienced a serious physical assault; whether a partner or child had ever had a life-threatening illness or accident; whether a child of theirs had died; whether there was alcohol or substance abuse in the family before the participant was aged 18; whether they were physically abused by a parent before the age of 18; and whether they were physically abused by someone other than a parent before the age of 18. Another two questions on childhood sexual abuse were also included: sexual abuse by a parent before the age of 18; and sexual abuse by someone other than a parent before the age of 18. No further information on duration or severity of the events in question was sought. The two childhood sexual abuse items were collapsed to form a single childhood sexual abuse item for analysis. Similarly, the two childhood physical abuse items were also collapsed. The number of “yes” responses was summed to create a cumulative measure of SLEs for use in the current analysis. Table 1 displays the frequency of “yes” responses to each event. Participants were grouped for analysis according to how many life events they endorsed: 0 events (n ⫽ 1,955), 1 event (n ⫽ 1,071), 2 events (n ⫽ 459), or 3 or more events (n ⫽ 280).

Covariates Other information concerning potential confounds, such as demographic characteristics, socioeconomic status, health conditions, health behaviors, mental health, and medication use, was also gathered and entered into multivariable models.

Sociodemographic Information Participant age, sex, and highest level of education (none/primary, secondary, or tertiary and higher) was recorded. Household income was recorded and represented in quintiles for analysis. The highest level of education completed by the participant’s father was also collected to provide an indicator of childhood socioeconomic status.

Diagnosed Disease and Health Behaviors Respondents were asked whether they had ever received a doctor’s diagnosis of a number of cardiovascular conditions: heart

Table 1 Type and Frequency of Life Events Type of event

n

%

Fire, flood, other natural disaster Partner/child addicted to drugs/alcohol Victim of a serious physical assault Partner/child had a life-threatening illness/accident Death of a child Problematic parental alcohol or drug use (before age of 18) Victim of physical abuse (before age of 18) Victim of sexual abuse (before age of 18)

188 306 227 908 368 385 305 278

5.0 8.2 6.0 24.1 9.8 10.2 8.1 7.4

Note.

N ⫽ 3,765.

767

failure, angina, heart attack, stroke or transient ischemic attack, heart murmur, abnormal heart rhythm, and diabetes. Body mass index (BMI) was also calculated for all respondents who participated in a health assessment. Depression was assessed during the health assessment using the 8-item Center for Epidemiologic Studies Depression Scale (CES-D; Radloff, 1977). Symptoms of anxiety were assessed as part of the SCQ using the 7-item Anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A; Zigmond & Snaith, 1983). Higher scores on both scales are indicative of higher levels of depression and anxiety, respectively. Physical activity was assessed using the 8-item short form of the International Physical Activity Questionnaire (IPAQ; Craig et al., 2003). This questionnaire was used to derive a categorical variable for analysis representing low, medium, and high levels of physical activity using the IPAQ protocol (see http://www.ipaq.ki.se). Problem drinking was assessed by the CAGE questionnaire (Mayfield, McLeod, & Hall, 1974). This is a 4-item scale with a yes/no response format. A score of 2 or higher out of 4 is considered clinically significant for the identification of problem drinking, with sensitivity of 93% and a specificity of 76% (Bernadt, Taylor, Mumford, Smith, & Murray, 1982). Smoking was recorded as current, past, or never.

Medications Self-reported medication use was recorded during CAPI and confirmed by cross-checking with medication labels. Medications were classified according to the Anatomical Therapeutic Classification (see http://www.whocc.no/atc_ddd_index/). A dichotomous variable was generated to indicate if a respondent was taking any antihypertensive medication. For this analysis, antihypertensive medications were defined as blood pressure⫺modifying agents and comprised diuretics (C03), beta-blockers (C07), calcium channel blockers (C08), angiotensin-converting enzyme inhibitors/ angiotensin-receptor blockers (C09), and antiadrenergic agents and combinations of antiadrenergic agents with the other pharmaceuticals above (C02). Psychotropic medications were also classified. They were defined as nervous system drugs comprising antiParkinson drugs (N04), psycholeptics (N05) and psychoanaleptics (N06), and parasympathomimetics (N07A).

