Exercise-induced albuminuria is associated with perivascular renal sinus fat in individuals at increased risk of type 2 diabetes.

AIMS/HYPOTHESIS: Microalbuminuria represents an established surrogate marker of early diabetic nephropathy and glomerular microangiopathy. Increasing evidence is emerging of a role of perivascular adipose tissue (PVAT) as an important link between obesity, insulin resistance and both macro- and microangiopathy. It is not known whether perivascular renal sinus fat (RSF) has an impact on microalbuminuria in the prediabetic stage. We investigated whether RSF quantified by MRI is associated with microalbuminuria before or after exercise. METHODS: Non-diabetic individuals at increased risk of type 2 diabetes were recruited into the Tübingen Lifestyle Intervention Program (TULIP); 146 participants took part in the analysis. RSF was measured in axial MRI sections at the level of the renal artery. Urine was collected before and after exercise stress testing. RESULTS: Participants (age 47 ± 12 years; mean ± SD) reached a mean exercise load of 176 ± 49 W, with a mean arterial peak pressure (MAPP) of 112 ± 14 mmHg. After adjusting for sex, age, visceral adipose tissue (VAT) and MAPP during exercise, RSF was significantly associated with postexercise albumin/creatinine ratio (ACR; p = 0.006). No association between RSF and baseline BP could be observed after adjusting for confounders (p = 0.26), and there was no association between RSF and baseline ACR either (p = 0.2). CONCLUSIONS: RSF is associated with exercise-induced albuminuria independently of sex, age, VAT and MAPP in a non-diabetic cohort at diabetic risk. We conclude that PVAT in the renal sinus may play a role in the pathogenesis of microalbuminuria.

The secretion pattern of perivascular fat cells is different from that of subcutaneous and visceral fat cells.

AIMS/HYPOTHESIS: We have previously found that the mass of perivascular adipose tissue (PVAT) correlates negatively with insulin sensitivity and post-ischaemic increase in blood flow. To understand how PVAT communicates with vascular vessels, interactions between perivascular, subcutaneous and visceral fat cells with endothelial cells (ECs) were examined with regard to inflammatory, metabolic and angiogenic proteins. To test for possible in vivo relevance of these findings, circulating levels of the predominant secretion product, hepatocyte growth factor (HGF), was measured in individuals carefully phenotyped for fat distribution patterns. METHODS: Mono- and co-cultures of human primary fat cells with ECs were performed. mRNA expression and protein production were studied using Luminex, cytokine array, RealTime Ready and ELISA systems. Effects of HGF on vascular cells were determined by WST assays. In patients, HGF levels were measured by ELISA, and the mass of different fat compartments was determined by whole-body MRI. RESULTS: In contrast with other fat cell types, PVAT cells released higher amounts of angiogenic factors, e.g. HGF, acidic fibroblast growth factor, thrombospondin-1, serpin-E1, monocyte chemotactic protein-1 and insulin-like growth factor-binding protein -3. Cocultures showed different expression profiles from monocultures, and mature adipocytes differed from pre-adipocytes. HGF was preferentially released by PVAT cells and stimulated EC growth and smooth muscle cell cytokine release. Finally, in 95 patients, only PVAT, not visceral or subcutaneous mass, correlated independently with serum HGF levels (p = 0.03; r = 0.225). CONCLUSIONS: Perivascular (pre-)adipocytes differ substantially from other fat cells with regard to mRNA expression and protein production of angiogenic factors. This may contribute to fat tissue growth and atherosclerotic plaque complications. Higher levels of angiogenic factors, such as HGF, in patients with increased perivascular fat mass may have pathological relevance.

Effects of a lifestyle intervention in metabolically benign and malign obesity.

