Correction to: A prospective, longitudinal monocentric study on laser Doppler imaging of microcirculation: comparison with macrovascular pathophysiology and effect of adalimumab treatment in early rheumatoid arthritis.

In the Original article, the legend of Figures 3 and 4 are interchanged and line number 387 is incomplete.

A prospective, longitudinal monocentric study on laser Doppler imaging of microcirculation: comparison with macrovascular pathophysiology and effect of adalimumab treatment in early rheumatoid arthritis.

Increased cardiovascular (CV) morbidity and mortality have been found in rheumatoid arthritis (RA). Tumour necrosis factor α (TNF-α) inhibitors may improve vascular function. In the first part of this study, we determined microcirculation during postoocclusive reactive hyperemia (PORH) representing endothelial function. In a nonselected population (n = 46) we measured flow-mediated vasodilation (FMD) of the brachial artery and laser Doppler flow (LDF) by ultrasound. Among LDF parameters, we determined TH1 (time to half before hyperemia), TH2 (time to half after hyperemia), Tmax (time to maximum) and total hyperemic area (AH). We measured von Willebrand antigen (vWF:Ag) by ELISA. In the second part of the study, we assessed the effects of adalimumab treatment on microcirculatory parameters in 8 early RA patients at 0, 2, 4, 8 and 12 weeks. We found significant positive correlations between FMD and LDF Tmax (R = 0.456, p = 0.002), FMD and TH2 (R = 0.435, p = 0.004), and negative correlation between vWF:Ag and Tmax (R = - 0.4, p = 0.009) and between vWF:Ag and TH2 (R = - 0.446, p = 0.003). Upon adalimumab therapy in early RA, TH2 times improved in comparison to baseline (TH2baseline = 26.9 s vs. TH24weeks = 34.7 s, p = 0,032), and this effect prolonged until the end of treatment (TH28weeks = 40.5, p = 0.026; TH212weeks = 32.1, p = 0.013). After 8 weeks of treatment, significant improvement was found in AHa (AHbaseline = 1599 Perfusion Units [PU] vs. AH8weeks = 2724 PU, p = 0.045). The PORH test carried out with LDF is a sensitive option to measure endothelial dysfunction. TH1 and TH2 may be acceptable and reproducible markers. In our pilot study, treatment with adalimumab exerted favorable effects on disease activity, endothelial dysfunction and microcirculation in early RA patients.

Early morphologic and functional changes of atherosclerosis in systemic sclerosis-a systematic review and meta-analysis.

OBJECTIVE: Cardiopulmonary manifestations have an important impact on the life expectancy of SSc patients. Functional and morphological macrovascular changes may appear early before the development of ischaemic symptoms. Several non-invasive methods are used in cardiovascular risk assessment. Heterogeneous data are available regarding these in SSc. We aimed to perform a systematic review and meta-analysis to characterize the importance of atherosclerosis in SSc. METHODS: A systematic literature search was performed to identify controlled studies on carotid intima-media thickness, flow- or nitrate-induced vasodilatation (flow-mediated dilatation, nitroglycerine-mediated dilatation), pulse wave velocity, augmentation index and ankle-brachial pressure index. Outcomes were pooled with the random-effects model. RESULTS: Thirty-five studies comprising a total of 1292 SSc patients qualified. Intima-media thickness, pulse wave velocity and ankle-augmentation index were higher and flow-mediated dilatation lower in SSc patients [standardized mean difference (SMD) 0.65 (95% CI: 0.29, 1.01), 0.62 (95% CI: 0.35, 0.88), 0.96 (95% CI: 0.45, 1.47) and -0.68 (95% CI: -1.39, -0.34), respectively, P < 0.01 for each]. Nitroglycerine-mediated dilatation and ankle-brachial pressure index were lower, but not significantly [SMD: -0.16 (95% CI: -0.50, 0.18) and -0.39 (95% CI: -0.91, 0.13), respectively]. Data showed high to moderate inconsistency and significant heterogeneity. Meta-regression analysis of the SMD and the disease duration found a regression coefficient of 0.086, P = 0.014, confirming that parameters of the included SSc population may have contributed to the heterogeneity. CONCLUSION: Meta-analysis of the published observational studies confirms that abnormalities attributable to macrovascular involvement are significantly more prevalent in SSc patients compared with controls. Considering the increasing importance of cardiovascular disease in SSc, a more widespread use of cardiovascular risk assessment is warranted.

