الگوهای کورتیزول و واکنش پذیری شریان براکیال در یکا محیط باسترس بالا

Abstract Chronic stress can result in frequent or persistent challenges of the hypothalamic-pituitary-adrenal (HPA) axis resulting in abnormal cortisol patterns and increased risk for cardiovascular disease (CVD). Police work is an environment replete with stress. The present article describes associations between cortisol, a biomarker of stress, and brachial artery flow mediated dilation (FMD) in police officers. A random sample stratified on gender (n = 100, 33% women) was generated from officers in a mid-sized urban department. Four salivary cortisol parameters were derived: after awakening, following a standardized high protein meal challenge, during the entire day, and after a dexamethasone suppression test. Continuous scan B-Mode ultrasound was used to measure percent change in brachial artery FMD following occlusion and release. Elevated cortisol secretion after awakening was significantly associated with impaired FMD in women, reflected by an inverse trend. Adjustment for age, smoking, and alcohol consumption did not appreciably alter this trend. A similar result was not evident among male officers. Responses of other cortisol challenges to the HPA axis were not associated with FMD. In conclusion, increased cortisol secretion after awakening was independently associated with impaired FMD in female police officers only, indicating a possible link between HPA axis stress response and subclinical CVD. However, because associations were not found with other cortisol parameters and were not evident in male officers, replication of these findings with a prospective study design may be warranted.

Introduction Stress may be described as a biosocial process that places undue strain on persons resulting in psychological and biological changes which increase the risk for disease (Cohen et al., 1997). The hypothalamic-pituitary-adrenal (HPA) axis is central to the body's responses to stress and consequently is often a focal point in research concerning stress. The status of the HPA axis can be assessed by measurements of cortisol secretion using various challenge procedures (McEwen, 2000 and Rosmond et al., 1998). A normal cortisol pattern may be described as having a high degree of variation, with a morning peak, an evening nadir, and an appropriate response to challenges. HPA dysregulation due to prolonged or extreme stress has been associated with inefficient turning on or shutting off of the cortisol response (McEwen and Seeman, 1999 and McEwen, 2004). It has been suggested that abnormal cortisol patterns can result from frequent or persistent challenges of the HPA axis and constitute a major risk for disease including central obesity, insulin resistance, cardiovascular problems, hypertension, and depression (Chrousos, 1998, Haddy and Clover, 2001 and McEwen, 1998). Psychological stress has been associated with an increased risk of cardiovascular events (McEwen, 1998). However, the effect of stress and implications for cardiovascular risk are not well understood. Endothelial dysfunction is an important early stage in atherogenesis, and brachial artery flow mediated dilation (FMD) is endothelium-dependent (Widlansky et al., 2003). The physiology of FMD and methodologic guidelines for its measurement have been discussed (Adams et al., 1996, Corretti et al., 2002 and Herrington et al., 2001). Brachial ultrasound measurements of arterial diameter are taken before and during a transient increase in blood flow. This increase in blood flow is caused by the inflation and subsequent release of a blood pressure cuff on the forearm. This procedure provides a noninvasive evaluation of brachial artery flow mediated vasodilation (FMD) (Corretti et al., 2002). Under these experimental conditions the FMD response is a marker for the endothelial response to flow induced shear stress which includes the release of nitric oxide (NO) leading to vasodilation. The magnitude of endothelial dysfunction in coronary arteries has been linked with the degree of coronary atherosclerosis detected by angiography (Zeiher et al., 1991). The presence of endothelial dysfunction has been associated with increased risk of cardiovascular disease (Verma et al., 2003). Although the underlying biologic mechanisms have not yet been established, HPA axis dysfunction and the associated cortisol dysregulation have been linked to endothelial dysfunction in two experimental studies in humans. In one study, endothelial dysfunction resulting from an acute mental stress challenge was prevented by blocking the production in cortisol with a pharmacological agent (Broadley et al., 2005). In a second study by Broadley et al. (2006), blocking cortisol production attenuated the endothelial dysfunction seen in patients with treated major depression. The ability of the HPA axis to respond to challenge may be compromised by chronic stress such as that experienced in a high stress occupation like policing. Hans Selye (1984) recognized police work as highly stressful. Police work has been described as “civilian combat” (Violanti, 1996). Police officers face the distinct possibility of exposure to psychologically disturbing events in their work including shootings, physical assault, witnessing violence and familial abuse, handling dead bodies, and disaster scenes such as 9/11 or Hurricane Katrina in New Orleans (Paton and Smith, 1996). Although police officers are considered a healthy working population, notably higher mortality rates for cardiovascular disease (CVD) have been found in police cohorts when compared to the general population. CVD has occurred at a higher rate in policemen with fewer years of service, suggesting that work-related factors such as stress may play a part (Violanti et al., 1998). In one of the few large prospective studies of police officers, the Helsinki Police Study identified a number of independent risk factors for coronary heart disease (CHD) (Pyorala et al., 1998). A study of Iowa state police officers found that public safety officers had a higher probability of developing CHD than did the Framingham study population (Franke et al., 1997). Additional studies have found police to have higher rates for heart disease, homicide, and suicide (Forastiere et al., 1994, Dubrow et al., 1988 and Quire and Bluont, 1990). The Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) baseline study was conducted to establish a population-based sample designed to identify stress and subclinical cardiovascular biomarkers in police work (Violanti et al., 2006). The present article describes findings from the BCOPS study concerning associations between the stress biomarker cortisol and FMD in a sample of police officers.

