The European Journal of Public Health Advance Access originally published online on October 26, 2006
The European Journal of Public Health 2007 17(4):340-347; doi:10.1093/eurpub/ckl247
Health Inequalities |
The role of low grade inflammation as measured by C-reactive protein levels in the explanation of socioeconomic differences in carotid atherosclerosis
M Rosvall1, G Engström2, L Janzon2, G Berglund2 and B Hedblad2
1 Department of Health Sciences, Lund University Malmö, Sweden
2 Department of Clinical Sciences, Lund University Malmö, Sweden
Correspondence: Maria Rosvall, Department of Health Sciences, Malmö University Hospital, SE-205 02 Malmö, Sweden, tel: + 46 40 33 10 00, fax: + 46 40 33 70 96, e-mail: maria.rosvall{at}smi.mas.lu.se
Received March 22, 2006, accepted September 27, 2006
 |
Abstract |
|---|
 Top Abstract Materials and methodsResultsDiscussionReferences |
|---|
Background: The role of inflammation as part of the explanation of socioeconomic differences in carotid atherosclerosis has not been specifically investigated. Methods and Results: The associations between socioeconomic position (SEP), C-reactive protein (CRP), and preclinical carotid atherosclerosis were investigated in a general population sample of 3921 middle-aged Swedish men and women. Common carotid intima-media thickness (IMT) and presence of carotid plaque (focal IMT > 1.2 mm) were determined by B-mode ultrasound. The results showed that low SEP was associated with increased levels of CRP, independently of established risk factors. Furthermore, common carotid IMT increased with increasing CRP-levels. Presence of carotid plaque increased with increasing CRP-levels in men, but not in women. While the socioeconomic differences in carotid IMT were weak, there were associations between low educational level and carotid plaque prevalence with an age- and sex-adjusted odds ratio (OR) of 1.39 (95% CI: 1.21, 1.59). A similar association was seen for having a manual occupation, OR = 1.23 (95% CI: 1.07, 1.42). The age- and sex-adjusted absolute differences in carotid plaque prevalence were 9% with regard to educational level and 7% with regard to occupational status. Adjustment for CRP caused only a minor attenuation of the association between SEP and carotid atherosclerosis. Conclusions: The association between SEP and carotid atherosclerosis as measured by carotid IMT and carotid plaque could only to a minor extent be referred to differences in low grade inflammation as measured by CRP.
Keywords: atherosclerosis, carotid arteries, c-reactive protein, socioeconomic position
The fact that cardiovascular disease (CVD) morbidity and mortality rates are higher in people with low socioeconomic position (SEP) has been described in several studies from many countries.1–3 Furthermore, there is increasing evidence of an inverse association between SEP and the degree of carotid atherosclerosis.4–12 While most studies of carotid IMT have found the associations to be largely mediated by known atherosclerotic risk factors,4–6,8 studies of later atherosclerotic manifestations such as carotid stenosis have shown only a minor role of established risk factors in the explanation of the SEP differences.8,10 The role of inflammation as part of the explanation of these socioeconomic differences has not yet been specifically investigated.
It is now generally accepted that individuals with high levels of acute phase reactants have an increased risk of future CVD.13,14 Some studies have shown an association between the degree of atherosclerosis and levels of inflammatory markers,15–19 however, there are also studies where no such association could be found.20 There are only a few studies that have investigated the association between SEP and inflammatory markers and most of the results from such studies have shown an inverse association between SEP and levels of inflammatory markers such as CRP, serum amyloid A (SAA), as well as fibrinogen,19,21–26 although there are studies where only weak or no associations were found.27,28 The purpose of the present study was to investigate the role of low grade inflammation as measured by plasma levels of CRP, in explaining the association between SEP and common carotid IMT and carotid plaque in a middle-aged population of Swedish men and women.