AIMS/HYPOTHESIS: We and others recently characterised metabolically benign or healthy obesity (MHO). In the present study we investigated whether a lifestyle intervention is sufficient to place obese insulin-resistant (OIR) individuals in a position where the possible metabolic consequences are similar to those for MHO individuals. METHODS: A total of 262 non-diabetic individuals participated in a 9 month lifestyle intervention programme. Obese individuals (BMI ≥ 30.0 kg/m(2)) were stratified, based on their insulin sensitivity (IS) estimated from an OGTT, into MHO (IS in the upper quartile, n = 26) and OIR (IS in the lower three quartiles, n = 77). Total body and visceral fat were measured by magnetic resonance (MR) tomography and liver fat by (1)H-MR spectroscopy. RESULTS: During the intervention, visceral fat decreased significantly in both groups (both p ≤ 0.009), whereas total body and liver fat decreased only in the OIR group (p < 0.0001; MHO p = 0.12 for total body fat and p = 0.47 for liver fat). IS improved in the OIR group (p < 0.0001), but remained essentially unchanged in the MHO group (p = 0.30). However, despite the significant increase in the OIR group, IS at follow-up barely exceeded 50% of the IS of the MHO group (OIR 9.30 ± 0.53 arbitrary units [AU]; MHO 16.41 ± 1.05 AU; p < 0.0001). CONCLUSIONS/INTERPRETATION: IS improves during the lifestyle intervention in OIR individuals. However, it does not reach a level where adequate protection from type 2 diabetes and cardiovascular disease is expected. Thus, stratification of obese individuals based on their metabolic phenotype is important to identify those who are likely to need early pharmacological treatment in addition to the lifestyle intervention.

Reversal of experimental diabetic neuropathy by VEGF gene transfer.

The pathogenetic basis for diabetic neuropathy has been enigmatic. Using two different animal models of diabetes, we have investigated the hypothesis that experimental diabetic neuropathy results from destruction of the vasa nervorum and can be reversed by administration of an angiogenic growth factor. Nerve blood flow, as measured by laser Doppler imaging or direct detection of a locally administered fluorescent lectin analogue, was markedly attenuated in rats with streptozotocin-induced diabetes, consistent with a profound reduction in the number of vessels observed. A severe peripheral neuropathy developed in parallel, characterized by significant slowing of motor and sensory nerve conduction velocities, compared with nondiabetic control animals. In contrast, 4 weeks after intramuscular gene transfer of plasmid DNA encoding VEGF-1 or VEGF-2, vascularity and blood flow in the nerves of treated animals were similar to those of nondiabetic control rats; constitutive overexpression of both transgenes resulted in restoration of large and small fiber peripheral nerve function. Similar experiments performed in a rabbit model of alloxan-induced diabetes produced comparable results. These findings support the notion that diabetic neuropathy results from microvascular ischemia involving the vasa nervorum and suggest the feasibility of a novel treatment strategy for patients in whom peripheral neuropathy constitutes a secondary complication of diabetes.

Endothelial dysfunction is detectable in young normotensive first-degree relatives of subjects with type 2 diabetes in association with insulin resistance.

BACKGROUND: Endothelial dysfunction (ED) is regarded as an early step in the development of atherosclerosis. Among the pathogenetic factors leading to atherosclerosis, the role of insulin resistance and hyperinsulinemia as independent risk factors is still under debate. In this study, we examined the association between ED and insulin resistance in normotensive and normoglycemic first-degree relatives (FDRs) of patients with type 2 diabetes mellitus (DM). METHODS AND RESULTS: Endothelium-dependent and -independent vasodilation of the brachial artery was measured with high-resolution ultrasound (13 MHz) in 53 normotensive FDRs (21 men, 32 women; mean age, 35 years) with normal oral glucose tolerance, 10 age- and sex-matched normal control subjects, and 25 DM patients (mean age, 57 years). According to the tertiles of the clamp-derived glucose metabolic clearance rate (MCR), the FDRs were further classified as insulin resistant with an MCR or =7.8 mL. kg(-1). min(-1), and borderline with an MCR of 5.9 to 7.7 mL. kg(-1). min(-1). Flow-associated dilation was 4.1+/-0.9% in insulin-resistant FDRs, 6.7+/-1.1% in borderline FDRs, 9.0+/-1.2% in insulin-sensitive FDRs (P=0.002), 7.7+/-2.9% in control subjects (P=NS versus FDRs), and 3.8+/-1.0% in DM patients (P=0.03). In multiple regression analysis, low MCR was significantly correlated with ED independent of age, sex, smoking, body mass index, percent body fat, serum insulin, and lipids. CONCLUSIONS: There is a significant association between ED and insulin resistance in young FDRs of DM subjects independent of the classic cardiovascular risk factors.

Intense cholesterol lowering therapy with a HMG-CoA reductase inhibitor does not improve nitric oxide dependent endothelial function in type-2-diabetes--a multicenter, randomised, double-blind, three-arm placebo-controlled clinical trial.

