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

Department of Social Medicine, University of Bristol, UK.
Thrombosis and Haemostasis (Impact Factor: 4.98). 06/2005; 93(5):955-63. DOI: 10.1267/THRO05050955
Source: PubMed


A cross sectional and prospective analysis of 3,745 British women aged 60-79 years at baseline was undertaken. Among these women there were 570 prevalent cases of coronary heart disease (CHD) and 151 new cases among 12,641 person-years of follow up of women who were free of CHD at baseline. Both fibrinogen and CRP were associated with indicators of socioeconomic position in childhood and adulthood and there was a cumulative effect of socioeconomic position from across the life course. The age-adjusted odds ratio (95% confidence interval) of prevalent CHD for a 1 unit (1 g/L) increase in fibrinogen was 1.29 (1.12, 1.49); with full adjustment for all potential confounding factors this attenuated to 1.09 (0.93, 1.28). The hazards ratio for incident CHD among those free of disease at baseline was 1.28 (1.00, 1.64); with full adjustment for all potential confounding factors this attenuated to 1.09 (0.84, 1.44). Similar effects of adjustment for confounding factors were seen for the associations between CRP and both prevalent and incident CHD. By contrast, the strong positive association between smoking (an established causal risk factor for CHD) and CHD was not attenuated by adjustment for life course socioeconomic position or other risk factors. We conclude that fibrinogen and CRP predict CHD but may not be causally related to it.

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    • "This may reflect that the Carstairs score is a more 'immediate' reflection of social deprivation rather than lifetime socio-economic status measured elsewhere (e.g. British women's heart and health study; Lawlor et al, 2005). Furthermore, the Carstairs score (which includes measures of local male unemployment, and head of household's social class categories IV and V) is probably naturally more suited to measuring deprivation in men, helping explain some of the sex-specific differences noted in this study. "
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    ABSTRACT: Circulating inflammatory markers [plasma fibrinogen, viscosity and C-reactive protein (CRP)] have been associated with cardiovascular risk factors. In part, these associations may reflect 'upstream' changes in pro-inflammatory cytokines - interleukin (IL)-6, IL-18 and tumour necrosis factor (TNF)alpha. These variables were measured in 1666 men and women aged 25-64 years and their associations with risk factors were studied. All six markers increased significantly with age. IL-18 and TNFalpha levels were higher, and fibrinogen levels lower, in males. Oral contraceptive use increased levels of CRP, whilst postmenopausal women had elevated IL-18 levels. Inflammatory markers were also associated with components of the metabolic syndrome. Most inflammatory markers showed an increasing trend with alcohol consumption in men and a decreasing trend in women, and increasing trends with level of smoking. Inflammatory markers generally showed strong positive associations with social deprivation. After adjustment for classical risk factors, IL-6, IL-18 and TNFalpha retained significant associations with social deprivation only in men (P < 0.008). We conclude that pro-inflammatory cytokines are associated with several cardiovascular risk factors including social deprivation, and may mediate some of their associations with 'downstream' inflammatory markers (fibrinogen, viscosity and CRP).
    Preview · Article · Jun 2008 · British Journal of Haematology
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    • "Both sets of findings are consistent with previous studies showing similar associations between other CVD risk factors and SEP and race/ethnicity [3,4,8-10,63]. Although the notion that CRP levels are causally associated with CVD has been challenged by Mendelian Randomization studies, there is little question that CRP constitutes a reliable marker for low-grade inflammation that identifies high-risk individuals [26,29]. "
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    ABSTRACT: Socioeconomic and racial/ethnic factors strongly influence cardiovascular disease outcomes and risk factors. C-reactive protein (CRP), a non-specific marker of inflammation, is associated with cardiovascular risk, and knowledge about its distribution in the population may help direct preventive efforts. A systematic review was undertaken to critically assess CRP levels according to socioeconomic and racial/ethnic factors. Medline was searched through December 2006 for population-based studies examining CRP levels among adults with respect to indicators of socioeconomic position (SEP) and/or race/ethnicity. Bibliographies from located studies were scanned and 26 experts in the field were contacted for unpublished work. Thirty-two relevant articles were located. Cross-sectional (n = 20) and cohort studies (n = 11) were included, as was the control group of one trial. CRP levels were examined with respect to SEP and race/ethnicity in 25 and 15 analyses, respectively. Of 20 studies that were unadjusted or adjusted for demographic variables, 19 found inverse associations between CRP levels and SEP. Of 15 similar studies, 14 found differences between racial/ethnic groups such that whites had the lowest while blacks, Hispanics and South Asians had the highest CRP levels. Most studies also included adjustment for potential mediating variables in the causal chain between SEP or race/ethnicity and CRP. Most of these studies showed attenuated but still significant associations. Increasing poverty and non-white race was associated with elevated CRP levels among adults. Most analyses in the literature are underestimating the true effects of racial/ethnic and socioeconomic factors due to adjustment for mediating factors.
    Full-text · Article · Feb 2007 · BMC Public Health
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    • "obesity and alcohol) and might also be weaker after further adjustment for intraindividual variability in confounders (Fibrinogen Studies Collaboration, 2005). Few studies in this meta-analysis adjusted for socioeconomic position, a strong confounder in some studies (Lawlor et al, 2005). Whether or not fibrinogen plays a causal role in arterial disease or thrombosis is uncertain. "
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    ABSTRACT: The risk of venous or arterial thrombosis is routinely assessed by clinical variables (risk factors) supplemented by measurement of blood lipids and glucose for arterial thrombotic events. Haematological tests that might play a role in risk prediction include haemostatic variables, haematocrit and inflammatory markers (erythrocyte sedimentation rate, plasma viscosity, white cell count). Recent epidemiological studies of these phenotypes and related genotypes are reviewed. For the risk prediction of first venous thrombosis, screening for thrombophilias in 'high-risk' situations does not appear clinically effective or cost-effective; with the possible exception of women considering oral hormone replacement therapy. General screening after a first venous event to predict recurrence (or risk in asymptomatic relatives) does not appear effective; with the possible exception of d-dimer, which requires further study. For risk prediction of first arterial thrombosis, screening adds little to prediction by current clinical risk scores. Screening of persons after a first arterial event, or with atrial fibrillation (e.g. with D-dimer for stroke prediction), requires further study. In conclusion, haematological tests have very limited roles in the prediction of cardiovascular risk, and should only be used according to evidence-based guidelines. The need for management studies is highlighted.
    Preview · Article · Jun 2006 · British Journal of Haematology
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