1 Department of Community Medicine, Lund University, University Hospital, Malmö, Sweden.
2 Department of Medicine, Orthopedics, and Surgery, Lund University, University Hospital, Malmö, Sweden.
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ABSTRACT |
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atherosclerosis; carotid arteries; sex factors; socioeconomic factors
Abbreviations: CI, confidence interval; IMT, intima-media thickness; OR, odds ratio
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INTRODUCTION |
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The underlying biologic pathways by which socioeconomic conditions can promote cardiovascular disease are not clearly understood. A higher prevalence of unfavorable lifestyle factors such as smoking and physical inactivity in lower social classes may act via biologic risk factors such as high blood pressure, elevated plasma cholesterol, and fibrinogen to produce the observed social differences in cardiovascular morbidity and mortality (1316
). However, these factors taken together are considered to only partially account for the social class differences (11
, 15
, 17
). Other potential pathways might involve differences in hormonal status and psychosocial factors, which may play important roles in the atherosclerotic process (18
20
).
While many studies linking coronary heart disease to social factors have focused on the late stages of atherosclerotic disease such as coronary mortality, a deeper understanding of possible causal mechanisms might be reached by focusing on the earlier stages of coronary heart disease, such as the clinically latent part of the atherosclerotic process (7, 21
). This provides an opportunity to study factors of importance for preclinical atherosclerosis and also reduces the potential risk of misclassification because of a downward socioeconomic mobility due to manifest cardiovascular disease.
Technical advances in ultrasound scanning have made it possible to observe the process of atherogenesis noninvasively at different vascular beds in general populations (22, 23
). Carotid atherosclerosis assessed by ultrasound has been found to be related to general atherosclerosis and especially to coronary atherosclerosis in angiographic studies (24
26
) and has also been found to predict future occurrence of coronary events (27
29
). Thus, examination of the carotid arteries by B-mode ultrasonography has been shown to be a reliable and noninvasive way of assessing the atherosclerotic process in large populations.
So far, few studies have tried to link socioeconomic factors to the atherosclerotic process. Cross-sectional and prospective studies from Finland (including only men) and from the United States have found an inverse relation between various measures of socioeconomic status and carotid intima-media thickness (IMT) (3032
).
To our knowledge this is the first study that includes a comparison between men and women regarding socioeconomic differences in carotid IMT as well as carotid stenosis in relation to atherosclerotic risk factors. The overall aim of our study is to investigate to what degree socioeconomic status is related to preclinical manifestations of atherosclerosis in middle-aged men and women. We also want to examine the contribution of biologic factors, lifestyle factors, and psychosocial factors in this context and to investigate whether their potential mediating role differs between men and women.
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MATERIALS AND METHODS |
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The sociodemographic composition of the study population of the Malmö Diet and Cancer Study shows no marked deviations from the general population of Malmö in the same age bracket concerning distribution of age, sex, and marital status. A random 50 percent of those who entered the Malmö Diet and Cancer Study between October 1991 and February 1994 and who were born between 1926 and 1945 were invited to take part in a study of the epidemiology of carotid artery disease (34).
In February 1992 questions assessing psychosocial factors were added to the baseline questionnaire. Since we used these variables in our analyses, we have included the subjects participating in the Malmö Diet and Cancer Study between February 1992 and February 1994 who completed the questionnaire (n = 10,196) and who accepted the invitation to the carotid artery disease study (n = 4,884). The cohort of the Malmö Diet and Cancer Study was approached in two different ways. During the time period between 1992 and 1994, 68 percent of the participants were selected by probability sampling and personal invitation and 32 percent were volunteers. A total of 353 subjects were excluded from the analyses because of missing data on the laboratory tests, together with 127 subjects excluded because of excessive time lags among ultrasound investigation, baseline examination, and laboratory examination and 228 individuals excluded because of the presence of known cardiovascular disease. The remaining 4,176 subjects, 2,463 women and 1,713 men aged 4668 years, constitute the study population.
