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Keywords:

  • deep vein thrombosis;
  • deep venous thromboembolism;
  • mental stress;
  • pulmonary embolism;
  • socio-economic status

Abstract

  1. Top of page
  2. Abstract
  3. Background
  4. Population and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosure of Conflict of Interests
  10. References

Summary. Background: The link between psychosocial factors and coronary heart disease is well established, but although effects on coagulation and fibrinolysis variables may be implicated, no population-based study has sought to determine whether venous thromboembolism is similarly related to psychosocial factors. Objective: To determine whether venous thromboembolism (deep vein thrombosis or pulmonary embolism) is related to psychosocial factors. Patients/methods:  A stress questionnaire was filled in by 6958 men at baseline from 1970 to 1973, participants in a cardiovascular intervention trial. Their occupation was used to determine socio-economic status. Results: After a maximum follow-up of 28.8 years, 358 cases of deep vein thrombosis and/or pulmonary embolism were identified through the Swedish hospital discharge and cause-specific death registries. In comparison with men who, at baseline, had no or moderate stress, men with persistent stress had increased risk of pulmonary embolism [hazard ratio (HR)=1.80, 95% CI: 1.21–2.67]. After multivariable adjustment, the HR decreased slightly to 1.66 (95% CI: 1.12–2.48). When compared with manual workers, men with white-collar jobs at intermediate or high level and professionals showed an inverse relationship between occupational class and pulmonary embolism (multiple-adjusted HR=0.57, 95% CI: 0.39–0.83). Deep vein thrombosis was not significantly related to either stress or occupational class. Conclusion: Both persistent stress and low occupational class were independently related to future pulmonary embolism. The mechanisms are unknown, but effects on coagulation and fibrinolytic factors are likely.


Background

  1. Top of page
  2. Abstract
  3. Background
  4. Population and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosure of Conflict of Interests
  10. References

Stress and other psychosocial factors are important causes of coronary heart disease [1–3], but the pathophysiological processes underlying this phenomenon are not clear. Several studies have demonstrated links between psychosocial variables and increased blood clotting and decreased fibrinolysis [4,5]. However, whether this translates into other disease processes involving coagulation mechanisms is not known. Venous thromboembolic disease probably has a different etiology from coronary disease [6], but both disorders involve coagulation processes, and accordingly, a link between psychosocial factors and venous thromboembolism could indicate an influence on blood clotting factors.

Venous thromboembolism is a serious, potentially fatal disorder and one of the major manifestations of cardiovascular disease, with an age-standardized incidence of first-time venous thromboembolism estimated at 2 per 1000 person-years in persons aged 45 years and over. The disease occurs more frequently in men than in women [7]. Only a handful of prospective population studies exist [6–10], and no studies on psychosocial factors and venous thromboembolism have been reported. We therefore aimed to assess prospectively the effect on venous thromboembolism of the association between psychological stress and socio-economic status, two factors that have been associated with increased risk of coronary disease [1–3,11–13].

Population and methods

  1. Top of page
  2. Abstract
  3. Background
  4. Population and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosure of Conflict of Interests
  10. References

Data were derived from a random sample of 9998 Göteborg men born between 1915 and 1922 and between 1924 and 1925, 7495 of whom took part in a screening investigation for a cardiovascular intervention trial from 1970 to 1973 [14]. Of these men, 7046 filled out a stress questionnaire [15] (70.5% of the sample) and form the basis of the present analysis. Psychological stress was assessed by a single question, similar to that used in a large cardiovascular survey [1], with stress defined as feeling irritable, feeling filled with anxiety, or as having sleeping difficulties because of conditions at work or at home. Participants were asked to report how often they had felt stress, using the following response options: 1 = never, 2 = some period ever, 3 = several periods during the past year, 4 = several periods during the past 5 years, 5 = persistent stress during the past year, and 6 = persistent stress during the past 5 years. Analyses were done defining 1 and 2 as no or little stress, 3 and 4 as moderate stress, and 5 and 6 as persistent stress. Occupation was coded into five classes according to the Swedish socio-economic classification system (Socio-Economic Index): (i) unskilled and semiskilled workers; (ii) skilled workers; (iii) foremen in industrial production and assistant non-manual employees; (iv) intermediate non-manual employees; and (v) employed and self-employed professionals, higher civil servants, and executives [16]. In the analyses, we combined unskilled and skilled manual workers into one group, and classes 4 and 5 into one group labeled white-collar, at intermediate or high level, professionals. Men who could not be classified, mostly because of early retirement, formed a separate group. Standard cardiovascular risk factors were measured as previously described [14]. With one cigarette as the equivalent of 1 g day–1, smoking was categorized as: (i) never; (ii) former smoker; (iii) 1–14 g day–1; and (iv) 15 g or more per day. Leisure-time physical activity was defined as low (mainly sedentary), medium (at least 4 h week–1 of moderate activity such as walking), or high (vigorous activity for 3 h or more per week). A history of diabetes or of treatment for hypertension was recorded. Alcohol abuse was defined as having been registered with the Swedish Board of Social Welfare for medical or legal problems attributed to alcohol abuse (e.g. drunken driving) [16]. During the first 12-year follow-up, there were no significant differences in outcomes regarding cardiovascular disease, cancer or all-cause mortality between the intervention and control groups, chiefly because trends in risk factors were similar [14].Thus, we consider the study group to be representative of the general Göteborg male population.

