Psychosocial stress and atherosclerosis: family and work stress accelerate progression of coronary disease in women. The Stockholm Female Coronary Angiography Study
Abstract.
Objective. To examine the impact of psychosocial stress, experienced in the family and work life, on the progression of coronary atherosclerosis in women cardiac patients.
Design. Longitudinal follow-up study. The mean luminal diameter change over 3 years was averaged over 10 predefined coronary segments, representing the entire coronary tree. Stress in family life was measured by using the Stockholm Marital Stress Scale and that of work life by the demand-control questionnaire.
Subjects. Amongst patients enrolled in the Stockholm Female Coronary Angiography Study, 80 women were evaluated for stress exposure and coronary atherosclerosis progression using serial quantitative coronary angiography.
Results. Multi-variable-controlled mixed models anova analyses revealed that women with high stress from either family or work had significant disease progression over 3 years, whereas those with low stress had only slight progression. In women who were free of stress from either family or work life, i.e. they were satisfied with both of these life domains, the coronary artery changes had regressed. Their mean coronary luminal diameter increased by 0.22 mm (95% CI: 0.10; 0.35 mm) when compared with women who experienced stress from both sources, whose luminal diameter decreased by 0.20 mm (95% CI: −0.14; −0.25). These associations were independent of baseline luminal diameter and standard cardiovascular risk factors, including age smoking, hypertension and HDL at baseline.
Conclusions. Stress from family or work life may accelerate coronary disease processes in women, whereas relative protection may be obtained from a satisfactory job and a happy marriage.
Introduction
Evidence from epidemiological observations suggest that psychosocial factors contribute to the pathogenic coronary process in women as in men, independently of clinical risk markers, but the nature of the stressors in women is less well known than in men [1].
We have previously shown that the stress arising in family relations seems to be more important than stress at work in women. The prognosis and long-term survival was poorer in women coronary patients who experienced high marital stress compared with women in harmonious dyadic relationships [2]. Stress at work by itself did not worsen prognosis, but the combined effects of stress arising in both spheres was associated with the worst health outcome [3].
To examine whether these influences directly affect the underlying coronary artery changes, we conducted a prospective study of coronary atherosclerosis progression, using repeat quantitative coronary angiography (QCA) with a 3-year interval between angiographic examinations. We examined the role of stress experienced at work, at home in dyadic relations, and the combined effects of exposure to both types of stress. We hypothesized that stress from family and work in combination would yield the most extensive acceleration of coronary disease progression in women.
Materials and methods
Study population
The study population came from the Stockholm Female Coronary Risk study that included all women patients (n = 292) aged 30–65, with a mean age of 56 years, who were admitted for acute myocardial infarction (AMI) or unstable angina pectoris (UAP) in greater Stockholm during 1991–1994. Patients were examined three to 6 months after hospitalization. All enrolled patients consented to participate, and the Regional Research Committee at Karolinska Institute approved the study. Detailed information about medical history, lifestyle and socio-demographic data were collected. Anthropometric measures, a full lipid, and routine laboratory profile were assessed. Psychosocial questionnaires were mailed to the subjects prior to their visit to the research clinic. These were completed at home and brought to the research clinic. Each questionnaire was checked for problems and missing data by the research nurse [4].
Amongst the 292 women patients, 131 women were enrolled in the Stockholm Female Coronary Angiography Study to be evaluated by means of QCA, repeated after 3 years. QCA was introduced and implemented in a continuing collaboration between the Karolinska University Hospital, Stockholm (Svane) and the Texas Medical Center, Houston (Kirkeeide), ensuring calibration and standardization of angiograhic procedures. Contingent upon access to the calibrated angiography laboratories, 131 women patients were enrolled for QCA at baseline. These patients did not differ from the full study group of 292 patients, in age, marital status and socio-economics, residential area, clinical or psychosocial characteristics [5].
At follow-up 3 years later, three women had died and 12 further women had declined a second angiogram, leaving 116 women who underwent repeat QCA. Ten of these reexaminations yielded poor questions angiograms and a further three were not comparable with the baseline angiogram. To examine the effects of psychosocial stress, women who were either cohabiting or were employed outside the home (n = 80) were included in the analyses. Women who were living alone and did not have a job (n = 23) had no reports of job- or marital stress and were not eligible for these analyses.