|
Materials and methods |
|---|
|
TopAbstractMaterials and methodsResultsDiscussionReferences |
|---|
Study population
The subjects in this study constituted a sub-cohort of the large, population-based Malmö Diet and Cancer Study (MDCS) cohort.29,30 The participants have been described elsewhere.30 In short, the sociodemographic distribution showed no marked deviations from the general population of Malmö in the same age bracket concerning educational level, type of employment, marital status, and percentage living alone.30 A random 50% of those born between 1926 and 1945 who entered the MDCS from October 1991 and February 1994 (n = 12445) were invited to take part in a study on the epidemiology of carotid artery disease.31 We included those individuals who accepted the invitation to join the carotid artery disease study and had completed a self-administered questionnaire including questions on social and psychosocial factors, that was completed as part of baseline examination (n = 4884).8 Subjects were considered to have CVD if they had been treated for myocardial infarction and/or stroke according to the national or regional myocardial infarction register or stroke register. Subjects with known CVD (97 men and 35 women) were excluded from the analyses. Another 345 individuals were excluded due to missing laboratory results, 150 individuals due to missing data on C-reactive protein (CRP) and 336 subjects who were over 65 years of age (retirement age in Sweden) at time of the baseline investigation. The remaining 3921 subjects, 2318 women, and 1603 men aged 46–65 years constitute the study population.
Cardiovascular risk factors
Risk factors were estimated through laboratory tests, examination at baseline, and the questionnaire administered at the baseline visit. Details of assessment procedures regarding smoking habits (never, former, and current smoker), alcohol consumption, leisure-time physical activity, diabetes mellitus, measurements of blood pressure (mm Hg), low density lipoprotein (LDL), high density lipoprotein (HDL), whole blood glucose, body mass index (BMI), use of blood pressure lowering medication, and treatment for hyperlipidemia have been reported previously.10 In short, the blood samples were analysed for lipoprotein lipids (high density lipoprotein (HDL), low density lipoprotein (LDL)) and glucose according to standard procedures at the Department of Clinical Chemistry, Malmö University Hospital. Serum concentration of LDL-cholesterol was calculated using Friedewald's formula. Alcohol consumption was quantified by answers from the questionnaire concerning the consumption of alcohol during the last month. Those with no recorded alcohol consumption during the last year were categorized as abstainers. Participants were categorized into never smokers, former smokers, and current smokers. Leisure time physical activity was a composite measure of 18 different leisure time activities as queried in the health questionnaire and dichotomized into low and modest/vigorous physical exercise at the lowest quartile. Systolic and diastolic blood pressure were measured after supine rest for 5 min. Antihypertensive treatment and treatment for hyperlipidemia were self-assessed by questionnaire. BMI 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, used anti-diabetic medication or had a fasting whole venous blood glucose 
6.1 mmol/l. The analysis of C-reactive protein (CRP) was analysed in frozen plasma samples gathered at the baseline examination using the Tina-quant®CRP latex high sensitivity assay (Roche Diagnostics, Basel, Switzerland) on an ADVIA® 1650 Chemistry System (Bayer Healthcare, NY, USA). Study samples were analysed as discrete samples and results were read in 6 s intervals for 1 min time period following 5 min incubation. The mean value of these measurements was the reported result.
Menopausal status, age at menopause, and use of hormone replacement therapy (HRT) were assessed by baseline questionnaire. Menopausal status was categorized as pre-, perimenopausal, or postmenopausal. Premenopausal status was defined as having menstruation at baseline examination, perimenopausal women were those having menstruated within the two years before baseline examination but who had no menstruation at baseline examination, while postmenopausal status was defined as having no menstruation in the two years before baseline examination.
Measurement of carotid IMT and carotid plaque
Participants underwent B-mode ultrasonography (Acuson 128 CT system) of the right carotid artery. IMT of the common carotid artery (CCA) and presence of carotid plaque were measured according to a standardized protocol by trained, certified sonographers as previously published.32 In short, the bifurcation area of the right common carotid artery was scanned within a pre-defined ‘window’ comprising 3 cm of the right common carotid artery, the bifurcation, and 1 cm of the internal and external carotid artery, respectively, for the occurrence of plaque (defined as a focal thickening of IMT > 1.2 mm). 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 analysing system.33 IMT was then determined off-line as the mean wall thickness 1 cm proximal to the bifurcation. Each image was analysed without knowledge of the subject's identification code to minimize the possibility of observer bias. Methods of quality control have been published previously.34 The mean absolute difference between two measurements in percent 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).
Measurement of educational level
Information on educational level was assessed by a self-administered questionnaire. Educational level was classified into two categories based on the length of educational attainment, i.e., 8 years of education or less and 9 years of education or more.
