Plasma indices of angiogenesis in rheumatoid disease: relationship to cardiovascular risk factors and cardiac function.

INTRODUCTION: Rheumatoid Disease (RD) is associated with increased rates of cardiovascular disease (CVD). Angiogenesis is central to RD, and well-recognized in CVD. We hypothesised that plasma levels of two indices associated with angiogenesis, vascular endothelial growth factor (VEGF) and angiogenin, would be higher among RD patients compared to healthy controls (HC), would relate to CVD risk factors, calculated 10-year coronary heart disease (CHD) and stroke risk scores. METHODS: 144 clinic patients with established RD and 63 HC were recruited in a cross-sectional study. RD patients were grouped according to the presence (RD-CVD, n=73 or absence (non-CVD RD; n=71) of CVD risk factors. Angiogenin and VEGF levels were quantified by ELISA. RESULTS: There were no significant differences for VEGF or angiogenin, between RD-CVD, non-CVD RD and HC groups (p=NS). Calculated risks for both CHD (p=0.017) and stroke (p=0.016) were higher when RD-CVD was compared to non-CVD RD and HC. Upon multivariate analysis, methotrexate use (p=0.006) and prior mycocardial infarction (MI) (p=0.034) were associated with higher angiogenin levels; body mass index (BMI) (p=0.034) and presence of RD (p=0.029) itself predicted lower levels. For RD patients, serum creatinine (p<0.001) and CRP levels, VEGF levels, and NSAID/COX2 inhibitor use (all p<0.05) were independently associated with CHD risk; plasma VEGF and serum creatinine levels were independently associated with stroke risk (p<0.05). CONCLUSIONS: Although levels of angiogenin were not significantly different between HC and RD patients, RD may have some influence on their variation. Methotrexate use and prior MI predicted higher angiogenin levels, whilst levels of VEGF were negatively associated with 10-year CHD and stroke risk.

Plasma indices of endothelial and platelet activation in Rheumatoid Disease: relationship to cardiovascular co-morbidity.

BACKGROUND: Rheumatoid Disease (RD) is associated with ischaemic heart disease (IHD). We sought to investigate whether abnormalities of endothelial function and platelet activation in patients with established RD were related to co-morbid cardiovascular risk factors. METHODS: In a cross-sectional study, RD patients with no cardiac risk factors and normal cardiac function (RD, n=73), those with cardiovascular disease or risk factors and normal cardiac function (RD-risk, n=59), and those with left ventricular systolic dysfunction (RD-LVSD, n=21) were recruited, and compared to healthy controls (HC, n=76). Plasma levels of von Willebrand factor (vWF, an index of endothelial damage/dysfunction), soluble E-selectin (sE-sel, a marker of endothelial activation), and soluble P-selectin (sP-sel, an index of platelet activation) were studied. RESULTS: Plasma levels of vWF and sP-sel (but not sE-sel) were significantly higher among 153 RD patients compared to controls (p=0.002 and p<0.001, respectively). Levels of vWF progressively rose with increasing cardiovascular risk across the four subgroups (p for trend<0.001). Previous IHD was independently associated with vWF levels, and diabetes mellitus (DM) was similarly associated with all three markers. RD itself and beta-blocker use were associated with sP-sel. CONCLUSION: Plasma levels of vWF and sP-sel are higher among RD patients. Levels of vWF were particularly influenced by cardiac risk factor status, and associated with known IHD and DM.

Left ventricular systolic dysfunction in rheumatoid disease: an unrecognized burden?

OBJECTIVES: This study sought to ascertain whether left ventricular systolic dysfunction (LVSD) is more common among clinic patients with rheumatoid disease (RD) compared with the general population, and to assess the diagnostic utility of brain natriuretic peptide (BNP). BACKGROUND: Patients with RD are at increased risk of ischemic heart disease. However, there are few large echocardiographic studies identifying cardiac dysfunction in RD. We hypothesized that LVSD would be more prevalent in RD patients than in the general population. METHODS: A total of 226 hospital out-patients with RD (65% women) underwent clinical evaluation, electrocardiography (ECG), echocardiography, and plasma BNP assay (218 patients). Prevalence of LVSD was compared with local population estimates. RESULTS: Definite LVSD (left ventricular ejection fraction <40%) occurred in 5.3% of the RD group: standardized prevalence ratio, 3.20; 95% confidence interval, 1.65 to 5.59. Median BNP values were higher in patients with LVSD compared with those without: 16.6 pmol/l versus 8.5 pmol/l, p < 0.005, although values between the two groups overlapped. One in nine patients with an abnormal ECG had definite LVSD. CONCLUSIONS: Definite LVSD was three times more common in RD patients than in the general population. Given the prognostic benefits of treating LVSD, echocardiographic screening of RD patients with an abnormal ECG may be worthwhile.

Rheumatoid disease and the heart: from epidemiology to echocardiography.

Rheumatoid disease (RD) is a common chronic inflammatory condition associated with progressive joint destruction. Sufferers of RD experience reduced life expectancy, reflected in the increased standardised mortality rates reported in several studies over the last 50 years. Most studies indicate that the increased mortality affecting this population is mainly due to cardio-vascular disease. Epidemiological data have revealed an increased risk of developing ischaemic heart disease and heart failure in RD. The increased risk of ischaemic heart disease may result from traditional risk factors but data suggest that RD may confer risk independently. Although pericardial involvement, valvopathy and myocarditis are the most well-recognised cardiac manifestations of RD, and constitute a rheumatoid heart disease, these features are relatively benign. The current prevalence of rheumatoid heart disease in the era of early administration of disease-modifying therapy requires evaluation.