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Rheumatology 2001; 40: 703-704
© 2001 British Society for Rheumatology
Letters to the Editor |
Rheumatoid arthritis and cardiovascular disease may share similar risk factors
1 Milpark Hospital and
2 Department of Rheumatology, Johannesburg Hospital, University of the Witwatersrand, Johannesburg and
3 National Research Foundation, Pretoria, South Africa
SIR, We read with interest the article by D. Symmons and B. Harrison on risk factors for the development of inflammatory polyarthritis (IP) and rheumatoid arthritis (RA) [1]. These authors have recently made several contributions to the search for associations between genetic as well as environmental factors and the development of RA and IP. They conclude by stating that elucidation is needed of the mechanisms by which some of the risk factors that have been identified may mediate the development of IP [1]. It is therefore of interest that several of the respective risk factors similarly predispose to cardiovascular disease (CVD) [2– 4]. These include obesity, smoking, decreased antioxidant and unsaturated fat intake, diabetes mellitus, no alcohol intake and, although controversial at this stage, infections, reduced serum dehydroepiandrosterone sulphate (DHEAS) levels and psychological and physical stressors. Also, in a prospective study on 52 800 subjects, raised serum cholesterol concentrations were found to predict the development of rheumatoid factor-positive RA in women and rheumatoid factor-negative RA in men [4]. In a recent study, we found significantly higher cholesterol/high-density lipoprotein cholesterol ratios in 87 patients (38 RA, 29 spondyloarthropathy and 20 undifferentiated inflammatory arthritis) compared with those in 30 age- and sex-matched healthy controls, even after controlling for the following significant predictors: body mass index, erythrocyte sedimentation rate and insulin resistance (in preparation). Raised serum apolipoprotein (a) concentrations were reported recently to be unrelated to disease activity or treatment and to be genetically determined in RA [5].
Insulin resistance mediates CVD in obesity [6]. The prevalence of RA is 0.5–1.0% worldwide except in native American Indian populations, e.g. Pima Indians, in whom a prevalence of 5.3% was reported [7]. This population experiences a very high frequency of obesity, insulin resistance and type 2 diabetes. Although CVD is uncommon in Pima Indians, this may be due to a low frequency of heavy smoking, lower cholesterol levels, a younger age at onset of type 2 diabetes and enhanced susceptibility to renal disease [6]. RA is associated with a 70% excess CVD mortality in this population [8].
Since the report by Heikkila et al. [9] on normal androgen levels prior to RA onset, Masi et al. [10] have again confirmed reduced serum dehydroepiandrosterone sulphate (DHEAS) concentrations as a risk factor for RA in their premenopausal patients. This is of interest in the present context, as a low serum DHEAS concentration was found to be a stronger predictor of death from CVD and ischaemic heart disease than were obesity, fasting plasma glucose, smoking, systolic blood pressure and serum cholesterol [3]. This difference remained significant after adjustment for these other risk factors as well as for age [3]. Ageing is associated with an increased incidence of both CVD and RA, and this mirrors decreasing serum-DHEAS concentrations [11, 12]. DHEA decreases circulating amounts of plasminogen activator inhibitor type 1 and tissue plasminogen activator antigen [13], and is an immunosuppressant [11].
The notion that CVD and RA may share similar predisposing factors could yield an understanding of the mechanisms underlying the identified associations between environmental factors and RA onset. The pathogenesis of atherosclerosis is now known to involve more than cholesterol accumulation in the blood vessel wall, plaque rupture and thrombosis. It entails endothelial dysfunction followed by the development of an inflammatory infiltrate [14]. In case–control studies, raised interleukin-6 concentrations were identified prior to disease onset in both CVD and RA [11, 15]. Endothelial dysfunction was postulated as a mechanism whereby smoking contributes to RA onset [11]. At the intracellular level, activation of the proinflammatory gene transcription factor nuclear factor 
B is thought to play a pivotal role in the pathogenesis of both RA [16] and CVD [17].
In conclusion, while RA selects for women at a younger age than men and CVD for men at a younger age than women [11], several non-gender related risk factors are shared by CVD and RA. Whether this indicates similarities in the underlying pathogenetic mechanisms in RA (and other IPs) and CVD deserves confirmation. This could yield new strategies in the prevention and treatment of this disease.
Notes
Correspondence to: P. H. Dessein, PO Box 1012, Melville 2109, Johannesburg, South Africa. 
Accepted 27 November 2000
References
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Symmons D, Harrison B. Early inflammatory polyarthritis: results from the Norfolk Arthritis Register with a review of the literature. I. Risk factors for the development of inflammatory polyarthritis and rheumatoid arthritis. Rheumatology2000;39:835–43.
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Reply
ARC Epidemiology Research Unit and 1North Manchester General Hospital, Manchester, UK
We thank Drs Dessein, Stanwix and Moomal for their interest in our review paper [1, 2]. We agree that there are many intriguing similarities between the risk factors for rheumatoid arthritis and those for coronary artery disease. We also agree that the descriptive epidemiology of these two conditions is not the same. Rheumatoid arthritis has a predilection for women and coronary artery disease for men. The risk with regard to age is not exactly the same either. There is obviously much to be learned by considering the role of inflammation in the aetiology of coronary artery disease, and from considering whether rheumatoid arthritis is a risk factor for coronary artery disease or whether these two diseases represent separate end points of a similar pathological process.
Notes
Correspondence to: D. P. M. Symmons, ARC Epidemiology Research Unit, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
References
- Symmons D, Harrison B. Early inflammatory polyarthritis: results from the Norfolk Arthritis Register with a review of the literature. I. Risk factors for the development of inflammatory polyarthritis and rheumatoid arthritis. Rheumatology2000;39:835–43.
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Harrison B, Symmons D. Early inflammatory polyarthritis: results from the Norfolk Arthritis Register with a review of the literature. II. Outcome at three years. Rheumatology2000;39:939–49.
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