Measurement of occupational status
Data on occupation were obtained from the self-administered questionnaire that was proffered at baseline examination. It yielded information on the subject's present occupation. Those who were unemployed (n = 205), housewives (n = 112) or had a disability pension or early pension (n = 895) at the time of baseline examination were coded according to their most recent occupation. Persons who were farmers (n = 15) and owners of business enterprises (n = 166) were excluded because of their unclear status in relation to the other groups of the socioeconomic scale. Occupational status among those currently employed, assessed by answers to questions concerning job titles and work tasks, formed the basis for classification into socioeconomic index (SEI) groups, according to the criteria of Statistics Sweden.35 Statistics Sweden has used these criteria for national demographic statistics publications over the course of almost two decades. SEI classifications take into consideration the educational background needed to qualify for a particular job, additional employment prerequisites, job responsibility levels, and specific duties to be performed. The SEI groups were then combined into two SEP categories: non-manual employees and manual workers.
Statistical methods
Age-adjusted differences in cardiovascular risk factors, carotid IMT, and carotid plaque by CRP-levels were analysed by linear regression models for continuous variables and by logistic regression models for dichotomous variables (SPSS computer software v. 11.0). Age- and sex-adjusted differences in CRP levels between various socioeconomic categories were analysed by linear regression models for continuous variables and by logistic regression models for dichotomous variables (SPSS computer software v. 11.0). Furthermore, adjustments were made for current smoking, alcohol consumption, low physical activity, BMI, diabetes mellitus, systolic blood pressure, treatment for hyperlipidemia, treatment for hypertension, and LDL/HDL-ratio. Age- and sex-adjusted differences in IMT between various socioeconomic categories were analysed by linear regression models, whereas age- and sex-adjusted differences in the prevalence of carotid plaque were analysed by logistic regression models (SPSS computer software v. 11.0). Moreover, adjustments were made for risk factors as well as CRP. These analyses were also performed stratified by sex. To explore whether there were socioeconomic differences in presence of carotid plaque in groups with similar degrees of CRP-levels, stratified analyses based on levels of CRP were made.
|
Results |
|---|
|
TopAbstractMaterials and methodsResultsDiscussionReferences |
|---|
Table 1 presents the sociodemographic characteristics, distribution of cardiovascular risk factors, and carotid ultrasonographic measures in the study population.
|
C-reactive protein, cardiovascular risk factors, and carotid atherosclerosis
Age-adjusted trends in cardiovascular risk factor levels by CRP-levels (i.e., <1 mg/L, 1–3 mg/L, >3 mg/L) showed a similar pattern in men and women (table 2); i.e., those with higher CRP levels generally showed more unfavourable levels of cardiovascular risk factors, compared with those with lower CRP levels (p for trend < 0.05). Among women, there was a relationship between use of hormone replacement therapy (HRT) and CRP-levels, in that use of HRT was more common at higher CRP-levels (p for trend < 0.001). Common carotid IMT increased with increasing CRP-levels in both men and women. While presence of carotid plaque increased with increasing CRP-levels among men (p for trend < 0.001), no such pattern of association was seen in women. This was also true even after adjustment for use of HRT and menopausal status.
|
Socioeconomic position and C-reactive protein
Table 3 provides age- and sex-adjusted means and prevalences of CRP comparing the levels across the two categories of educational level. Generally, individuals with <9 years of education showed higher levels of CRP compared with individuals with 9 years of education or more (p < 0.05). This was true among both men and women (data not shown) and also when using three educational categories (<9 years of education, 9–12 years of education and >12 years of education). This pattern was only somewhat reduced after adjustment for current smoking, alcohol consumption, low physical activity, BMI, diabetes mellitus, treatment for hyperlipidemia, systolic blood pressure, treatment for hypertension, and LDL/HDL-ratio. A similar pattern of association was seen for occupational status (data not shown).
|
Socioeconomic position and common carotid intima media thickness
The age- and sex-adjusted socioeconomic differences in common carotid IMT were rather small. For example, those with low educational attainment (<9 years of education) showed a common carotid IMT of 0.77 mm, while those with higher educational attainment (9 years of education or more) had a common carotid IMT of 0.76 mm. However, this difference was not statistically significant. Additional adjustment for CRP-levels only marginally reduced this difference. A similar pattern of association was seen for occupational status (data not shown).
