Send letter to journal:
Re: Rheumatoid factor and heart disease: supporting evidence regarding increased risk of mortality

Dear Editor,

A recent study in Heart by Edwards and colleagues found an interesting association between rheumatoid factor (RF) and ischaemic heart disease [1]. We examined independently the related issue of the role of systemic inflammation in relation to clinical outcome in a forthcoming study [2]. This subsequent study reports an association between systemic inflammation, as measured by C-reactive protein (CRP), and all cause mortality (n = 22,982). We also found a weak association with heart disease but the study was, we believe, statistically underpowered to properly evaluate this outcome. In light of the findings reported by Edwards and colleagues, here we report supplementary data from a sub-group of subjects from the CRP [2] study where data were available characterising RF (n = 3,588). The objective of this report was to characterise survival over a four year period from first CRP observation in this sub-groups of subjects where RF data were also available.

Details of the data source and the general methods were published elsewhere [2]. In brief, data were routine data from hospital, record- linked sources in Cardiff and the Vale of Glamorgan. A Cox proportional hazards model (CPHM) was developed using SPSS for Windows v14. We evaluated a number of potential model covariates including age, sex, prior disease (cancer, diabetes, vascular disease), general morbidity at baseline (total days in hospital in year prior to first CRP observation), and CRP itself. RF was measured in IU/ml and included in the model as a continuous variable following logarithmic transformation.

The mean age of the 3,588 evaluable subjects was 62 years and 33% were female. The CPHM of survival determined a strong association between RF and survival (hazard ratio [HR] for log RF = 1.229; p = 0.008). Furthermore, CRP (log transformed), was also included simultaneously in this statistical model (HR = 1.495; p < 0.001) in preference to other factors such as a history of diabetes and cancer. As expected, age and being male also increased risk of death in the CPHM. The association between RF and all cause mortality is illustrated in figure 1.

Data from this study supports findings from the study by Edwards and colleagues, and shows that RF not only predicts the likelihood of ischaemic heart disease but it also predicts the likelihood of all cause mortality. Furthermore, data from this subgroup of subjects showed that CRP and RF were independent risk factors for all cause mortality. Thus, they are likely to represent distinct inflammatory processes that increase the risk of adverse outcome.

Yours sincerely,

Craig J. Currie Department of Medicine, School of Medicine, Cardiff University, Cardiff UK currie@cardiff.ac.uk

Pete Conway Health Economics, Wyeth Europa Limited, Maidenhead, UK

Chris D. Poole 360° Research Limited, Penarth, UK

Acknowledgement: This study was funded by Wyeth Europa. PC is a full time employee of Wyeth Europa.

Figure 1 Four-year risk of death as a function of increasing rheumatoid factor following standardisation for age, sex and C-reactive protein level.

References

1. Edwards CJ, Syddall H, Goswami R, Goswami P, Dennison EM, Arden NK, Cooper C, on behalf of the Hertfordshire Cohort Study Group.
The autoantibody rheumatoid factor may be an independent risk factor for ischaemic heart disease in men.
Heart 2007;0:1–5. doi: 10.1136/hrt.2006.097816

Send letter to journal:
Re: Rheumatoid Factor-? Is it a biomarker of inflammation or an independent risk factor for IHD

Dear Editor,

I read with interest the original article by Christopher J Edwards et al about the possibility of Rheumatoid factor being an independent risk factor for Ischaemic Heart Disease (1).The contribution of inflammation to the initiation and progression of coronary atherosclerosis is well established.I agree this study adds support to the importance of inflammation in atherosclerosis. The concept of autoimmunity and the direct role of RF in the pathogenesis of atherosclerotic disease process are fascinating and will act as a basis to future research.

The key unanswered question is whether RA is a marker of inflammation or an indedependant risk factor for IHD.As acknowledged by the authors it may be difficult to draw a firm conclusion from this cross sectional study. It may have been useful if the authors correlated RA to well established markers of inflammation such as C-reactive protein (2).Screening patients using RF is probably not justified at present until further research.

References

1) Christopher J Edwards, Holly Syddall, Rajee Goswami, Priya Goswami, Elaine Dennison, Nigel Arden, and Cyrus Cooper
Rheumatoid Factor may be an Independent Risk Factor for Ischaemic Heart Disease
Heart 2007; 0:hrt.2006.097816v1