Results 3.1. Characteristics of the sample Table 2 provides selected characteristics of the police sample by gender. Although average age was similar for women and men (43.7 and 44.0 years, respectively), a greater proportion of women were in the 40- to 49-year-old age group (60.6% vs. 35.7%). A greater proportion of male than female officers had more than 20 years of police service (31.0% vs. 12.1%, respectively). The majority of officers were at the rank of police officer (48%). Current and former smoking considered together was more prevalent in women than in men officers (62% vs. 47%, respectively). Male and female officers had similar diurnal AUCg and lunch AUCi levels. Compared with male officers, female officers had higher awakening AUCi (0.201 vs. 0.006 (nmol/l) hours in thousands, respectively) and dexamethasone suppression ratio (0.134 vs. 0.067, respectively). Table 2. Selected characteristics of study population by gender. Characteristic Women Men Total n % n % n % Age (years)a 33 43.7 (41.6–45.8) 42 44.0 (41.2–46.8) 75 43.9 (42.1–45.6) Age group (years) < 40 8 24.2 14 33.3 22 29.3 40–49 20 60.6 15 35.7 35 46.7 ≥ 50 5 15.2 13 30.9 18 24.0 Education ≤ High school 6 18.2 4 9.5 10 13.3 College < 4 yrs 9 27.3 14 33.3 23 30.7 College 4+ yrs 18 54.5 24 57.1 42 56.0 Years of service 1–5 5 15.2 9 21.4 14 18.7 6–10 6 18.2 5 11.9 11 14.7 11–15 8 24.2 7 16.7 15 20.0 16–20 10 30.3 8 19.1 18 24.0 20+ 4 12.1 13 31.0 17 22.7 Rank Police officer 17 51.5 19 45.2 36 48.0 Sergeant/lieutenant 6 18.2 9 21.4 15 20.0 Captain 2 6.1 5 11.9 7 9.3 Detective 3 9.1 7 16.7 10 13.3 Other 5 15.1 2 4.8 7 9.3 Smoking status Current 5 17.2 5 13.2 10 14.9 Former 13 44.8 13 34.2 26 38.8 Never 11 37.9 20 52.6 31 46.3 Alcohol drinks/week 0 9 31.0 6 15.8 15 22.4 < 1 8 27.6 10 26.3 18 26.9 1–7 10 34.5 14 36.8 24 35.8 > 7 2 6.9 8 21.1 10 14.9 Cortisol parameters Diurnal AUCga,b,c 19 5.749 (4.764–6.939) 31 6.207 (5.018–7.675) 50 6.029 (5.212–6.974) Lunch AUCia,b 24 0.077 (− 0.003–0.158) 35 0.145 (− 0.035–0.325) 59 0.118 (0.008–0.227) Awakening AUCia,b 22 0.201 (0.104–0.299) 33 0.006 (− 0.089–0.100) 55 0.084 (0.013–0.156) DSTa,c,d 23 0.134 (0.077–0.221) 32 0.067 (0.045–0.097) 55 0.087 (0.063–0.120) Abbreviations: AUCg, area under the curve with respect to ground; AUCi, area under the curve increase above baseline; DST, dexamethasone suppression test. a Values are means [95% confidence intervals (C.I.)]. b Units are (nmol/l) hours expressed in thousands. c Back transformed means. d DST is the ratio of post- to pre-dexamethasone suppression test. Table options 3.2. Percent change in brachial artery dilation by gender Table 3 provides mean percent change in brachial artery dilation by gender. While the absolute increase in FMD was slightly greater in men (0.21 mm) than in women (0.17 mm), the overall mean percent change in brachial artery diameter from baseline to maximum was slightly higher for female compared to male officers (4.59% vs. 4.41%). Table 3. Mean percent change in brachial artery dilation by