Measurement of psychosocial factors
Marital stress was measured by using the Stockholm Marital Stress Scale (SMSS) that was developed in our research laboratory [2]. It is focused on sources of stress in marital life, and estimates the quality of the emotional relationship with the spouse. A high score indicates high marital stress (range: 0–14). Each response indicating exposure to a stressor gets a stress score of one, meaning that differences in relative severity between the various stressors are not accounted for. An adequate internal consistency and satisfactory construct validity have been found in both a representative sample of the general female population of Stockholm (Cronbach's α = 0.77) and in the patient group under study (Cronbach's alpha = 0.74) (2, 5). Marital stress was categorized as mild or absent (lower tertile, score 0–1), moderate (middle, 2–3) and high (upper tertile, 4–14).
Job strain was measured by using the Swedish short version of the Karasek demand-control questionnaire (DCQ), which has been tested for consistency and reliability in the Swedish population [6]. Internal consistency was found to be satisfactory in this patient population (Cronbach's alpha = 0.69). Psychological work demands refer to high work pace, deadlines, conflicting demands and high time pressure. Control at work (decision latitude) refers to the combination of authority over decisions and skill discretion. Job strain is computed as the ratio between psychological demands and decision latitude. A high ratio indicates high demand and/or low decision latitude (range: 0.38–1.5). Job strain was categorized as low (lower tertile, score 0.38–0.67), moderate (middle, 0.68–0.86) and high (upper tertile: 0.86–1.5).
The combination of marital stress and job strain was categorized as women patients who experienced: (i) neither marital stress nor job strain (lower tertile in both domains); (ii) moderate stress of any kind (middle tertile) in any of them, and (iii) either high job or marital stress (higher tertile in either of the domains).
Quantitative coronary angiography
Selective coronary arteriography was performed at the Department of Thoracic Radiology at Karolinska University Hospital using the Judkins’ technique and a standard clinical angiographic procedure. Before and after intracoronary injection of nitroglycerine, identical angiographic projections were obtained. A standard clinical angiographic procedure was followed. After engaging the coronary segment under study with the injection catheter, the angiographic view was optimized with short test injections. During a breath hold, filming was started before contrast injection to show the catheter. Dye was injected to opacify the segments of interest for at least three cardiac cycles. Imaging conditions (angiographic view angles, catheter size and field size) were recorded in an arteriography procedure log. At the end of the procedure, the distal 10 cm of each catheter was saved and labelled for later identification and measurement. All angiograms were recorded as cine films with a frame rate 25 frames/second.
The Angiographic Image Processing Laboratory of the Division of Cardiology, University of Texas performed computer-assisted quantitative evaluations of the angiographic films. For each angiogram, absolute luminal diameter (mm) was measured in 10 predefined coronary segments. Mean segment diameter was calculated as the mean of all diameters measured along a given segment. Special procedures were undertaken to replicate the biologic and imaging conditions of the original angiogram at the 3-year follow-up. The evaluation procedure was blinded to the patient's identity and the order of examinations. The progression of atherosclerosis was evaluated by using the mean luminal diameter change over time by subtracting the first from the second measurement (7,8,9).
Covariates
Age at examination was obtained from the census register. Educational level was classified into mandatory (less or equal to ≤9 years) and high school or college/university (more than 9 years). Smoking status was categorized as ever (current or former smokers) versus never. Alcohol consumption was reported as the habitual weekly intake of beer, wine, strong spirits and calculated as average daily consumption of absolute alcohol in grams. Physical exercise was assessed according to the World Health Organization questionnaire and categorized as sedentary or active lifestyle. Body mass index (BMI) was calculated as weight (kg)/height (m2).