All men were followed up from the date of their baseline examination until 31 December 1998 for a maximum of 28.8 [mean 22.9 (±6.7)] years. A computer file of the men in the study was run against the Swedish national register on cause of death and the Swedish hospital discharge register. Among 7046 men who responded to the stress question, 446 were identified as having had a diagnosis of either only deep vein thrombosis or pulmonary embolism with or without deep vein thrombosis over a 28-year follow-up. Deep vein thrombosis was defined as a discharge with a primary or secondary diagnosis code of 451,00, 451,98 or 451,99, and pulmonary embolism as a discharge or death with a primary or secondary diagnosis of 450 [International Classification of Diseases, Eighth revision (ICD 8)] and 451B, or 415 [International Classification of Diseases, Ninth revision (ICD 9)] and I26, or I80 [International Classification of Diseases, 10th revision (ICD 10)]. We excluded 73 men because they died of malignant disease within 2 years after having been diagnosed with deep vein thrombosis or pulmonary embolism. Of 196 cases diagnosed with deep vein thrombosis, we were able to retrieve 151 hospital case records for validation (77%). Of 177 cases diagnosed with pulmonary embolism, 153 case records (86%) were retrieved. Thirteen cases of deep vein thrombosis and two of pulmonary embolism were excluded because the diagnoses were found to be incorrect. In cases where records could not be found, we accepted the registered diagnosis. In all cases except 12, objective verification was found in the retrieved records (phlebography or ultrasound for deep vein thrombosis, and scintigraphy, computed tomography or autopsy for pulmonary embolism); however, a diagnosis of pulmonary embolism was accepted if there were symptoms of pulmonary embolism in conjunction with objective evidence of deep vein thrombosis. The 12 cases without objective verification occurred early, with strong clinical symptomatology, and were treated with oral anticoagulants. Altogether, 358 cases of either deep vein thrombosis or pulmonary embolism were included (183 deep vein thrombosis, 175 pulmonary embolism) and compared with 6600 men without pulmonary embolism or deep vein thrombosis (total=6958 men). Of the 358 cases of deep vein thrombosis or pulmonary embolism, 162 had been hospitalized within the previous 3 months. The subjects gave informed consent at the baseline investigation. The follow-up procedures were approved by the Ethics Committee for Medical Research at Göteborg University.

All analyses were done using sas software (version 9.1; SAS Institute, Carey, NC, USA). Cross-sectional associations for continuous variables were tested using Fisher’s test or Pearson’s correlation tests. All tests were two-tailed. Prospective analyses were accomplished using Cox proportional hazards regression models to identify factors related to a diagnosis of deep vein thrombosis and/or pulmonary embolism. Time at risk was calculated to first hospitalization with a deep vein thrombosis and/or pulmonary embolism diagnosis, to death, or to 31 December 1998. To measure the relationships between potential confounding factors and outcome, occupational class and stress were entered simultaneously into the regression models, together with body mass index (BMI), serum cholesterol concentration, height (entered as continuous variables), smoking (entered as never, former smoker, 1–14 g day–1, 15 g or more per day), leisure-time physical activity (entered as low, medium, and high) and treatment for hypertension, diabetes, and alcohol abuse (entered as dichotomous variables). Variables were only kept in the final multivariate regression models if they met the criterion of < 0.15. We checked the assumption of proportional hazards for each endpoint and for the variables that we studied by entering an interaction variable (variable × time) into the Cox regression model. The impact of these terms was not significant on the model fit, indicating that the assumption holds.