Socioeconomic position and carotid plaque
The age- and sex-adjusted carotid plaque prevalence was 9 percent-units higher among those with 8 years of education or less than among those with 9 years of education or more and 7 percent-units higher among those with manual occupations than among those with non-manual occupations. Table 4 shows the adjusted odds ratios of carotid plaque in the carotid bifurcation area in relation to educational level and occupational status. Adjustment for risk factors markedly reduced the occupational differences in carotid plaque prevalence odds, whereas adjustment for CRP only slightly reduced the odds ratios, from OR = 1.23 (95% CI, 1.07, 1.42) to 1.22 (95% CI, 1.06, 1.41). Further adjustment for CRP after initial adjustment for risk factors did not additionally reduce these odds ratios of having carotid plaque comparing those holding manual occupations with those holding non-manual occupations. A similar pattern of association was seen with regard to differences in carotid plaque prevalence odds by educational attainment, with the exception of a less pronounced reduction in odds ratios after adjustment for risk factors. Our analyses showed a similar, but somewhat weaker, association between educational level and carotid plaque prevalence among those aged 46–55, OR = 1.28 (95% CI, 1.02, 1.59), compared to those aged 56–65, OR = 1.46 (95% CI, 1.23, 1.74), (data not shown). Due to the fact that there was no association between CRP-levels and carotid plaque in women, stratified analyses based on sex were made. As seen in table 4, adjustment for CRP levels was associated with a more pronounced reduction in ORs of carotid plaque in men (i.e., 12%), from OR = 1.33 (95% CI, 1.08, 1.64) to 1.29 (95% CI, 1.04, 1.59), while no such reduction was seen in women. A similar pattern of association was seen with regard to occupational status, while no reduction could be seen in women. However, as seen in the analyses on men and women taken together, CRP did not additionally reduce the odds ratios of carotid plaque after adjustment for risk factors had been made in either men or women. We also made analyses only including those vocationally active, and the results were similar to those seen in the whole population. For example, the odds ratio of carotid plaque, in the age- and sex-adjusted model, among those holding a manual occupation was 1.25 (95% CI; 1.05, 1.49).
|
To explore whether there were socioeconomic differences in presence of carotid plaque in groups with similar degrees of CRP-levels, stratified analyses were made. As seen in figure 1, men with low education and with CRP
3 mg/L showed an increased OR of carotid plaque, 1.29 (95% CI: 1.01, 1.64), compared to men with high education with CRP 3 mg/L (reference group). For men with high education and with CRP > 3 mg/L the OR was 1.43 (95% CI: 0.99, 2.06). Having both low education and CRP > 3 mg/L were associated with an OR of 1.92 (95% CI: 1.40, 2.73). Women with low education and with CRP 3 mg/L also showed an increased OR of carotid plaque, 1.63 (95% CI: 1.22, 2.00), compared to women with high education with CRP 3 mg/L (reference group). However, among women with CRP levels exceeding 3 mg/L there were no educational differences in presence of carotid plaque. A similar pattern of association was seen for occupational status (data not shown).
|
|
Discussion |
|---|
|
TopAbstractMaterials and methodsResultsDiscussionReferences |
|---|
The results showed that the increased prevalence of atherosclerosis in the carotids seen in lower SEP groups could only to a small extent be referred to socioeconomic differences in low grade inflammation as measured by the acute phase reactant, CRP. Thus, even though low SEP was strongly associated with CRP, independently of potential mediating factors such as, e.g., smoking and factors related to the metabolic syndrome and the fact that CRP levels were associated with the extent of carotid atherosclerosis, there was only a minor attenuation of the association between SEP and carotid atherosclerosis and more so in men than in women.
