Metabolic cardiovascular risk burden and atherosclerosis in African black and Caucasian women with rheumatoid arthritis: a cross-sectional study.

OBJECTIVES: The impact of metabolic risk factors on atherosclerotic cardiovascular disease (ACVD) in patients with rheumatoid arthritis (RA) from developing populations is currently unknown. We examined the relationships of the metabolic syndrome (MetS) and its components with carotid artery atherosclerosis in African women with rheumatoid arthritis (RA) from a developing black and developed Caucasian population. METHODS: We assessed the associations of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) defined MetS and its criteria with high resolution B-mode ultrasound determined common carotid artery intima-media thickness (cIMT) and carotid artery plaque in multivariable regression models in 104 black and 93 Caucasian women with RA. RESULTS: The MetS prevalence was 30.8% in black compared to 9.7% in Caucasian women with RA (adjusted odds ratio [95% confidence interval]=10.11 [1.76-58.03] [p=0.009]). Population origin impacted on the relationships of metabolic risk factors with atherosclerosis. In Caucasian women, the MetS was associated with cIMT (p=0.036) and MetS triglycerides and the number of MetS criteria were each associated with both cIMT (p=0.01 and p=0.028, respectively) and plaque (p=0.049 and p=0.02, respectively); by contrast, in black women, MetS blood pressure was related to cIMT (p=0.04). CONCLUSIONS: A high overall metabolic cardiovascular risk burden as disclosed by markedly prevalent MetS in women with RA from developing groups of black African descent was not associated with atherosclerosis. This calls for systematic rigorous cardiovascular risk management irrespective of metabolic risk factor profiles in African black women with RA.

Differences in coronary heart disease prevalence and risk factors in African and White patients with type 2 diabetes.

Coronary heart disease (CHD) is rare in sub-Saharan Africans; there are few data in African diabetic populations. We therefore evaluated the prevalence of CHD and conventional risk factors in 744 consecutive African (A, n=448) and White European (W, n=296) subjects with type 2 diabetes. CHD was present in 4% of A and in 23% of W (p<0.001). Compared with W, the A groups had lower total cholesterol (TC) and triglyceride (TG) levels: men: TC-W, 5.76 (S.D., 1.36) and A, 4.98 (1.29)mmol/l; TG-W, 2.10 (IQR,1.40-3.00) and A, 1.60 (1.10-2.55)mmol/l; women: TC-W, 5.85 (1.31) and A, 5.20 (1.24); TG-2.00 (1.40-2.90) and A, 1.40 (1.00-2.03)mmol/l (p< or =0.0022 for each comparison). The A had significantly lower TG:HDL-C ratios (an index of insulin resistance) (p=0.004) and were less likely to have (estimated) small dense LDL-C particles (p< or =0.038). In subjects with established CHD traditional risk factors were similar in A and W. Regression analysis revealed that CHD associated in A with serum creatinine (p=0.0015) and TC (p=0.038) and with TG in W (p=0.0072). We conclude that the rarity of CHD in diabetic Africans can be explained by contributions of low TC levels and probably lesser insulin resistance and its consequences; renal disease may be an important additional risk factor.

Aminotransferases are associated with insulin resistance and atherosclerosis in rheumatoid arthritis.

