Psychosocial factors have been repeatedly associated. Is High Job Strain Associated With Hypertension Genesis?

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1 AJH 2006; 19: Is High Job Strain Associated With Hypertension Genesis? Michel Ducher, Catherine Cerutti, Gilles Chatellier, and Jean-Pierre Fauvel Background: The aim of this analysis was to test, in a large sample of normotensive subjects, the short-term influence of job strain on the onset of hypertension. Methods: According to the questionnaire of Karasek et al, job strain was divided into four modalities: (high strain, low strain, passive, and active) based on job demand (eg, the need to work hard and quickly) and job latitude (eg, control over skill use, time allocation, and organizational decisions) scores. High strain (HS) was defined by a high demand and a low job decision latitude. Individual data obtained in 926 (age 41 6 years) healthy normotensive or newly diagnosed hypertensive subjects were analyzed. Subjects participated in two prospective work site surveys designed to assess the influence of job strain on hypertension development. Relationships between job strain modalities and work site blood pressure (BP) levels were assessed using a general linear model. A complementary analysis using the the Pearson coefficient (Z analysis) was implemented to explore nonlinear or scattered relationships between job strain and onset of hypertension. Results: Systolic BP (SBP) was linearly related significantly to BMI and alcohol consumption, whereas diastolic BP (DBP) was related to age. The linear model did not find any relationship between SBP or DBP and job strain modalities. Using the Z analysis, development of systolic hypertension (SBP 140 mm Hg) was significantly associated with high job strain (P.001). Conclusions: Our results suggest that there is no global relationship between job strain and BP levels. However our methodology revealed a significant association between job strain and work site BP in a predominantly male subgroup of newly diagnosed hypertensive subjects exposed to high job strain. Am J Hypertens 2006;19: American Journal of Hypertension, Ltd. Key Words: Job strain, stress, cardiovascular risk factor, statistical dependence. Psychosocial factors have been repeatedly associated with an increased risk of cardiovascular disease. Among psychosocial factors, job strain has mostly been evaluated using mainly the Job Demand Control (JD-C) model 1 3 and the Effort Reward Imbalance (ERI) model. 1,2,4 Job strain has been repeatedly associated with an increased risk of cardiovascular disease in both men and women. 1 7 However the effect of job strain on blood pressure (BP) is still subject to debate Most but not all cross-sectional or short-term studies report that subjects exposed to high job strain have higher BP or heart rate (HR). At a 3-year interval, in the few subjects chronically exposed to high job strain, Schnall et al reported a persistent effect of high job strain on ambulatory BP. 20 In the long run, however, a relationship between job strain 8 or feelings about work environment 19 and BP was not found. Suspected physiologic effects of job strain that could increase BP include mainly sympathetic pathways 14,21 and pituitary adrenocortical hormones, a highly deleterious combination. 6 Discrepancies between studies might be caused by population sampling, study design, follow-up duration, or BP recording. 6,7 One of the most confusing factors might be the intraindividual variability of job strain with time. Because job strain varies with time, its effect on BP is difficult to evaluate. To study the influence of job strain on BP, both job strain and BP should be simultaneously recorded. Furthermore, if job strain is related to BP, very little is still known about the effect of job strain on the onset of hypertension, which is the most relevant clinical outcome. In this analysis, we have pooled data from two studies that simultaneously recorded BP and job strain status both in normotensive subjects and in those with newly diagnosed hypertension. Subjects and Methods Subjects The analysis was conducted in 926 healthy subjects (men and women) included in two studies (mean age 41 6 Received June 22, First decision December 28, Accepted December 29, From the Département de Néphrologie et Hypertension, UMR MA 103 Hôpital E. Herriot, Lyon, France (MD), J-PF, EA 3740, Université Claude Bernard, Lyon, France (CC), Département d Informatique Hospitalière, Hôpital Européen Georges Pompidou, 20, rue Leblanc, Paris, France (GC). Corresponding author Prof. Jean-Pierre Fauvel, Département de Néphrologie et Hypertension Artérielle, Hôpital E. Herriot, Lyon Cedex 03 France; jean-pierre.fauvel@chu-lyon.fr /06/$ by the American Journal of Hypertension, Ltd. Downloaded from doi: /j.amjhyper Published by Elsevier Inc.