The increased levels of inflammatory markers associated with atherosclerosis might reflect a response to established risk factors or infections (e.g., Chlamydia or Helicobacter) causing inflammation as part of atherosclerotic disease.13,36 CRP has also been regarded as a risk factor, i.e., part of the causal pathway leading to atherosclerosis.13,14 For example, CRP might play a direct role in promoting the inflammatory component of atherosclerosis through an increased expression of adhesion molecules in the vascular wall and by activation of the complement system.37,38 Theoretically, if the acute phase reactants reflect an epiphenomenon of atherosclerotic disease, there should be a strong correlation between the extent of atherosclerosis and levels of inflammatory markers. However, it has also been argued that inflammatory markers may measure other characteristics than atherosclerotic mass. These characteristics may include the activity of lymphocyte and macrophage cells within a plaque13 or a predisposition to exaggerated inflammatory responses, which could be genetically determined.39
While CRP-levels have shown a dose–response relationship to cardiovascular disease risk in prospective studies independently of cardiovascular risk factors,37,40,41 the data on the association with the extent of carotid atherosclerosis are inconclusive.13 While some studies have shown such an association, others have not. In our study, common carotid IMT was related to CRP-levels in both men and women. However, late atherosclerotic changes such as carotid plaque was only related to CRP-levels in men, while no such pattern could be seen in women. Adjusting for use of HRT, shown to be related to CRP-levels,42–44 did not change the absence of an association in women.
SEP is known to be strongly associated with established cardiovascular risk factors as well as cardiovascular disease. Recent studies have also shown an association between SEP and levels of acute phase reactants such as CRP and fibrinogen, independently of established risk factors,21,24–26 whereas in some studies this association was markedly reduced after such adjustments.19 In our study, there was an association between SEP and CRP even after adjustment for smoking, alcohol consumption, low physical activity, BMI, diabetes mellitus, systolic blood pressure, treatment for hyperlipidemia, treatment for hypertension, and LDL/HDL-ratio. Thus, theoretically, socioeconomic differences in low grade inflammation due to other factors than established risk factors might be part of the explanation of socioeconomic differences in carotid atherosclerosis. However, socioeconomic differences in carotid atherosclerosis could only to a minor extent be explained by differences in CRP, even before adjustment for established risk factors. This might perhaps partly be due to the fact that the atherosclerotic disease process starts already in childhood and then continuous throughout life, where a cross-sectional measurement of inflammatory activity at one point in time gives room for potential misclassification and might be too crude a measure of the inflammatory disease process, even though there were strong associations with both SEP, established risk factors and carotid atherosclerosis.
Certain methodological issues need to be addressed. First, misclassification of end-point is a potential cause of bias. During later years high-resolution B-mode ultrasonography has been shown to be a valid method of monitoring atherosclerotic changes non-invasively in the carotid arteries in large populations.34,45,46 Earlier studies have shown an association between carotid IMT as well as presence of carotid plaque and future risk of coronary events47–50 as well as stroke.48,51–54 Although, the bifurcation area is the segment where carotid plaques are most common observed, carotid plaques located at other places in, for example, the distal part of the internal carotid artery or outside the pre-defined ‘window’ of the carotid artery were not encompassed in this study. However, assessment of plaque status was performed blinded to clinical information, the reproducibility was good,34 and if misclassification had occurred, it is likely to be non-differential. We therefore regard B-mode ultrasonography as a valid and reliable measure of the extent of the general atherosclerotic process.
Misclassification of exposure is a potential cause of bias. The classification of occupational status, as a measure of socioeconomic position, was based on information concerning the latest occupation. Unlike prospective longitudinal studies, cross-sectional studies recruit people that already have a disease, with potential problems of a downward social mobility due to the disease.55 However, the mean time in latest occupation was 21 years, which indicates that this measure was rather stable over time in our sample and the proportion of subjects with a downward social mobility due to CVD ought to be small. Since we investigated preclinical atherosclerosis, downward socioeconomic mobility due to cardiovascular symptoms is an unlikely likely source of bias. Educational level, usually attained in early adulthood, should not to be influenced by clinical atherosclerotic disease, which occurs later in life. The use of education as a marker of SEP has been shown to be reliable, have a low non-response rate and, as it is usually attained in early adulthood, is not subject to reverse causation.1 However, education might be a problematic indicator in a study covering a wide range of different age-cohorts, i.e., social and economical values might differ between various birth cohorts.1,56 Our analyses showed a similar, but somewhat weaker, association between educational level and carotid plaque prevalence among those aged 46–55 compared to those aged 56–65.
CRP has been argued to be a good indicator of low grade inflammation since the levels appear reasonably stable over time with little seasonal or diurnal variation.57,58 Using the MDCS population, CRP has been shown to be related to the risk of future cardiovascular events with adjusted rate ratios with high ( 2.8 mg/L) as compared to low CRP of 2.07 (95% CI: 1.18, 3.65) for men and 2.58 (95% CI: 1.40, 4.74) for women (unpublished data, 2005).