Information on education and occupation was obtained from a self-administered questionnaire that was completed as part of a baseline examination. Those who were unemployed (n = 207; 5 percent), had a disability pension (n = 628; 15 percent), or were retired (n = 538; 13 percent) at the time of the baseline examination were coded according to the most recent occupation. Persons who were homemakers (n = 111; 3 percent) were excluded from the analyses based on occupation, together with farmers (n = 8; 0.2 percent) and owners of business enterprises (n = 414; 10 percent) because of their unclear status in relation to the other groups of the socioeconomic scale. We also made a separate set of analyses based on occupational status where we excluded individuals who were unemployed or had a disability pension.
Educational level was classified into three categories. "Primary education" included those who had less than 9 years of education, "some secondary education" included those who had 9 and up to 11 years of education, and "completed secondary education" included those who had completed secondary school (12 years) and those who had education at the college or university level (table 1). Data on education were not available for four individuals.
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Carotid atherosclerosis was assessed by B-mode ultrasound. All ultrasound examinations were performed by trained, certified sonographers (36). The examination procedure has been described previously (34
). IMT was determined in the far wall of the right distal common carotid artery according to the leading edge principle, using a specially designed computer-assisted analyzing system (37
). IMT was then determined off-line as the mean wall thickness 1 cm proximal to the bifurcation. The bifurcation area of the right common carotid artery was further scanned within a predefined window comprising 3 cm of the distal common carotid artery, the bulb, and 1 cm of the internal and external carotid artery, respectively, for the occurrence of plaques. The degree of stenosis was determined by visually judging the plaque on-line and determining to what extent the plaque protruded into the lumen. At regular intervals (<3 weeks) during the ultrasound investigation procedure, intra- and interobserver variation analyses were performed. The mean absolute difference between two measurements in percentage with one observer measuring carotid IMT was 9.0 (standard deviation, 7.2) percent (r = 0.77) and, when using two observers, was 8.7 (standard deviation, 6.2) percent (r = 0.85). Corresponding values for the measurements of carotid stenosis assessed by Kendall's tau were as follows:
= 0.65 and
= 0.72, respectively.
Of the 4,176 individuals who underwent examination by ultrasound, 29 subjects (0.7 percent) had to be excluded from the analysis of IMT and 276 subjects (7 percent) were excluded from the analysis of carotid stenosis because of technical difficulties. The crude range of mean carotid IMT was 0.361.58 mm for women and 0.442.15 mm for men. The carotid artery was categorized as normal/minimal stenosis (less than 15 percent reduction of the luminal diameter) and as having moderate to severe stenosis (15 percent reduction or more; n = 922; 24 percent) (38). The latter category is labeled carotid stenosis in this paper.
Earlier studies have shown that psychosocial factors, such as social network and social support, are associated with cardiovascular disease (39, 40
). In this study, social network was operationalized as social participation, defined as participation in formal and informal groups in society such as attending the theater, church, evening courses, and sports activities (41
, 42
). Social support was operationalized as emotional support reflecting the individual's experience of receiving care, encouragement of personal value, and feelings of confidence and trust (41
, 42
). These instruments have been evaluated regarding reliability and validity in a previous study (43
), and they have been found to be associated with cardiovascular risk factors and to predict cardiac event rate and overall mortality (41
, 44
). The scores from each index were dichotomized into high/low as close to the lowest tertile as possible. Cohabiting status was measured and dichotomized into living alone or not.
Menopausal status, age at menopause, and use of hormone replacement therapy (n =399; 17 percent) were assessed by baseline questionnaire. Menopausal status was categorized as premenopausal, perimenopausal, or postmenopausal. Premenopausal status was defined as having menstruation at baseline examination, perimenopausal women were those having menstruated within the 2 years before baseline examination but who had no menstruation at baseline examination, and postmenopausal status was defined as having no menstruation in the 2 years before baseline examination.