2 AJH July 2006 VOL. 19, NO. 7 JOB STRAIN AND HYPERTENSION DEVELOPMENT 695 years). Both studies were prospective and aimed to analyze the influence of job strain on BP in working populations. The two studies shared the same inclusion criteria. All subjects included in this analysis were found to be normotensive (BP 140/90 mm Hg) on the previous mandatory annual work site examination. Inclusion criteria included normal findings on a full clinical examination, normal results of a dipstick urine analysis, and no use of medication known to interfere with BP. The first study was a prospective cohort study that aimed to quantify hypertension prevalence and 1-year incidence in healthy workers. Physicians from various work environments (eg, manufacturing, service industries, or transportation, with the exception of the agricultural sector) participated in the study. All subjects signed an informed consent at inclusion. One year later, all incident hypertensive subjects were included in the ancillary job strain substudy. Each hypertensive (203 cases, BP 140/90 mm Hg) was matched according to age ( 10 years) and sex with two normotensive subjects (406 controls subjects, BP 140/90 mm Hg) attending the visit immediately afterward. Matching was successful. None of the 609 normotensive or hypertensive volunteers refused to fill out the questionnaire; however 14 questionnaires were incompletely filled out and thus not used in the analysis. The second study was conducted in subjects employed full-time in a chemical company. With the use of a register, 473 normotensive subjects were eligible for the study. Among them, 370 volunteered to participate in the study that included a job strain questionnaire. Of these, 317 fulfilled the inclusion criteria and provided signed informed consent. At the inclusion visit, 282 were still normotensive, whereas 35 were newly diagnosed hypertensive subjects. In this study, seven questionnaires were incompletely filled out and therefore not used in the analysis. Because the two studies shared the same main objective, were realized in normotensive (at baseline) working populations by work site physicians, and used the same questionnaire to classify job strain, individual data were pooled. The first and the second studies were approved by the Comités de protection des personnes dans la recherche Biomédicale of Grenoble and Lyons respectively. diastolic BP (DBP) levels were defined as follows for the analysis of dependence between events: low normal (SBP 100 mm Hg or DBP 70 mm Hg); normal (SBP 100 to 119 mm Hg, or DBP 70 to 79 mm Hg), pre-hypertensive (SBP 120 to 139 mm Hg, or DBP 80 to 89 mm Hg); and hypertensive (SBP 140 mm Hg or DBP 90 mm Hg). Psychosocial Factors The job contents questionnaire developed by Karasek et al 3 can be characterized as focusing on the psychologic and social structure of the work situatio: issues relevant to work demands, decision-making opportunities, social interactions. Physical aspects of work are also measured but in a very general manner. Karasek et al 3 argued that work stress results from the combined effects of the demands of a work situation and the range of decision-making freedom (latitude) available to the worker facing those demands. Decision latitude is an operationalization of the concept of control and has often been defined as the combination of job decision-making authority and the opportunity to use and develop skills on the job. The job strain model states that the combination of high job demands and low job decision latitude will lead to negative physical health outcomes such as hypertension and cardiovascular disease. In our study, each subject completed a French-language version of the selfadministered questionnaire packet developed by Karasek et al, which included 14 items to assess job demand and job decision latitude. 3 The job strain questionnaire used was a translation of the job contents questionnaire. The translation had been performed in 1993 by psychologists, sociologists, work site physicians, and stress specialists. A reverse translation was made to assess the quality of the French translation. The questionnaire is very close to the Canadian version that was fully validated by Larocque et al. 25 Median values of demand (median value 31) and latitude (median value 64) divided the subjects into four Analysis of BP In both studies, sitting BP measurements were taken by work site physician during working hours in the work place. In both studies, work site BPs were measured three times after a 5-min rest using a cuff appropriate for arm size. The average of the last two of the three BP measurements was considered. In the first study, a training session was organized for all work site physicians to standardize BP measurements using an OMRON 705 CP (OMRON, Matsusaka Co Ltd., Japan). In the second study, BP was measured by one trained physician using a mercury sphygmomanometer. Four systolic BP (SBP) and four FIG. 1. Definition of job strain modalities as a function of job demand and job decision latitude.