Results

  1. Top of page
  2. Abstract
  3. Background
  4. Population and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosure of Conflict of Interests
  10. References

Baseline characteristics of men with and without venous thromboembolism during follow-up are given in Table 1. Men who developed venous thromboembolism were heavier and taller, with higher diastolic blood pressure and more hypertension and diabetes. They were less often non-manual workers but admitted to persistent stress more often.

Table 1.   Baseline risk factors according to diagnosis at follow-up
 No venous thromboembolism, = 6600Venous thromboembolism during follow-up, = 358P-value
Age at baseline, mean (SD) (years)51.5 (2.3)51.9 (2.2)0.003
Body mass index, mean (SD) (kg m−2)25.5 (3.2)26.1 (3.2)< 0.001
Height, mean (SD) (m)1.76 (0.06)1.77 (0.06)0.004
Serum cholesterol, mean (SD) (mmol L−1)6.45 (1.15)6.39 (1.13)0.59
Systolic blood pressure, mean (SD) (mmHg)149 (22)150 (23)0.46
Diastolic blood pressure, mean (SD) (mmHg)94 (13)97 (13)0.003
Treatment for hypertension [% (n)]5 (353)9 (33)0.004
Current smoking [% (n)]51 (3337)44 (157)0.015
Sedentary leisure time [% (n]25 (1646)27 (96)0.42
Diabetes [% (n)]2 (117)4 (14)0.004
History of alcohol abuse [% (n)]7 (439)9 (33)0.066
Persistent stress [% (n)]15 (1017)20 (70)0.036
Non-manual occupational class [% (n)]29 (1920)24 (85)0.030

Significant age-adjusted predictors of future venous thromboembolism over follow-up included obesity, being tall, treatment for hypertension, diabetes, and alcohol problems (Table 2). The hazard ratio (HR) for obesity, in comparison with normal weight, was 2.16 [95% CI: 1.56–3.00]; HRs of similar magnitude were observed for treatment of hypertension and alcohol problems, whereas diabetics had a 3-fold increase in risk as compared with non-diabetics. The HR for height > 179 cm was 1.52 (95% CI: 1.13–2.05) when compared with height < 172 cm. Systolic blood pressure, serum cholesterol concentration, smoking and low leisure-time physical activity were not significantly related to outcome.

Table 2.   Age-adjusted hazard ratios of venous thromboembolism as a function of cardiovascular risk factors
Cardiovascular risk factorObservation yearsCases per 100 000 observation years (n) Age-adjusted hazard ratio (95% CI)
Body mass index (kg m−2)
 < 2574 497188 (140)1.00
 25–3072 582234 (170)1.24 (0.99–1.55)
 > 3012 073398 (48)2.16 (1.56–3.00)
 P for trend  < 0.0001
Height (m)
 < 17239 652179 (71)1.00
 172–17538 910203 (79)1.13 (0.82–1.57)
 176–17938 122249 (95)1.41 (1.04–1.56)
 > 17942 468266 (113)1.52 (1.13–2.05)
 P for trend  0.004
Serum cholesterol (mmol L−1)
 < 5.739 118248 (97)1.00
 5.7–6.341 485212 (88)0.87 (0.66–1.17)
 6.4–7.141 650206 (86)0.87 (0.65–1.16)
 > 7.135 550225 (80)0.95 (0.70–1.27)
 P for trend  0.60
Systolic blood pressure (mmHg)
 < 13341 127216 (89)1.00
 133–14538 345222 (85)1.01 (0.75–1.37)
 146–16141 075243 (98)1.08 (0.81–1.44)
 > 16138 391224 (86)1.01 (0.75–1.35)
 P for trend  0.26
Treatment for hypertension
 No151 206215 (325)1.00
 Yes7947415 (33)1.95 (1.37–2.80)
 P  0.0003
Smoking
 Never smoker48 773244 (119)1.00
 Former smoker33 675244 (82)1.01 (0.77–1.34)
 1–14 g day−146 547219 (102)0.90 (0.69–1.17)
 15 g day−1 or more29 620182 (54)0.78 (0.56–1.07)
 P for trend  0.11
Leisure-time physical activity
 Sedentary38 354250 (96)1.00
 Moderate93 366225 (210)0.90 (0.71–1.14)
 Active25 875193 (50)0.77 (0.55–1.09)
 P for trend  0.11
Diabetes
 No156 870219 (344)1.00
 Yes2282613 (14)3.02 (1.77–5.16)
 P  < 0.0001
History of alcohol abuse
 No149 776217 (325)1.00
 Yes9377352 (33)1.75 (1.22–2.50)
 P  0.002

