**1. Introduction**

234 Rheumatoid Arthritis – Etiology, Consequences and Co-Morbidities

Richter, J. G., A. Becker, H. Schalis, T. Koch, R. Willers, C. Specker, R. Monser, and M.

Ruehlman, L. S., P. Karoly, and A. Taylor. 2008. Perceptions of chronic pain's interference

Ryan, S., and E. Wylie. 2005. An exploratory survey of the practice of rheumatology nurses

Sokka, T. 2005. Assessment of pain in rheumatic diseases. *Clin Exp Rheumatol* 23 (5 Suppl

Stucki, G., A. Cieza, S. Geyh, L. Battistella, J. Lloyd, D. Symmons, N. Kostanjsek, and J.

Tasiemski, T., N. Angiaszwili-Biedna, and M. Wilski. 2009. Assessment of objective and

Taylor, B., and S. Davis. 2006. Using the extended PLISSIT model to address sexual

Tristano, A. G. 2009. The impact of rheumatic diseases on sexual function. *Rheumatol Int* 29

van Berlo, W. T., H. B. van de Wiel, E. Taal, J. J. Rasker, W. C. Weijmar Schultz, and M. H.

van Lankveld, W., G. Ruiterkamp, G. Naring, and D. J. de Rooij. 2004. Marital and sexual satisfaction in patients with RA and their spouses. *Scand J Rheumatol* 33 (6):405-8. Vanwesenbeeck, I. 2009. Doing gender in sex and sex research. *Archives of Sexual Behaviour*

Ware, J. E., Jr., and C. D. Sherbourne. 1992. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. *Med Care* 30 (6):473-83. Weerakoon, P., M. K. Jones, R. Pynor, and E. Kilburn-Watt. 2004. Allied health professional

Vliet Vlieland, T. P. 2007. Non-drug care for RA--is the era of evidence-based practice

World Health Organization. 2006. Defining sexual health. Report of a technical consultation

Ying, K. N., and A. While. 2007. Pain relief in osteoarthritis and rheumatoid arthritis: TENS.

Yoshino, S., and S. Uchida. 1981. Sexual problems of women with rheumatoid arthritis. *Arch* 

rheumatoid arthritis in Morocco. *Joint Bone Spine* 73 (3):278-83.

Stausmire, J. M. 2004. Sexuality at the end of life. *Am J Hosp Palliat Care* 21 (1):33-9.

factors. . *Sexuality and Disability* 26 (3):123-136.

*Ortop Traumatol Rehabil* 11 (4):346-59.

healthcare needs. *Nurs Stand* 21 (11):35-40.

multicenter study. *Clin Rheumatol* 26 (1):30-8.

connotations. *J Allied Health* 33 (3):189-93.

*Br J Community Nurs* 12 (8):364-71.

*Phys Med Rehabil* 62 (3):122-3.

approaching? *Rheumatology (Oxford)* 46 (9):1397-404.

3 (1):44-53.

39):S77-84.

(8):853-60.

38 (6):883-898.

Organisation.

93.

Schneider. 2011. An ask-the-expert service on a rheumatology web site: Who were the users and what did they look for? *Arthritis Care Res (Hoboken)* 63 (4):604-11. Rkain, H., F. Allali, I. Jroundi, and N. Hajjaj-Hassouni. 2006. Socioeconomic impact of

with sexual functioning: The role of gender, treatment status, and psychosocial

addressing the sexuality of patients with rheumatoid arthritis. *Musculoskeletal Care*

Schouten. 2004. ICF Core Sets for rheumatoid arthritis. *J Rehabil Med* (44 Suppl):87-

subjective quality of life in people with rheumatoid arthritis - preliminary study.

van Rijswijk. 2007. Sexual functioning of people with rheumatoid arthritis: a

students' perceived level of comfort in clinical situations that have sexual

on sexual health. In *Sexual health document series*. Geneva: World Health

Despite the therapeutic advances in RA that have led to reduced pain, joint destruction and disability, as many as 50% of patients are at risk of death from a cardiovascular event (Maradit-Kremers et al., 2005; Stevens et al., 2005). Inexplicable by the usual traditional risk factors, the accelerated atherosclerosis (Gaonzalez-Gay et al., 2005) has been postulated to result from the increased systemic inflammatory burden of rheumatoid disease (Del Rincon et al., 2001; Gabriel et al., 1999; Kremers & Gabriel, 2006; McEntegart et al., 2001).

The metabolic syndrome (MetS) is a composite diagnosis, combining phenotypic features that portend an increased risk for cardiovascular disease (CVD). The syndrome consists of visceral obesity, atherogenic dyslipidemia, hypertension, and impaired fasting glucose/glucose tolerance test or overt diabetes mellitus (DM) (National Cholesterol Education Program, 2001). Studies have reported the presence of MetS to be associated with an approximate 2- fold increased risk for incident cardiovascular morbidity and mortality (Lakka et al., 2002), a 2.1 fold increase for initial stroke (Najarian et al., 2006), and 3.5 fold increased risk for Type II DM (Lorenzo et al., 2003). The complex interplay of genetic and environmental factors, insulin resistance and inflammation, are all believed to contribute to the pathogenesis of the syndrome.