BACKGROUND: Serum aminotransferase concentrations are reportedly strongly associated with insulin resistance, an established cardiovascular risk factor that is not routinely assessed in clinical practice. We therefore explored the possibility that serum aminotransferase concentrations are as closely related to large artery disease as insulin resistance in rheumatoid arthritis (RA). METHODS: Carotid artery plaque (ultrasonography), insulin resistance and liver enzymes (prior to methotrexate (MTX) were determined in 77 consecutive patients with RA (43 with and 34 without MTX). RESULTS: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were associated with insulin resistance in univariate analysis (R = 0.54, p < 0.0001 and R = 0.36, p = 0.001, respectively) and after adjustment for age, gender and waist circumference (partial R = 0.43, p = 0.0001 and partial R = 0.37, p = 0.001, respectively). ALT and AST concentrations were higher in patients with plaque as compared to in those without plaque (ALT (u/l): 27 2223242526272829303132 versus 20 181920212223, p = 0.02; AST (u/l): 25 2122232425262728 versus 20 19202122, p = 0.02). The odds ratios [95% CI] for plaque were 1.92 [1.14-3.24] (p = 0.01), 1.93 [1.17-3.16] (p = 0.009) and 1.82 [1.13-2.93] (p = 0.01) for 1 SD increase in ALT (~10 u/l) and AST (approximately 6 u/l) concentrations and in logarithmically transformed homeostasis model assessment of insulin resistance (HOMA-IR) (~0.2 uU.mmol/ml.l), respectively. After adjustment for the potentially confounding characteristics of age, sex, hypertension and hypothyroidism in logistic regression models, ALT (p = 0.049) and AST concentrations (p = 0.027) remained associated with plaque whereas the HOMA-IR did not (p = 0.08). AST concentrations (p = 0.049) were associated with plaque independent of insulin resistance whereas the HOMA-IR (p = 0.1) was not associated with plaque independent of AST concentrations. CONCLUSION: Within currently recommended reference ranges, serum aminotransferase concentrations may be strongly associated with insulin resistance and atherosclerosis in patients with RA. The measurement of aminotransferase concentrations could be a useful tool in cardiovascular risk stratification in patients with RA.

Carotid artery intima-media complex thickening in patients with relatively long-surviving type 1 diabetes mellitus.

OBJECTIVE: The factors responsible for premature coronary atherosclerosis in patients with type 1 diabetes are ill defined. We therefore assessed carotid intima-media complex thickness (IMT) in relatively long-surviving patients with type 1 diabetes as a marker of atherosclerosis and correlated this with traditional risk factors. DESIGN: Cross-sectional study of 148 patients with relatively long-surviving (>18 years) type 1 diabetes (76 men and 72 women) attending the Centre for Diabetes and Endocrinology, Johannesburg. METHODS: The mean common carotid artery IMT and presence or absence of plaque was evaluated by high-resolution B-mode ultrasound. Their median age was 48 years and duration of diabetes 26 years (range 18-59 years). Traditional risk factors (age, duration of diabetes, glycemic control, hypertension, smoking and lipoprotein concentrations) were recorded. Three response variables were defined and modeled. Standard multiple regression was used for a continuous IMT variable, logistic regression for the presence/absence of plaque and ordinal logistic regression to model three categories of "risk." RESULTS: The median common carotid IMT was 0.62 mm (range 0.44-1.23 mm) with plaque detected in 28 cases. The multiple regression model found significant associations between IMT and current age (P=.001), duration of diabetes (P=.033), BMI (P=.008) and diagnosed hypertension (P=.046) with HDL showing a protective effect (P=.022). Current age (P=.001) and diagnosed hypertension (P=.004), smoking (P=.008) and retinopathy (P=.033) were significant in the logistic regression model. Current age was also significant in the ordinal logistic regression model (P<.001), as was total cholesterol/HDL ratio (P<.001) and mean HbA(1c) concentration (P=.073). CONCLUSIONS: The major factors influencing common carotid IMT in patients with relatively long-surviving type 1 diabetes are age, duration of diabetes, existing hypertension and HDL (protective) with a relatively minor role ascribed to relatively long-standing glycemic control.

Diabetogenic effect of tacrolimus in South African patients undergoing kidney transplantation1.

