Points to consider in cardiovascular disease risk management among patients with rheumatoid arthritis living in South Africa, an unequal middle income country.

BACKGROUND: It is plausible that optimal cardiovascular disease (CVD) risk management differs in patients with rheumatoid arthritis (RA) from low or middle income compared to high income populations. This study aimed at producing evidence-based points to consider for CVD prevention in South African RA patients. METHODS: Five rheumatologists, one cardiologist and one epidemiologist with experience in CVD risk management in RA patients, as well as two patient representatives, two health professionals and one radiologist, one rheumatology fellow and 11 rheumatologists that treat RA patients regularly contributed. Systematic literature searches were performed and the level of evidence was determined according to standard guidelines. RESULTS: Eighteen points to consider were formulated. These were grouped into 6 categories that comprised overall CVD risk assessment and management (n = 4), and specific interventions aimed at reducing CVD risk including RA control with disease modifying anti-rheumatic drugs, glucocorticoids and non-steroidal anti-inflammatory drugs (n = 3), lipid lowering agents (n = 8), antihypertensive drugs (n = 1), low dose aspirin (n = 1) and lifestyle modification (n = 1). Each point to consider differs partially or completely from recommendations previously reported for CVD risk management in RA patients from high income populations. Currently recommended CVD risk calculators do not reliably identify South African black RA patients with very high-risk atherosclerosis as represented by carotid artery plaque presence on ultrasound. CONCLUSIONS: Our findings indicate that optimal cardiovascular risk management likely differs substantially in RA patients from low or middle income compared to high income populations. There is an urgent need for future multicentre longitudinal studies on CVD risk in black African patients with RA.

The need for tighter rheumatoid arthritis control in a South African public health care center.

OBJECTIVE: Medical facilities are restricted in public health care centers in South Africa and patients that enroll in these centers are socioeconomically deprived. We investigated the impact of rheumatoid arthritis (RA) on disability in both a public health care and a private care center. METHODS: The disability index of the Health Assessment Questionnaire (HAQ-DI) and an extensive range of disease and non-disease-related patient characteristics were recorded in 359 RA subjects, 196 public care and 163 private care patients. We compared the data between both patient groups and identified potential predictors of the HAQ-DI by univariate and multivariable logistic regression analysis. RESULTS: The median (range) HAQ-DI was 1.625 (0 to 3) in the public care patients and 0.500 (0 to 3) in the private care patients (P < 0.0001). As compared with private care patients, public care patients were more often African (P < 0.0001) and of mixed ancestry (P < 0.01) and less often White (P < 0.0001). Public care patients also had higher current disease activity scores (P < 0.0001) (except for tender joint counts and the erythrocyte sedimentation rate), higher cumulative disease activity or disease severity scores (joint deformities) (P < 0.0001), a higher frequency of tuberculosis (P < 0.01), and were more often treated with prednisone (P < 0.0001). In multivariable logistic regression models, a HAQ-DI of >1 was independently predicted by current disease activity (swollen joint count) (P < 0.004), cumulative disease activity (joint deformities) (P < 0.005), being under public care (P < 0.008), and prednisone use (P < 0.04). Racial differences were not independently predictive of disability. CONCLUSION: Results of disease outcome measurements were poorer in our public care patients than in our private care patients. Facilities that allow for tighter disease activity control of RA are needed in South African public care centers.

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.

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

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.

Glucocorticoids and insulin sensitivity in rheumatoid arthritis.

OBJECTIVE: To evaluate the effects of glucocorticoids on cardiovascular (CV) risk in rheumatoid arthritis (RA). METHODS: We recorded demographic, clinical, disease outcome, and treatment variables in 92 consecutive RA patients who were not taking lipid-lowering or antidiabetic medications. Fasting blood tests were taken for determination of lipids, ultra sensitive C-reactive protein (CRP), rheumatoid factor, insulin, and glucose. Insulin sensitivity was determined using the Quantitative Insulin Sensitivity Check Index (QUICKI). RESULTS: Seventy-four (80%) patients were women, 80 Caucasian, 9 Asian, 2 of mixed ancestry and 1 Black. Their mean (95% confidence interval, CI) age, disease duration, and followup duration at our clinic were 56 (54-58), 11 (9-13) and 6 (5-6) years, respectively. Thirty-seven (40%) patients had received oral prednisone [cumulative dose 4.8 (2.0-8.5) g; duration one month to 20 years], and all patients had received pulsed (intraarticular, intramuscular, and/or intravenous) methylprednisolone [cumulative dose 2.0 (1.6-2.6) g]. Glucocorticoids were not associated with obesity, hypertension, or dyslipidemia. Having taken prednisone and high yearly frequencies of pulsed glucocorticoid administrations were associated with decreased insulin sensitivity (p < 0.05). After controlling for body mass index, ever having taken prednisone and high doses of pulsed glucocorticoids were independently associated with decreased insulin sensitivity (p < 0.05). CONCLUSION: Previous exposure to oral prednisone and high doses of pulsed glucocorticoids were associated with decreased insulin sensitivity in RA. Since decreased insulin sensitivity is an independent risk factor for CV disease, glucocorticoids may contribute to the excess CV event rates 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.