Conceived and designed the experiments: AS MGM AL. Performed the experiments: AS MH KO SV. Analyzed the data: AS MH KO SV. Wrote the paper: AS MGM AL.
The authors have declared that no competing interests exist.
There are pronounced socioeconomic disparities in coronary heart disease, but the extent to which these primarily reflect gradients in underlying coronary artery disease severity or in the clinical manifestation of advanced disease is uncertain. We measured the relationship between socioeconomic status (SES) as indexed by grade of employment and coronary artery calcification (CAC) in the Whitehall II epidemiological cohort, and tested the contribution of lifestyle, biological and psychosocial factors in accounting for this association.
CAC was assessed in 528 asymptomatic men and women aged 53–76 years, stratified into higher, intermediate and lower by grade of employment groups. Lifestyle (smoking, body mass index, alcohol consumption, physical activity), biological (blood pressure, lipids, fasting glucose, inflammatory markers) and psychosocial factors (work stress, financial strain, social support, depression, hostility, optimism) were also measured. Detectable CAC was present in 293 participants (55.5%). The presence of calcification was related to lifestyle and biological risk factors, but not to grade of employment. But among individuals with detectable calcification, the severity of CAC was inversely associated with grade of employment (p = 0.010), and this relationship remained after controlling for demographic, lifestyle, biological and psychosocial factors. Compared with the higher grade group, there was a mean increase in log Agatston scores of 0.783 (95% C.I. 0.265–1.302, p = 0.003) in the intermediate and 0.941 (C.I. 0.226–1.657, p = 0.010) in the lower grade of employment groups, after adjustment for demographic, lifestyle, biological and psychosocial factors.
Low grade of employment did not predict the presence of calcification in this cohort, but was related to the severity of CAC. These findings suggest that lower SES may be particularly relevant at advanced stages of subclinical coronary artery disease, when calcification has developed.
There is a pronounced socioeconomic gradient in coronary heart disease, with greater morbidity and mortality among people of lower socioeconomic status (SES) as defined by occupational position, education and income
This study investigated the relationship between SES and coronary artery calcification (CAC) in a well-characterized healthy older population cohort in which associations between SES as defined by grade of employment, cardiovascular risk factors, coronary heart disease incidence and psychosocial factors have already been established
All participants gave full informed consent, and ethical approval was obtained from the UCLH Committee on the Ethics of Human Research. The Heart Scan study involved a sub-sample of participants in the Whitehall II cohort, recruited for the assessment of CAC in 2006 to 2008. The Whitehall II epidemiological cohort is a sample of 10,308 London-based civil servants recruited in 1985–1988 when aged 35–55 years to investigate demographic, psychosocial and biological risk factors for coronary heart disease
Grade of employment was used as the indicator of SES, since this has previously been shown both in the original Whitehall and Whitehall II studies to predict cardiovascular risk and mortality
Coronary artery calcification was performed using electron beam computed tomography (GE Imatron C-150, San Francisco, CA) as described elsewhere
Height and weight were measured by an experienced nurse, from which body mass index (BMI) was computed. Blood pressure was measured while seated using a digital monitor. A fasting blood sample was drawn for the analysis of total cholesterol, high density lipoprotein (HDL) cholesterol, plasma triglycerides, fasting glucose, high sensitivity C-reactive protein and interleukin (IL) 6, using methods described previously
Participants reported whether or not they were currently in paid employment, current smoking status, and weekly alcohol intake by questionnaire. Physical exercise was assessed by enquiring about the frequency of moderate and vigorous activities, and responses were classified into three categories: none, up to twice per week, and three times per week or more. Work stress was assessed in terms of job demands and job control, and financial strain, social support, social networks, depression, hostility and optimism were measured using standard questionnaires
The associations between grade of employment and lifestyle, biological and psychosocial factors were analyzed using analysis of variance for continuous and chi-squared statistics for categorical variables respectively. Detectable CAC was recorded in 293 (55.5%) of participants. The distribution of CAC scores violated the statistical assumptions underlying linear modeling even after log transformation, making them unsuitable for linear regression analysis of the complete sample. Associations between CAC and grade of employment were therefore analyzed in two ways. Firstly, logistic regression was used to investigate associations with the presence vs absence of CAC. Socioeconomic status was modeled as a categorical variable based on the three grade of employment groups. Second, the CAC scores of individuals with detectable calcification were log transformed, and were subsequently normally distributed. Analysis of covariance was therefore carried out on log transformed CAC scores with grade of employment as a between-person factor. Four models were tested: model 1 included demographic factors (gender, age, employment status, and statin use) as covariates. Lifestyle factors (BMI, smoking, alcohol consumption, and physical activity) were added in model 2, biological risk factors (systolic blood pressure, fasting total cholesterol, HDL-cholesterol, triglycerides, fasting glucose, C-reactive protein and IL-6) in model 3, and psychosocial factors (financial strain, social network size, social support, depressed mood, hostility, and optimism) in model 4. None of the variables included in these models showed multicollinearity according to variance inflation factor and tolerance values.