BACKGROUND: Diabetes mellitus (DM) is a complication of tacrolimus therapy. This prospective study evaluated the prevalence of DM in South African black and white patients receiving tacrolimus after kidney transplantation and factors that could identify patients before transplantation who may be at risk of developing DM. METHODS: Fasting blood samples from 17 patients (11 black, 6 white) were analyzed immediately pretransplantation and at 1 and 3 months posttransplantation for glucose, HbAIC, insulin, C-peptide, free fatty acids, lipids, urea, and creatinine. Insulin resistance (IR) was calculated using the homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) formulas. RESULTS: Eight patients (47%) became diabetic (six black, two white), and nine patients (five black, four white) remained nondiabetic. Mean glucose concentrations in the diabetic group were significantly higher at 1 month (P=0.03) and 3 months (P=0.01). Mean insulin level was also significantly raised at 3 months (P=0.01) as was HbAIC (P=0.001). C-peptide concentrations did not change significantly in either group. Significant correlations emerged between fasting glucose concentrations at 3 months posttransplantation and initial HOMA (r=0.486; P=0.048) and initial QUICKI (r=-0.582; P=0.014). CONCLUSIONS: Occurrence of DM was high and somewhat greater in black patients. IR was the main mechanism involved, together with inadequate beta-cell compensation. IR pretransplantation predicts the subsequent development of DM.

Subclinical hypothyroidism is associated with insulin resistance in rheumatoid arthritis.

We investigated the prevalence of subclinical hypothyroidism and its association with insulin resistance and other cardiovascular (CV) risk factors in rheumatoid arthritis (RA). We recorded thyroid function tests, insulin resistance markers comprising the Homeostasis Model Assessment for insulin resistance (HOMA-IR), the Quantitative Insulin Sensitivity Check Index (QUICKI) and triglycerides/high-density lipoprotein (HDL) cholesterol ratios, and other CV risk factors in 126 patients with RA. Fifteen (12%) were taking thyroxine for hypothyroidism and 14 (11%) had subclinical hypothyroidism (thyrotropin > 4 mU/L and normal free thyroxine levels). Compared to the 97 euthyroid patients, the QUICKI was lower and the HOMA-IR higher in treated (p = 0.031 for both) and subclinical (p = 0.004 for both) hypothyroid cases while the triglycerides/HDL cholesterol ratios were higher in subclinical (p = 0.039) but not in treated hypothyroid (p = 0.365) cases. Treated hypothyroid patients were more often hypertensive (n = 11 [75%]) than euthyroid patients (n = 36 [37%]) (p = 0.008). No other differences in characteristics were found among the three groups. After controlling for potentially confounding variables, subclinical hypothyroidism remained independently predictive of the HOMA-IR and QUICKI (p

Diabetes mellitus and hypothyroidism: Strange bedfellows or mutual companions?

Clinicians should be cognizant of the close relationship that exists between two of the most common endocrine disorders, primary hypothyroidism and diabetes mellitus. This applies to patients with both type 1 and type 2 diabetes mellitus (T1DM and T2DM respectively). However, the association is greater in T1DM, probably because of the shared autoimmune predisposition. In patients with T2DM, the relationship is somewhat weaker and the explanation less clear-cut. Factors such as dietary iodine deficiency, metformin-induced thyroid stimulating hormone suppression and poor glycemic control may all be implicated. Further translational research is required for greater clarification. Biochemical screening for abnormal thyroid function in individuals who have diabetes is warranted, particularly in females with T1DM, and therapy with L-thyroxine appropriately instituted if hypothyroidism is confirmed.

The waist circumference of risk in black South african men is lower than in men of European ancestry.