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 it is an end-point which could be expected to be asymptomatic in a vast majority of cases (particularly since all individuals with known CVD were excluded from the analyses).
In conclusion, the results showed that low SEP was strongly associated with increased levels of CRP, independently of established risk factors. Furthermore, CRP-levels were associated with the extent of carotid atherosclerosis, and more so in men than in women. However, there was only a minor attenuation of the association between SEP and carotid atherosclerosis as measured by carotid IMT and carotid plaque after adjustment for CRP.
The Ethics Committee at Lund University approved the study. All participants gave informed consent.
| Key points
|
|
References |
|---|
|
TopAbstractMaterials and methodsResultsDiscussionReferences |
|---|
1 Lynch J, Kaplan G. Socioeconomic position. In: Social Epidemiology—Berkman L, Kawachi I, eds. (2000) Oxford: Oxford University Press.
2 Kaplan GA, Keil JE. Socioeconomic factors and cardiovascular disease: a review of the literature. Circulation (1993) 88:1973–98.
3 Labarthe D. Epidemiology and Prevention of Cardiovascular Diseases. A Global Challenge (1998) Gaithersburg: Aspen Publishers.
4 Lynch JW, Kaplan GA, Salonen R, et al. Socioeconomic status and carotid atherosclerosis. Circulation (1995) 92:1786–92.
5 Diez-Roux AV, Nieto J, Tyroler HA, et al. Social inequalities and atherosclerosis. The atherosclerosis risk in communities study. Am J Epidemiol (1995) 141:960–72.
6 Lynch JW, Kaplan GA, Salonen R, et al. Socioeconomic position and progression of carotid atherosclerosis: prospective evidence from the Kuopio Ischemic Heart Disease Risk Factor Study. Arterioscler Thromb Vasc Biol (1997) 17:513–9.
7 Ebrahim S, Papacosta O, Whincup P, et al. Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent disease in men and women. Stroke (1999) 30:841–50.
8 Rosvall M, Östergren P-O, Hedblad B, et al. Occupational status, educational level and the prevalence of carotid atherosclerosis in a general population sample of middle-aged Swedish men and women. Results from the Malmö Diet and Cancer Study. Am J Epidemiol (2000) 152:334–46.
9 Lamont D, Parker L, White M, et al. Risk of cardiovascular disease measured by carotid intima-media thickness at age 49-51: lifecourse study. BMJ (2000) 320:273–8.
10 Rosvall, Östergren P-O, Hedblad B, et al. Life-course perspective on socioeconomic differences in carotid atherosclerosis. Arterioscler Thromb Vasc Biol (2002) 22:1704–11.
11 Gallo LC, Troxel WM, Matthews KA, et al. Occupation and subclinical carotid artery disease in women: are clerical workers at greater risk? Health Psychol (2003) 22:19–29.[CrossRef][Web of Science][Medline]
12 Nordstrom CK, Diez Roux AV, Jackson SA, et al. The association of personal and neighborhood socioeconomic indicators with subclinical cardiovascular disease in an elderly cohort. The cardiovascular health study. Soc Sci Med (2004) 59:2139–47.[CrossRef][Web of Science][Medline]
13 Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation (2003) 107:499–511.
14 Libby P, Ridker P. Inflammation and atherosclerosis: role of C-Reactive protein in risk assessment. Am J Med (2004) 116(Suppl 6A):9S–16S.[CrossRef][Medline]
15 Tataru MC, Heinrich J, Junker R, et al. C-reactive protein and the severity of atherosclerosis in myocardial infarction patients with stable angina pectoris. Eur Heart J (2000) 21:1000–8.
16 Madsen T, Skou HA, Hansen VE, et al. C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease. Am J Cardiol (2001) 88:1139–42.[CrossRef][Web of Science][Medline]
17 Gronholdt ML, Sillesen H, Wiebe BM, et al. Increased acute phase reactants are associated with levels of lipoproteins and increased carotid plaque volume. Eur J Vasc Endovasc Surg (2001) 21:227–34.[CrossRef][Web of Science][Medline]
18 Jousilahti P, Salomaa V, Rasi V, et al. The association of C-reactive protein, serum amyloid A and fibrinogen with prevalent coronary heart disease—baseline findings of the PAIS project. Atherosclerosis (2001) 156:451–6.[CrossRef][Web of Science][Medline]
19 Kivimaki M, Lawlor DA, Jounala M, et al. Lifecourse socioeconomic position, C-reactive protein, and the carotid intima-media thickness in young adults. The cardiovascular in young Finns study. Arterioscler Thromb Vasc Biol (2005) 25:2197–202.