There was no difference in the proportion of men and women in the three grade of employment groups, but lower grade participants were an average 2 years older than those in higher and intermediate grade groups (p = 0.004, see
Higher grade of employment (n = 199) | Intermediate grade of employment (n = 209) | Lower grade of employment (n = 120) | P |
|
Men/women | 108/91 | 124/85 | 51/69 | 0.094 |
Age (years) | 62.3 (5.5) | 62.6 (5.4) | 64.4 (6.0) | 0.005 |
Paid employment (%) | 85 (42.7%) | 72 (34.4%) | 41 (34.2%) | 0.79 |
Current smokers (%) | 10 (5.0%) | 12 (5.7%) | 8 (6.7%) | 0.31 |
Body mass index(kg/m2) | 25.7 (0.28) | 25.9 (0.27) | 26.1 (0.36) | 0.42 |
Alcohol intake (units/w) | 11.31 (0.62) | 8.13 (0.60) | 7.11 (0.80) | 0.001 |
Moderate/vigorous physical activity (%): | ||||
None | 21 (10.6%) | 22 (10.5%) | 20 (16.7%) | 0.15 |
Up to 2/week | 118 (59.3%) | 126 (60.3%) | 72 (60.0%) | |
3/week or more | 60 (30.2%) | 61 (29.2%) | 28 (23.3%) | |
Systolic blood pressure (mmHg) | 122.3 (1.13) | 123.9 (1.09) | 126.4 (1.45) | 0.025 |
Total cholesterol (mmol/l) | 5.95 (0.07) | 5.81 (0.07) | 5.79 (0.09) | 0.15 |
HDL-cholesterol (mmol/l) | 1.78 (0.03) | 1.67 (0.03) | 1.62(0.04) | 0.002 |
Triglycerides (mmol/l) | 1.21 (0.06) | 1.20 (0.05) | 1.36 (0.71) | 0.10 |
Fasting glucose (mmol/l) | 5.19 (0.04) | 5.18 (0.04) | 5.18 (0.05) | 0.88 |
C-reactive protein (µg/ml) | 1.68 (0.15) | 1.58 (0.15) | 1.72 (0.20) | 0.87 |
IL-6 (pg/ml) | 1.78 (0.09) | 1.76 (0.09) | 1.92 (0.12) | 0.36 |
Job demands (%) | 66.8 (1.35) | 58.5 (1.32) | 47.8 (1.75) | 0.001 |
Job control (%) | 68.7 (1.22) | 59.5 (1.19) | 51.4 (1.59) | 0.001 |
Financial strain (%) | 4.55 (1.23) | 12.54 (1.19) | 14.15 (1.60) | 0.001 |
Social network (0–11) | 4.49 (0.11) | 4.04 (0.11) | 3.94 (0.15) | 0.003 |
Social support (%) | 75.37 (1.74) | 72.06 (1.68) | 69.98 (2.26) | 0.060 |
Depressed mood (CESD) (0–60) | 6.09 (0.47) | 6.98 (0.45) | 7.02 (0.61) | 0.23 |
Hostility (0–10) | 21.83 (1.67) | 27.71 (1.63) | 30.36 (2.20) | 0.002 |
Optimism (%) | 68.50 (1.19) | 64.26 (1.15) | 62.88 (1.55) | 0.004 |
Mean (s.e.m.) and N (%).
HDL = high density lipoprotein, IL-6 = interleukin 6. CESD = Center for Epidemiologic Studies Depression scale.