Risk factors were estimated through laboratory tests, examination at baseline, and through the questionnaire administered at the baseline visit. The blood samples were analyzed for lipoprotein lipids (high density lipoprotein, low density lipoprotein) and glucose according to standard procedures at the Department of Clinical Chemistry, Malmö University Hospital. The serum concentration of low density lipoprotein cholesterol was calculated using the formula of Friedewald et al. (45). Supine systolic and diastolic blood pressure measurements were taken after supine rest for 10 minutes. Smoking and alcohol consumption were assessed by questionnaire. Alcohol consumption was quantified by answers from the questionnaire concerning the consumption of alcohol during the last month (46
). This consumption was categorized into tertiles. Those with no recorded alcohol consumption during the last year were categorized as abstainers. Physical activity at leisure time was assessed as a total activity score based on the participant's answers in the questionnaire and dichotomized into low and modest/vigorous physical exercise at the lowest quartile. The different activities were scored according to duration and effort (47
). Body mass index was calculated by dividing a person's weight (kg) by the square of his height (m). Subjects were classified as having diabetes mellitus if they reported the diagnosis in the questionnaire, if they had a fasting whole venous blood glucose of
6.7 mmol/liter, or if they were taking medication for diabetes mellitus. Antihypertensive treatment and treatment for hyperlipidemia were self-assessed by questionnaire. Subjects were considered to have cardiovascular disease if they confirmed treatment or hospitalization for myocardial infarction, stroke, and/or intermittent claudication in the questionnaire. Using this definition, men had a prevalence of cardiovascular disease of 7.7 percent (n = 142) and women, 3.1 percent (n = 79). Subjects with known cardiovascular disease were excluded from the analyses.
Differences in IMT among various socioeconomic categories were analyzed by multiple linear regression models and by tests for linear trends for continuous variables (SPSS version 7.5 computer software; SPSS, Inc., Chicago, Illinois). Odds ratios for carotid stenosis prevalence were estimated by logistic regression models. Linear trends in odds ratios were investigated by including occupational and educational groups as ordinal covariates in the logistic regression model. Tests of trend in risk factor pattern and mean IMT by educational level and occupational status were assessed for continuous variables by including occupation and education as ordinal covariates in the linear regression models, and by the Cochran-Mantel-Haenszel test of association stratified by age group for dichotomous variables (SPSS version 7.5 computer software). Adjust-ment for risk factors was made in two steps. First, only lifestyle factors (smoking, alcohol consumption, and physical activity) were included in the model, and then biologic risk factors (low density lipoprotein cholesterol, high density lipoprotein cholesterol, systolic blood pressure, body mass index, prevalent diabetes, treatment for hypertension, and hyperlipidemia) were added in a second model. Additional adjustment for psychosocial factors was made in the analyses of carotid stenosis and, among women, adjustments for use of hormone replacement therapy and menopausal status were also made. The interaction of socio-economic status with sex was investigated by including interaction terms in the regression equations and comparing models using likelihood ratio tests (for logistic models) and F tests (for linear models).
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RESULTS |
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Atherosclerotic risk factors and psychosocial factors
Risk factor levels were found to vary with social position. Tables 2 and 3 provide means and prevalences (percentages) for atherosclerotic risk factors and psychosocial factors across categories of socioeconomic status. Age-adjusted trends in risk factor distribution by educational level and occupational status showed a similar pattern; that is, individuals in lower socioeconomic status groups had a more unfavorable risk factor pattern compared with individuals in higher socioeconomic status groups. This pattern was stronger in women than in men.
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Because of the unexpected findings of the direction of the association between occupational status and IMT among women, we also did analyses on the relations among educational level, occupational status, and common carotid IMT in women after dividing the subjects into two groups. Women with a thinner IMT (below the median value (0.75 mm)) made up one group, and subjects with a thicker IMT (above the median value) made up the other group. In the former group, we found that IMT tended to be thinner among those with higher education but thicker among those with higher occupational status (p = 0.021). However, there was no association between carotid stenosis and IMT (p = 0.57) in this group. In the latter group (IMT above the median), we indeed observed such an association (p < 0.001), where also IMT was thinner among those with higher education (p = 0.010) and tended to be thinner among those with higher occupational status. Men with an IMT both above and below the median value (0.79 mm) showed a clear association with carotid stenosis (p = 0.022 and p < 0.001, respectively).
Carotid stenosis
Table 6 shows that in the age-adjusted model, women with only primary education had a higher carotid stenosis prevalence odds than women with completed secondary education (odds ratio (OR) = 2.04, 95 percent confidence interval (CI): 1.53, 2.73). The same pattern was observed for men, but the association was weaker and not statistically significant (OR = 1.27, 95 percent CI: 0.98, 1.64). The associations were only slightly diminished after adjustment for lifestyle factors and biologic risk factors and, thus, remained statistically significant for women.