Statistical Analysis Bivariate associations between BP variables and potential covariates of interest were explored using chi-square tests of association for categorical variables and one-way analysis of variance (ANOVA) for normally distributed continuous measures. The Kruskal⫺Wallis equality of populations rank test was applied for bivariate analyses of continuous variables with a skewed distribution (CES-D score, HADS-A score, and age). Bivariate associations between the percentage SBP and DBP recovery over time and SLE group were analyzed using a mixed ANOVA. Because the number of participants who exhibited a pattern of nonrecovery of BP (n ⫽ 191) was too small for analysis by life event frequency, individuals who exhibited a pattern of either partial recovery or nonrecovery of BP after orthostasis were collapsed for analyses to form an ‘impaired recovery“ group (Lagro et al., 2014). These were individuals who had recovered less than 95% of their baseline SBP/DBP by 60 s post stand. Logistic

FEENEY, DOOLEY, FINUCANE, AND KENNY

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regression modeling was employed to investigate the association between BP recovery patterns and life events, adjusting for possible confounders. The first model tested the association between the number of SLEs reported and the odds of exhibiting a pattern of impaired BP recovery after standing, adjusting for age, sex, and education only. The second model was additionally adjusted for symptoms of depression and anxiety, childhood and adult socioeconomic status, and poor health behaviors. A third model was fitted, including further adjustment for antihypertensive and psychotropic medication use, and cardiovascular conditions. A fourth and final model examined the effect of also adjusting for the degree of initial drop in BP on stand (BP nadir).

Supplemental Analyses To investigate the relationship between orthostatic BP recovery and individual life events, additional logistic regression models were fitted. First, the independent association between each event and orthostatic BP recovery was examined in a series of separate models. Second, the impact of each event was explored together in a single model. Third, given empirical evidence that childhood abuse negatively impacts on mental and physical health in adulthood (e.g., Draper et al., 2008; Irish, Kobayashi, & Delahanty, 2010), and considering that sexual abuse and physical abuse in childhood often co-occur (Dong et al., 2004), the independent relationship between having experienced any abuse in childhood (physical and/or sexual in nature) and BP recovery was explored. All models were adjusted for covariates (as per the fourth model above). Statistical significance was set at p less than .05. Analyses were carried out using Stata, Version 12.

Results A total of 5,035 individuals (corresponding to 62% of the target sample) participated in a center-based health assessment during which the beat-to-beat measurement of orthostatic BP was carried out. Of the 5,035, 4,237 completed the SLE questionnaire in full, of whom 3,765 had no missing data on any of the BP variables and thus were eligible for analysis. This group differed from those who had missing data on the measures in that they were younger, better educated, had better self-reported health, and had fewer selfreported cardiovascular conditions (see Table 2).

Covariates Table 3 shows the characteristics of the sample by the number of SLEs experienced. Individuals reporting three or more SLEs were slightly younger than the other groups. In general, those who had experienced more SLEs were more likely to be female, have attained a tertiary education, and report that their father had attained a post-primary-level education. However, the proportion of individuals falling into the lowest quintile for household earnings increased with increasing number of life events, as did the proportion meeting the criteria for problem drinking and those who were current smokers. Individuals reporting a greater number of life events also had lower levels of physical activity. There was no association observed between life events and BMI. Individuals

Table 2 Differences on Key Demographic and Health Variables Between Those Who Had Full Data on Life Event and Blood Pressure Measures (Included Sample) and Those Missing Data on Either Life Event and/or Blood Pressure Measures (Excluded Sample) M (SD) or %

Characteristics

Included sample (n ⫽ 3,765)

Excluded sample (n ⫽ 4,410)

p

Age, years Sex (female) Tertiary education Low household income Fair/poor self-rated health Cardiovascular condition CES-D score

61.6 (8.2) 53.6 37.7 10.3 11.2 12.7 5.2 (6.5)

65.7 (10.6) 54.7 22.4 12.2 15.2 16.7 6.4 (7.7)

⬍.001 .334 ⬍.001 .002 ⬍.001 ⬍.001 ⬍.001

Note. N ⫽ 8,175. CED-D ⫽ Center for Epidemiologic Studies Depression Scale.

who reported a greater number of life events had higher mean scores on the CES-D and HADS-A, indicating higher levels of depression and anxiety, respectively, and were more likely to use psychotropic medications, though not antihypertensive medications. They were also more likely to report a doctor’s diagnosis of heart murmur.