Menopause was defined as cessation of menses since 6 months and women's menopausal status was classified as premenopausal status, postmenopausal status with and postmenopausal status without hormone replacement therapy. Family history of coronary heart disease (CHD) was defined as having at least one close family member diagnosed with AMI. The clinical diagnosis at the index event was categorized into AMI or UAP. Severity of angina pectoris symptoms was graded as: I no angina, II mild angina, III moderately severe angina, and IV very severe angina, by the Canadian Cardiovascular Society Scale for Angina Pectoris [7]. Patients were categorized as either having severe angina or mild (III+IV), or no angina (I+II). A detailed medical history including hyperlipidemia, hypertension, diabetes and left ventricular dysfunction, as well as medication was obtained during the clinical and examination and verified by scrutiny of hospital charts. Medications were classified as: aspirin, beta-blockers, ACE inhibitors, calcium antagonists and lipid-lowering medication including statins as well as medication for diabetes, including insulin [4]. Only three statin users were found.
All blood samples were drawn in the morning after an overnight fast. Samples were frozen and sent in batches to the analysing laboratory. Total cholesterol was determined by enzymatic methods. An HDL determination was based on the isolation of LDL and VLDL from serum by precipitation. The cholesterol content of the supernatant was measured enzymatically by using an automated Multichannel Analyzer [10]. Plasma fibrinogen (g L−1) was determined by using a polymerization rate method [11].
Statistical analyses
We conducted mixed model analyses to assess the influence of psychosocial factors on disease progression. In all analyses, we used the absolute changes in the mean luminal diameter as the primary measures of atherosclerosis progression. To control for inter-correlations of segments within subject, segments were treated as experimental units clustered within individuals. We performed segment-specific analyses on repeated QCA data. As segment data in a specific subject can be statistically dependent, we clustered the experimental units (i.e. segments) within a given patient [12]. All repeated measures analyses were implemented by using PROC MIXED under sas version 8.02 for Windows (SAS institute Inc, Cary, NC, USA). In these models, change in the mean segment diameter served as the dependent variable, each psychosocial factor and clinical covariable as fixed effects, and coronary segments as random effects when accounting for the statistical dependence between segment data within an individual. We conducted crude, age-adjusted and basic multivariate-adjusted analyses. Age, smoking history, hypertension and HDL were included in the basic multivariate adjusted models. In a second set of models, we further adjusted for education, sedentary lifestyle, marital status, menopausal status, alcohol consumption, diagnosis of AMI/UAP at the index event, angina severity, fibrinogen, total/HDL cholesterol ratio, BMI, left ventricular dysfunction, diabetes, family history of CHD and use of medications. Each of these factors was introduced into the basic multivariate model mentioned above, one at a time. Using the Log-likelihood comparison test, the degree of improvement in model fit with entry of marital and work stress variables was 30 with 10 d.f., which corresponds to P < 0.001.
Results