Disturbances in nitric oxide (NO) metabolism resulting in endothelial dysfunction play a central role in the pathogenesis of atherosclerosis in hypercholesterolemia and in individuals with type 2 diabetes. It is unclear whether lipid lowering therapy with HMG-CoA-reductase inhibitors might improve endothelial function in subjects with type 2 diabetes as it is demonstrated in non-diabetic subjects with hypercholesterolemia. We examined the influence of 0.2 mg and 0.8 mg cerivastatin on endothelial function in a multicenter, randomised, double-blind, and three-arm placebo-controlled clinical trial. Endothelial function was assessed by nitric oxide-dependent flow mediated vasodilatation (FMD) of the brachial artery. A total of 103 patients with type 2 diabetes were enrolled in the study. Bayer Company undertook a voluntary action to withdraw cerivastatin from market, therefore the study was terminated earlier. At this point 77 patients were randomised, of which 58 completed the study (mean age 60 +/- 8 years, HbA1c 7.4 +/- 0.9 %). At baseline mean FMD was disturbed in all three therapy arms (5.18 +/- 2.31 % in the placebo group, 3.88 +/- 1.68 in the 0.2-mg cerivastation group, and 4.86 +/- 2.25 in the 0.8-mg cerivastatin group). Despite a significant reduction in cholesterol and LDL-cholesterol-levels after 12 weeks of treatment (decrease in LDL-cholesterol - 26.8 +/- 13.9 % in the 0.2-mg group and - 40.3 +/- 16.0 % in the 0.8-mg group, p = 0.0001, ANCOVA) there was no difference in flow mediated vasodilatation (p = 0.52 and p = 0.56 vs. placebo, respectively, ANCOVA). HbA1c, CRP, and HDL-cholesterol did not change during the study. Furthermore no difference in safety profile between cerivastatin and placebo was found. Despite a significant improvement in lipid profile under statin therapy, no improvement of endothelial dysfunction in terms of nitric oxide bioavailability could be detected.

Flow associated (endothelium dependent) vasodilation and TSH-levels in young normotensive and normoglycemic subjects.

BACKGROUND: Endothelial dysfunction (ED) is regarded as an early step in the development of atherosclerosis. Recent experimental data showed a crosstalk between endothelial NO-synthase activity and thyrotropin production. Therefore we studied whether basal TSH can predict flow associated vasodilation (FAD) in a cohort of healthy young subjects with normal TSH levels. PATIENTS AND METHODS: FAD was evaluated in 60 normotensive and normoglycemic subjects (mean age 34 years; range 18-50). The mean thyrotropin level was 1.43 +/- 0.11 microU/ml (range 0.18-3.52 microU/ml). RESULTS: Comparing subjects in the upper, middle and lower tertile of TSH (2.38 +/- 0.14 microU/ml, 1.23 +/- 0.04 microU/ml and 0.65 +/- 0.06 microU/ml respectively) there was no difference in terms of the classical cardiovascular risk factor profiles (24 h blood pressure, HDL- and LDL-cholesterol, triglycerides, oral glucose load and body fat content). Regarding the vascular parameters, we could neither find an independent association with FAD (7.0 +/- 1.1%, 6.4 +/- 1.0% and 5.8 +/- 1.1% respectively) nor with endothelial independent vasodilation (after application of glycerol trinitrate GTN, 17.3 +/- 1.9%, 18.4 +/- 1.7% bzw. 17.5 +/- 1.6% respectively) between the groups. Furthermore, we could not find a significant association between free thyroid hormones (fT3/fT4) and FAD or GTN-induced vasodilation. CONCLUSION: TSH has no predictive value towards endothelial dysfunction in subjects with thyrotropin levels within the normal range.

Endovascular aneurysm repair of abdominal aortic aneurysms: standards, technical options and advanced indications.

UNLABELLED: Since the introduction of endovascular aneurysm repair (EVAR) in 1991, the endovascular therapy with newest stent grafts has assumed a prominent role in the clinical management of abdominal aortic aneurysms (AAA) with a superior perioperative mortality of EVAR and an equivalent mid-term outcome, compared to open surgery. Newest techniques using chimney or periscope grafts and customized fenestrated and branched stent grafts allow the endovascular treatment of complex pararenal AAA. This article reviews EVAR in the treatment of AAA, evidence based results and advanced indication by newest interventional techniques and technical developments. KEY POINTS: • EVAR has become standard treatment of abdominal aortic aneurysm with equivalent results to open surgery.• Technical advancements and the introduction of newest stent grafts continually expand the indication of EVAR.• Chimney- and periscope grafts as well as custom-made prothesis systems allow endovascular treatment of complex para- and suprarenal aneurysms.