The overall prevalence of MetS in the US population, as evaluated by the National Health and Nutrition Examination Survey (NHANES III), is 23.1%, and increases with age to as high as 44% in those 65 years or older (Ford et al., 2002). Several studies have established an increased prevalence of insulin resistance and increased risk for CVD in RA patients (Dessein et al., 2002a, 2002b). However, there are few reports regarding MetS in RA, and the

<sup>\*</sup> I. Sabahi1, J.S. Richards1, T.R. Mikuls2, B.V. Rangan3, A. Reimold3, G.W. Cannon4, D. Johnson5 and L. Caplan6

*<sup>2</sup>Omaha Veterans Affairs and University of Omaha, Omaha, NE, USA* 

*<sup>3</sup>Dallas Veterans Affairs and University of Texas Southwestern, Dallas, TX, USA* 

*<sup>4</sup>George E. Wahlen Veterans Affairs and University of Utah, Salt Lake City, UT, USA 5Jackson Veterans Affairs and University of Mississippi, Jackson, MS, USA* 

*<sup>6</sup>Denver Veterans Affairs and University of Colorado, Denver, CO, USA* 

Association of Cardiovascular Disease

ischemic attack, or peripheral vascular disease).

**2.4 Statistical analysis** 

**3. Results** 

with the Metabolic Syndrome in a Predominantly Male Cohort with Rheumatoid Arthritis 237

erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), total swollen and tender joint count (0-28 joints), patient global well-being 100 mm visual analog scale, modified health assessment questionnaire (MD-HAQ, 0-3) and three-variable Disease Activity Score (DAS28-3v; a composite measure based on swollen/tender joint counts and ESR) (Bawa et al., 2005; Prevoo et al., 1995). The three-variable DAS was used in place of a four variable

Disease-modifying anti-rheumatic therapy (DMARD), biologic treatments, and prednisone use were also recorded at the most recent visit. DMARD agents included methotrexate, sulfasalazine, hydroxychloroquine, and leflunomide; biologic treatments included antitumor necrosis factor (adalimumab, etanercept, infliximab), anti-signal 2 inhibitor (abatacept) and anti-CD20 (rituximab) agents. Patient report of ever or never smoking was tabulated, and subjects were categorized based on a history of CVD (documentation of prior coronary artery disease, myocardial infarction, angina, cerebrovascular event, transient

Descriptive statistics were used to define the group. Group comparisons, based on the presence/absence of MetS, were performed using Chi-square for categorical variables and a one-way ANOVA for continuous data. Odds ratios (OR) and 95% confidence intervals were used to assess the association of MetS with prevalent CVD and were calculated using multivariable logistic regression, adjusting for age, sex, smoking status (ever vs. never), and the current use of DMARDs and/or biologic therapies. Given the reported antiinflammatory effect of select lipid lowering agents (statins) in RA, we performed a subanalysis in subjects with MetS to examine the association of statin use with measures of

Six-hundred seventy-one patients were included in this study (Table 1). The study cohort included 53 (7.9%) women, had a mean age of 65.4 years [SD10.8], and a mean disease duration of 13.7 years [SD 11.5]. The majority were Caucasian (n = 543, 80.9%). Four hundred and twelve (61.4%) had radiographic changes consistent with RA, and 312 (46.5%) had nodules. Approximately 58.3% were on a traditional DMARD at their most recent clinic visit, while an additional 25.8% were receiving a combination of a biologic agent with a traditional DMARD. Fifty three percent of the study cohort was receiving prednisone. The mean DAS28 was 3.2 [SD 1.3] and CRP was 1.3 [SD 1.9] mg/dl. The majority (78.8%) were either previous or current smokers. One-hundred eighty-nine subjects satisfied the modified criteria for MetS, corresponding to a prevalence of 28.2% (95 % CI 24.7-31.7). There were no significant differences in subject demographics, measures of disease severity or activity, use of biologic agents or DMARDS, prednisone use, or smoking status in RA subjects with MetS compared to those without MetS (Table 1). In a subanalysis of subjects with and without MetS, there were no significant differences in measures of disease activity in those taking statins compared to individuals not taking statins (data not shown). As expected, disease components of MetS were far more common in those with the syndrome in comparison to those without MetS (Figure 1). Of note, a BMI that exceeded 30 kg/m2 was present in only one-third of study patients, but comprised 66% of MetS patients and only 20% of individuals without MetS. The use of anti-hypertensive and lipid lowering agents

disease activity. All analyses were performed using SAS (SAS Inc, Cary, NC).

DAS to minimize the impact of missing data from patient global scores.

existing data reflect variations in the populations studied (Crowson et al., 2011; Karvounaris et al., 2007). Data from Europe and the US have shown associations between the syndrome and the inflammatory burden of RA.

Most data on RA, including reports related to MetS and CVD, are comprised mainly of females. The few reports on RA in males indicate a more severe course of disease, and worse outcome (Ford et al., 2002; Janghorbani et al., 1993; Jawaheer et al., 2006; Mikuls et al., 2011). Further, elderly males more often have comorbid diseases such as diabetes mellitus and hypertension that places them at even greater risk for CVD.

Therefore we sought to examine the prevalence and relationship of MetS to RA disease burden and CVD in a primarily elderly, male RA cohort.
