Arterial stiffness in a muscular artery in women with longstanding rheumatoid arthritis compared with healthy controls and patients with traditional cardiovascular risk factors.

Pulse wave velocity (PWV), a marker of arterial stiffness, reflects vascular dysfunction and is associated with cardiovascular risk. Rheumatoid arthritis (RA) is associated with profound changes in vascular function and premature death, mainly caused by cardiovascular diseases. The aim of this study was to investigate arterial stiffness in the brachial artery (a muscular type of artery) as measured by PWV in women with longstanding RA and to compare the results with healthy controls and to patients with traditional cardiovascular risk factors without RA. A total of 80 female participants underwent non-invasive measurement of PWV. Participants were allocated to one of three groups: patients with longstanding RA (disease duration >5 years) without traditional cardiovascular risk factors (n = 30), patients with traditional cardiovascular risk factors (n = 20) and healthy controls (n = 30). Patients and controls were matched for age. PWV was significantly higher in RA patients (8.6 +/- 0.9 m/s) as compared with healthy controls (8.1 +/- 0.7 m/s; P = 0.02). PWV was virtually the same in RA patients and patients who had traditional cardiovascular risk factors (8.6 +/- 1.5 m/s; NS). PWV was also higher in this group as compared with healthy controls, but this difference did not reach statistical significance (NS). RA is associated with a higher PWV as compared with healthy controls and is comparable to patients with known traditional risk factors. This reflects vascular dysfunction in patients with RA.

The place of methotrexate perioperatively in elective orthopedic surgeries in patients with rheumatoid arthritis.

No clear consensus exists on whether methotrexate (MTX) should be continued or whether this therapy should be discontinued for a few weeks in patients with rheumatoid arthritis (RA) undergoing surgery. Continued MTX therapy may impair wound healing, but discontinuation of the therapy may increase the risk of flares. In this article we review published data on the perioperative management of MTX in patients with RA undergoing elective orthopedic surgery. Eight papers on this topic could be identified. These studies compare continued vs. discontinued MTX therapy or MTX therapy vs. therapies other than MTX. Summing up the published data, continued MTX therapy appears to be safe perioperatively and seems also to be associated with a reduced risk of flares. None of the examined papers addresses the issue of safety in connection with comorbidities, age or high doses of MTX.

Patients with rheumatoid arthritis undergoing surgery: how should we deal with antirheumatic treatment?

OBJECTIVES: To review published data on the perioperative management of antirheumatic treatment and perioperative outcome in patients with rheumatoid arthritis (RA). METHODS: The review is based on a MEDLINE (PubMed) search of the English-language literature from 1965 to 2005, using the index keywords "rheumatoid arthritis" and "surgery". As co-indexing terms the different disease-modifying antirheumatic drugs (DMARDs) as well as nonsteroidal anti-inflammatory drugs (NSAIDs) and "glucocorticoids" were used. In addition, citations from retrieved articles were scanned for additional references. Furthermore, because the number of published articles is so limited, relevant abstracts presented at congresses were included in the analysis. RESULTS: Continuation of methotrexate (MTX) appears to be safe in the perioperative period. Only a limited number of studies address the use of leflunomide and the results are conflicting. Because of the very long drug half-life, its discontinuation would need to be of long duration and is probably not necessary. Data on hydroxychloroquine do not show increased risks of infection. Regarding sulfasalazine, there are no studies from which definite answers could be drawn on whether it should be withheld perioperatively. Preliminary data show that the risk of infections during treatment with TNF-blocking agents may be lower than initially expected. The only available recommendation (Club Rhumatismes et Inflammation, CRI) suggests discontinuing the drugs before surgery for several weeks, depending on the risk of infection and the drug used. They should not be restarted until wound healing is complete. To avoid the antiplatelet effect during surgery, NSAIDs other than aspirin should be withheld for a duration of 4 to 5 times the drug half-life. Patients with chronic glucocorticoid therapy and suppressed hypothalamic-pituitary-adrenal (HPA) axis need perioperative supplementation. CONCLUSIONS: While continuation of MTX likely is safe, data on other DMARDs are sparse. In particular, more data on the perioperative use of the biologic agents are needed.

Administration of infliximab in general practitioners' offices is safe.