3 696 JOB STRAIN AND HYPERTENSION DEVELOPMENT AJH July 2006 VOL. 19, NO. 7 Table 1. Characteristics of subgroups of subjects classified by job strain modalities Group High strain Active Passive Low strain N Male (%) Age (y) BMI (kg/m 2 ) Alcohol score Inclusion SBP Inclusion DBP year SBP year DBP * 81 9* Job latitude * * Job demand * 27 3* BMI body mass index; DBP diastolic blood pressure; HR heart rate; SBP systolic blood pressure. Data are mean SD. * P.05 v high strain. groups (Fig. 1). Subjects showing job demand higher than the median and job decision latitude lower than the median represented the high-strain group (HS). Subjects reporting high latitude and high demand were in the active (A) group. Subjects with low demand and low latitude were in the passive (P) group; and subjects with low demand and high latitude were in the low-strain group (LS). Eleven subjects did not fill in the entire questionnaire and were not classified. Recorded Covariables During the annual working visit, subjects were given a routine medical examination that included a full history, a physical examination, body mass index (BMI) determination, and assessment of alcohol intake. Alcohol intake was ranked according to five levels (designated as 1 to 5) by interview: 1 drink per week, 1 drink per day, 1 to 2 drinks per day, 3 to 4 drinks per day, and 4 drinks per day. Statistical Analysis Complete data were obtained in 903 subjects (232 HT and 671 NT) of the 926 subjects included in the study. Data are expressed as mean standard deviation. The normal distribution of each variable was checked using the Kolmogorov-Smirnov test. Comparisons of means used analysis of variance followed by the Bonferroni post hoc test. A general linear model was implemented to find relationships between BP and both categorical (job strain, alcohol intake) and continuous variables (BMI, age). To complete statistical analyses classically performed in epidemiology, a complementary analysis (Z analysis) using the Person coefficient was used to explore nonlinear or scattered relationships. 26 In the present study, the coefficient determined the strength of association between one level of BP and one modality of job strain. For the Z analysis, 16 comparisons were made for SBP and for DBP. According to the Bonferroni correction for multiple comparisons, a value of P.003 was considered to be significant. All statistical analyses were performed with Statistica 6.0 software (StatSoft Inc., Tulsa, OK). A value of P.05 was considered significant. Results Mean values of anthropometric, cardiovascular, and psychosocial variables according to job strain categories are summarized in Table 1. Hypertensive subjects were slightly older (2.3 years as an average) and had a higher BMI (1.8 kg/m 2 as an average) than normotensive subjects (Tables 2 and 3). Values of SBP, DBP, HR, age, and BMI were normally distributed. The generalized linear model representing SBP or DBP as a function of age, BMI, alcohol, and job strain modalities showed that SBP was positively related to BMI (P.001) and to alcohol consumption (P.01). The DBP was positively related to age (P.001). Analysis of variance found that mean values of age, BMI, alcohol consumption, and SBP were similar in the four job strain modalities (high strain, active, passive, low strain), as shown in Table 1. The different job strain modalities were associated with different DBP values (P.05). Post hoc tests showed that DBP was significantly higher (P.01) in the HS group than in the P and LS groups (Table 1). The Z analysis isolated subgroups of subjects whose job strain modalities were significantly associated with SBP or DBP levels. The high strain modality was associated with the hypertensive SBP level (HS/SBP-HT subgroup, n 57, 0.10, P.001). The passive modality was significantly associated with the low-normal DBP grade (P/DBP-NT subgroup, n 49, 0.11, P.001). The active and the low strain modalities were not related to SBP or DBP modalities (Fig. 2). In subjects with systolic hypertension, the mean characteristics of subjects were not different between job strain subgroups (Table 2) except with regard to alcohol score, which was significantly higher in A/SPB-HT than in