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Psychosocial factors were added in a final model (tables 6 and 7). However, low educational level and low occupational status were still associated with an increased carotid stenosis prevalence odds among women even after this adjustment (OR = 1.99, 95 percent CI: 1.43, 2.80, and OR = 1.64, 95 percent CI: 1.17, 2.34, respectively). Among men, there were no associations among low educational level, low occupational status, and carotid stenosis in the final model (OR = 1.14, 95 percent CI: 0.85, 1.53, and OR = 0.93, 95 percent CI: 0.68, 1.27, respectively).
Menopausal status and the use of hormone replacement therapy were also considered in the analyses of carotid stenosis. Since 98 percent of women aged 55 years or more were postmenopausal, the analyses based on menopausal status were restricted to women aged 4654 years. Analyses based on the use of hormone replacement therapy were restricted to women aged 55 years or more. Women aged 4654 years with low education had a higher age-adjusted carotid stenosis prevalence odds than women with high education (OR = 2.44, 95 percent CI: 1.43, 4.15), even after adjustment for menopausal status (OR = 2.54, 95 percent CI: 1.50, 4.44) (table 8). Women in manual occupations also had a higher carotid stenosis prevalence odds than women in high- or medium-level nonmanual occupations (OR = 2.22, 95 percent CI: 1.18, 4.16), which persisted after adjustment for menopausal status (OR = 2.33, 95 percent CI: 1.22, 4.45). Current use of hormone replacement therapy did not change the associations between carotid stenosis and socio-economic status. The inverse relation between carotid stenosis prevalence and education among women aged 55 years or more remained nearly unchanged after adjustment for current use of hormone replacement therapy (table 9). Adjustment for current use of hormone replacement therapy among women aged 4554 years yielded similar results, with a persisting inverse relation among educational level, occupational status, and carotid stenosis prevalence.
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DISCUSSION |
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The only previous population-based study on the relation between socioeconomic status and carotid IMT including both men and women found an inverse relation between various measures of socioeconomic status and carotid IMT (32). However, these results were adjusted for sex in the multivariate model instead of stratified by sex. Educational level and income were the measures of socioeconomic status that showed the greatest socioeconomic differences in carotid IMT. Furthermore, these associations were eliminated after adjustment for risk factors.
The classification of occupational status, as a measure of socioeconomic status, was based on information concerning the latest occupation. Unlike cohort studies, cross-sectional studies recruit people that already have a disease, with potential problems of a downward social mobility due to the disease (48). However, the mean time in latest occupation was 21 years, which indicates that this measure was rather stable over time in our sample and that the proportion of subjects with a downward social mobility due to cardiovascular disease ought to be small. We also considered the possibility of a health-related selection out of the workforce, by excluding unemployed individuals and individuals having a disability pension (n = 835) from the analyses; these exclusions, however, did not lead to any major changes of the initial associations. Perhaps most importantly, since we investigated preclinical atherosclerosis, dependent misclassification because of downward socioeconomic mobility due to cardiovascular symptoms does not seem to be a likely source of bias.
Among women, occupational status as a measure of socioeconomic status showed less striking socioeconomic differences in atherosclerosis compared with educational level. In Sweden there is a clear segregation of the labor market based on sex, in that a majority of occupations (regardless of occupational status level) draws more than 80 percent of its members from one of the sexes (49). Therefore, aspects of the occupational hierarchy could be different for men and women. It is also well known that men and women often are found at different hierarchical levels even in the same occupational category, which might not be picked up by our instrument. For example, it is shown that women more often than men tend to hold occupations characterized by job strain. Despite all these potential problems of bias in the classification of occupational status among women, the graded relation between occupational status defined by Statistics Sweden and myocardial infarction incidence, as well as ischemic heart disease mortality, has been shown to be more evident in women than in men (12
, 50
52
). Educational level, usually attained in early adulthood, ought not to be influenced by clinical atherosclerotic disease, which occurs later in life.
During later years, high-resolution B-mode ultrasonography has been shown to be a valid method of monitoring atherosclerotic changes noninvasively in the carotid arteries in large populations (22, 23
, 34
). The extent of carotid atherosclerosis is known to reflect general atherosclerosis and especially the extent and severity of coronary atherosclerosis (24
26
, 38
). In this study, reproducibility of the ultrasound method was monitored at regular intervals during the study and was found to be reasonably good. The sonographers did not have any information on the socioeconomic position of the subject being examined, making a dependent misclassification due to exposure unlikely. We therefore regard B-mode ultrasonography as a valid and reliable measure of the extent of the general atherosclerotic process.