Infliximab is used in the treatment of various diseases, such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis (PA), Crohn's disease (CD) and ankylosing spondylitis (AS). In most countries, infliximab is given in hospitals or infusion centers, which are experienced in the management of infusion reactions. Because of this side effect, general practitioners (GPs) might refuse to administer infliximab in their offices. The aim of this study was to investigate the safety of infliximab administration in GPs' offices. Health system in the provincial state of Upper Austria (Austria) provides reimbursement of biological treatment only in outpatient care. Infliximab is due to cost effectiveness usually administered by GPs after a specific training and initialisation of treatment by specialists in the hospital. We sent out a form to 42 cooperating GPs, containing 20 questions concerning the administration of infliximab. Thirty-four forms were returned and evaluated. Altogether, 69 patients (2 patients per doctor mean) were treated with infliximab (1-42 months; 21 months mean). The overall observation period was 697 patients-months. During this period, 487 infusions (14.5 infusions per doctor mean) were administered. From five doctors, seven adverse events (AE) in six patients were reported. In all seven cases, infusion was discontinued; two had allergic reactions and five had nausea or cardiac symptoms, not definitely of allergic origin. Severe adverse events (SAE), defined as shock, emergency treatment or hospitalisation during or after infliximab administration were reported by two doctors. In contrast, SAE during the infusion of other drugs (e.g. analgetics, vitamins) were previously seen by 16 doctors, showing the overall possibility of infusion reactions with commonly prescribed drugs. Almost all (31/34) confirmed the overall safety of infliximab administration in GP's patient care. The administration of infliximab by specially trained general practitioners with background guidance through rheumatologist or gastroenterologist centers seems to be a safe and acceptable way to provide long-term treatment with infliximab to patients in need of biological treatment.

Diurnal variation of pulse wave velocity assessed non-invasively by applanation tonometry in young healthy men.

PURPOSE: Pulse wave velocity (PWV) is at least partially controlled by vascular tone. Vascular tone and underlying physiological processes such as sympathetic activity, plasma catecholamin, and cortisol levels have been shown to follow diurnal variations. MATERIALS AND METHODS: Carotid-to-radial PWV was non-invasively assessed by applanation tonometry in 21 young (26.5+/-2.3 years) healthy men at three different time points (8:00 hr, 12:00 hr, 17:00 hr) during a day. Additionally, heart rate, systolic, diastolic and mean blood pressure, and radial pulse pressure were assessed at the same time points. RESULTS: The mean PWV was significantly higher at 8:00 hr compared with the mean PWV assessed at later time points. No significant differences were found between mean PWV at 12:00 hr and at 17:00 hr. When PWV was corrected for blood pressure, the difference between values at 8:00 hr and 12:00 hr was no longer significant. Systolic, diastolic and mean blood pressure were significantly lower at 17:00 hr compared with those at 8:00 hr. CONCLUSION: A small but significant diurnal variation of PWV was observed in young healthy men, which might have been caused at least partly by variations of blood pressure. This finding could be of value, when PWV is used in human research. Thus, in longitudinal investigations the measurements should be performed at similar time points in the course of a day, in order to obtain comparable data. Additionally, our observations ought to be of assistance to studies in which novel pharmacological compounds with activity on the vasculature are investigated.

Hypocalcemic tetany in the newborn as a manifestation of unrecognized maternal primary hyperparathyroidism.

Primary hyperparathyroidism (PHP) during pregnancy is a very rare event that increases maternal and perinatal morbidity and mortality. We present a case in which hypocalcemic tetany of the neonatal infant - caused by transient hypoparathyroidism in the child - finally revealed asymptomatic maternal PHP. An apparently healthy 30-year-old woman had an uneventful pregnancy and delivery. On the 15th postpartal day, the newborn developed hypocalcemic tetany. After receiving supplementation of calcium and vitamin D, the child developed without further pathological findings. Laboratory and radiological studies in the mother led to a diagnosis of maternal PHP. An adenoma of the right lower parathyroid gland was subsequently removed. The search for the cause of hypocalcemia in a newborn should not focus on the patient alone. Examining the apparently healthy mother and approaching the case in a multidisciplinary fashion may benefit both the child and the mother.