BACKGROUND: Central obesity measured by waist circumference is a cardiovascular disease (CVD) risk factor; however, the waist circumference of risk in populations of African descent has not been identified. The International Diabetes Federation currently suggests that cutoffs established in men of European descent be applied to sub-Saharan men-a waist circumference ≥94 cm. SUBJECTS AND METHODS: Participants were 203 South African black men with type 2 diabetes mellitus (T2DM). They were divided into quartiles of waist circumference (>88 cm, 88-94 cm, 95-103 cm, >103 cm). Cardiovascular risk factors, including insulin resistance (IR), measured by modified homeostasis model assessement of IR (HOMA-IR), and the triglycerides-to-high-density lipoprotein cholesterol (TG-to-HDL-C) ratio, were compared across quartiles. RESULTS: Age, duration of diabetes, glycosylated hemoglobin (HbA1c), blood pressure, urinary albumin excretion, and smoking were similar across waist circumference quartiles. Overall, for both lipids and measures of IR, there was variation across waist circumference quartiles, but no significant differences between quartiles 2 and 3. Therefore, data from these two quartiles were pooled. Between the first and second+third (88-103 cm) quartiles, there were significant differences in HDL-C (1.30±0.43, 1.10±0.43 mmol/L, P=0.003), TG (medians 1.10, 1.60 mmol/L P<0.001), low-density lipoprotein cholesterol (LDL-C; 2.40±0.93, 2.85±1.03 mmol/L, P=0.01), non-HDL-C (3.05±1.18, 3.70±1.16 mmol/L, P=0.002), HOMA-IR (medians 0.90, 2.10, P<0.001), and TG-to-HDL-C ratio (medians 0.89, 1.17, P<0.001). Additional comparisons were made between men with waist circumference <90 cm and 90-93 cm. Values for each lipid and for IR parameters were more favorable in the <90-cm group (all P<0.05). CONCLUSIONS: For black South African diabetic men, CVD risk substantially increased with waist circumference >90 cm. The waist circumference cut point of >94 cm has the potential to misclassify many black South African diabetic men at risk for CVD.

The effect of features of the metabolic syndrome on atherosclerotic risk in relatively long-surviving patients with type 1 diabetes.

BACKGROUND: Increasing numbers of patients with type 1 diabetes (T1DM) are developing features of the metabolic syndrome. The additional effect of this on the development of atherosclerosis, as inferred by the carotid artery intima media thickness (IMT), has not previously been assessed. The aim of this study was to assess the effect of features of the metabolic syndrome on carotid artery IMT in a cohort of long-surviving patients with T1DM. METHODS: Long-surviving patients with T1DM attending the Centre for Diabetes and Endocrinology were assessed regarding their risk factor profile. All underwent measurement of carotid artery IMT. In all, 156 patients who had T1DM for more than 18 years had their carotid artery IMT measured. All had been attending the clinic for over 10 years, and past clinical and laboratory records were available. RESULTS: A total of 37 patients had metabolic syndrome according to the International Diabetes Federation (IDF) definition. Those with metabolic syndrome had a significantly increased carotid artery IMT (P = 0.003) compared to those without the syndrome. There was a significant relationship between the number of features of metabolic syndrome and increased atherosclerotic risk according to the carotid artery IMT (P = 0.01). A significant correlation was found between carotid artery IMT and both waist circumference (P < 0.001) and insulin resistance (P = 0.005). CONCLUSIONS: In long-surviving patients with T1DM, those that develop metabolic syndrome are more likely to have thicker carotid artery IMT, and, by inference, be at higher risk of atherosclerosis and possibly cardiovascular disease. A linear relationship was present between both waist circumference and insulin resistance and carotid artery IMT.

Independent role of conventional cardiovascular risk factors as predictors of C-reactive protein concentrations in rheumatoid arthritis.

OBJECTIVE: We elucidated whether factors that determine systemic inflammation in the general population independently contribute to C-reactive protein (CRP) concentrations in rheumatoid arthritis (RA). METHODS: The association between factors known to be associated with systemic inflammation in the general population (age, sex, lifestyle variables, metabolic syndrome features, and estrogen use) and high sensitivity CRP (hs-CRP) concentrations independent of the Disease Activity Score 28 (DAS28) was determined in 94 patients with RA. RESULTS: In all patients, the DAS28 (p < 0.0001), ever smoking (p

Influence of nonclassical cardiovascular risk factors on the accuracy of predicting subclinical atherosclerosis in rheumatoid arthritis.