Psychosocial and standard risk factors did not substantially differ between all those women who had complete data on repeat QCA (n = 103) and women who also had information on job or marital stress (n = 80).
Women patients with high marital stress were more likely to be premenopausal than those with lower stress. Patients with high job stress were more likely to be overweight, but less likely to be current smokers than women with lower stress. More women patients with moderate or high job stress also had hyperlipidemia than those with low job stress (Table 1).
| Marital stress | Job strain | |||||||
|---|---|---|---|---|---|---|---|---|
| Absent/low (n = 21) | Moderate (n = 18) | High (n = 30) | P for trend | Low (n = 21) | Moderate (n = 29) | High (n = 21) | P for trend | |
| Age (years) | 57.5 ± 6.8 | 54.1 ± 6.9 | 54.2 ± 8.7 | 0.25 | 56.2 ± 4.9 | 52.7 ± 709 | 53.0 ± 6.1 | 0.11 |
| Diagnosis at index event of | 0.06 | 0.56 | ||||||
| AMI% | 76.2 | 50.0 | 43.3 | 38.1 | 48.3 | 33.3 | ||
| UAP% | 23.8 | 50.0 | 56.7 | 61.9 | 51.7 | 66.7 | ||
| Family history of CHD (yes)% | 42.9 | 38.9 | 60.0 | 0.31 | 38.1 | 55.2 | 52.4 | 0.52 |
| Medical history% | ||||||||
| Mild/nonanginal symptoms (I + II) | 28.6 | 50.0 | 42.3 | 0.44 | 40.0 | 40.7 | 30.0 | 0.65 |
| Severe anginal symptoms (III + IV) | 71.4 | 50.0 | 57.7 | 60.0 | 59.3 | 70.0 | ||
| Left ventricular dysfunction | 15.0 | 18.8 | 24.1 | 0.80 | 15.8 | 14.8 | 4.8 | 0.47 |
| Hyperlipidemia | 47.4 | 29.4 | 37.4 | 0.54 | 10.0 | 44.8 | 38.9 | 0.03 |
| Hypertension | 47.4 | 29.4 | 51.9 | 0.35 | 25.0 | 55.2 | 44.4 | 0.11 |
| Diabetes mellitus | 9.5 | 16.7 | 23.3 | 0.47 | 23.8 | 6.9 | 4.8 | 0.09 |
| Menopausal status | 0.04 | 0.46 | ||||||
| Premenopausal | 9.5 | 22.2 | 40.0 | 14.3 | 31.0 | 33.3 | ||
| Postmenopausal with HRT | 23.8 | 5.6 | 3.3 | 19.0 | 6.9 | 14.3 | ||
| Postmenopausal without HRT | 66.7 | 72.2 | 56.7 | 66.7 | 62.1 | 52.4 | ||
| Education% | 0.98 | 0.15 | ||||||
| 1–9 years | 61.9 | 61.1 | 63.3 | 47.6 | 65.5 | 76.2 | ||
| More than 9 years | 38.1 | 38.9 | 36.7 | 52.4 | 34.5 | 23.8 | ||
| Cigarette smoking% | 0.45 | 0.04 | ||||||
| Current smokers | 33.3 | 27.8 | 20.0 | 47.6 | 17.2 | 14.3 | ||
| Former smokers | 61.9 | 50.0 | 60.0 | 47.6 | 58.6 | 71.4 | ||
| Never smokers | 4.8 | 22.2 | 20.0 | 4.8 | 24.1 | 21.3 | ||
| Sedentary lifestyle% | 19.1 | 16.7 | 23.3 | 0.93 | 71.4 | 75.9 | 71.4 | 0.92 |
| Alcohol intake (g day−1) | 5.6 ± 7.8 | 8.8 ± 8.3 | 5.5 ± 9.7 | 0.41 | 5.1 ± 5.9 | 5.5 ± 8.1 | 2.8 ± 4.1 | 0.35 |
| Body mass index (kg m2) | 27.6 ± 3.7 | 27.9 ± 5.4 | 27.1 ± 4.1 | 0.78 | 27.7 ± 5.1 | 25.8 ± 3.6 | 28.8 ± 4.1 | 0.05 |
| Serum levels of | ||||||||
| total/HDL cholesterol | 4.6 ± 1.8 | 4.6 ± 1.5 | 4.8 ± 1.3 | 0.84 | 4.1 ± 1.4 | 4.4 ± 1.7 | 5.0 ± 1.5 | 0.19 |
| fibrinogen (g L−1) | 3.4 ± 0.8 | 3.7 ± 1.0 | 3.7 ± 1.0 | 0.80 | 3.4 ± 0.8 | 3.9 ± 1.0 | 3.8 ± 1.0 | 0.25 |
| Medication use% | ||||||||
| Aspirin | 76.2 | 77.8 | 85.7 | 0.68 | 71.4 | 62.1 | 70.0 | 0.75 |
| ACE inhibitors | 4.8 | 11.8 | 10.7 | 0.75 | 14.3 | 13.8 | 5.3 | 0.59 |
| Beta blockers | 71.4 | 72.2 | 92.9 | 0.09 | 81.0 | 62.1 | 80.0 | 0.23 |
| Calcium antagonists | 33.3 | 33.3 | 21.4 | 0.62 | 25.0 | 37.9 | 45.0 | 0.41 |
| Insulin | 4.8 | 17.7 | 14.8 | 0.40 | 15.0 | 0 | 5.3 | 0.06 |
| Lipid-lowering drugs | 14.3 | 11.1 | 10.0 | 0.89 | 4.8 | 13.8 | 9.5 | 0.71 |
- Figures represent per cent (%) for categorical variables and mean ± SD for continuous variables. AMI, acute myocardial infarction; UAP, unstable angina pectoris; CHD, coronary heart disease; HRT, hormone replacement therapy; HDL, high-density lipoproteins.