Prevalence, severity and predictors of HOMA-estimated insulin resistance in diabetic and nondiabetic patients with end-stage renal disease.

BACKGROUND: Prevalence of insulin resistance (IR) is increased in type 2 diabetes and in end-stage renal disease (ESRD). IR is associated with advanced atherosclerosis and is an independent predictor for cardiovascular disease in diabetes and ESRD patients. We investigated prevalence, severity, predictors and relation to vascular diseases by the homeostasis model assessment (HOMA-IR) in diabetic and nondiabetic ESRD patients. METHODS: ESRD patients with type 2 diabetes (n = 27) and nondiabetic ESRD patients (n = 35) were included in the study. IR was assessed with the HOMA-IR using fasting glucose and insulin levels. Additionally, serum levels of C-peptide, HbA1c, triglycerides, cholesterol and C-reactive protein and blood pressure were assessed. RESULTS: Median HOMA-IR was significantly higher in the diabetic ESRD patients than in the nondiabetic ESRD patients (6.3 [range 0.7-61.7] vs. 2.4 [range 0.3-5.7]; p < 0.001). Systolic blood pressure and triglycerides were significantly higher in patients with higher HOMA-IR, whereas HDL cholesterol was significantly lower in those patients. Only nondiabetic patients with increased HOMA-IR had significantly higher C-peptide levels than those with lower HOMA-IR (14.9 + 5.7 vs. 9.0 + 4.3, p = 0.004). Vascular disease prevalence was significantly higher in diabetic patients with higher HOMA-IR than in those with lower HOMA-IR. CONCLUSIONS: Prevalence and severity of HOMA-IR was greater in diabetic ESRD patients than in those without diabetes. In diabetic patients low HDL cholesterol was the only predictor for higher HOMA-IR, whereas in nondiabetic patients a high C-peptide level was the only predictor for higher HOMA-IR. The prevalence of vascular diseases is associated with higher HOMA-IR in ESRD patients.

Improvement of glycemic control after a 3-5 day insulin infusion in type 2-diabetic patients with insulin resistance can be maintained with glitazone therapy.

INTRODUCTION: Insulin resistance is a common problem in obese patients with type 2 diabetes. In a prospective randomized study, we investigated the improvement of metabolic control after a 3-5 day period of intravenous insulin infusion in poorly insulin-treated, overweight type 2-diabetic patients with and without additional glitazone therapy. METHODS: Twenty-eight overweight patients (BMI > 28) with poorly insulin-treated type 2 diabetes (HbA1c > 8%) requiring > 80 IU insulin/day received a continuous insulin infusion for 3-5 days (initially 4-6 IU insulin/hour). Thereafter, 14 of the patients also received pioglitazone (15 mg/day). The two groups were compared for HbA1c, mean blood glucose (MBG), body weight, cholesterol, triglycerides and insulin requirement (IU/day) three months before insulin infusion, during infusion, and at three and six months after the infusion. RESULTS: Glycemic control was immediately improved under insulin infusion in both groups: MBG was reduced from 188 +/- 32 mg/dl at baseline to 142 +/- 28 mg/dl at the end of insulin infusion (p < 0.05). In the group receiving pioglitazone, the mean HbA1c three months after the insulin infusion was 16% lower and after six months 17% lower than baseline values (p < 0.02). Concomitantly, the required insulin dose decreased significantly by 15% after three months and 18% after six months (p < 0.02). Two patients (14%) were non-responders (< 10% reduction of required insulin dose). In the group without pioglitazone the mean HbA1c level three months after insulin infusion was 10% lower (p < 0.05) than at baseline; at six months the HbA1c value was the same as that before the infusion. The required insulin dose was 10% lower after three months and only 3% lower after six months (NS). Four patients (28%) were non-responders. DISCUSSION: Short-term insulin infusion therapy is effective in improving metabolic control and, concomitantly, in reducing insulin requirement in poorly insulin-treated type 2-diabetic patients; however, these effects are mostly limited to three months. With additional glitazone treatment after the insulin infusion, the improvement in metabolic control and the reduced insulin requirement can be maintained for more than six months.

Diurnal variation of arterial stiffness and subendocardial perfusion noninvasively assessed using applanation tonometry in healthy young men.