OBJECTIVE: To determine whether nontraditional risk factors increase the accuracy of predicting the presence of carotid artery plaque based on traditional cardiovascular risk factors only in patients with rheumatoid arthritis (RA). METHODS: We identified risk factors that were independently associated with ultrasonographically located plaque. In predicting carotid artery plaque, the area under the curve (AUC) of the receiver-operating characteristic (ROC) curve for the combination of traditional and nontraditional risk factors was compared to the AUC of the ROC curve for traditional risk factors and nontraditional risk factors considered separately in 91 patients with RA. RESULTS: Thirty-one (34%) patients had carotid artery plaque. The 3 traditional risk factors of age > 55 years, hypertension, and ever-smoking, and the 3 nontraditional risk factors of a disease duration > 8 years, polymorphonuclear cell count > 4.5 x 10(6)/l, and hypothyroidism were each independently associated with the presence of plaque (odds ratios 2.08-8.78; p = 0.001-0.02). The percentage of patients with plaque was 0, 10%, 50%, and 83% in patients with 0-1, 2, 3, and 4-6 of these risk factors, respectively. In predicting plaque, the AUC of the ROC curve for the combination of traditional and nontraditional risk factors (0.90 +/- 0.03) was greater than that for either traditional (0.80 +/- 0.05; p = 0.006) or nontraditional (0.80 +/- 0.04; p = 0.005) risk factors considered separately. CONCLUSION: The combination of disease duration, polymorphonuclear cell counts, and thyroid status increased the accuracy of predicting subclinical atheroma in patients with RA. We believe that our findings merit external validation.

Insulin resistance and impaired beta cell function in rheumatoid arthritis.

OBJECTIVE: To identify factors that regulate glucose metabolism in rheumatoid arthritis (RA). METHODS: We evaluated the homeostatic model assessment of insulin resistance (HOMA-IR) and beta cell function (HOMA-B) in 94 RA patients. We investigated the relationship between characteristics known to affect glucose metabolism in the general population (age, abdominal obesity [waist circumference], hypertension, antihypertensive therapy) as well as characteristics of RA (disease activity, glucocorticoid therapy) and insulin resistance and beta cell function. RESULTS: Patients with high-grade inflammation (high-sensitivity C-reactive protein value >1.92 mg/liter) (n = 81) were more insulin resistant than patients with low-grade inflammation (n = 13), whereas beta cell function was similar in both groups. Insulin resistance and beta cell function were similar in both groups after adjustment for waist circumference. All recorded characteristics except for age were associated with HOMA-IR or/and HOMA-B in univariate analyses. In mixed regression models, abdominal obesity and patient's assessment of disease activity (by visual analog scale) were predictors of insulin resistance. The Disease Activity Score assessed using 28-joint counts for swelling and tenderness, tender joint count, and patient's assessment of disease activity were associated with reduced beta cell function, and the cumulative dose of glucocorticoids was associated with enhanced beta cell function. The cumulative glucocorticoid dose in all study patients was a mean of only 536 mg (95% confidence interval 239-1,173). In patients with high-grade inflammation, age was further associated with impaired beta cell function, whereas use of angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers was associated with enhanced beta cell function. CONCLUSION: The modifiable factors of abdominal obesity, antihypertensive therapy, disease activity, and use of glucocorticoids appear to affect glucose metabolism in RA.

Biomarkers of endothelial dysfunction, cardiovascular risk factors and atherosclerosis in rheumatoid arthritis.

Cardiovascular event rates are markedly increased in rheumatoid arthritis (RA), and RA atherogenesis remains poorly understood. The relative contributions of traditional and nontraditional risk factors to cardiovascular disease in RA await elucidation. The present study comprises three components. First, we compared biomarkers of endothelial dysfunction (vascular cell adhesion molecule [VCAM]-1, intercellular adhesion molecule [ICAM]-1 and endothelial leucocyte adhesion molecule [ELAM]-1) in 74 RA patients and 80 healthy control individuals before and after controlling for traditional and nontraditional cardiovascular risk factors, including high-sensitivity C-reactive protein (hs-CRP), IL-1, IL-6 and tumor necrosis factor-alpha. Second, we investigated the potential role of an extensive range of patient characteristics in endothelial dysfunction in the 74 RA patients. Finally, we assessed associations between biomarkers of endothelial dysfunction and ultrasonographically determined common carotid artery intima-media thickness and plaque in RA. The three biomarkers of endothelial dysfunction, as well as hs-CRP, IL-1, IL-6 and tumor necrosis factor-alpha, were higher in patients than in control individuals (P < 0.0001). Patients were also older, exercised less and had a greater waist circumference, blood pressure and triglyceride levels (P

Traditional and nontraditional cardiovascular risk factors are associated with atherosclerosis in rheumatoid arthritis.

