Relationships of inflammatory and haemostatic markers with social class: results from a population-based study of older men.

Haemostatic and inflammatory markers have been hypothesised to mediate the relationship of social class and cardiovascular disease (CVD). We investigated whether a range of inflammatory/haemostatic markers are associated with social class independent of chronic diseases and behavioural risk factors in a population-based sample of 2682 British men aged 60-79 without a physician diagnosis of CVD, diabetes or musculoskeletal disease requiring anti-inflammatory medications. Men in lower social classes had higher mean levels of C-reactive protein, fibrinogen, interleukin-6, white blood cell count, von Willebrand factor (vWF), factor VIII, activated protein C (APC) resistance, plasma viscosity, fibrin D-dimer and platelet count, compared to higher social class groups; but not of tissue plasminogen activator antigen, haematocrit or activated partial prothrombin time. After adjustment for behavioural risk factors (smoking, alcohol, physical activity and body mass), the associations of social class with vWF, factor VIII, APC resistance, plasma viscosity, and platelet count though weakened, remained statistically significant, while those of other markers were considerably attenuated. In this study of older men without CVD, the social gradient in inflammatory and haemostatic markers was substantially explained by behavioural risk factors. The effect of socio-economic gradient on the factor VIII-vWF complex, APC resistance, plasma viscosity and platelet count merits further study.

Adult socioeconomic position, C-reactive protein and interleukin-6 in the Whitehall II prospective study.

BACKGROUND: Prior studies on the association of inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6), with socioeconomic position (SEP) have been cross-sectional. Thus, the question of whether socioeconomic differences in CRP and IL-6 change over time remains unanswered. We examined the relationship between SEP and changes over 12 years in CRP and IL-6. METHODS: Data were for 4,750 middle-aged (mean 49.0 years, SD 5.9) civil servants from phases 3 and 7 of the Whitehall II study. Adult SEP was based on last known Civil Service employment grade. Covariates included sociodemographics, behavioural and biological risk factors, presence of diseases/illnesses, prescribed medications, work-related factors, labour market status and early life factors. RESULTS: Steep socioeconomic gradients observed at Phase 3 (p < 0.001) persisted in both CRP and IL-6 12 years later after adjustment for other risk factors. Adjustment for behavioural (diet and smoking), biological (mainly body mass index and total : HDL cholesterol ratio) and early life factors resulted in considerable attenuation but the inverse socioeconomic gradients remained statistically significant. Although CRP and IL-6 concentrations increased substantially over the 12-year period at every level of SEP, CRP and IL-6 did not change differentially according to SEP. CONCLUSION: Despite overall increases in CRP and IL6, relative differences by SEP remained unchanged so that socioeconomic gradients in both sexes persisted over the period observed.

Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study.

Combined oral contraceptives, oral hormone replacement therapy and thrombophilias are recognised risk factors for venous thromboembolism in women. The objective of this study was to assess the risk of thromboembolism among women with thrombophilia who are taking oral contraceptives or hormone replacement therapy, conducting a systematic review and metaanalysis. Of 201 studies identified, only nine met the inclusion criteria. Seven studies included pre-menopausal women on oral contraceptives and two studies included peri-menopausal women on hormone replacement therapy. For oral contraceptive use, significant associations of the risk of venous thromboembolism were found in women with factor V Leiden (OR 15.62; 95%CI 8.66 to 28.15); deficiencies of antithrombin (OR 12.60; 95%CI 1.37 to 115.79), protein C (OR 6.33; 95%CI 1.68 to 23.87), or protein S (OR 4.88; 95%CI 1.39 to 17.10), elevated levels of factor VIIIc (OR 8.80; 95%CI 4.13 to 18.75); and factor V Leiden and prothrombin G20210A (OR 7.85; 95%CI 1.65 to 37.41). For hormone replacement therapy, a significant association was found in women with factor V Leiden (OR 13.16; 95%CI 4.28 to 40.47). Although limited by the small number of studies, the findings of this study support the presence of interaction between thrombophilia and venous thromboembolism among women taking oral contraceptives. However, further studies are required to establish with greater confidence the associations of these, and other, thrombophilias with venous thromboembolism among hormone users.

Influence of socioeconomic status and job control on plasma fibrinogen responses to acute mental stress.

OBJECTIVE: An elevation in plasma fibrinogen may be one of the pathways through which low socioeconomic status increases cardiovascular disease risk. This study assessed the influence of socioeconomic status, job control, and social isolation on fibrinogen responses to acute stress. METHODS: The study was conducted with 125 white men and 96 white women aged 47 to 58 years, drawn from the Whitehall II cohort. Socioeconomic status was indexed by grade of employment, with 82 high, 75 intermediate, and 64 low grade participants. Plasma fibrinogen and hematocrit were assessed at baseline, immediately after performance of color-word and mirror tracing tasks, and 45 minutes later. RESULTS: Plasma fibrinogen increased from baseline to stress (from 2.85 +/- 0.57 to 2.92 +/- 0.58 g/liter), remaining elevated 45 minutes after stress (2.89 +/- 0.58 g/liter, p <.001). Fibrinogen concentration was greater in the low than in the high or intermediate employment grade groups, independently of sex, age, body mass index, smoking status, and hematocrit. Fibrinogen responses to acute stress did not differ across employment grades. Women had higher fibrinogen levels than men, but this pattern was abolished in women taking hormone replacement therapy. Men experiencing low job control showed greater fibrinogen responses to acute stress than did those with high job control (p =.003). Fibrinogen levels were greater in socially isolated individuals, but social isolation did not affect responses to acute stress. CONCLUSIONS: Socioeconomic status and acute stress had independent effects on the plasma fibrinogen level. Low job control may influence cardiovascular disease risk in men partly through provoking greater fibrinogen stress responses.

Prolonged elevations in haemostatic and rheological responses following psychological stress in low socioeconomic status men and women.

Low socioeconomic status (SES) and psychological stress are associated with increased risk of coronary heart disease, and both may influence haemostatic responses. Von Willebrand factor (vWF), Factor VIII, plasma viscosity, haematocrit, blood viscosity, tissue plasminogen activator (t-PA) and fibrin D-dimer were measured at rest and following stressful tasks in 238 middle-aged British civil servants. SES was defined by grade of employment. Lower SES was associated with higher resting vWF, Factor VIII and plasma viscosity. Psychological stress stimulated increases in haemostatic and rheological factors. Initial stress responses did not vary with SES, but Factor VIII, plasma viscosity and blood viscosity remained more elevated 45 minutes post-stress in lower SES participants. High blood pressure stress reactivity was also associated with greater haemostatic responses. We conclude that lower SES is characterised by more prolonged elevations in procoagulant responses following psychological stress, and that these processes might contribute to increased cardiac risk.

The need for risk factor assessment in atherothrombotic vascular disease.

Risk factors for cardiovascular disease are characteristically associated with an increased likelihood of disease. Prospective studies of incident disease are less prone to bias than cross-sectional or case-control studies of prevalent disease. Meta-analyses of prospective studies provide more reliable estimates of the strength of association of risk factors with risk of disease than individual studies. Meta-analyses of intervention studies provide the most reliable estimates of reversibility of disease risk through prolonged reduction of classical risk factors (e.g., blood pressure, serum cholesterol). Emerging potential risk factors include markers of infection, inflammation, and thrombosis; their possible roles in causation and in risk prediction require much further study.