Apelin serum levels are not associated with early atherosclerosis or fat distribution in young subjects with increased risk for type 2 diabetes.

Apelin is proposed to possess protective cardiovascular properties and may furthermore promote favorable effects on glucose metabolism. First data in humans seem to support this hypothesis. Therefore we aimed to assess the meaning of apelin as an early risk indicator in young subjects prone to atherosclerosis and type 2 diabetes. Furthermore we examined the association of apelin serum levels with insulin sensitivity/resistance and body fat distribution as probably dependent cardiovascular risk factors. We examined 344 individuals (f/m=216/128, mean age 46±1 years) with an increased risk for type 2 diabetes. Apelin-36 serum levels were measured via ELISA. Endothelial dysfunction and intima media thickness (IMT) were assessed using high resolution ultrasound. Visceral adipose tissue (VAT) was measured with an axial T1-weighted fast spin echo technique with a 1.5 T whole-body imager. According to the study population's age, FMD (6.4±0.2%) and IMT (0.56±0.01 mm) were within the expected ranges. Gender or age had no influence on serum apelin levels. When looked at early stages of atherosclerosis, we could not detect a significant correlation between apelin serum levels and FMD or IMT. Blood pressure as well was unaffected by serum apelin levels. Furthermore, neither parameters of insulin sensitivity like insulin sensitivity index (ISI), nor fat distribution like BMI, grade of adiposity, total adipose tissue or VAT were associated with apelin serum levels. We conclude that apelin serum levels do not add further information on the cardiovascular-, or diabetes risk pattern in a diabetes prone population.

Reducing visceral adipose tissue mass is essential for improving endothelial function in type 2 diabetes prone individuals.

OBJECTIVE: In obesity, particularly increased visceral- (VAT), but not total (TAT) adipose tissue mass is a major source of proinflammatory cytokine expression and secretion. VAT, more than TAT, is associated with endothelial dysfunction (ED), which is an accepted risk factor for atherosclerosis. Consequently, we hypothesized that during a lifestyle intervention specifically a decrease in VAT, rather than TAT, is associated with improved ED and vascular adhesion molecules in type 2 diabetes prone subjects. METHODS: Analyses were done in 189 individuals (age: 45.4±0.8 years) at increased risk of type 2 diabetes, who underwent a 9-month lifestyle intervention. ED expressed as flow mediated dilation (FMD) of the brachial artery, sE-selectin, sV-CAM, sI-CAM, TAT and VAT (measured by magnetic resonance tomography) was determined. RESULTS: There was a mean decrease in body weight (-3%, p<0.0001), TAT (-7.6%, p<0.0001) and VAT (-12.5%, p<0.0001), while FMD increased (+9.1%, p=0.04). The change in FMD was not associated with change in body weight (p=0.35) or TAT (p=0.21) but with a decrease in VAT (r=-0.19, p=0.009). In a post hoc analysis, the subjects were divided by the median change in VAT into responders and non-responders. FMD increased only in the responders (from 6.2±0.4% to 8.0±0.5%, p=0.0005) but not in the non-responders (p=0.15). Also sE-selectin significantly decreased only in the responders (from 54±4 ng/ml to 47±3 ng/ml; p=0.03). CONCLUSION: During a lifestyle intervention, not weight loss or decrease in TAT, but decrease in VAT is associated with improved ED in individuals prone to type 2 diabetes. Therefore, primary cardiovascular prevention should focus specifically on reducing VAT rather than body weight alone.

Endothelial NO-synthase intron 4 polymorphism is associated with disturbed in vivo nitric oxide production in individuals prone to type 2 diabetes.