OBJECTIVE: To determine the association between cardiovascular (CV) risk factors and atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: The common carotid artery intima-media thickness (IMT) and plaque were evaluated by high resolution B-mode ultrasound in 74 consecutive patients with RA. Patients with an IMT > or = 0.60 mm and plaque were considered to have atherosclerosis and advanced atherosclerosis, respectively. Traditional risk factors as well as an extensive range of other clinical and laboratory variables were recorded. Methods used to analyze the data included logistic regression, classification and regression tree (CART), and factor analyses. RESULTS: Fifty-three (72%) patients had atherosclerosis, 23 (31%) had plaque, and 21 (28%) were free of atherosclerosis. In multivariable analysis, age and hypertension were independently associated with atherosclerosis and plaque (p < or = 0.04). Radiographic scores and polymorphonuclear cell counts were also strongly associated with plaque (p < or = 0.008). Uric acid concentrations were associated with atherosclerosis, and hypothyroidism was associated with plaque, both with borderline significance (p = 0.078 and 0.052, respectively). In CART analysis, age, polymorphonuclear cell counts, and joint space narrowing in the hands were considered to be the most important determinants of plaque, and 62% of patients could be classified correctly after cross-validation. Factor analysis (varimax rotation) revealed that age and uric acid levels were related to low glomerular filtration rates, polymorphonuclear cell counts to disease activity, and radiographic scores to disease duration, and hypertension was associated with high cholesterol levels. The 10-year risk for a coronary event estimated using the Framingham risk equation (calculated from traditional risk factors) was only 7% in patients with plaque. CONCLUSION: Atherosclerosis in RA is associated with the traditional CV risk factors age and hypertension, as well as nontraditional risk factors comprising current inflammation as reflected by polymorphonuclear cell counts, cumulative inflammation as disclosed by radiographic scores, and, to a lesser extent, with uric acid levels and hypothyroidism. Multiple risk factor assessment equations that are based on traditional risk factors only are likely to be insufficient to capture CV risk extent in RA.

High sensitivity C-reactive protein as a disease activity marker in rheumatoid arthritis.

OBJECTIVE: To elucidate the potential contribution of high sensitivity C-reactive protein (hs-CRP) testing in the assessment of disease activity in rheumatoid arthritis (RA). METHODS: We recorded clinical and psychological variables, the hs-CRP, and erythrocyte sedimentation rate (ESR) in 146 consecutive patients with RA. We analyzed the associations between the ESR and hs-CRP versus the other recorded variables. RESULTS: The median (interquartile range) ESR (mm/h) and hs-CRP (mg/l) were 15 (7-36) and 5 (2.3-13.9), respectively. Thirty-two (22%) patients had an hs-CRP < 2 mg/l, 61 (42%) an hs-CRP of 2-8 mg/l and 53 (36%) an hs-CRP > 8 mg/l. In patients with an hs-CRP of 2-8 mg/l, the swollen joint counts and the physician disease activity scales were higher, and remission rates were lower than in patients with an hs-CRP of < 2 mg/l. The hs-CRP was consistently more closely associated with disease activity, depression, and helplessness than was the ESR. CONCLUSION: High sensitivity CRP testing reveals systemic inflammation that is generally not detectable with routine CRP assays and that is associated with disease activity in RA.

Effects of disease modifying agents and dietary intervention on insulin resistance and dyslipidemia in inflammatory arthritis: a pilot study.

