Herwig Pieringer

Augmentation Index and Large-Artery Remodeling in Patients with Longstanding Rheumatoid Arthritis Compared with Healthy Controls

OBJECTIVE There is growing evidence of premature atherosclerosis in patients with rheumatoid arthritis (RA), leading to a higher rate of cardiovascular events than in the general population. The augmentation index (AIx), a marker of arterial stiffness, is an indicator of vascular function. The aim of the study was as follows: (1) to investigate whether AIx is increased in RA patients without traditional cardiovascular risk factors and (2) to evaluate whether there is an interrelationship with large artery remodeling as ascertained by carotid ultrasound. METHODS Thirty-six RA patients (age, 46.4 +/- 7.7 years; 31 female) were recruited. Patients were eligible for analysis if they had no traditional cardiovascular risk factors. AIx was assessed noninvasively during pulse wave analyses. For large artery remodeling the intima-media thickness (IMT) was measured in both common carotid arteries with ultrasound. Results were compared with 36 age- and sex-matched controls. RESULTS AIx was statistically significantly higher in RA patients as compared with controls (27.4 +/- 9.4% versus 18.4 +/- 9.0%; P < 0.001). In addition, IMT was significantly higher in RA patients (0.73 +/- 0.16 mm versus 0.65 +/- 0.12 mm; P = 0.01). In RA patients there was a positive correlation between IMT and AIx (r[IMT; AIx] = 0.45; P = 0.008). CONCLUSION AIx, a marker of arterial stiffness, as well as IMT, a marker of large-artery remodeling, are increased in RA patients without traditional cardiovascular risk factors. Measuring AIx might assist in better assessing the increased cardiovascular risk in RA patients.

Augmentation index in patients with rheumatoid arthritis and ankylosing spondylitis treated with infliximab

Premature atherosclerosis is linked to inflammation. Arterial stiffness is a marker of vascular dysfunction. We tested the hypothesis that treatment with infliximab, which is effective in reducing inflammation in rheumatoid arthritis (RA) and ankylosing spondylitis (AS), also lowers the augmentation index (AIx) in patients with active disease. We also analyzed the subendocardial viability ratio (SEVR), which is a measure of myocardial perfusion relative to cardiac workload. Included in the study were 30 patients (17 RA, 13 AS). Conventional treatment failed in all patients. The AIx and SEVR were determined by radial applanation tonometry before and after treatment with infliximab, at baseline and at week 7. After treatment with infliximab, Disease Activity Score for 28 joints (RA patients), Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index (AS patients), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) improved significantly (p < 0.001). The AIx for all patients increased from 22.0 ± 14.0% to 24.6 ± 13.0% (p = 0.03). The increase in the RA sub-group (p = 0.01) was also significant. The SEVR decreased from 148.6 ± 23.7% to 141.2 ± 23.7% (p = 0.04). Infliximab did not reduce the AIx in patients with RA and AS, although there were clinical improvements and CRP and ESR decreased. Instead, the AIx increased. This could negatively influence cardiac workload.

Risk factors for delayed kidney function and impact of delayed function on patient and graft survival in adult graft recipients

Abstract:  The influence of delayed kidney graft function on allograft outcome is described controversially in the literature. The aim of the study was to evaluate possible risk factors for delayed graft function (DGF) and investigate the impact of DGF on short‐ and long‐term renal allograft function. Two groups were formed: the first one consisted of patients who gained immediate graft function (IGF) (n = 64) after transplantation and the second group included patients with DGF (n = 31; with at least one dialysis needed in first week after transplantation). The DGF group had a statistically significant longer duration on dialyses prior to transplantation (DGF 54 vs. IGF 33 months; p < 0.05), on average more frequently a re‐transplantation (DGF 1.7 vs. IGF 1.3; p < 0.01), a longer re‐anastomosis time (DGF 52.9 vs. 44.2 min; p < 0.01), a lower systolic (DGF 136 ±24 mmHg vs. IGF 158 ± 25; p < 0.001) and diastolic blood pressure (DGF 78 ± 14 vs. IGF 89 ± 16 mmHg; p < 0.01) at admission to the hospital and a higher serum (S)‐creatinine at discharge (DGF 2.5 ± 1.6 vs. IGF 1.6 ± 0.4 mg/dL; p < 0.01). Prior to transplantation the DGF group had more often advanced vascular diseases (DGF 29.0 vs. IGF 12.5%; p < 0.01) and these patients incurred more frequently new ones during the next 3 yr after transplantation (DGF 22.6 vs. IGF 6.3%; p < 0.001). After 3 yr the graft survival tended to be lower in the DGF group (DGF 74.2 vs. IGF 84.4%; NS), but this difference was not statistically significant.

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.

Do statins reduce the cardiovascular risk in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) are at significantly higher risk of cardiovascular (CV) morbidity and mortality compared with the general population. Traditional CV risk factors cannot explain the total excess of CV morbidity and mortality in RA patients. At present, it is not clear whether treatment with statins might be of benefit in RA patients. The aim of the present systematic literature review is to summarize the published evidence concerning treatment with statins and its impact on CV events in RA patients.