Insulin resistance, as well as vascular disease, both share a relevant genetic background taking the influence of a positive family history of these disorders. On the other hand, insulin resistance is associated with a proatherosclerotic disturbance in nitric oxide dependent vasodilation, probably contributing to the link between these two disorders. We examined the association between nitric oxide dependent vasodilation (measured with high resolution ultrasound at 13 MHz) and three relevant NO-synthase (eNOS)-polymorphisms in 200 insulin resistant subjects participating in the Tuebinger Lifestyle Intervention Program (TULIP). This study revealed that carriers of the eNOS intron 4 polymorphism (aa 2.16%; ab 24.2%; bb 73.2%) show significantly worse endothelial, and thereby eNOS dependent vasodilation (p=0.03, multivariate ANOVA), as compared to wildtype carriers. The 5' UTR T-786C and the G894 T polymorphism did not show any influence on eNOS-activity. In subjects at increased risk to develop type 2 diabetes, the eNOS intron 4 polymorphism is independently associated with endothelial function as indicated by disturbed endothelial NO production. Due to the high prevalence and the relatively strong effect, this polymorphism might help to identify subjects at increased risk for atherosclerosis associated with overweight and insulin resistance.

Perivascular fatty tissue at the brachial artery is linked to insulin resistance but not to local endothelial dysfunction.

AIMS/HYPOTHESIS: Different ectopic fat depots, such as visceral or hepatic fat, are known to affect whole body insulin sensitivity. It has recently been hypothesised that differences in perivascular adipose tissue (PVAT) mass around resistance vessels may also contribute to insulin resistance, possibly via direct vascular effects leading to reduced capillary cross-sectional area in the muscle, which in turn affects muscular blood flow and glucose uptake. Based on this, the aim of the present study was to test whether PVAT around conduit arteries (i.e. the brachial artery) influences NO bioavailability, expressed as flow-mediated dilation (FMD), or insulin sensitivity in humans in vivo. METHODS: Insulin sensitivity was measured by OGTT in all 95 participants (59 women, 36 men; median age 47 years, range 19-66 years) and by the gold standard, a euglycaemic-hyperinsulinaemic clamp, in a randomly selected subgroup of 33 participants. Quantification of the different fat compartments, including PVAT around the brachial artery, was achieved by high-resolution magnetic resonance imaging (1.5 T). Blood flow and FMD were measured at the brachial artery using high-resolution (13 MHz) ultrasound, after 5 min of forearm occlusion. RESULTS: PVAT was negatively correlated with insulin sensitivity and the post-ischaemic increase in blood flow. The association between PVAT and insulin sensitivity (r = -0.54, beta = -0.37, p = 0.009) was independent of age, sex, visceral adipose tissue, liver fat, BMI and further cardiovascular risk factors. No correlation could be detected between PVAT and local endothelial function. However, we observed an independent association between PVAT and post-ischaemic increase in blood flow (r = -0.241; beta = -1.69; p = 0.02). CONCLUSIONS/INTERPRETATION: PVAT seems to play an independent role in the pathogenesis of insulin resistance. This may be due to direct vascular effects influencing muscular blood flow.

[Early systolic notched peripheral Doppler flow pattern as an indicator of functional obstruction of the common iliac artery after iatrogenic aortic dissection: a case report]. / Frühsystolisch eingekerbte periphere Dopplerflusssignale als Hinweis auf eine funktionelle Obstruktion der Arteria iliaca communis bei iatrogener Aortendissektion: ein Fallbericht.

We report on a 57-year-old male patient with typical claudication localised in the right thigh, following aortic valve replacement. The ankle brachial index under resting conditions is within normal range on both sides. A conspicuous monomorphic double-humped peripheral Doppler flow pattern with an early systolic notch extending to the baseline can be registered in all the arteries of the right lower limb. The flow patterns of all other peripheral arteries are properly configured and of triphasic morphology. As the underlying cause of the pathologically altered Doppler flow morphology, aortic dissection Type A can be detected, extending from the former cannulation site of the ascending aorta into the right common iliac artery. Its dissection membrane functionally occludes the right common iliac artery in the early systole, the effect being brief and reversible. The pathogenesis of this morphologically altered Doppler flow pattern and potential differential diagnoses are discussed in this case report, also considering the current literature.

Early carotid atherosclerosis in overweight non-diabetic individuals is associated with subclinical chronic inflammation independent of underlying insulin resistance.