Orthostatic BP Behavior: Bivariate Analyses Table 4 shows the mean BP values for each metric of interest, by number of SLEs. There was no effect of SLE group on baseline SBP, F(3, 3761) ⫽ 1.7, p ⫽ .165; or on baseline DBP, F(3, 3761) ⫽ 1.5, p ⫽ .201. There was also no effect of SLE group on baseline heart rate, F(3, 3761) ⫽ .89, p ⫽ .446. There was no significant association between the SLE group and the value of the SBP nadir (percent of baseline BP), F(3, 3761) ⫽ 1.8, p ⫽ .141. There was, however, a main effect of number of SLEs on the DBP nadir, F(3, 3761) ⫽ 3.8, p ⫽ .008. Contrasts revealed that individuals reporting one SLE had a lower DBP nadir than those reporting no SLEs (p ⫽ .006). None of the other between-group contrasts was significant. Figure 1 shows the mean (standard error) percentage of baseline SBP (see Figure 1a) and DBP (see Figure 1b) recovered at 20, 30, 60, 90, and 110 s post active stand, stratified according to the number of SLEs reported. A mixed ANOVA revealed a significant main effect of time, F(2, 7514) ⫽ 116.9, p ⬍ .001, and a significant main effect of SLE group on percentage SBP recovered up to 60 s post stand, F(3, 3757) ⫽ 3.4, p ⫽ .018. Post hoc testing showed that individuals reporting one SLE had poorer SBP recovery relative to those reporting no SLEs (p ⫽ .036). None of the other between-groups differences were statistically significant. A total of 1,428 individuals (37%) had recovered less than 95% of their baseline SBP and/or DBP by 60 s after stand and thus were characterized as exhibiting a pattern of impaired recovery as per Lagro et al. (2014). Further examination of SLE groups according to their likelihood of impaired recovery revealed a significant relationship between the number of life events reported and the percentage of individuals with impaired SBP recovery, ␹2(3) ⫽ 10.0, p ⫽ .018, which ranged from 28% of those reporting no life

LIFE EVENTS AND ORTHOSTATIC BLOOD PRESSURE

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Table 3 Characteristics of the Sample by the Number of Stressful Life Events Reported

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M (SD) or % Characteristics

0 events (n ⫽ 1,955 [51.9%])

1 event (n ⫽ 1,071 [28.5%])

2 events (n ⫽ 459 [12.2%])

3⫹ events (n ⫽ 280 [7.4%])

pⴱ

Age, years Sex (female) Tertiary education Low household income Father with postprimary education Problem drinker Current smoker Low exercise CES-D score HADS A score BMI, kg/m2 Antihypertensive use Psychotropic use Angina Heart failure Heart attack Heart murmur Diabetes Stroke/TIA Abnormal heart rhythm

61.4 (8.2) 51.3 34.3 10.3 17.0 11.2 13.7 25.6 3.8 (3.6) 4.9 (3.3) 28.6 (4.6) 31.4 6.8 3.7 0.6 3.0 4.3 6.6 2.0 6.3

62.0 (8.4) 54.7 40.2a 12.2 19.0 15.2a 10.6 27.1 4.4 (3.8)a 5.5 (3.6)a 28.5 (4.9) 33.7 9.1 4.2 0.8 4.7 5.2 6.2 3.0 7.2

62.0 (8.3) 56.9 44.3a 14.3 20.5 18.6a 15.9a,b 31.4 4.7 (4.1)a 5.9 (3.5)a 28.5 (4.8) 33.3 10.2 5.0 0.2 4.1 7.6a 6.3 3.9 6.3

60.1 (7.4)b,c 60.4a 40.7 17.6a 26.8a,b 23.5a,b 23.2a,b 28.9 6.2 (4.9)a,b,c 7.3 (4.2)a,b,c 28.7 (5.9) 33.6 16.1a,b 6.1 1.8 4.6 6.8 7.5 2.9 8.2

.008 .008 ⬍.001 .002 .002 ⬍.001 ⬍.001 .043 ⬍.001 ⬍.001 .888 .539 ⬍.001 .211 .067 .101 .017 .869 .080 .558

Note. N ⫽ 3,765. All pairwise comparisons were Bonferroni adjusted. BMI ⫽ body mass index; CES-D ⫽ Center for Epidemiologic Studies Depression Scale; HADS ⫽ Hospital Anxiety and Depression Scale; TIA ⫽ transient ischemic attack. a Significant difference at the .05 level relative to the 0 events group. b Significant difference at the .05 level relative to 1 event group. c Significant difference at the .05 level relative to the 2 events group. ⴱ p for overall trend.

events to 37% of individuals reporting three or more events. This relationship was not evident to the same extent for impaired DBP recovery, ␹2(3) ⫽ 5.6, p ⫽ .134.

