**2.4 Statistical analysis**

236 Rheumatoid Arthritis – Etiology, Consequences and Co-Morbidities

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

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

Therefore we sought to examine the prevalence and relationship of MetS to RA disease

Study patients enrolled in the ongoing Veterans Affairs Rheumatoid Arthritis (VARA) Registry prior to January 2009 were included in the study. The characteristics of this population have been previously described (Mikuls et al., 2007). Briefly, VARA is a multicenter chronic disease registry initiated in 2003 now including collection sites at VA Medical Centers across the U.S. The current study included participants from VA sites in Dallas, Denver, Jackson, Omaha, Salt Lake City, and Washington, DC. Rheumatoid arthritis (RA) patients with disease onset after age 18 years who fulfill American College of Rheumatology (ACR) classification criteria for RA (Arnett et al., 1988) are invited to enroll. Participating sites prospectively collect and archive clinical and laboratory observations associated with RA during routine visits and standard of care. VARA has been approved by the Institutional Review Board (IRB) and VA Research and Development Committee at each participating site. All subjects provide written consent for a single blood draw and ongoing review of

The NCEP/ATPIII criteria (National Cholesterol Education Program, 2001) for MetS were modified so that a body mass index (BMI) of ≥ 30 kg/m2 replaced waist/hip circumference. Because waist and hip measurements are not routinely available on study subjects, BMI was used as a surrogate for waist-to-hip circumference with the following rationale: a) weight and annual height measurements are routinely obtained on all our patients, b) data support BMI to be as accurate as waist circumference in identifying individuals for risk of CVD (Farin et al, 2006), c) BMI is included in the WHO definition for MetS (World Health Organization [WHO], 1999) and there appears to be at least modest levels of agreement between BMI and waist-tohip ratio in both men and women (Balkau et al., 2006), and d) to obviate the varied cut off points for waist circumference for different ethnic groups (Alberti et al., 2005). Additionally, documented prior use of disease specific medications were used as surrogates for the other three MetS components. Hence MetS was defined as presence of ≥ 3 of 4 criteria (BMI ≥ 30 kg/m2, anti-hypertensive, lipid lowering, and/or diabetes agents) (Grundy et al., 2005).

RA disease severity was assessed by rheumatoid factor (RF) positivity, duration of disease, presence of radiographic changes suggestive of RA (based on ACR criteria) and nodules at enrollment. Disease activity was assessed at the time of the most recent clinic visit by

and the inflammatory burden of RA.

**2. Patients and methods** 

their electronic medical records.

**2.3 Clinical measures** 

**2.2 Metabolic syndrome definition** 

**2.1 Study population** 

hypertension that places them at even greater risk for CVD.

burden and CVD in a primarily elderly, male RA cohort.

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