BACKGROUND: Arterial stiffness is at least partially controlled by vascular tone. Vascular tone and underlying physiological processes, e.g. sympathetic activity, have been shown to follow diurnal variations. METHODS: This study investigated whether arterial stiffness and perfusion of subendocardial myocardium relative to cardiac workload show diurnal variations under physiological conditions. The aortic augmentation index (AIx) and subendocardial viability ratio (SEVR) were measured noninvasively in 26 healthy young men (27.6 +/- 3.4 years) using applanation tonometry at three different times (8:00, 12:00, 17:00) during one day. RESULTS: Mean AIx was significantly higher and mean SEVR significantly lower at 8:00 than at the later times. No significant differences were found between mean AIx and mean SEVR at 12:00 and at 17:00. CONCLUSIONS: The observed diurnal variations of AIx and SEVR will be of value when applanation tonometry is used in human research. In order to arrive at comparable data in longitudinal investigations, measurements should be made at similar times during the course of a day. In addition, our observation should assist in studies in which novel pharmacological compounds with activity on the vasculature are investigated.

Type 2 diabetes in patients with end-stage renal disease is not associated with further increased serum inflammatory parameters.

BACKGROUND: Cardiovascular morbidity and mortality is markedly increased in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) and is further pronounced when diabetes mellitus is also present. As atherogenesis is mediated by inflammation of vessel walls and as evidence evolves that atherosclerosis and diabetes mellitus share a common inflammatory basis, we considered whether ESRD patients with additional diabetes mellitus exhibit increased inflammation levels exceeding those of ESRD patients without diabetes mellitus. METHODS: The study included 20 ESRD patients with type 2 diabetes mellitus and 16 non-diabetic ESRD patients on long-term HD. The patients' clinical characteristics and serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), soluble tumor necrosis factor receptor I (sTNF-RI), neopterin and fibrinogen were assessed. RESULTS: There were no significant differences in serum levels of CRP, IL-6, neopterin, sTNF-RI and fibrinogen found in ESRD patients with and without diabetes mellitus. HD duration correlated significantly with neopterin (r=0.515, p<0.001) and sTNF-RI (r=0.429, p<0.05) serum levels. HD led to a significant reduction in neopterin levels whereas CRP, IL-6 and sTNF-RI levels did not change significantly. CONCLUSIONS: With the inherent limitations of a small number of patients studied, we observed that the presence of type 2 diabetes mellitus in addition to ESRD was not associated with further increased serum levels of the examined inflammatory parameters. Our observations suggest that the worsened prognosis of diabetic ESRD patients is probably not explainable by superimposing inflammatory processes.

Recurrent calcinosis in consecutively transplanted kidney grafts.

Repeated renal transplant calcinosis is a rare event. We report a young woman in whom repeated calcinosis was observed in two consecutive renal transplants. Persistent secondary hyperparathyoidism and hyperphosphatemia due to impaired renal function were assumed as the pathogenic factors for calcinosis. Sub-total parathyroidectomy performed shortly after the third transplantation and good function of the renal graft have prevented calcinosis in the third graft for more than five years.

Erythropoietin requirement in patients with type 2 diabetes mellitus on maintenance hemodialysis therapy.