Rosuvastatin improves impaired endothelial function, lowers high sensitivity CRP, complement and immuncomplex production in patients with systemic sclerosis--a prospective case-series study.

INTRODUCTION: We studied the effect of rosuvastatin on endothelial and macrovascular function, cardiovascular risk factors and the complement pathway in patients with systemic sclerosis (SSc). METHODS: Altogether 28 patients with SSc underwent laboratory and complex vascular assessments before and after six months of 20 mg rosuvastatin treatment. Flow-mediated dilation (FMD) of the brachial artery, as well as carotid artery intima-media thickness (ccIMT), carotid-femoral and aorto-femoral pulse wave-velocity (PWV) were analyzed by ECG-synchronized ultrasound. Ankle-brachial index (ABI) was determined by Doppler, and forearm skin microcirculation was assessed by Laser Doppler perfusion monitoring. RESULTS: Brachial artery FMD significantly improved upon rosuvastatin therapy (2.2% ± 3.3% before versus 5.7% ± 3.9% after treatment, P = 0.0002). With regard to patient subsets, FMD significantly improved in the 21 lcSSc patients (from 2.1% to 5.6%, P = 0.001). In the seven dcSSc patients, we observed a tendency of improvement in FMD (from 3% to 6%, P = 0.25). Changes in PWV, ccIMT and ABI were not significant. Mean triglyceride (1.7 ± 0.97 versus 1.3 ± 0.46 mmol/l, P = 0.0004), total cholesterol (5.3 ± 1.6 mmol/l versus 4.2 ± 1.3 mmol/l, P = 0.0003), low density lipoprotein cholesterol (3.0 ± 1.3 versus 2.2 ± 1.0 mmol/l, P = 0.005) and C-reactive protein levels (CRP) (5.1 ± 5.2 versus 3.4 ± 2.7, P = 0.01) levels significantly decreased after rosuvastatin treatment. Mean C3, C4 and IC levels also decreased significantly as compared to pretreatment values. CONCLUSIONS: Six-month rosuvastatin therapy improves endothelial function and lowers CRP, C3, C4 and IC levels indicating possible favourable effects of this statin on the cardiovascular and immune system in SSc.

Comparative assessment of vascular function in autoimmune rheumatic diseases: considerations of prevention and treatment.

Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to increased cardio- and cerebrovascular disease risk. Traditional risk factors, as well as the role of systemic inflammation including cytokines, chemokines, proteases, autoantibodies, adhesion receptors and others have been implicated in the development of these vascular pathologies. The characteristics of vasculopathies may significantly differ depending on the underlying disease. While classical accelerated atherosclerosis has been associated with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or spondyloarthropathies (SpA), obliterative vasculopathy may rather be characteristic for systemic sclerosis (SSc) or mixed connective tissue disease (MCTD). Antiphospholipid antibodies have been implicated in vasculopathies underlying SLE, antiphospholipid syndrome (APS), RA and MCTD. There is also heterogeneity with respect to inflammatory risk factors. Cytokines, such as tumor necrosis factor-α (TNF-α) or interleukin 6 (IL-6) and immune complexes are primarily involved in arthritides, such as RA, SpA, as well as in SLE. On the other hand, autoantibodies including anti-oxLDL anti-cardiolipin and anti-ß2GPI are rather involved in SLE- and APS-associated vasculopathies. Regarding the non-invasive assessment of vascular function, endothelial dysfunction, overt atherosclerosis and vascular stiffness may be indicated by brachial artery flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and aortic pulse-wave velocity (PWV), respectively. These abnormalities have been described in most inflammatory rheumatic diseases. While ccIMT and stiffness are relatively stable, FMD may be influenced by many confounding factors. In addition to traditional vasculoprotection, immunosuppressive agents including corticosteroids, traditional and biologic DMARDs may have significant vascular and metabolic effects. The official EULAR recommendations on the assessment and management of cardiovascular disease in arthritides have just been published, and similar recommendations in connective tissue diseases are to be developed soon.