gender. Brachial artery diameter Women Men Total n Mean (S.D.) n Mean (S.D.) n Mean (S.D.) Baseline (pre-inflation) (mm) 33 3.72 (0.49) 42 4.91 (0.54) 75 4.39 (0.78) Maximum (post-release) (mm) 33 3.89 (0.51) 42 5.12 (0.52) 75 4.58 (0.80) Absolute difference from baseline to maximum (mm) 33 0.17 (0.12) 42 0.21 (0.15) 75 0.19 (0.14) Percent change from baseline to maximuma 33 4.59 (3.43) 42 4.41 (3.42) 75 4.49 (3.40) a Mean percent change in brachial diameter defined as: [(maximum from smoothing function minus mean of baseline measurements] × 100. Table options 3.3. Brachial diameter change by lifestyle variables Table 4 provides the mean percent change in brachial diameter by lifestyle and demographic characteristics for women and men. In female officers, a non-significant trend of increasing brachial artery percent change was found with increasing consumption of alcoholic beverages (P = 0.108), while an inverse trend was observed in male officers (P = 0.029). Table 4. Mean percent change in brachial artery diameter a by demographic and lifestyle characteristics for women and men. Characteristic Women Men N Mean S.D. N Mean S.D. Age group (years) < 40 8 6.05 2.88 14 4.59 2.41 40–49 20 3.96 3.63 15 5.30 4.41 ≥ 50 5 4.76 3.28 13 3.17 2.87 P-linear trend b 0.514 0.284 Education ≤ High school 6 5.74 3.22 4 5.19 4.29 College < 4 yrs 9 3.44 4.77 14 3.32 2.49 College 4+ yrs 18 4.78 2.68 24 4.91 3.72 P-linear trend 0.562 0.877 Years of service 1–5 5 6.59 3.27 9 4.31 2.17 6–10 6 6.76 2.13 5 5.64 7.13 11–15 8 2.66 2.46 7 4.52 2.20 16–20 10 3.64 4.17 8 4.53 2.62 20+ 4 5.08 2.84 13 3.86 3.52 P-linear trend 0.193 0.587 Rank Police officer 17 4.59 3.02 19 3.63 2.42 Sergeant/lieutenant 6 2.69 4.85 9 6.73 5.11 Captain 2 7.05 0.94 5 2.95 1.39 Detective 3 6.20 2.02 7 4.03 3.58 Other 5 4.91 3.92 2 6.25 0.80 P-value c 0.488 0.146 Smoking status Current 5 5.06 1.74 5 7.76 6.14 Former 13 5.10 3.89 13 3.96 3.57 Never 11 3.47 3.71 20 4.11 2.28 P-value 0.506 0.088 Alcohol (drinks/wk) 0 9 3.29 3.71 6 7.85 5.81 < 1 8 3.47 4.03 10 5.03 2.28 1–7 10 5.81 1.93 14 2.79 2.20 > 7 2 7.09 6.32 8 4.49 3.24 P-linear trend 0.108 0.029 a Mean percent change in brachial diameter defined as: [(maximum from smoothing function minus mean of baseline measurement) divided by mean of baseline measurements] × 100. b For ordinal covariates, a test of linear trend was performed using orthogonal polynomial coefficients. c For nominal covariates, the P-calue tests differences in mean percent change across the levels. Table options 3.4. Brachial diameter change and cortisol parameter measures Table 5 examines associations between percent change in brachial diameter and AUC measures of diurnal, awakening, lunch challenge, and DST cortisol parameters. The AUC cortisol response to awakening revealed a significant inverse trend in female officers such that the mean percent change in brachial artery diameter was lower for those in the highest AUC tertile (greatest cortisol response). Adjustment for age, education, smoking, and alcohol had minimal