4 AJH July 2006 VOL. 19, NO. 7 JOB STRAIN AND HYPERTENSION DEVELOPMENT 697 Table 2. Characteristics of incident systolic hypertensive and normotensive subjects subgroups stratified by job strain modalities Subgroup n Age (y) BMI (kg/m 2 ) Alcohol score SBP DBP HR (beats/min) Systolic hypertensive subjects HS/SBP-HT A/SBP-HT P/SBP-HT * LS/SBP-HT P.05 v A/SBP-HT Systolic normotensive subjects HS/SBP-NT A/SBP-NT P/SBP-NT LS/SBP-NT A active; HS high strain; HT hypertensive; LS low strain; NT normotensive; P passive. Data are mean SD. Systolic hypertension defined as systolic blood pressure (SBP) 140 mm Hg. P/SPB-HT (P.05). The other subgroups (NT-SBP, HT- DBP, and NT-DBP) were homogeneous in age, BMI, alcohol intake, and BP when stratified according to job strain modalities (Tables 2 and 3). The HS/SBP-HT subgroup, showing significant association between high SBP level and high-strain modality, represented 34% of the subjects with systolic hypertension. The odd ratio estimating the relative risk of hypertension in the high-strain subgroup was 1.84 (95% confidence interval 1.28 to 2.65; P.01). Discussion Our results suggest that there is no global relationship between job strain and BP levels. However our analysis revealed a significant association between job strain and BP in the subgroup of newly diagnosed hypertensive subjects exposed to high job strain. Relationships between job strain and hypertension development are still under debate. 6 9,11,13,16 19 These relationships are difficult to highlight, inasmuch as not all subjects may be affected and job strain highly varies with time. 20 Even short-term variations in daily work load have been noted to lead to parallel ambulatory SBP fluctuations in workers with low levels of job control. 27 Cross-sectional and short-term (1 year) studies generally conclude that job stress might contribute to hypertension, 9,11 15 whereas long-term studies do not support such an assertion. 8,19 Schnall et al reported a persistent effect of high job strain on ambulatory BP, but only in the few subjects exposed to high job strain both at the beginning and 3 years later at the end of the study. 20 Discrepancies between studies might be caused by the design of studies, the samples of populations studied, the use of ambulatory BP, 6 9,18,20 and the duration of follow-up. 28 Cross-sectional and short-term studies usually compare hypertensive subjects (treated or not treated) to normotensive subjects in a case-control design, whereas long-term studies are cohort studies. If a relationship between job strain and hypertension exists, it is of major interest to observe this relationship at the onset of hypertension. Our analysis Table 3. Characteristics of incident diastolic hypertensive and normotensive subjects subgroups stratified by job strain modalities Subgroup n Age (y) BMI (kg/m 2 ) Alcohol score SBP DBP HR (beats/min) Diastolic hypertensive subjects HS/DBP-HT A/DBP-HT P/DBP-HT LS/DBP-HT Diastolic normotensive subjects HS/DBP-NT A/DBP-NT P/DBP-NT LS/DBP-NT Data are mean SD. Diastolic hypertension defined as diastolic blood pressure (DBP) 90 mm Hg. Abbreviations as in Table 2.

5 698 JOB STRAIN AND HYPERTENSION DEVELOPMENT AJH July 2006 VOL. 19, NO. 7 High Strain n = 57 P<0.001 Active n = 149 P<0.01 Low strain Passive n = 84 P< SBP (mmhg) High Strain n = 45 P<0.01 Active Low strain Passive n = 49 P< DBP (mmhg) FIG. 2. Statistical significance (Z analysis) of associations between systolic blood pressure (SBP) or diastolic blood pressure (DBP) levels and job strain modalities. (In multiple comparisons, associations are significant a values of P.003).