Men with high systolic blood pressure were less likely to admit to persistent stress than men with low systolic blood pressure, whereas men treated for hypertension more often admitted to stress (Table 3), as did physically inactive men, smokers and men with alcohol problems. The cross-sectional association with occupational class was inverse for BMI but direct for height. There were borderline inverse associations between occupational class and serum cholesterol and systolic blood pressure. Men with low leisure-time physical activity or alcohol problems were more likely to have manual occupations. There was no significant relationship between occupational class and stress.

Table 3.   Cardiovascular risk factors by stress and occupational class
Cardiovascular risk factorNumberPersistent stress, n (%)Unskilled and skilled manual workers, n (%)
  1. Sixty-eight men had missing data for serum cholesterol, nine for systolic blood pressure, 23 for smoking, and 72 for physical activity.

  2. P-values were calculated from Pearson’s correlation tests across the whole distributions for all variables.

Body mass index (kg m−2)
 < 253232489 (15.1)1471 (45.5)
 25–303166494 (15.6)1512 (47.8)
 > 30560104 (18.6)274 (48.9)
 P    0.600.001
Height (m)
 < 1721759284 (16.2)1007 (57.3)
 172–1751691298 (17.6)833 (49.3)
 176–1791668255 (15.3)718 (43.1)
 > 1791840250 (13.6)699 (38.0)
 P for trend    0.50< 0.0001
Serum cholesterol (mmol L−1)
 < 5.71700283 (16.7)759 (44.7)
 5.7–6.31787250 (14.0)819 (45.8)
 6.4–7.11815297 (16.4)877 (48.3)
 > 7.11588251 (15.8)771 (48.6)
 P for trend    0.120.02
Systolic blood pressure (mmHg)
 < 1331745294 (16.9)793 (45.4)
 133–1451654259 (15.7)747 (45.2)
 146–1611804278 (15.4)862 (47.8)
 > 1611746255 (14.6)849 (48.6)
 P for trend < 0.00010.05
Treatment for hypertension
 No65721000 (15.2)3092 (47.1)
 Yes38687 (22.5)165 (42.8)
 P < 0.00010.58
Smoking
 Never smoker2033229 (11.3)901 (44.3)
 Former smoker1431211 (14.7)640 (44.7)
 1–14 g day−12084344 (16.5)1140 (54.7)
 15 g day−1 or more1387296 (21.3)564 (40.7)
 P < 0.00010.19
Leisure-time physical activity
 Sedentary1742402 (23.1)943 (54.3)
 Moderate4062537 (13.2)1864 (45.9)
 Active1082129 (11.9)415 (38.4)
 P < 0.0001< 0.0001
Diabetes
 No68271062 (15.6)3201 (46.9)
 Yes13125 (19.1)56 (42.8)
 P    0.590.086
History of alcohol abuse
 No6486968 (14.9)2921 (45.0)
 Yes472119 (25.2)336 (71.2)
 P < 0.0001< 0.0001
Occupational class
 Unskilled + skilled manual worker3257535 (16.4) 
 Lower officials, foremen1322190 (14.4) 
 White-collar at intermediate or high level, professionals2005259 (12.9) 
 P    0.15 
Mental stress
 None or little2642 1410 (53.4)
 Moderate3229 1312 (40.6)
 Persistent1087 535 (49.2)
 P  0.15

In comparison with men who at baseline had no or little stress, men with persistent stress had increased risk of pulmonary embolism (HR=1.80, 95% CI: 1.21–2.67) (Table 4). The HR was found to decrease slightly to 1.66 (95% CI: 1.12–2.48) after adjustment for diabetes, treatment for hypertension, smoking, occupational class, and height. In addition, there was an inverse relationship between occupational class and risk of pulmonary embolism (multiple-adjusted HR=0.57, 95% CI: 0.39–0.83) for men with white-collar jobs at intermediate or high level and professionals, with manual workers as reference. Full models (all factors were entered as potential confounders) and more parsimonious models (only significant variables were retained) gave very similar results. Furthermore, retaining or removing stress and/or occupational class in models investigating the other variable did not significantly influence the results. Neither stress nor occupational class was significantly related to deep vein thrombosis. If all cases of either pulmonary embolism or deep vein thrombosis were considered, there was still a significant effect of both stress (multiple-adjusted HR = 1.40, 95% CI 1.04–1.88) and low occupational class (multiple-adjusted HR = 0.71, 95% CI: 0.54–0.93).

