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.
ABSTRACT 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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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).British Journal of Haematology 06/2008; 141(6):852-61. DOI:10.1111/j.1365-2141.2008.07133.x · 4.96 Impact Factor
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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.British Journal of Haematology 06/2006; 133(3):232-50. DOI:10.1111/j.1365-2141.2006.06021.x · 4.96 Impact Factor
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ABSTRACT: Low socioeconomic position is known to be associated with greater coronary heart disease (CHD) risk in most developed countries. However, studies have largely focused on the association between socioeconomic position and CHD in middle-aged populations and little is known about the extent to which socioeconomic position affects CHD risk in later life. This thesis uses the British Regional Heart Study, a populationbased cohort of British men to investigate the extent of socioeconomic inequalities in CHD in older age and the possible pathways to these inequalities. Issues addressed in detail include trends in socioeconomic inequalities in CHD with increasing age and over time, the extent of socioeconomic inequalities in CHD in older age (60-79 years), the contribution of established and novel coronary risk factors to these inequalities, and the influence of early life socioeconomic position on CHD risk in later life. Although CHD mortality declined over the last two decades in Britain, relative social class differences in CHD did not narrow between 1980 and 2005. With increasing age (from 40-59 years to 65-84 years), relative social class inequalities in CHD narrowed, although absolute differences widened with age. Marked socioeconomic differences in CHD were present in older age; CHD risk increased from the highest to the lowest social class group. Socioeconomic differences in behavioural coronary risk factors (particularly cigarette smoking) could explain at least a third of these inequalities; inflammatory markers made some additional contribution. Lower socioeconomic position in childhood was associated with increased CHD risk in older age; part of this association was due to the relationship of childhood socioeconomic position with adult behavioural factors. Appreciable socioeconomic inequalities were also present in disability among older men with CHD. The results suggest that important socioeconomic inequalities in CHD persist in older age; the implications for public health and further epidemiological research are discussed.