Multiple Logistic Regression Analyses Systolic blood pressure. The results of Model 1 (see Table 5), adjusting for age, sex, and education, revealed that individuals who

reported at least one event were more likely to exhibit a pattern of impaired recovery than those who reported no events, with a dose-response relationship evident (one event: odds ratio [OR] ⫽ 1.22, 95% confidence interval [CI] [1.05, 1.43], p ⫽ .009; two events: OR ⫽ 1.30, 95% CI [1.06, 1.60], p ⫽ .013; three or more events: OR ⫽ 1.63, 95% CI [1.28, 2.08], p ⬍ .001). Adjustment for symptoms of depression and anxiety, childhood and adult socio-

Table 4 Orthostatic Blood Pressure Behaviour by the Number of Stressful Life Events Reported M (SD) or % Variable

0 events

1 event

2 events

3⫹ events

Baseline SBP (mm Hg) Baseline DBP (mm Hg) Baseline HR (bpm) BP drop and recovery (% of baseline) Nadir SBP Nadir DBP SBP at 20 s DBP at 20 s SBP at 30 s DBP at 30 s SBP at 60 s DBP at 60 s SBP at 90 s DBP at 90 s SBP at 110 s DBP at 110 s Impaired SBP recovery 60 s Impaired DBP recovery 60 s

135.9 (21.7) 73.3 (11.0) 65.5 (10.1)

136.9 (23.1) 73.4 (11.6) 65.4 (10.1)

137.5 (21.7) 74.1 (11.1) 66.1 (11.6)

134.2 (23.2) 72.3 (10.6) 65.7 (9.6)

71.5 (12.5) 64.9 (14.1) 97.7 (13.6) 94.1 (14.9) 100.1 (11.4) 99.5 (12.3) 100.2 (10.9) 100.6 (10.8) 100.7 (11.2) 100.5 (10.9) 100.6 (11.6) 100.4 (11.7) 28.2 26.6

70.4 (12.7) 63.1 (14.9) 96.5 (13.8) 92.5 (15.7) 98.8 (11.9) 98.3 (13.2) 99.3 (11.2) 99.7 (11.0) 100.3 (12.0) 100.0 (11.5) 100.4 (12.3) 99.8 (11.7) 31.0 29.9

71.3 (12.9) 65.0 (14.6) 97.3 (14.2) 93.7 (15.8) 99.3 (12.8) 98.7 (13.3) 99.8 (11.8) 99.9 (11.1) 100.7 (12.7) 100.2 (12.1) 100.8 (13.0) 99.9 (12.5) 31.1 25.5

70.9 (12.6) 64.2 (14.1) 96.1 (13.5) 92.6 (14.4) 98.5 (11.5) 98.3 (11.7) 98.6 (11.4) 99.5 (9.9) 99.8 (13.1) 100.1 (11.6) 100.0 (12.7) 100.0 (10.7) 36.8 30.0

Note.

BP ⫽ blood pressure; DBP ⫽ diastolic blood pressure; HR ⫽ heart rate; SBP ⫽ systolic blood pressure.

FEENEY, DOOLEY, FINUCANE, AND KENNY

770 SBP

b

0 Events 1 Event 2 Events 3+ Events

1.46], p ⫽ .03; 3 or more events: OR ⫽ 1.27, 95% CI [0.93, 1.74], p ⫽ .136; Model 2, see Table 5). Further adjustment for medications and cardiovascular health did little to alter the size of the coefficients, however, the inclusion of DBP nadir in the final model did attenuate the association, so that now those reporting one life event also no longer had increased odds of impaired DBP recovery following stand (Model 4, see Table 5).