20 Folsom AR, Pankow JS, Tracy RP, et al. Association of C-reactive protein with markers of prevalent atherosclerotic disease. Am J Cardiol (2001) 88:112–17.[CrossRef][Web of Science][Medline]
21 Wilson TW, Kaplan GA, Kauhanen J, et al. Association between plasma fibrinogen concentration and five socioeconomic indices in the koupio Ischemic Heart Disease Risk Factor Study. Am J Epidemiol (1993) 137:292–300.
22 Brunner E, Davey Smith G, Marmot M, et al. Childhood social circumstances and psychosocial and behavioural factors as determinants of plasma fibrinogen. Lancet (1996) 347:1008–13.[CrossRef][Web of Science][Medline]
23 Jousilahti P, Salomaa V, Rasi V, et al. Association of markers of systemic inflammation, C reactive protein, serum amyloid A, and fibrinogen, with socioeconomic status. J Epidemiol Community Health (2003) 57:730–3.
24 Owen N, Poulton T, Hay FC, et al. Socioeconomic status, C-reactive protein, immune factors, and responses to acute mental stress. Brain Behav Immun (2003) 17:286–95.[CrossRef][Web of Science][Medline]
25 Steptoe A, Kunz-Ebrecht S, Owen N, et al. Influence of socioeconomic status and job control on plasma fibrinogen responses to acute mental stress. Psychosom Med (2003) 65:137–44.
26 Lawlor DA, Smith GD, Rumley A, et al. Associations of fibrinogen and C-reactive protein with prevalent and incident coronary heart disease are attenuated by adjustment for confounding factors. British Women's Heart and Health Study. Thromb Haemost (2005) 93:955–63.[Web of Science][Medline]
27 Rosengren A, Wilhelmsen L, Welin L, et al. Social influences and cardiovascular risk factors as determinants of plasma fibrinogen concentration in a general population sample of middle aged men. BMJ (1990) 300:634–8.
28 Danesh J, Muir J, Wong YK, et al. Risk factors for coronary heart disease and acute-phase reactant proteins. A population-based study. Eur Heart J (1999) 20:954–9.
29 Berglund G, Elmståhl S, Janzon L, et al. The Malmö Diet and Cancer Study. Design and feasibility. J Int Med (1993) 233:45–51.[Web of Science][Medline]
30 Manjer J, Carlsson S, Elmståhl S, et al. The Malmö diet and cancer study: representivity, cancer incidence and mortality in participants and non-participants. Eur J Cancer Prev (2001) 10:489–99.[CrossRef][Web of Science][Medline]
31 Hedblad B, Nilsson P, Janzon L, et al. Relation between insulin resistance and carotid intima-media thickness and stenosis in non-diabetic subjects. Results from a cross-sectional study in Malmö, Sweden. Diabet Med (2000) 17:299–307.[CrossRef][Web of Science][Medline]
32 Berglund G, Riley WA, Barnes RW, et al. Quality control in ultrasound studies on atherosclerosis. J Int Med (1994) 236:581–6.[Web of Science][Medline]
33 Wendelhag I, Gustavsson T, Suurkula M, et al. Ultrasound measurement of wall thickness in the carotid artery. Fundamental principles and description of a computerized image analyzing system. Clin Physiol (1991) 11:565–77.[Web of Science][Medline]
34 Persson J. Ultrasound and Atherosclerosis. Evaluation of Methods, Risk Factors and Intervention [dissertation] (1997) Malmö: Lund University.
35 Swedish National Central Bureau of Statistics. Swedish Socioeconomic Classification (1982) Stockholm: The Bureau. Reports on statistical coordination. No. 4. (In Swedish).
36 Thom DH, Grayston JT, Siscovick DS, et al. Association of prior infection with Chlamydia pneumoniae and angiographically demonstrated coronary artery disease. JAMA (1992) 268:68–72.