Table 4.   Hazard ratios of deep vein thrombosis and pulmonary embolism in relation to mental stress and occupational class
Risk factorNumberObservation yearsCases per 100 000 observation years (n) Age-adjusted hazard ratio (95% CI) Multiple-adjusted hazard ratio (95% CI)*
  1. *The final models for deep vein thrombosis included age, diabetes, body mass index, and height; the final models for pulmonary embolism included age, diabetes, treatment for hypertension, and height; and the final models for all venous thromboembolism included age, diabetes, treatment for hypertension, alcohol, body mass index, and height.

Deep vein thrombosis
 Mental stress
  None or little258160 552102 (62)1.001.00
  Moderate315673 009126 (92)1.24 (0.90–1.71)1.27 (0.92–1.75)
  Persistent104623 080126 (29)1.26 (0.81–1.96)1.21 (0.78–1.89)
 Occupational class
  Not classifiable3567695208 (16)1.88 (1.10–3.22)1.65 (0.96–2.84)
  Unskilled + skilled manual worker316472 043112 (81)1.001.00
  Lower officials, foremen129629 730131 (39)1.17 (0.80–1.71)1.13 (0.77–1.66)
  White-collar at intermediate or high level, professionals196747 173100 (47)0.87 (0.61–1.25)0.81 (0.56–1.17)
Pulmonary embolism
 Mental stress
  None or little258060 450101 (61)1.001.00
  Moderate313772 663100 (73)1.01 (0.72–1.41)1.03 (0.73–1.45)
  Persistent105823 200177 (41)1.80 (1.21–2.67)1.66 (1.12–2.48)
 Occupational class
  Not classifiable3587640236 (18)1.86 (1.12–3.08)1.58 (0.95–2.64)
  Unskilled + skilled manual worker317672 149129 (93)1.001.00
  Lower officials, foremen128329 52088 (26)0.69 (0.45–1.06)0.65 (0.42–1.01)
  White-collar at intermediate or high level, professionals195847 00381 (38)0.62 (0.43–0.91)0.57 (0.39–0.83)
All venous thromboembolism
 Mental stress
  None or little264261 447200 (123)1.001.00
  Moderate322974 083223 (165)1.12 (0.89–1.42)1.14 (0.90–1.44)
  Persistent108723 622296 (70)1.53 (1.14–2.05)1.40 (1.04–1.88)
 Occupational class
  Not classifiable3747907430 (34)1.85 (1.28–2.67)1.60 (1.10–2.31)
  Unskilled + skilled manual worker325773 393237 (174)1.001.00
  Lower officials, foremen132230 105216 (65)0.91 (0.69–1.22)0.90 (0.68–1.21)
  White-collar at intermediate or high level, professionals200547 747178 (85)0.74 (0.57–0.96)0.71 (0.54–0.93)

Discussion

  1. Top of page
  2. Abstract
  3. Background
  4. Population and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosure of Conflict of Interests
  10. References

The results of this investigation show, for the first time, that psychosocial factors may be involved in the pathophysiological processes leading to pulmonary embolism. Men who reported persistent stress in midlife were more likely to be diagnosed with pulmonary embolism over an extended follow-up, whereas high socio-economic status, as measured by occupational class, was protective against pulmonary embolism. These associations were independent of age and several other factors.

Despite the fact that deep vein thrombosis and pulmonary embolism are major sources of morbidity and mortality [17] and frequent complications of other disorders leading to hospitalization [18], there are few prospective studies dealing with these disorders. In one such study, Tsai et al. [6] identified 215 cases of deep vein thrombosis and pulmonary embolism in six US communities. Like the present study, these authors found no relationship with cigarette smoking, elevated serum cholesterol, or physical inactivity. The HR associated with obesity in their study was similar to the one found in the present study, with an approximate doubling in risk. We had no specific measure of abdominal obesity, which was identified as a strong risk factor in another Swedish study [10]. Although a link between obesity and venous thromboembolism has long been recognized, the relationship between height and venous thromboembolism was unexpected. However, a similar association was found in male US health professionals [19].