During the 3-year follow-up, there was more pronounced coronary artery luminal diameter narrowing in women with high marital stress than those with mild or no stress. The same pattern was seen for job stress (Table 2). Similar results were observed when marital stress and job stress were analysed as continuous variables. A one-point increase in standardized marital stress score was associated with 0.05 mm (P = 0.007) of luminal diameter narrowing. A one-point increase in standardized job strain was accompanied by 0.06 mm (P = 0.0006) narrowing.
| Segments | Baseline diameter | Age-adj. changes* | Multi-adj. changes* | Age-adj. per cent changes* | Multi-adj. per cent changes* | |
|---|---|---|---|---|---|---|
| Marital stress | ||||||
| Low | 151 | 3.24 ± 0.65 | −0.002 (0.06, −0.06) | 0.04 (0.11, −0.04) | 0.10 (2.06, −1.86) | 1.13 (−1.16, 3.43) |
| Moderate | 126 | 2.93 ± 0.52 | −0.077 (−0.14, −0.01) | −0.09 (−0.02, −0.16) | −2.51 (−0.38, −4.64) | −3.0 (−0.77, −5.23) |
| High | 188 | 2.97 ± 0.58 | −0.137 (−0.08, −0.19) | −0.15 (−0.09, −0.21) | −4.16 (−2.41, −5.90) | −4.6 (−2.74, −6.48) |
| P for trend | 0.18 | 0.007 | 0.0003 | 0.007 | 0.0004 | |
| Job strain | ||||||
| Low | 176 | 3.28 ± 0.57 | −0.05 (0.01, −0.11) | −0.04 (0.02, −0.11) | −1.41 (0.33, −3.16) | −1.13 (0.84, −3.10) |
| Moderate | 193 | 2.96 ± 0.61 | −0.05 (0.01, −0.10) | −0.09 (−0.03, −0.15) | − 1.94 (−0.29, −3.60) | −2.97 (−1.21, −4.73) |
| High | 147 | 3.40 ± 0.60 | −0.16 (−0.10, −0.023) | −0.20 (−0.13, −0.27) | −4.35 (−2.48, −6.20) | −5.19 (−3.07, −7.31) |
| P for trend | 0.03 | 0.008 | 0.002 | 0.057 | 0.017 | |
| Marital + job strain | ||||||
| Low + low | 38 | 3.11 ± 0.65 | 0.20 (0.32, 0.08) | 0.22 (0.10, 0.35) | 6.53 (10.25, 2.80) | 7.13 (11.05, 3.21) |
| Moderate/low | 298 | 2.97 ± 0.52 | −0.06 (−0.02, −0.10) | −0.09 (−0.04, 0.13) | −2.25 (−0.90, −3.55) | −2.94 (−1.52, −4.35) |
| High/high | 218 | 3.26 ± 0.66 | −0.18 (−0.13, −0.23) | −0.20 (−0.14, −0.25) | −4.98 (−3.43, −6.53) | −5.37 (−3.69, −7.04) |
| P for trend | 0.13 | <0.0001 | <0.0001 | <0.0001 | <0.0001 | |
- *Multivariate models adjusted for age, smoking history, hypertension, and HDL.
In multivariable analyses, a significant dose–response effect was observed: women coronary patients with either high marital stress or high job strain had the greatest progression. Women with either moderate marital stress or job strain had moderate progression, whereas women who had neither job- nor marital stress had regressed in respect to mean luminal diameter of their coronary vessels (Table 2, Fig. 1).
Mean per cent (%) luminal diameter changes (95% confident intervals) over a 3-year period according to baseline marital and job stress. High stress from marriage or job. Moderate stress from marriage or job. No stress from marriage and job. Negative value indicates progression and positive value means regression. 1 = no stress. 2 = moderate or high stress from one source. 3 = moderate or high stress from two sources.
In the next step, further confounders were introduced into basic multivariate models. These variables were added one at a time. They consisted of education, marital status, exercise habits, BMI, menopausal status, alcohol consumption, diagnosis of AMI/UAP, fibrinogen, left ventricular dysfunction, diabetes, family history of CHD and use of medications. Results remained virtually the same. Confounding by other standard clinical risk factors could not be verified.