Patients with rheumatoid arthritis (RA) experience excess cardiovascular disease (CVD). We investigated the effects of disease-modifying antirheumatic drugs (DMARD) and dietary intervention on CVD risk in inflammatory arthritis. Twenty-two patients (17 women; 15 with RA and seven with spondyloarthropathy) who were insulin resistant (n = 20), as determined by the Homeostasis Model Assessment, and/or were dyslipidemic (n = 11) were identified. During the third month after initiation of DMARD therapy, body weight, C-reactive protein (CRP), insulin resistance, and lipids were re-evaluated. Results are expressed as median (interquartile range). DMARD therapy together with dietary intervention was associated with weight loss of 4 kg (0-6.5 kg), a decrease in CRP of 14% (6-36%; P < 0.006), and a reduction in insulin resistance of 36% (26-61%; P < 0.006). Diet compliers (n = 15) experienced decreases of 10% (0-20%) and 3% (0-9%) in total and low-density lipoprotein cholesterol, respectively, as compared with increases of 9% (6-20%; P < 0.05) and 3% (0-9%; P < 0.05) in diet noncompliers. Patients on methotrexate (n = 14) experienced a reduction in CRP of 27 mg/l (6-83 mg/l), as compared with a decrease of 10 mg/l (3.4-13 mg/l; P = 0.04) in patients not on methotrexate. Improved cardiovascular risk with DMARD therapy includes a reduction in insulin resistance. Methotrexate use in RA may improve CVD risk through a marked suppression of the acute phase response. Dietary intervention prevented the increase in total and low-density lipoprotein cholesterol upon acute phase response suppression.

Cardiovascular risk in rheumatoid arthritis versus osteoarthritis: acute phase response related decreased insulin sensitivity and high-density lipoprotein cholesterol as well as clustering of metabolic syndrome features in rheumatoid arthritis.

Rheumatoid arthritis (RA) patients experience a markedly increased frequency of cardiovascular disease. We evaluated cardiovascular risk profiles in 79 RA patients and in 39 age-matched and sex-matched osteoarthritis (OA) patients. Laboratory tests comprised ultrasensitive C-reactive protein (CRP) and fasting lipids. Insulin sensitivity (IS) was determined by the Quantitative Insulin Sensitivity Check Index (QUICKI) in all OA patients and in 39 of the RA patients. Ten RA patients were on glucocorticoids. RA patients exercised more frequently than OA patients (chi2 = 3.9, P < 0.05). Nine RA patients and one OA patient had diabetes (chi2 = 4.5, P < 0.05). The median CRP, the mean QUICKI and the mean high-density lipoprotein (HDL) cholesterol were 9 mg/l (range, 0.5-395 mg/l), 0.344 (95% confidence interval [CI], 0.332-0.355) and 1.40 mmol/l (95% CI, 1.30-1.49 mmol/l) in RA patients, respectively, as compared with 2.7 mg/l (range, 0.3-15.9 mg/l), 0.369 (95% CI, 0.356-0.383) and 1.68 mmol/l (95% CI, 1.50-1.85 mmol/l) in OA patients. Each of these differences was significant (P < 0.05). After controlling for the CRP, the QUICKI was similar in RA and OA patients (P = 0.07), while the differences in HDL cholesterol were attenuated but still significant (P = 0.03). The CRP correlated with IS, while IS was associated with high HDL cholesterol and low triglycerides in RA patients and not in OA patients. A high CRP (>/= 8 mg/l) was associated with hypertension (chi2 = 7.4, P < 0.05) in RA patients. RA glucocorticoid and nonglucocorticoid users did not differ in IS and lipids (P > 0.05). Excess cardiovascular risk in RA patients as compared with OA patients includes the presence of decreased IS and HDL cholesterol in RA patients. The latter is only partially attributable to the acute phase response. The CRP, IS, HDL cholesterol, triglycerides and hypertension are inter-related in RA patients, whereas none of these relationships were found in OA patients.