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.

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

ZusammenfassungEin primärer Hyperparathyreoidismus in der Schwangerschaft tritt sehr selten auf und ist mit einer erhöhten mütterlichen und kindlichen Morbidität und Mortalität verbunden. Wir präsentieren einen Fall, bei dem eine hypokalzämische Tetanie des Neugeborenen – bedingt durch einen passageren Hypoparathyreoidismus im Kind – letztendlich zur Entdeckung eines nicht diagnostizierten primären Hyperparathyreoidismus der Mutter führte. Eine offensichtlich gesunde 30-jährige Frau hatte eine unauffällige Schwangerschaft und Geburt. Am fünfzehnten postpartalen Tag entwickelte das Neugeborene eine hypokalzämische Tetanie. Nach Gabe von Vitamin D und Kalzium sistierten die Krämpfe und die weitere Entwicklung des Kindes war völlig normal. Die weitere Evaluierung der Mutter führte zur Diagnose eines maternalen primären Hyperparathyreoidismus. In der Folge wurde ein Adenom an der rechten unteren Nebenschilddrüse entfernt. Die Suche nach den Ursachen einer Hypokalziämie bei Neugeborenen soll sich nicht nur auf den betroffenen Patienten beziehen. Die Untersuchung der offensichtlich gesunden Mutter und der multidisziplinäre Zugang können sowohl dem kleinen Patienten als auch der Mutter Genesung erbringen.SummaryPrimary 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.

Using cyclophosphamide in inflammatory rheumatic diseases

Cyclophosphamide (CYC), primarily introduced into clinical practice as an anti-cancer substance, is a potent immunosuppressive drug. Today, it is used in a number of organ- or life -threatening autoimmune diseases such as systemic vasculitides or connective tissue diseases. While being effective, CYC has a small therapeutic index and is associated with significant toxicity. CYC has been used in oncology in a variety of diseases and a lot of data has been derived from this area. This knowledge is often extrapolated to the rheumatologic settings. However, besides some similarities substantial differences between these two specialties considering the underlying diseases as well as the kind of application of the drug exist. The aim of the present review is to describe the general characteristics of the use of CYC from the rheumatologists point of view, including pharmacologic and pharmacokinetic properties, drug interactions, toxicity and possible preventive and/or therapeutic measures; all of which are important to consider when using this particular drug in the treatment of inflammatory rheumatic diseases.

Will Antirheumatic Treatment Improve Cardiovascular Outcomes in Patients with Rheumatoid Arthritis

In recent years, the scientific community has gained significant insight into the complex interaction between inflammation and the cardiovascular system in patients with rheumatoid arthritis (RA), which leads to increased cardiovascular (CV) morbidity and mortality in these patients. Our common understanding of this association is that persistent inflammation contributes to the development of premature atherosclerosis. Consequently, the question arises whether control of inflammation with antirheumatic treatment will be able to improve CV outcome. While there are a lot of data that demonstrate improvement of numerous CV surrogate markers in patients treated with virtually all antirheumatic drug classes, there is much less information about the possible translation of these beneficial effects into improved CV outcome. In summary, the published evidence suggests that tumor necrosis factor (TNF) alpha inhibitors may improve CV outcome. The same is true for methotrexate (MTX). However, it is not clear whether MTX works via suppression of inflammation or through drug specific mechanisms. For other traditional disease-modifying antirheumatic drugs and biologic therapies, there are no convincing data for improved CV outcome. Only a few drugs (glucocorticoids and NSAIDs) have been associated with increased CV risk. Treating RA aggressively, as recommended by current guidelines, is likely to have a beneficial effect on CV outcomes.