Diabetes is known to be a risk factor for the severity of anemia in non-dialyzed patients with renal failure. The aim of this study was to evaluate differences in hemoglobin (Hb) response to erythropoietin (EPO) in diabetic and nondiabetic patients on chronic hemodialysis (CHD). Sixty-four patients on CHD were included in the study: 24 type 2 diabetics (mean age, 59+/-11 years; 10 men, 14 women) and 40 nondiabetics (age, 53+/-14 years; 21 men, 19 women). All patients received a fixed dose of 50 mg ferric saccharate and EPO per week, dosed individually to achieve a target Hb level of 12 g/dl. Hb levels, ferritin, transferrin saturation (TSAT), EPO requirement (IU/kg/week), folic acid, vitamin B12 and C-reactive protein (CRP) were measured every two months. Additionally, the incidence of infectious diseases during the observation period of six months was evaluated, and a univariate correlation analysis of CRP and EPO requirements was performed in both groups. Patients with and without diabetes were divided into two groups each: those with normal CRP and those with elevated CRP. The EPO requirements of these groups were compared. Under identical iron substitution the mean Hb level increased more, but not significantly, in non-diabetic patients than in diabetic patients. After 6 months the mean Hb levels were 12.1+/-1.2 versus 11.5+/-1.2 g/dl (NS), although the actual EPO requirement was higher in diabetic than in non-diabetic subjects (244+/-122 versus 183+/-118 IU/kg/week; p<0.05). CRP after 6 months was significantly higher in diabetic than in non-diabetic patients (2.6+/-2.2 versus 1.5+/-1.3 mg/dl; p<0.05), as was the incidence of infectious disease (n/patient/month) (0.24 versus 0.08; p<0.05). The correlation coefficient between CRP and EPO requirements was statistically significant in both diabetic (r=0.547 p<0.01) and non-diabetic subjects (r=0.577; p<0.001). All other laboratory indices were similar in both groups. In the diabetic patients with normal CRP (n=6) the Hb levels achieved after six months were similar to those of non-diabetic patients (n=10) with normal CRP (11.9+/-1.1 versus 12.1+/-1.2%), and the required EPO was comparable. We conclude that the Hb response to EPO is reduced in diabetic patients on CHD. This elevated EPO requirement may be explained by a greater prevalence of infectious diseases, characterized by a significantly higher CRP level, in these patients. Other causes for the elevated EPO requirement could be excluded.

Heart rate, ejection duration and subendocardial viability ratio in patients with rheumatoid arthritis as compared to controls.

AIM: Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality. In the general population, an increased heart rate is associated with increased mortality. Only a few studies have investigated heart rate in RA patients and compared the results with patients that do not have RA (n-RA). Therefore, little is known as to whether an increased heart rate, at least in part, could explain the increased mortality found in RA patients. The aim of the present study was to investigate whether heart rate is increased in RA patients. METHODS: In this cross-sectional study, heart rate was determined in a total of 282 patients (131 RA, 151 n-RA). In addition, non-invasive pulse wave analysis of the radial artery was performed to determine cardiac ejection duration using the Sphygmocor apparatus. Furthermore, the subendocardial viability ratio (SEVR), a marker of cardiac workload, was investigated, whereby higher values indicate a more favorable supply/demand relationship for the myocardium. Patients using chronotropic drugs were not included in the study. RESULTS: Heart rate was virtually the same in RA patients (71.9 ± 11.2 beats/min [bpm]) as compared with controls (72.3 ± 11.7 bpm; P > 0.05). Also SEVR (RA 144 ± 25% vs. n-RA 147 ± 27%; P > 0.05) and ejection duration (RA 321 ± 24 ms vs. n-RA 318 ± 24 ms; P > 0.05) were comparable between the groups. CONCLUSION: It could not be shown that heart rate in RA patients differs significantly from heart rate in controls. Therefore, heart rate does not appear to explain or contribute to the increased cardiovascular risk found in RA patients.

Higher mortality of patients on haemodialysis with pancreatic diabetes compared to type 2-diabetes.

In rare cases (1-8%) diabetic patients with end-stage renal disease (ESRD) suffer from diabetic nephropathy (dNP) due to pancreatic diabetes mellitus (PDM). Aim of this study was to investigate differences in the outcome of patients with PDM and those with type 2 diabetes.In a retrospective study we evaluated 96 diabetic patients, who started hemodialysis (HD) in our dialysis centre (1997-2005). In 12 patients PMD was diagnosed, and 84 patients had type 2 diabetes. In both groups we compared vascular risk factors and prevalence of vascular diseases at the start of dialysis. We also evaluated incidence of malnutrition, and 5-year survival in both patient groups.The vascular risk factors were similar in both patient groups, also the prevalence of vascular diseases at the initiation of HD was similar in both groups. In the patients with PDM the mean BMI (kg/m2) was lower (22 + 3 versus 25 + 3), and also their serum albumin was lower (2.7 + 0.3 versus 3.4 + 0.3 g/dl, p < 0.05). Four of these patients (33%) developed malnutrition (BMI < 18.5). In the patients with PDM the age adjusted 5-year survival was significantly lower (8% versus 27%, p < 0.05) than in the type 2 diabetic patients.Conclusions in HD-treated patients with type 2 diabetes or PDM the prevalence of vascular diseases was not significantly different. The lower survival of PDM patients can be related to poor nutrition status.