6 AJH July 2006 VOL. 19, NO. 7 JOB STRAIN AND HYPERTENSION DEVELOPMENT 699 is the first the main outcome of which is the onset of hypertension. All subjects were normotensive (BP 140/90 mm Hg) 1 year ago at the mandatory work site examination. Because classical statistical methods did not find any relationship between job strain and hypertension development, we performed a complementary analysis designed to explore nonlinear relationships. Classical approaches to investigate the effects of psychosocial factors on cardiovascular characteristics used analysis of variance to compare means between groups, 11,16,29 linear regressions or logistic regressions. Linear regressions focused on the shape of the relationship between variables using covariance properties. In our study, the lack of significant adjustment of a linear model linking BP and job strain confirms that there is no relationship between these variables in the whole population. If such a relationship exists, it might concern only some of the subjects exposed to high job strain. To analyze relationships among four job strain modalities and four BP levels, it was better to use a coefficient of association than logistic regression, because the latter could only take into account two modalities for the outcome. The heuristic Z analysis that does not imply that an a priori general model increases the statistical power. Using the Pearson coefficient, the Z analysis tests the strength of association for each possible combination of two modalities of categorical variables. Thus the Z analysis enables a data selection based on statistical dependence to highlight associations (ie, job strain and development of hypertension) that might be masked by noisy data. Our analysis is thus well suited to isolate subgroups of subjects whose job strain might be associated with onset of hypertension. The Z analysis has been first validated to assess the baroreflex sensitivity from BP and HR time series. 30 The methodology was then successfully applied in clinical pharmacology 31 and in epidemiology. 26,32 In the present analysis, an SBP 140 mm Hg was significantly linked with the HS modality in 34% of newly diagnosed and in never-treated hypertensive subjects. This HS/SBP-HT subgroup had the same characteristics as the other hypertensive subgroup not exposed to a high job strain. Thus high job strain appeared to be the main characteristic of hypertension in this subgroup. The significant odds ratio (OR 1.84; 95% CI 1.28 to 2.65; P.01) to estimate the relative risk of hypertension in this subgroup confirmed the results of our analysis. The statistical dependence between high SBP and high job strain, observed only in a subgroup of subjects with incident hypertension might explain in part the controversial results of previous studies. Our results obtained in newly diagnosed hypertensive subjects confirmed our hypothesis of a short-term influence of job strain on hypertension onset but only in a subgroup of subjects exposed to high job strain. Our results obtained in a relatively young, predominantly male population show that job strain related hypertension is not restricted to female gender as recently reported in a large-scale cross-sectional study. 33 Hypertension onset in older subjects is associated with other characteristics such as menopausal status, renal function, and vascular properties that are modified by the ageing process. Family history of hypertension, which was reported to influence hypertension onet in an HS group, 10 was not analyzed in our study. Parental history of hypertension, which was recorded only in the second study, was linked to hypertension onset but was independent of job strain status. Hypertension status was based on office BP measurements as recommended by international recommendations. The lack of ABP monitoring to exclude white coat hypertension can be regarded as a limitation of our study. 6,7 However, work place BP also takes into account additional pressure attributable to job activity. 34,35 Furthermore increasing the statistical power in our analysis revealed that job strain effects can also be found using workplace BP. In conclusion, this analysis confirms that high job strain is linked to hypertension onset in a subgroup of relatively young, predominantly male subjects; and it allows quantification of the proportion of newly diagnosed hypertensive subjects whose BP depends on job strain. Among subjects exposed to high job strain, the 34% of subjects who will develop hypertension would have profited from a job strain reduction program. 36 Acknowledgments The authors thank Madame Bertheux-Beaufrere for translation support. 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