Modelling the exposure variables as standardized continuous variables further supported these results. Finally, introducing an interaction term of the two stress scales in combination yielded a significant interaction between the two variables (P < 0.001), suggesting an independent effect of combined stress exposure.
Discussion
In this 3-year follow-up of women patients who were aged 30–65 years and hospitalized for an acute coronary event in Stockholm, we found that women who at base-line reported being stressed had an accelerated disease progression over the following 3 years: the absolute mean luminal diameter decreased by 5.2% (95% CI: 3.1; 7.3) in women with job strain and by 4.6% (95% CI: 2.7; 6.5) in women with marital stress. In contrast, absence of stress from any of these sources seemed protective: the mean luminal diameter of the coronary tree widened by 7.1% (95% CI: 3.2; 11.1), suggesting regression of the coronary disease. These associations were independent of baseline luminal diameter and of standard risk factors. They also remained unchanged after further control for a wide variety of coronary risk factors.
Marital stress and progression of CHD
We have previously reported that marital stress worsens prognosis in women with coronary disease. During 5-year follow-up, women with marital stress had three times the risk of cardiac death, recurrent AMI or revascularization [2]. The present finding that women patients with high marital stress had accelerated disease progression suggests an underlying pathogenic mechanism. With higher stress women experienced more severe disease progression as assessed by QCA.
Our results are in agreement with the findings of the Healthy Women's Study [13], demonstrating atherosclerosis progression in women's carotid arteries with exposure to marital discord. They are also consistent with the finding that lack of perceived social support increased the risk of new and recurrent [14] AMI, and accelerated progression of coronary disease [15]. Using two different psychosocial concepts, namely stress and social support, we found that clinical effects were inter-related and accompanied by progression of underlying coronary artery disease.
In laboratory stress provocation, differences between men and women in relation to marital discord have been demonstrated. Marital conflict has been associated with higher levels of catecholamines, corticotropin and growth hormone in women, but not in men [16]. Increased cardiovascular reactivity during marital conflict has been related to hostility amongst men but not in women. Women's reactivity, however, was provoked by hostile responses in husbands [17].
Job strain and progression of CHD
Our findings that high job strain was associated with progression of coronary disease are in line with previous studies [18, 19]. As adjusting for potential confounders did not reduce the associations, standard risk factors are unlikely to explain our findings.
Because deleterious health behaviours may be part of the causal pathway by which adverse psychosocial stress influences progression of atherosclerosis, adjustment for these variables may mean over-adjustment. Furthermore, although there are few studies of women's coronary atherosclerosis, there is sufficient evidence for the conclusion that job strain is associated with elevated risk of coronary episodes also in women. Studies with null findings [20, 21] suffer from methodological flaws in the design of the studies and the measures of job strain used. This bias could be ruled out as virtually all women of the full study group were or had been employed until their cardiac event, reflecting the high employment rates in the normal population of Swedish women at the time.
Combined stress exposure and progression of CHD
To simplify the interpretation of results, we have relied on categorical representation of stress measures. In addition, however, we also analysed stressors as standardized continuous variables and found graded, dose–response effects of similar magnitude for each unit of increase in each of the two stress scales.
Furthermore, modelling the interaction between stressors as a separate term yielded a significant independent effect on progression. A cautious interpretation suggests that those women who had both types of long-term stress simultaneously had a further increased and accelerated disease progression as a consequence of the double exposure.
Study strengths and limitations
The most challenging finding of the present study is that coronary atherosclerosis may have regressed in women who were free of stress. This has not previously been reported in the literature. The magnitude of the luminal diameter change is similar to that reported by the authors of Lifestyle Heart Trial. Using the same QCA methodology, they found a regression up to 4.5% after 1 year and 7.9% after 5 years [8].
A strength of the present study is that marital stress could be quantified by a psychometrically evaluated and standardized instrument, the SMSS, and job strain was assessed by using the DCQ that has been used in several epidemiological studies and has been claimed to be a good predictor by various reviews [22, 23]. The progression of atherosclerosis was evaluated by using QCA, a reliable method to quantify, with more objectivity than in clinical evaluations, the precise underlying process of coronary atherosclerosis progression.