Our study is based on a community-based sample of the general population, which makes it less sensitive to selection bias than samples based on workplace or populations in clinical settings. Furthermore, there is no apparent reason to believe that preclinical atherosclerotic manifestations would influence the subjects' participation differentially with respect to socioeconomic group, since preclinical atherosclerosis is an endpoint that could be expected to be asymptomatic in a vast majority of cases (particularly since all individuals with known cardiovascular disease were excluded from the analyses).
Although men showed more advanced atherosclerotic changes in the carotids than women in terms of a higher prevalence of carotid stenosis, the socioeconomic differences in the prevalence of carotid stenosis were greater among women, independently of which measure of socio-economic status that was used. The socioeconomic differences in atherosclerotic risk factors were also more pronounced among women than among men. The same pattern can be seen in Sweden concerning morbidity and mortality from coronary heart disease. In spite of the goal to reduce health inequalities, the socioeconomic differences in coronary morbidity and mortality are widening, especially among women (12, 52
). This suggests that low socioeconomic status might have different implications on cardiovascular health for men and women. In our study, only a small part of the female socioeconomic difference could be explained by established atherosclerotic risk factors. Even though the cross-sectional nature of our study gives room for some misclassification of risk factors (48
), these measures were sufficiently precise to explain the associations found between IMT and occupational status in men and IMT and education in women. This indicates the possibility of sex differences in the mechanisms connecting socioeconomic status to atherosclerosis.
Estrogen has been shown to have beneficial effects on blood lipids (53, 54
), to decrease fibrinogen (53
), and to increase the distensibility of the carotid arteries (55
). However, evidence that natural menopause is an independent risk factor for coronary heart disease is not convincing (56
, 57
). Information on the relation among menopause, hormone replacement therapy, and atherosclerosis is sparse, and the results from the few published studies are contradictory. One recent study from the United States on middle-aged women found little evidence of an association between carotid IMT and menopausal status or hormone replacement therapy (56
). However, another study on older women did find an inverse association between estrogen use and carotid IMT (58
). Studies on the relation between hormone replacement therapy and coronary atherosclerosis determined by angiography have shown a lower prevalence of atherosclerotic changes among hormone replacement therapy users compared with nonusers (18
, 19
). However, in our study, differences in menopausal status or current use of hormone replacement therapy could not explain the higher carotid stenosis prevalence odds found in lower socioeconomic status groups.
Another potential explanation of the sex differences in atherosclerosis could be attributed to psychosocial factors linked with sex roles (59, 60
). In animal experiments, social status has been shown to be inversely related to the degree of atherosclerosis (61
, 62
). Psychosocial factors are known to affect men and women differently (63
68
). It is known that increased levels of catecholamines, such as those resulting from environmental stress, could contribute to coronary disease through a variety of mechanisms, and it has been shown that there are sex differences in the cardiovascular and neuroendocrine response to stressors (69
73
). However, including psychosocial factors in the analyses could not explain the associations between socioeconomic status and carotid stenosis. Other possible explanations not assessed by the psychosocial factors included in our analyses might involve differences in the structural positions in society including multiple roles of both work and family life, where socioeconomic status could be associated with the availability of balancing these roles (68
, 74
). Differences in stressful conditions at work might also be important to consider (75
, 76
).
In conclusion, we believe that our findings are reasonably unbiased and show that the atherosclerotic process is associated with socioeconomic status in both men and women. Although men showed more advanced atherosclerotic changes in the carotids than women, the socioeconomic differences in the prevalence of carotid stenosis were greater among women, where only a small part of these differences seemed to be explained by established risk factors. Socioeconomic differences in hormonal status and psychosocial factors could not explain the higher prevalence of carotid stenosis among women with low educational attainment and occupational status. The results suggest sex differences in the implications of low socioeconomic status on atherosclerosis, where still unknown pathways might play a main role.
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ACKNOWLEDGMENTS |
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NOTES |
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REFERENCES |
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