Gender differences in cardiovascular risk of patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid Arthritis (RA) is a chronic inflammatory disease, affecting women more than men, with a more aggressive course in women. DESIGN: A prospective study that recruited 58 patients (46 women aged 56 ± 12 years) with active long-standing RA disease (>12 months). Our goals were to measure their endothelial function, part of the cardiovascular risk assessment. METHODS: The Brachial Artery method measured endothelial function (the flow mediated percent change [FMD percentage] of the brachial artery diameter). A senior Rheumatologist clinically evaluated all subjects. Mann Whitney rank sum test estimated gender differences among the RA patients. RESULTS: Median FMD% change for men was -6.07%, while median FMD% change for women was 0.44% (Z = 2.38, P = 0.01). Baseline Brachial artery diameter was larger in men (Z = 2.52, P = 0.01); however, tender joints count and BMI were greater in women (Z=-2.24, P = 0.01; Z=-3.99, P = 0.001), respectively. CONCLUSIONS: Women with RA have significantly better endothelial function than men with RA. It means that even though RA is 3-fold more prevalent in women, women are more protected from atherosclerotic coronary artery disease and cardiac events.

Inhibition of endothelial progenitor cells may explain the high cardiovascular event rate in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) patients may suffer cardiovascular (CV) events much more than the general population, and CV disease is the leading cause of death in patients with RA. Our hypothesis was that impaired function of endothelial progenitor cells may contribute to endothelial dysfunction and the clinical CV events of patients with RA. METHODS: About 27 RA patients (9 males and 18 females) with an active disease and 13 healthy subjects who served as the control group (nine males and four females) were enrolled to this prospective study. The ability to grow in culture colony-forming units of endothelial progenitor cells (CFU-EPCs) was measured, as well as their endothelial function using high-resolution ultrasonography of the brachial artery, and levels of C reactive protein (CRP) in the serum. For statistical analysis, we used the Student's t-test. RESULTS: As a group, patients with RA were older (P < 0.0001), had severe endothelial dysfunction (P<0.0001), with impaired ability to grow CFU-EPCs (P<0.0001), and a higher inflammatory state (P = 0001). No difference was observed in BMI. All RA patients had an active disease (DAS28 3.9 ± 0.9) for 9.2 ± 6.5 years. The same differences were observed in both genders. CONCLUSIONS: Patients with RA had an impaired ability to grow EPCs and severe endothelial dysfunction. Inability to grow colonies of EPCs reflects the impaired regenerative capacity of patients with RA and may explain the endothelial dysfunction and the high CV event rate among patients with RA.

Endothelial function in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) patients are at higher risk of accelerated atherosclerosis. AIMS: To assess endothelial dysfunction in RA to find a possible mechanistic pathway that will explain the clinical phenomenon. METHODS: A prospective study recruited 44 RA patients with an active long standing (>12 months) disease. All underwent a detailed assessment of disease activity. To estimate the endothelial function the brachial artery method was performed, measuring flow mediated diameter percent (FMD%) change. Clustering analyses (hierarchical and k-means) were performed. Patients were compared to healthy subjects. RESULTS: Forty four RA patients (54.42 ± 11.14 years, females (72.7%)) with co-morbidities (70.5%), not taking tumor necrosis factor-blockers or disease modifying anti rheumatic drugs (63.6%). Only 6 (13.6%) had a normal endothelial function. Hierarchical and k-means clustering techniques showed statistically significant differences among the three clusters concerning disease activity score-28 (DAS-28)- erythrocyte sedimentation rate (ESR) (P = 0.000), DAS-28- C-reactive protein (CRP; P = 0.001), clinical disease activity index (P = 0.002), simplified disease activity index (P = 0.001), ESR (P = 0.000), (CRP) (P = 0.003) and FMD% (P = 0.009). The group with the highest FMD% values exhibited the lowest clinical scores and laboratory parameters. Patients with the lowest FMD% values co-clustered with subjects with positive but low FMD% changes and elevated clinical and laboratory parameters. CONCLUSIONS: Our study confirmed the feasibility of exploiting endothelial function in clinical practice as an early predictor of atherosclerosis in RA patients.

Vascular responsiveness in type 2 diabetes mellitus (T2DM).

BACKGROUND: Diabetic retinopathy is used for staging of progression of micro and macro-vascular complications of patients with DM. Our hypothesis was that diabetic patients at different stages of retinopathy would have different vascular responsiveness that will be used as a surrogate marker of macro-vascular disease for risk assessment of cardiovascular complications. METHODS: A prospective study enrolled 96 patients. Twenty-three healthy volunteers (44 ± 11 years), 25 diabetic patients without retinopathy (63 ± 11 years), 25 patients with non-proliferative retinopathy [NPDR] (62 ± 9 years) and 23 patients with proliferative diabetic retinopathy [PDR] (59 ± 10 years). All patients underwent an ophthalmologic examination to diagnose retinopathy staging, and vascular responsiveness evaluation that included endothelial function evaluation (using the brachial artery method to measure flow mediated diameter change (FMD%)) and measuring the ankle-brachial blood pressure ratio, a measure of arterial stiffness. RESULTS: Endothelial function was severely impaired in all diabetic patients. Patients with PDR had an FMD% of -3.1 ± 6.6%, patients with NPDR had -3.3 ± 9.2%, patients without retinopathy -1.9 ± 7.4% (P = NS between all groups of patients). Healthy controls had an FMD% of 16.5 ± 7.5% with a significant difference (P < 0.001) compared with each group of patients. No difference in FMD% was observed among patients (P = 0.93 between PDR and NPDR groups, P = 0.54 between NPDR and no retinopathy groups and P = 0.71 between patients without retinopathy and those with PDR).The ankle brachial (ABI) ratio was 1.03 ± 0.28 in the PDR group, 1.14 ± 0.24 in the NPDR group and 0.97 ± 0.18 in the no-retinopathy group. Healthy volunteers had an ABI of 1.07 ± 0.18. No difference was observed between ABI of PDR and NPDR patients (P = 0.17) and between patients without retinopathy and PDR patients (P = 0.91). However, a significant difference was observed between the NPDR and no-retinopathy groups (P = 0.008). No significant difference was found between ABI ratios when compared with the control group (P = 0.62 for PDR, P = 0.26 for NPDR and P = 0.07 for the no-retinopathy group). No difference was observed in age and BMI among all groups of patients (P = NS for all). Patients were older (P < 0.001) and had a higher BMI (P < 0.001). Interestingly there was no difference in height among groups of patients, but controls were significantly taller compared with each group of patients (P < 0.02). CONCLUSIONS: All patients with T2DM had severe endothelial dysfunction with no difference among the different retinopathy groups. In our patients, all patients had a normal arterial stiffness but patients without retinopathy who had the highest arterial stiffness. We could not distinguish vascular traits that would define diabetic patients at the highest risk to develop cardiovascular complications.