Supplemental Analyses

Time post stand DBP

% of baseline DBP recovered

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% of baseline SBP recovered

a

0 Events 1 Event 2 Events 3+ Events

Time post stand

Figure 1. Percentage of baseline blood pressure recovered at various time points after active stand by number of stressful life events: systolic blood pressure (a) and diastolic blood pressure (b). Values are mean (standard error of the mean). DBP ⫽ diastolic blood pressure; SBP ⫽ systolic blood pressure.

economic status, and health behaviors (Model 2, see Table 5), and antihypertensive/psychotropic medications and cardiovascular health (Model 3, see Table 5) did little to attenuate the observed relationships. However, final adjustment for the SBP nadir (Model 4, see Table 5) reduced the size of the coefficients somewhat so that the odds of impaired SBP recovery were no longer significantly increased among individuals reporting one event relative to those reporting no events, at the 5% level (p ⫽ .078). However, reporting two events and reporting three or more events remained associated with increased odds of impaired recovery, with individuals reporting three or more events having the greatest odds of impaired recovery (two events: OR ⫽ 1.33, 95% CI [1.03, 1.73], p ⫽ 031; three or more events: OR ⫽ 1.56, 95% CI [1.12, 2.16], p ⫽ .009). Diastolic blood pressure. A slightly different pattern was evident for DBP. Model 1 revealed a significant difference in the odds of impaired recovery for individuals who reported one event and those who reported three or more events, compared with no events (one event: OR ⫽ 1.27, 95% CI [1.09, 1.48,] p ⫽ .002; three or more events: OR ⫽ 1.42, 95% CI [1.09, 1.83], p ⫽ .008). However, there was no difference in the odds associated with reporting two events. Further adjustment for additional possible confounders in Model 2 reduced the odds of impaired recovery for individuals reporting one event and three or more events so that the latter group no longer had a significantly greater likelihood of impaired DBP recovery (one event: OR ⫽ 1.22, 95% CI [1.02,

Separate models examining the association between individual life events and impaired orthostatic BP recovery revealed a significant effect of having had a spouse, partner, or child addicted to drugs or alcohol on the odds of impaired SBP recovery (p ⫽ .012), and of having a spouse, partner, or child with a life-threatening illness or accident (p ⫽ .036), adjusting for other covariates. This relationship was only observed for SBP and not for DBP recovery. Furthermore, none of the other events showed a significant association with impaired recovery. When all SLEs were entered into a single model, the relationship between impaired SBP recovery and having a spouse, partner, or child addicted to drugs or alcohol or with a life threatening illness remained marginally significant (p ⫽ .044 and p ⫽ .027, respectively). There was no significant relationship between the reported experience of physical and/or sexual abuse as a child and the odds of either impaired SBP (p ⫽ .152) or impaired DBP (p ⫽ .533) recovery. Tables can be found online in the supplemental materials.

Discussion The current study revealed that the reporting of SLEs is associated with impaired recovery of SBP after standing. A doseresponse relationship was observed with respect to SBP recovery, such that individuals who reported a greater number of SLEs were more likely to have failed to fully recover their BP 1 min after standing from a supine position. There was no significant relationship between the number of life events reported and DBP recovery after adjustment for covariates. Prior stress exposure has been associated with an altered BP response to socioevaluative tasks and situations. Several studies have shown a blunting of SBP reactivity to laboratory stressors in individuals with high exposure to stressful life experiences (Boyce et al., 1990; Carroll et al., 2005; Lovallo, Dickensheets, Myers, Thomas, & Nixon, 2000). However, there is very little data to date on the relationship between prior stress exposure and the BP response to physiological challenge. Only one previous study investigated the association between indices of stress and orthostatic BP behavior. The authors examined heart rate variability and beat-to-beat BP behavior in a small group (n ⫽ 126) of middleaged patients presenting with chronic psychosocial stress (and nonstressed controls), both at rest and during an active stand. They found higher sympathetic activity at rest in the stress group, but these same individuals exhibited a reduction in sympathetic drive during the active stand (Lucini, Di Fede, Parati, & Pagani, 2005). In concordance with their beat-to-beat BP measurement data, the results of the current study also show a greater relationship between higher stress (in this case, the experience of multiple SLEs) and SBP rather than DBP recovery after stand using the same method in a larger, nonclinical cohort.

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Table 5 Logistic Regression Analyses of the Association Between the Number of SLEs and Odds of Impaired Recovery of Blood Pressure (Less Than 95% of Baseline at 60 S Post Stand) Model 1a OR

95% CI

Model 2b OR

Model 3c

95% CI

Model 4

d

OR

95% CI

OR

95% CI

1.22ⴱ 1.32ⴱ 1.61ⴱⴱ

[1.02, 1.45] [1.05, 1.66] [1.20, 2.16]

1.19 1.33ⴱ 1.56ⴱⴱ

[0.98, 1.45] [1.03, 1.73] [1.12, 1.73]

1.22ⴱ 1.03 1.26

[1.02, 1.46] [0.80, 1.32] [0.92, 1.72]