Several limitations need to be born in mind when interpreting the findings. First, 13 of 116 (11%) of women patients did not have valid repeated QCA measurements. It is unlikely that selection bias would have influenced our results, as baseline characteristics did not vary between the participants and nonparticipants. Secondly, marital stress and job strain were measured at base-line, and may have been subject to change during follow-up. The same applies to standard and other risk factors. Thirdly, although we have controlled for many confounders in multivariate analyses, residual confounding cannot be ruled out. Fourthly, our study population consisted of middle-aged women patients, who had been hospitalized with coronary disease. Thus, our results may not generalize to older women with coronary disease or women who are not hospitalized. Fifthly, to measure stress with two different methods (interview or survey) in two different domains may not be entirely comparable. Patients may report their stress experiences differently in a personal interview compared with a written test. However, job strain based on a structured interview and on DCQ survey showed similar effects on coronary risk [7].
In addition, using coronary artery segments as experimental units rather than individual patients in the mixed model may limit the interpretation of psychosocial information that is tied to the patient. The change over time in mean coronary artery segment diameter, indicating atherosclerotic progression/regression, however, was monitored in each segment separately. As the segments are the target of the process, the mixed model procedure was considered as the most adequate statistical procedure. In this way, dependency between segments and individuals was accounted for in the statistical analysis.
Possible explanations
Chance is an unlikely explanation for our findings, as the association with progression of coronary disease was apparent when marital stress and job strain were analysed both as categorical and as continuous variables. Self-report bias is unlikely to be important because the progression of disease was measured by using QCA and the study design was prospective. Bias attributable to loss to follow-up is also unlikely, as all patients who underwent both baseline and follow-up QCA evaluations were included in the study.
Potential explanations of atherosclerosis regression are concerned with emotional and behavioural consequences of partner interaction. Perhaps, women in harmonious relationships benefit from positive social control, promoting healthier habits. A supportive spouse may become even more supportive when a partner is facing serious heart health problems, and such support is known to have direct and indirect physiological impact [24]. Women with little or no stress may also have been more prone to follow medical advice; they may more easily adhere to medication prescriptions and benefit from counselling than women with high stress [25].
The associations between psychosocial stress and progression of atherosclerosis may be true and causal. It is known that emotional stressors precipitate the onset of AMI both in men and in women [26]. As has been shown in men, acute psycho-physiological responses to stressors may also be exaggerated in women who are chronically burdened with prolonged exposure to marital stress. It is conceivable that stress both triggers the acute onset of AMI and promotes enhanced progression of atherosclerosis, endothelial dysfunction and plaque instability [27].
Recent evidence [28] points at the combination of high demand and low control as relevant to endothelial damage with prolonged effects of such stress reactions. These results may explain the findings in the present study. If women are repeatedly exposed to stressful situations, they may respond with physiological reactions that accelerate the atherosclerotic process. A similar reasoning could apply to stress from other sources and the evidence in the present study points at the possible strong interaction between stresses in the two spheres [3].
Psychosocial stress may accelerate the atherosclerotic process via two pathways [25]: on one hand, via neuroendocrine mechanisms affecting blood lipids [23] and plasma fibrinogen [24], increasing blood pressure reactivity [25] or catecholamines and cortisol [26] and other physiological regulatory mechanisms [27]. On the other hand, stress could exert its influence on progression of the disease via modification of coronary risk factors, such as lack of adherence to healthier lifestyles and to medical therapy. In patients with the combination of marital and work stress, the stressors could acutely trigger coronary events in vulnerable people in the final stages of coronary disease [29–34].
Conclusions
The findings from the present study suggest that stress from either marital relationships or from work may worsen prognosis and accelerate progression of women's coronary disease. In contrast, however, absence of both marital stress and job strain may protect middle-aged women patients against progression of atherosclerosis.
Conflict of interest statement
There is no conflict of interest.
Acknowledgements
This work was supported by grant # HL 45785 from the US National Institutes of Health, grants from the Swedish Bank Tercentenary Fund, the Swedish Medical Research Council and the Swedish Council for Work Life Research and the Swedish Labor Market Insurance Company, all to Kristina Orth-Gomér. We are grateful to Dr Stuart Mac Donald for valuable comments on statistical procedures.