Increased arterial stiffness as the marker of vascular involvement in systemic sclerosis.

OBJECTIVE: Endothelial dysfunction and vasculopathy of the small and large vessels are crucial pathogenic factors in systemic sclerosis (SSc). Accelerated atherosclerosis and impaired flow-mediated vasodilation have been described in SSc. We evaluated arterial stiffness in patients with SSc compared to healthy controls. METHODS: Augmentation index (AI) and pulse wave velocity (PWV) of the brachial artery were measured in 40 patients with SSc and 35 age and sex matched healthy controls using an arteriograph system. RESULTS: AI was significantly higher in SSc patients (9.02) compared to controls (-41.15) (p < 0.0001). PWV was similarly higher in patients with SSc (9.67 m/s) than in controls (8.00 m/s) (p = 0.0017). PWV was significantly higher in patients with localized SSc (10.04 +/- 2.01 m/s) compared to those with diffuse SSc (8.39 +/- 1.87 m/s) (p = 0.034). There was a significant, positive linear correlation between AI and PWV (r = 0.32, p = 0.045). We also observed significant correlations between AI and age (r = 0.31, p = 0.048), PWV and age (r = 0.36, p = 0.021), and PWV and disease duration (r = 0.40, p = 0.011) in SSc patients. CONCLUSION: Increased AI and PWV of the aorta in comparison to age and sex matched healthy controls indicate increased large-vessel stiffness in patients with SSc. PWV and AI are reproducible indicators of the presence and degree of arterial stiffening. Because arterial stiffness may correlate with disease duration and age in patients with SSc, it may be a useful diagnostic test in the assessment of arterial function. Increased vascular stiffness may be therapeutically targeted by statins and other vasoprotective agents during the management of SSc.

Evaluation of antibodies to oxidized low-density lipoprotein and assessment of C-reactive protein in acute coronary syndrome and stable coronary artery disease.

The aim was to measure the level of antibodies to oxidized LDL (oxLDL) and C-reactive protein (CRP) in the serum of patients with acute coronary syndrome (ACS). The results were correlated with data obtained from patients with stable coronary artery disease (stable CAD) and healthy controls. Thirty-three patients with ACS and 62 stable CAD patients were enrolled in the study. Fifty healthy individuals served as controls. The evaluation of anti-oxLDL autoantibodies was performed by ELISA, while CRP levels were measured by turbidimetry. The level of antibodies to oxLDL was significantly higher in both groups of patients with ACS and stable CAD compared to controls. The comparison between the acute and stable groups showed that anti-oxLDL levels were higher in the acute group, but because of high SD, the difference was not significant. By performing group analysis, anti-oxLDL levels were found to be significantly higher in ACS patients with unstable clinical state (circulatory insufficiency, malignant arrhythmias, recurring ischemic pain, need for urgent coronary intervention and death). CRP level in patients with ACS was significantly higher than in those with stable CAD. A positive correlation was found between anti-oxLDL antibodies and CRP levels both in patients with ACS and stable CAD. The association between the two biomarkers was stronger in the ACS group. In conclusion, our findings support the notion that the presence of antibodies to oxLDL, a plaque-specific antigen, plays a major role as a predictor of complicated manifestations of ACS.