1.14 0.98 1.11

[0.93, 1.40] [0.74, 1.30] [0.78, 1.58]

Systolic blood pressure 0 SLEs (ref) 1 SLE 2 SLE 3⫹ SLEs

1.22ⴱⴱ 1.30ⴱ 1.63ⴱⴱⴱ

[1.05, 1.43] [1.06, 1.60] [1.28, 2.08]

1.22ⴱ 1.32ⴱ 1.62ⴱⴱ

[1.03, 1.45] [1.05, 1.67] [1.21, 2.17]

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Diastolic blood pressure 0 SLEs (ref) 1 SLE 2 SLE 3⫹ SLEs

ⴱⴱ

1.27 1.09 1.42ⴱⴱ

[1.09, 1.48] [0.87, 1.36] [1.09, 1.83]

ⴱ

1.22 1.04 1.27

[1.02, 1.46] [0.81, 1.33] [0.93, 1.74]

Note. CI ⫽ confidence interval; OR ⫽ odds ratio; SLE ⫽ stressful life event. a Adjusted for age, sex, and education. b Model 1 plus adjustment for father’s education, current household income, depression, anxiety, smoking, problem drinking, and exercise intake. c Model 2 plus adjustment for antihypertensive and psychotropic medication use and cardiovascular health. d Model 3 plus adjustment for blood pressure nadir. ⴱ p ⬍ .05. ⴱⴱ p ⬍ .01. ⴱⴱⴱ p ⬍ .001

The finding of a relationship between the number of events experienced and SBP but not DBP recovery after adjustment is also supported by the literature on SLEs and cardiovascular reactivity (Boyce & Chesterman, 1990; Carroll et al., 2005; Matthews et al., 2001) and recovery (Steptoe, Donald, O’Donnell, Marmot, & Deanfield, 2006). Carroll et al. 2005 have conjectured that it is the indices of cardiovascular regulation primarily driven by betaadrenergic input that appear to be altered by high exposure to SLEs. SBP rises steadily with age, whereas DBP tends to increase toward midlife and decline thereafter (Burt et al., 1995). It thus appears that SBP is more vulnerable to age-related changes in ANS physiology and is more closely related to cardiovascular risk in older adults than DBP (Kannel, Gordon, & Schwartz, 1971; Prospective Studies Collaboration, 2002; Staessen, Wang, & Thijs, 2003). Age- and inflammatory-related changes in arterial vessel wall stiffness increase SBP through changes in peripheral resistance, thus high stress exposure may also influence SBP reactivity to challenge as a result of chronic activation of inflammatory and immune pathways (Black, 2002). With regard to the possible prognostic significance of an association between cumulative exposure to stress and orthostatic SBP response, it is it notable that both Lagro et al. (2014) and Fedorowski et al. (2010) found that impaired SBP rather than DBP recovery was the stronger predictor of mortality and morbidity in their respective studies. In terms of a mechanism by which stress could alter orthostatic hemodynamics, it is plausible that diminished cardiovascular reactivity might arise from prolonged or repeated activation of the ANS in response to the accumulation of stressors over time—a “wear and tear” consistent with the theory of allostatic load (McEwen, 2000). A desensitization of baroreceptors secondary to repeated overproduction of catecholamines could eventually result in a suboptimal sympathetic response to orthostatic drops in BP (Broadley, 1996). The findings from the supplemental analyses examining the impact of individual life events on BP recovery provide some support for this hypothesis. Although analyses revealed a significant effect of having had a spouse/partner or child with a life-threatening illness and having had a spouse/partner or

