Rheumatoid Arthritis & Atherosclerosis Is Research Proposal

Excerpt from Research Proposal :

Though this work focuses specifically on the risk factors of atherosclerosis for RA patients and how to better identify them prior to clinical presentation of atherosclerosis the work is also insightful in that it builds a case for the connection between RA clinical presentations and atherosclerosis, in general. To move forward from this progressive idea is the fact that research has indicated that there is an even greater connection between RA patients and increased Carotid intima-media thickness (cIMT), which has served as a preclinical predictor in non-RA patients for cardiovascular events, but has now been shown to be even greater in progressive severity in RA patient, but especially in those with RA symptomology that has lasted longer than 20 years. This high grade of cIMT is also an indication of increased inflammation, in addition to increased plaque deposits in the carotid arteries.

A cIMT has previously been found to be increased in patients with longstanding RA [3]: those with long duration (> 20 years) had a higher cIMT compared with patients of the same age but shorter disease duration (< 7 years). Hannawi and colleagues extend these findings by reporting that an increased cIMT was already evident in RA patients as early as within 12 months of symptom onset and was determined mainly by age and C-reactive protein [1]. Both research groups conclude that their findings support the concept that the high-grade inflammation associated with RA, in addition to causing joint disease, also accelerates the process of atherosclerosis in these patients. Hannawi and colleagues suggest explicitly that 'inflammation which precedes the onset of joint symptoms in RA promotes the development of atherosclerotic disease well before the first manifestations of joint disease...' [1]. This would be consistent with studies showing that, compared with people who do not develop RA later in life, those who do develop the disease have elevated C-reactive protein levels many years before the diagnosis of RA [4]. (Veldhuijzen van Zanten & Kitas, 2008, p. 102)

The indications of these results are significant in that the common denominator between RA and atherosclerosis has been simultaneously linked with the development of increased inflammation, even without the RA as a factor. The work stresses a collaborative level of research for both disorders and a significant link between inflammation and atherosclerosis that has previously only been limitedly researched and developed. The study uses a test for atherosclerosis (cIMT) to detect atherosclerosis in RA patients prior to and following clinical presentation of active atherosclerosis. This suggests that there is a strong link between the two diseases and inflammation.

Researchers and clinicians have been seeking the so called "holy grail" of atherosclerosis for a long time, having previously and possibly falsely associating incidence with high LDL cholesterol, a link which has been questioned almost from its inception but has led to significant treatment modalities for the reduction of LDL being utilized in high risk and non-high risk patients.

Systemic inflammation may then prove to be one of the most effective and cost effective tools for the development of screening tools for patients with and without RA who may develop atherosclerosis. Early detection is essential to halting the progression in both groups and recent RA findings indicate that associating high levels of general inflammation in all patients is a good screening tool for atherosclerosis. See Figure 2 for cIMT comparisons between early onset RA and control studies.

Laboratory, clinical and epidemiological studies suggest that immune dysregulation and systemic inflammation play important roles in the accelerated atherosclerosis of RA [2,3]. Although CV events are major consequences of CV disease, these complications develop over years, and the time course of epidemiologic and clinical studies has been reduced using B-mode ultrasound measurement of the carotid intima-media thickness (cIMT) and of carotid plaque to study early atherosclerotic changes noninvasively [4,5]. cIMT values measured by ultrasound correlate closely with direct measurement of the local and systemic atherosclerotic burden in pathology studies and with clinical CV endpoints [4,6]. Ultrasonographic assessment of common carotid atherosclerosis is a feasible, reliable, valid and cost-effective method for both population studies and clinical

Coassociation of carotid intima media thickness, age and rheumatoid arthritis inflammatory activity. The carotid intima media thickness (cIMT) was measured in 37 rheumatoid arthritis (RA) patients with disease duration <12 months and in 37 control subjects matched for age, sex and cardiovascular risk factors. The cIMT was plotted against (top left) age at RA diagnosis, (top right) age of controls, or (bottom left) the C-reactive protein (CRP) level at first presentation with RA. (Bottom right) CRP at first presentation plotted against history of smoking. Data presented as mean ± standard deviation. * p < 0.05 (Hannawi et al. Arthritis Research & Therapy 2007 9:R116 doi:10.1186/ar2323) trials of atherosclerosis progression and regression [7]. (Hannawi, Haluska, Marwick, & Thomas, 2007, NP)

The implications of the fact that even in early onset RA there are significant indication associated with Atherosclerosis type inflammation is substantial in the correlate between both diseases and potential future treatment protocols. There may in fact be a day when detection and treatment for atherosclerosis is developed as a protocol including as much treatment for inflammation as treatment for high LDL cholesterol, with accompanying lifestyle risk factor reduction, wherever possible. There may in fact be a day when atherosclerosis risk factors indicate relatively cost effective screening, in all patient classes as well as treatment for mitigating inflammation responses, which have been shown to increase progression and severity of atherosclerosis with and without RA and if recent research has much to say about it treatment protocols may be advanced very soon. (Montecucco & Mach, October 2008, NP)


Hannawi, S. Haluska, B. Marwick, T.H. & Thomas R. (2007) Atherosclerotic Disease is Increased in Recent-onset Rheumatoid Arthritis: a Critical role for Inflammation Arthritis Research & Therapy 9:R116doi:10.1186/ar2323 Retrieved September 28, 2008. http://arthritis-research.com/content/9/6/R116.

Margolis, S. (February 2007) Atherosclerosis and Rheumatoid Arthritis. Johns Hopkins Medicine NP Retrieved September 28, 2008. http://health.yahoo.com/experts/heartdisease/3614/atherosclerosis-and-rheumatoid-arthritis/

Montecucco, F. & Mach, F. (October 16, 2008) Common Inflammatory Mediators Orchestrate Pathophysiological Processes in Rheumatoid Arthritis and Atherosclerosis. Rheumatology, doi:10.1093/rheumatology/ken395 Retrieved October 28, 2008. http://rheumatology.oxfordjournals.org/cgi/content/abstract/ken395

Pasceri, V., Yeh, E.T.H. (1999) a Tale of Two Diseases: Atherosclerosis and Rheumatoid Arthritis Circulation: Journal of the American Heart Association, 100, 2124-2126. Retrieved October 2, 2008. http://circ.ahajournals.org/cgi/content/full/100/21/2124

Ravnskov, U. Is Atherosclerosis Caused by High Cholesterol? QJM: AN International Journal of Medicine. 95, 397-403. Retrieved October 1, 2008. http://qjmed.oxfordjournals.org/cgi/content/full/95/6/397

Roman, M.J. Moeller, E. Davis, a. Paget, S.A. Crow, M, K. Lockshin, M.D Sammaritano, L. Devereux, R.B. Schwartz, J.E. Levine, D.M. Salmon, J.E. (February 2006) Preclinical Carotid Atherosclerosis in Patients with Rheumatoid Arthritis. Annals of Internal Medicine 144(4) 249-257. Retrieved October 2, 2008. http://www.annals.org/cgi/reprint/144/4/249.pdf

Veldhuijzen van Zanten J.J. & Kitas, G.D. (2008) Inflammation, Carotid Intima-media Thickness and Atherosclerosis in Rheumatoid Arthritis. Arthritis Research and Therapy 10(1) 102. Retrieved September 15, 2008. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2374455

Rheumatoid Arthritis & Atherosclerosis

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