We found no relationship between serum cholesterol and venous thromboembolism, consistent with other studies [6,20]. In contrast, elevated levels of triglycerides and low levels of low-density lipoprotein have been associated with higher risk in women [20], which is in keeping with findings on obesity. Diabetes has been associated with a 3-fold increase in risk [21]. Findings on smoking have been diverging, with some studies finding an association [10,22] and other studies not finding one [23]. Despite the well-known effects of smoking on coagulation and fibrinolysis, we were unable to identify smoking as a risk factor in the present study. Because we excluded men with terminal cancer, and many cancers are smoking-related, a link with smoking might be underestimated in our study. However, when men with terminal cancer were included in the analysis, there was still no relationship between smoking and venous thromboembolism.

A link between nervous stress and phlebothrombosis was, in fact, suggested more than half a century ago, long before genetic factors were identified, in a case history of a young woman with fatal pulmonary embolism. Supported by some experimental work, the author attributed the cause of death to severe stress [24]. Because there are virtually no studies systematically examining the role of psychosocial factors in the development of deep vein thrombosis and pulmonary embolism, external corroboration of our findings from other data is difficult. However, in a Danish inpatient registry study, patients hospitalized with manic/depressive bipolar disorder had a significant 61% increased occurrence of pulmonary embolism when compared with controls [25]. In addition, one study found an increased risk of venous thromboembolism in elderly people using some types of antipsychotic agents [26]. Concerning socio-economic status, a study linking a death certificate diagnosis of pulmonary embolism with health census data in Washington County, USA found that residents with less than 8 years of education had higher rates of pulmonary embolism than those with more schooling [27]. Given the fact that comparatively little is known about risk factors for venous thromboembolism, we are unable to explain why the association between the two psychosocial factors that we measured (stress and socio-economic status) was found for pulmonary embolism but not for deep vein thrombosis.

Limitations

Despite the fact that this is one of the largest series of cases reported in a prospective study, our study is limited in several ways. Firstly, there is the problem of diagnostic error, in that we were unable to retrieve, or objectively verify, diagnosis in all cases and that we did not have strict, predefined diagnostic criteria. However, in four out of five cases, records were retrieved that, with few exceptions, supported the diagnosis. Secondly, stress is a subjective and difficult construct, in that there is no consensus regarding either definition or measurement of stress. Over a long follow-up, stress levels will obviously vary, but men with a high level may also have had a personality more sensitive to external stressors. At the same time, occupational class, as a marker of socio-economic status, could be seen as a more permanent stressor. Our findings are strengthened by the fact that two measures of psychosocial factors were both associated with risk of future venous thromboembolism. Further study is needed to determine whether our findings can be expanded to other psychosocial dimensions, such as depression or type D personality. Thirdly, there may have been residual or undetected confounding from alcohol abuse or other risk factors. However, our findings are consistent with and expand upon previous research on cardiovascular disease and psychosocial factors. Fourth, the events leading up to an episode of deep vein thrombosis or pulmonary embolism are complicated and often involve other morbidity, implying that psychosocial variables might reflect an overall propensity for illness. Smoking, another strong determinant of morbidity and of premature mortality, was unrelated to venous thromboembolism, however. Hence, even though the trigger of an episode of pulmonary embolism could be a fracture or hospitalization for any cause, there are probably still predisposing factors (such as obesity or psychosocial circumstances) that, in conjunction with a triggering factor, are links in a causal chain. Potentially, stress may be a marker of subclinical disease; however, as most events occurred after several years, this is unlikely to explain the link between stress and venous thromboembolism. We were unable to differentiate with certainty primary from secondary events; further study is needed to determine risk factors for truly primary events.

Conclusion

  1. Top of page
  2. Abstract
  3. Background
  4. Population and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosure of Conflict of Interests
  10. References

Our finding that venous thromboembolism is related to psychosocial factors ties in with research concerning stress, coronary disease [1–3,11–13], and stroke [28]. Other studies have demonstrated an association between psychosocial variables and increased blood clotting and decreased fibrinolysis [4,5]. Although it is clear that pathophysiological processes in veins and arteries differ, blood clotting is evident in both, and accordingly, some similarities may be expected. In any event, more research is needed to identify patients at risk for venous thromboembolism.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Background
  4. Population and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosure of Conflict of Interests
  10. References

This study was supported by the Swedish Research Council, the Swedish Council for Working Life and Social Research, and the Swedish Heart and Lung Foundation.

References

  1. Top of page
  2. Abstract
  3. Background
  4. Population and methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Acknowledgements
  9. Disclosure of Conflict of Interests
  10. References
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