child addicted to drugs or alcohol on SBP recovery, the associations were only marginally significant, and none of the other life events was significantly related to BP recovery. This suggests that, in the current study at least, exposure to several major life events had a greater impact on recovery from orthostasis than any particular event in isolation. Other evidence to support a stress-related impairment of the baroreflex comes from the psychiatric literature. Posttraumatic stress disorder (PTSD) has been associated with lower baroreceptor sensitivity at rest (Hughes, Dennis, & Beckham, 2007). Attenuated parasympathetic withdrawal during a stressful task in PTSD patients has also been reported (Cohen et al., 1998), which the authors have argued might result from a chronic hyperactivation of the ANS leading to a reduction in the normal parasympathetic withdrawal in response to the stressor. Of course, it must be acknowledged that often the biobehavioral changes evident in PTSD patients are not observed in similarly exposed individuals without a diagnosis of PTSD (Buckley, Holohan, Greif, Bedard, & Suvak, 2004; Brown, LaBar, Haswell, Gold, & Mid-Atlantic MIRECC Workgroup, 2013). The aging process itself has also been associated with a decoupling of the ANS (Petrofsky & Lind, 1975) and impairment of the baroreflex (Gribbin, Pickering, Sleight, & Peto, 1971). This would likely render stress-related changes in autonomic function more pronounced in older compared with younger adults. Evidence suggests that postural change in older adults increases the risk of cerebral hypoperfusion. For example, orthostatic stress has been associated with declines in frontal cortical blood oxygenation and blood volume in elderly but not younger adults (Mehagnoul-Schipper, Colier, & Jansen, 2001; MehagnoulSchipper, Vloet, Colier, Hoefnagels, & Jansen, 2000). Similarly, in a small sample of older adults with autonomic failure and matched controls, a relative decline in oxygenated hemoglobin was observed in response to postural change (Hunt et al., 2006). These findings raise the possibility that a slow recovery of BP after orthostasis in older adults may render them vulnerable to cerebral hypoperfusion, thereby increasing the risk of falls and syncope and

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damage to the microvasculature. The latter has long-term implications for increasing vulnerability to and/or acceleration of cognitive impairment and neurodegenerative disease (Kuo & Lipsitz, 2004; Matsubayashi et al., 1997), which, in turn, might further exacerbate autonomic dysfunction.

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Study Limitations There are several limitations of the current study that must be acknowledged. First, data on the experience of SLEs was gathered as a binary (yes/no) variable. Participants were not asked any further details about the exact nature, duration, or severity of their stressful experience. Thus, the effect of the likely heterogeneity of their experiences on the individuals could not be explored. It is also probable that participants had experienced other highly stressful events during their lifetime that were not captured by this inventory. Furthermore, for several of the events listed, it was possible for the event in question to be still ongoing. Notwithstanding these limitations, similar life events questionnaires have proved useful tools with which to study the effects of lifetime stress exposure in both small, experimental (Roy et al., 1998; Armbruster et al., 2011), and large population studies (Keinan, Shrira, & Shmotkin, 2012). Second, TILDA participants who did not answer the SLE inventory were necessarily omitted from the study. It is possible that these individuals may have been more adversely affected by past stressful experiences and thus did not want to answer questions about them, in which case the true magnitude of the relationship between life events and BP recovery may have been underestimated. The same principle applies to individuals who did not participate in a health center assessment and therefore did not have their beat-to-beat BP measured. These participants were, on average, older, had higher levels of disability, and poorer self-rated health than those who opted only for a modified home health assessment (Kearney, Cronin, O’Regan, Kamiya, Whelan, et al., 2011). Therefore, the loss of participants who did not complete a health center assessment may also have led to an underestimation of the relationship between SLEs and orthostatic BP behavior. There is a small possibility that a recall bias exists, whereby individuals with poor cognitive function may underreport events compared with those with better cognitive function. However, participants in the current study were relatively young and, even if such a bias were to exist, one would expect an underestimation of the true relationship between stress exposure and BP regulation, given growing empirical support for an association between autonomic dysfunction and impaired cognition (Frewen, Finucane, Savva, Boyle, & Kenny, 2014; Frewen et al., 2013). A sensitivity analyses was conducted to explore the possibility that such a bias would alter the results, restricting the sample to those who scored higher than 26 out of 30 on the Montreal Cognitive Assessment (Nasreddine et al., 2005); however, the association between number of SLEs and SBP recovery persisted. The cutoff values used in the current study to categorize participants into different patterns of recovery after active stand are based on those used by Lagro et al. (2014), as applied to their SBP data. Our group has also shown that impairment of SBP recovery of a similar magnitude is associated with frailty in communitydwelling older adults (Romero-Ortuno et al., 2011). The clinical

significance of these groupings, however, merits continued research.

Conclusion Retrospective reporting of a greater number of SLEs was associated with impaired SBP recovery after orthostasis in a large sample of community-dwelling older adults from TILDA. This study is unique in being the first of its size to investigate the relationship between stress and orthostatic BP behavior using beat-to-beat measurement. Repeated follow-up is required to determine whether this association has prognostic value and to elucidate the causal pathways involved.

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Received April 14, 2014 Revision received October 15, 2014 Accepted October 26, 2014 䡲