37 Lagrand WK, Visser CA, Hermens WT, et al. C-reactive protein as a cardiovascular risk factor: more than an epiphenomenon? In: Circulation. 1999;100::96–102.
38 Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation (2000) 102:2165–8.
39 Dupuis J, Larson MG, Vasan RS, et al. Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study: Evidence for susceptibility loci on 1q. Atherosclerosis (2005) 182:307–14.[CrossRef][Web of Science][Medline]
40 Koenig W, Sund M, Frohlich M, et al. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men. Results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort study, 1984 to 1992. Circulation (1999) 99:237–42.
41 Cushman M, Arnold AM, Psaty BM, et al. C-reactive protein and the 10-year incidence of coronary heart disease in older men and women: the cardiovascular health study. Circulation (2005) 112:25–31.
42 Kwok S, Charlton-Menys V, Pemberton P, et al. Effects of dydrogesterone and norethisterone, in combination with oestradiol, on lipoproteins and inflammatory markers in postmenopausal women. Maturitas (2006) 53:439–46.[CrossRef][Web of Science][Medline]
43 Hu P, Greendale GA, Palla SL, et al. The effects of hormone therapy on the markers of inflammation and endothelial function and plasma matrix metalloproteinase-9 level in postmenopausal women: The postmenopausal estrogen progestin intervention (PEPI) trial. In: Atherosclerosis (2006) 185:347–52.[CrossRef][Web of Science][Medline]
44 Langer RD, Pradhan AD, Lewis CE, et al. Baseline associations between postmenopausal hormone therapy and inflammatory, haemostatic, and lipid biomarkers of coronary heart disease. The Women's Health Initiative Observational Study. Thromb Haemost (2005) 93:1108–16.[Web of Science][Medline]
45 Grobbee DE, Bots ML. Carotid artery intima-media thickness as an indicator of generalized atherosclerosis. J Int Med (1994) 236:567–73.[Web of Science][Medline]
46 Salonen R, Salonen JT. Determinants of carotid intima-media thickness: A population-based ultrasonography study in eastern Finnish men. J Int Med (1991) 229:225–31.[Web of Science][Medline]
47 Chambless LE, Heiss G, Folsom AR, et al. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993. Am J Epidemiol (1997) 146:483–94.
48 Bots ML, Hoes AW, Koudstaal PJ, et al. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation (1997) 96:1432–7.
49 O'Leary DH, Polak JF, Kronmal RA, et al. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med (1999) 340:14–22.
50 Rosvall M, Janzon L, Berglund G, et al. Incident coronary events and case-fatality in relation to common carotid IMT. J Intern Med (2005) 257:430–7.[CrossRef][Web of Science][Medline]
51 Geroulakos G, Domjan J, Nicolaides A, et al. Ultrasonic carotid artery plaque structure and the risk of cerebral infarction on computed tomography. J Vasc Surg (1994) 20:263–6.[Web of Science][Medline]
52 Hollander M, Bots ML, Del Sol AI, et al. Carotid plaques increase the risk of stroke and subtypes of cerebral infarction in asymptomatic elderly: the Rotterdam Study. Circulation (2002) 105:2872–7.
53 Chambless LE, Folsom AR, Clegg LX, et al. Carotid wall thickness is predictive of incident clinical stroke: the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol (2000) 151:478–87.
54 Rosvall M, Janzon L, Berglund G, et al. Incidence of stroke is related to carotid IMT even in the absence of plaque. Atherosclerosis (2005) 179:325–31.[CrossRef][Web of Science][Medline]
55 Liberatos P, Link BG, Kelsey JL. The measurement of social class in epidemiology. Epidemiol Rev (1988) 10:87–121.[Web of Science][Medline]
56 Hallqvist J. Socioeconomic Differences in Myocardial Risk. Epidemiological Analyses of Causes and Mechanisms (1998) Stockholm, Sweden: Department of Public Health Sciences, Division of Social Medicine. (Thesis).
57 Vigushin DM, Pepys MB, Hawkins PN. Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease. J Clin Invest (1993) 91:1351–1357.[Web of Science][Medline]
58 Meier-Ewert HK, Ridker PM, Rifai N, et al. Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects. Clin Chem (2001) 47:426–430.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||