CAC was present in 293 (55.5% of participants), with 166 (31.4%) having Agatston scores <100, 76 (14.4%) between 100 and 399, and 51 (9.7%) scores of 400 or over. Detectable calcification was positively related to age (p<0.001), and was more common among men than women (68.1% vs 41.0%), a difference that remained significant after adjustment for age (p<0.001). The associations between presence of CAC and risk factors are summarized in
Factor | Comparison unit | Odds of CAC adjusted for age and gender (95% C.I.) | |
Current smoker | Non-smokers | 2.389 (1.035 to 5.517) | 0.041 |
Body mass index | Unit increase | 1.044 (0.995 to 1.095) | 0.077 |
Alcohol intake | Unit increase | 1.011 (0.989 to 1.033) | 0.34 |
Moderate/vigorous physical activity | Level increase | 1.543 (1.131 to 2.105) | 0.006 |
Systolic blood pressure | 1 mm increase | 1.013 (1.001 to 1.025) | 0.032 |
Total cholesterol | 1 mmol/l increase | 1.226 (1.015 to 1.481) | 0.034 |
HDL-cholesterol | 1 mmol/l increase | 0.947 (0.613 to 1.463) | 0.81 |
Triglycerides | 1 mmol/l increase | 1.122 (0.872 to 1.443) | 0.37 |
Fasting glucose | 1 mmol/l increase | 1.031 (0.709 to 1.500) | 0.87 |
C-reactive protein | 1 µg/ml increase | 0.977 (0.895 to 1.066) | 0.60 |
IL-6 | 1 pg/ml increase | 1.014 (0.879 to 1.171) | 0.85 |
Grade of employment | Reduced grade level | 0.831 (0.651 to 1.061) | 0.14 |
The Agatston scores of the 293 participants with detectable CAC were positively related to age (p<0.001), and were greater in men than women (p = 0.011) and in statin users (p<0.001). Agatston scores also showed a significant association with grade of employment (p = 0.010), with greater CAC in lower grade men and women after adjusting for age, gender, employment status, and statin use (
Error bars are standard errors of the mean. Model 1 is adjusted for age, gender, employment status, and statin use. Model 2 is additionally adjusted for BMI, smoking, alcohol consumption and physical activity. Model 3 is additionally adjusted for systolic blood pressure, total and HDL-cholesterol, triglycerides, fasting glucose, IL-6 and C-reactive protein. Model 4 is additionally adjusted for financial strain, social network size, social support, job demands, job control, depressed mood, hostility, and optimism.
Grade of employment group | Agatston score (Log) | Mean difference (95% C.I.) adjusted for demographic factors |
Mean difference (95% C.I.) adjusted for demographic and lifestyle factors |
Mean difference (95% C.I.) adjusted for demographic, lifestyle and biological factors |
Mean difference (95% C.I.) adjusted for demographic, lifestyle, biological and psychosocial factors |
||||
P | P | P | P | ||||||
Higher | 3.75±1.84 | Reference | Reference | Reference | Reference | ||||
Intermediate | 4.25±1.83 | +0.596 (0.140 to 1.052) | 0.011 | +0.660 (0.197 to 1.123) | 0.005 | +0.722 (0.255 to 1.189) | 0.004 | +0.783 (0.265 to 1.302) | 0.003 |
Lower | 4.64±1.92 | +0.824 (0.242 to 1.405) | 0.006 | +0.884 (0.296 to 1.472) | 0.003 | +0.961 (0.358 to 1.565) | 0.002 | +0.941 (0.226 to 1.657) | 0.010 |
Analyses of 293 participants with detectable coronary calcification.
Model 1 adjusted for age, gender, employment status, and statin use.
Model 2 as for Model 1, plus BMI, smoking, alcohol consumption and physical activity.
Model 3, as for Model 2, plus systolic blood pressure, total and HDL-cholesterol, triglycerides, fasting glucose, IL-6 and C-reactive protein.
Model 4, as for Model 3, plus financial strain, social network size, social support, job demands, job control, depressed mood, hostility, and optimism.
This study investigated the association between SES defined by grade of employment and subclinical coronary artery disease as indexed by CAC, in a well-characterized sample of healthy older men and women. The presence of CAC was more common with advancing age, and was related to gender, biological and lifestyle risk factors. It was not, however, associated with grade of employment. But among participants with detectable CAC, Agatston scores were inversely related to grade of employment. A social gradient was present, with the greatest CAC in the lowest grade of employment group, and moderate CAC in the intermediate grade participants. These disparities were largely unaffected by controlling statistically for lifestyle, biological and psychosocial risk factors.
Previous studies of SES differences in CAC have been inconsistent. Colhoun et al
There is consistent evidence that SES is associated with carotid IMT and plaque independent of risk factors
We found that the presence of CAC was associated with greater blood pressure, lower HDL-cholesterol levels, smoking and greater adiposity. Similar effects have been observed previously
The pathways responsible for the association between lower grade of employment and more severe CAC are not certain. The relationship was not dependent on differences in lifestyle, biological or psychosocial risk factors. However, other unmeasured factors in these domains may have contributed
This study was designed to investigate associations between grade of employment and subclinical coronary artery disease in a healthy sample of older men and women, so we excluded individuals with manifest coronary heart disease or clinically defined conditions such as hypertension and diabetes. It is notable that smoking levels were low, and did not exceed 7% even in the lower SES group, and risk profiles were healthier than in the wider Whitehall II study
We are grateful to Yoichi Chida, Romano Endrighi, Nadine Messerli-Bürgy, Bev Murray, and Cicely Walker for their contribution to data collection.