influence on these trends P = 0.081 unadjusted vs. P = 0.020 adjusted). A nearly significant inverse trend of decreasing mean FMD with increasing diurnal cortisol AUC and the AUC lunch response were also observed in women after full adjustment P = 0.082 and P = 0.048, respectively). The responses to the high protein lunch and DST were not associated with percent change in brachial artery diameter in women. Percent change in FMD was not associated with these four cortisol parameters in men. Regarding the DST cortisol parameter, adjustment for the individual variation in the time interval between the pre-dexamethasone collection (at bedtime) and the post-dexamethasone collection (awakening) did not alter the associations observed. Table 5. Gender-specific percent change in brachial artery diameter by cortisol parameter tertile. Women Men Unadjusted Age-adjusted Risk factor-adjusteda Unadjusted Age-adjusted Risk factor-adjusteda Cortisol parameter Cortisol tertile n b Mean S.D. Mean S.E. n Mean S.E. n b Mean S.D. Mean S.E. n Mean S.E. Diurnal AUCg Low 6 5.66 2.03 5.81 1.12 6 6.47 1.35 10 3.28 1.97 3.21 0.77 10 3.20 0.88 Medium 7 5.32 3.53 5.49 1.04 7 5.51 1.31 11 5.64 3.48 6.01 0.74 11 5.82 0.83 High 6 4.29 2.23 3.95 1.16 6 3.26 1.17 10 3.33 2.23 2.99 0.78 6 3.24 1.13 P-linear trend c 0.324 0.209 0.082 0.871 0.814 0.451 Lunch AUCi Low 8 4.41 5.38 4.52 1.38 8 4.27 1.45 11 3.69 2.31 3.57 1.09 9 3.44 1.17 Medium 8 4.62 2.30 4.40 1.39 7 6.23 1.93 12 4.24 2.48 4.28 1.03 10 4.39 1.11 High 8 4.52 3.35 4.64 1.38 6 2.54 2.09 12 4.70 5.09 4.76 1.03 12 5.03 1.00 P-linear trend 0.518 0.344 0.048 0.218 0.185 0.222 Awakening AUCi Low 7 5.32 2.04 5.20 0.98 6 5.85 1.07 11 4.07 2.91 4.11 0.88 10 4.22 1.12 Medium 8 6.19 3.00 6.26 0.91 8 6.24 1.00 11 4.20 3.53 4.12 0.88 11 3.89 1.00 High 7 2.30 2.49 2.34 0.98 6 1.69 1.01 11 4.03 2.20 4.06 0.88 8 4.70 1.22 P-linear trend 0.081 0.100 0.020 0.889 0.935 0.699 log2 (DST) Low 7 5.21 3.80 5.48 1.16 6 5.92 1.29 10 3.84 2.22 3.77 0.95 9 4.24 0.96 Medium 8 5.58 1.72 5.46 1.06 6 4.85 1.18 11 4.28 2.73 4.30 0.90 8 4.28 1.07 High 8 5.60 3.12 5.48 1.06 7 5.65 1.18 11 4.23 3.65 4.27 0.90 11 4.27 0.95 P-linear trend 0.813 0.999 0.597 0.970 0.937 0.755 Abbreviations: AUCg, area under the curve with respect to ground; AUCi, area under the curve increase above baseline; DST, dexamethasone suppression test. a Risk factor model adjusted for age, education, smoking and alcohol intake. b The number of participants by tertiles is the same for unadjusted and age-adjusted. c Based on linear regression. Table options In addition, the associations between the continuous form of the cortisol parameters and the mean percent change in brachial artery diameter were also examined using simple linear regression. The correlation coefficients for women were as follows: diurnal AUCG = − 0.239, AUCI lunch = − 0.139, AUCI waking = − 0.380, and DST = 0.052. For men, the correlation coefficients were as follows: diurnal AUCG = 0.030, AUCI lunch = 0.213, AUCI waking = 0.025, and DST = 0.007.