Hemodialysis in patients older than 65 years with end-stage renal failure

BackgroundDuring recent years, the number of patients with end-stage renal disease (ESRD) has been rising worldwide. Especially older patients and those with diabetes contribute to this rise. The aim of the present study was to evaluate whether patients older than 65 years with type 2 diabetes, who started first dialysis, have a higher prevalence of vascular diseases and co-morbidities, show a higher incidence of vascular complications and/or have a higher mortality rate than elderly non-diabetic patients with ESRD.Patients and methodsIn this study, 82 consecutive patients with ESRD, who had either type 2 diabetes or did not have diabetes and who had started chronic hemodialysis (HD) in our dialysis center during the years 1994 to 2002, were included. Patients were included when they were older than 65 years. Patients were divided into two groups: those with diabetes (DM) (n = 47) and those without diabetes (nDM) (n = 35). For both groups the number of co-morbidities as well as the prevalence of vascular diseases and vascular risk-factors at the start of HD was evaluated. In addition, the incidence of vascular complications was registered over a 3-year observation period. In both groups serum(S)-creatinine, blood urea nitrogen (BUN), creatinine clearance, hemoglobin, fasting blood glucose, HbA1c (in diabetic patients), cholesterol, triglycerides and phosphorus were evaluated.ResultsAt the start of HD the creatinine clearance was significantly higher in diabetic subjects (nDM 7.1 ± 2.1 vs DM 9.5 ± 4.4 ml/min/1.73 m2; p < 0.005). For S-creatinine the difference was not statistically significant (nDM 8.7 ± 3.3 mg/dl vs DM 7.4 ± 2.4; p = 0.07). Fasting blood glucose was significantly higher in diabetic patients (p < 0.001). BUN, hemoglobin, phosphorus and lipids were not significantly different in both groups. There was no statistically significant difference in systolic or diastolic blood pressure, but a higher amount of antihypertensive drugs were necessary in the DM group for blood pressure control (p < 0.01). In both groups there was a high prevalence of vascular diseases at the start of HD. In the diabetic patients the prevalence of peripheral vascular disease was significantly higher. Furthermore, in the first and second year significantly more vascular complications were observed in the DM group (p < 0.01). Survival was low in both groups. The 3-year survival was 20.0% in non-diabetic and 17.0% in diabetic patients (NS).ConclusionPatients older than 65 years with ESRD have a low survival with and without type 2 diabetes. The mortality rate was only slightly higher in the diabetic group and was not statistically significant. The prevalence of vascular diseases and co-morbidities is high in both groups; however, the incidence of cardiovascular complications was significantly higher in our diabetic patients.ZusammenfassungHintergrundIn den letzten Jahren ist die Zahl von Patienten mit terminaler Niereninsuffizienz weltweit stetig gestiegen. Vor allem ältere Patienten und jene mit Diabetes stellen den Hauptzuwachs dar. Ziel der vorliegenden Arbeit war es zu untersuchen, ob Patienten mit Typ 2 Diabetes über 65 Jahre, die eine Hämodialyse benötigen, eine höhere Prävalenz an vaskulären Erkrankungen und Komorbiditäten haben, eine höhere Inzidenz an vaskulären Komplikationen aufweisen und/oder eine höhere Sterblichkeit haben, als jene Patienten ohne Diabetes.Patienten und Methodik82 konsekutive Patienten mit Typ 2 Diabetes oder ohne Diabetes über 65 Jahre mit terminaler Niereninsuffizienz, die zwischen 1994 und 2002 an unserem Zentrum hämodialysepflichtig wurden, wurden in die Studie eingeschlossen. Die Patienten wurden in 2 Gruppen geteilt: jene mit Diabetes (DM) (n = 47) und jene ohne Diabetes (nDM) (n = 35). Für beide Gruppen wurden die Zahl der Komorbiditäten sowie die Prävalenz der vaskulären Erkrankungen und Risikofaktoren zum Zeitpunkt des Dialysebeginns erhoben. Weiters wurde die Inzidenz vaskulärer Komplikationen während des ersten Dreijahresintervall untersucht. In beiden Gruppen wurden Serum-(S-)-Kreatinin, BUN, Kreatininclearence, Hämoglobin, Nüchtern-Blutzucker, HbA1c (bei Diabetikern), Cholesterin, Triglyzeride und Phosphor ermittelt.ErgebnisseZum Zeitpunkt des Dialysestarts war die Kreatininclearence bei Diabetikern signifikant höher (nDM 7,1 ± 2,1 vs. DM 9,5 ± 4,4 ml/ min/1,73m2; p<0,005). Für das S-Kreatinin war der Unterschied nicht statistisch signifikant (nDM 8,7 ± 3,3 mg/dl vs. DM 7,4 ± 2,4; p = 0,07). Der Nüchtern- Blutzucker war bei Diabetikern signifikant höher (p < 0,001). BUN, Hämoglobin, Phosphor und die Lipide waren in den beiden Gruppen vergleichbar. Selbiges gilt für systolischen und diastolischen Blutdruck. Es waren aber mehr Antihypertensiva in der Gruppe der Diabetiker notwendig (p < 0,01). In beiden Gruppen fand sich eine hohe Prävalenz an vaskulären Erkrankungen zu Beginn der Dialyse. In der Gruppe der Diabetiker war die Prevalenz der peripheren arteriellen Verschlusskrankheit statistisch signifikant häufiger. Weiters war die Anzahl an vaskulären Komplikationen im ersten und zweiten Jahr nach dem Dialysebeginn bei Diabetikern statistisch signifikant höher (p<0,01). Die Überlebensrate war in beiden Gruppen niedrig. Das 3-Jahres-Überleben lag bei Nicht- Diabetikern bei 20,0% und bei Diabetikern bei 17,0% (NS).SchlussfolgerungPatienten über 65 Jahre mit terminaler Niereninsuffizienz haben eine niedrige Überlebensrate. Das gilt sowohl für Patienten mit Typ 2 Diabetes als auch für Patienten ohne Diabetes. Die Sterblichkeitsrate war bei Diabetikern nur gering höher. Die Prävalenz von vaskulären Erkrankungen war in beiden Gruppen hoch. Die Inzidenz kardiovaskulärer Komplikationen während des Untersuchungsintervalls war jedoch bei Diabetikern höher.