Rheumatoid arthritis is an independent risk factor for an increased augmentation index regardless of the coexistence of traditional cardiovascular risk factors.

BACKGROUND: Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity. It was previously shown that the augmentation index (AIx), a marker of vascular dysfunction, is higher in RA patients without traditional cardiovascular risk factors than in healthy controls. In this study we determined whether the impact of RA on the AIx is diminished in the context of coexisting, strong cardiovascular risk factors. PATIENTS AND METHODS: A total of 411 participants were included [203 with RA; 208 in the non-RA (n-RA) group]. Pulse-wave analysis was performed on the radial artery using applanation tonometry. The impact of RA on the AIx was determined in a single and in a multiple linear regression model. RESULTS: The mean unadjusted AIx was 30.5 ± 9.0% for RA patients and 24.0 ± 11.0% for the n-RA group (P < 0.001). In the regression model, the following variables are statistically significant at approximately the same level (P < 0.001); the order of impact of these variables is age > diastolic blood pressure > sex > RA > height > smoking status. RA, height, and smoking had a nearly equal impact on the AIx. CONCLUSIONS: The AIx is increased in RA patients regardless of the coexistence of traditional cardiovascular risk factors, thereby reflecting vascular dysfunction in this population. The impact of RA on the vascular system is comparable to that of smoking.

Metabolic control and vascular diseases under oral antidiabetic drug versus insulin therapy and/or diet alone during the first year of hemodialysis in type 2 diabetic patients with ESRD.

INTRODUCTION: Uremic type 2 diabetic patients on hemodialysis need various types of antidiabetic therapies. The aim of the present study was to identify differences between patients on oral antidiabetic drug therapy or insulin substitution or diet therapy alone during their first year of hemodialysis. PATIENTS AND METHODS: Sixty-four type 2 diabetic patients who had started hemodialysis (HD) at our dialysis center between 2003 and 2007 were included in the study. Kidney-transplanted patients (n = 1) and those with chronic infectious or malignant diseases (n = 4) were excluded. Patients were divided into three groups according to their antidiabetic therapy: group 1 consisted of patients on oral antidiabetic drug therapy (n = 12), group 2 of those on insulin therapy (n = 42), and group 3 of those being treated with diet alone (n = 10). At the start of HD and 12 months later, we measured fasting plasma glucose (FPG), HbA1c, the incidence of hypoglycemia (n/patient/month), cholesterol, triglycerides, body weight, and insulin requirements in the insulin-treated group. C-peptide was only measured at the start of dialysis. We evaluated changes in antidiabetic therapy during the first year on dialysis, and the prevalence of vascular disease in each group at the start of HD. RESULTS: FPG and HbA1c values were similar in all groups at the start of HD and after 1 year. Hypoglycemia occurred more frequently in insulin-treated patients; however, the difference was not significant. Cholesterol levels were similar in all groups, whereas triglycerides were significantly lower in insulin-treated patients (138 ± 28 vs. 176 ± 46 mg/dl; P < 0.05). Body weight was similar in all groups. No significant change in body weight was observed in any group after 12 months on dialysis. At the start of HD, C-peptide levels were lower in insulin-treated patients than in the other groups (1.8 ± 0.9 ng/ml vs. 2.2 ± 1.1 and 2.4 ± 1.1 ng/ml; P < 0.05). During the first 12 months on HD, two patients from group 1 were shifted to group 3 (diet alone), while four patients could reduce their drug dosage (33%). However, two subjects became insulin-dependent. In group 2, insulin therapy could be terminated in two cases, while the insulin dose could be reduced in 20 patients (48%). In group 3, one patient was switched to oral antidiabetic therapy. The prevalence of vascular disease was slightly higher in group 3 (NS). CONCLUSION: Within 1 year after the start of HD, the dose of sulfonylurea as well as insulin could be reduced in a large majority of patients. Metabolic control was similar in all groups. Only triglycerides were significantly lower in group 2. The frequency of hypoglycemia and the prevalence of vascular disease were just slightly higher in the group on insulin therapy.