Overweight in children and young adults is an increasing problem in Western industrialized countries with potential impact on cardiovascular morbidity. Whether early arterial wall thickening in these subjects mainly results from the often associated insulin resistance syndrome or from increased subclinical chronic inflammation probably triggered by adipose tissue is still under discussion. We therefore determined insulin sensitivity index (ISI) by performing an euglycaemic hyperinsulinaemic glucose clamp (insulin infusion rate 1 mU/kg/min) and high-sensitivity C-reactive protein (hsCRP) levels in relation to the intima-media thickness (IMT) at the common carotid artery (high resolution ultrasound; 13 MHz) in 81 young (age 33 +/- 1 years), moderately overweight subjects. To reduce the number of confounding variables, subjects with disturbances in glucose metabolism (75 g oral glucose tolerance test) and hypertension were excluded. As expected, higher BMI was positively correlated with increased IMT (r = 0.358; p = 0.001). After multiple regression analysis, hsCRP levels independently correlated to IMT (r = 0.251; p = 0.03), even after adjusting for age, sex, BMI, ISI, LDL cholesterol and smoking as cofactors. However, taking all above listed factors into account, glucose-clamp assessed insulin sensitivity was not correlated with IMT. Thus, overweight might trigger inflammatory mechanisms leading to vascular wall hypertrophy independent of the insulin resistance syndrome already early in life.

[Indicators of incipient atherosclerosis: demonstration of endothelial dysfunction with high-resolution ultrasound]. / Indikatoren einer beginnenden Atherosklerose: Erfassung der endothelialen Dysfunktion mittels hochauflösendem Ultraschall.

Endothelial function is thought to play a central role in the process of atherosclerosis, and in the pathogenesis of arterial hypertension and chronic heart failure. In the last decade a non-invasive ultrasound technique has been developed to measure endothelium-dependent vasodilation of the brachial artery which allows quantification of endothelial function. This method is based upon results in basic research, which show increased endothelial NO-production following the impact of shear forces on the endothelial surface. The resulting vasodilation can be quantified with high resolution ultrasound (7-13 MHz). The advantage of this technique is its non-invasive nature, which allows a risk-free use even in young individuals. Repeated measurements to control the success of medical intervention are also not problematic. Despite the possibility of widespread use because of its deceptively simple protocol, there are numerous factors affecting flow-mediated vascular reactivity. Details of the methods applied, variations in examination procedure, image acquisition, subjects preparation, equipment, training requirements and data interpretation are reviewed in this paper. Clinical studies of cardiovascular disease, risk factor profiles and the prognostic impact of measuring flow-mediated vasodilation are also discussed.

Impaired non-esterified fatty acid suppression is associated with endothelial dysfunction in insulin resistant subjects.

In a recent study, we found a significant association between insulin resistance (IR) and disturbed flow-associated (endothelial-dependent) vasodilation in first-degree relatives of subjects with type 2 diabetes. However, the mechanisms linking insulin resistance and endothelial dysfunction (ED) have not been fully elucidated. Experimental data have pointed out that non-esterified fatty acids (NEFA) have a modulating effect on NO-synthase activity, and therefore on endothelial function. The aim of our study was to evaluate whether insulin resistance associated impaired NEFA suppression is present in subjects with ED. We examined 53 first-degree relatives (FDR) of patients with type 2 diabetes (32f, 21 m, mean age 35 years). Endothelial function was measured as flow-associated vasodilation (FAD%) of the brachial artery. Insulin sensitivity was evaluated with a standard hyperinsulinemic glucose clamp (insulin infusion rate of 1 mU/kg/min). While under fasting conditions, NEFA did not differ between groups with high or low FAD (0.415+/-0.033 vs. 0.394 +/- 0.040 mmol/l; p = n. s.), reduced FAD% was significantly associated with higher non-esterified fatty acids concentrations during steady state of the glucose clamp (0.072+/-0.022 vs. 0.039+/-0.016mmol/l; p=0.04). This association was independent of insulin levels under fasting conditions and during the glucose clamp. In conclusion, our results reveal a significant association between endothelial dysfunction and impaired non-esterified fatty acid suppression in insulin resistant subjects. As insulin resistance of lipolysis is a feature of the insulin resistance syndrome, these results suggest that elevated NEFA concentrations could play a role linking endothelial dysfunction and insulin resistance in vivo.

[Influence of experience on intra- and interindividual variability in assessing peripheral endothelial dysfunction with high resolution ultrasound]. / Einfluss der Untersuchererfahrung auf intra- und interindividuelle Variabilität bei der Erfassung der peripheren Endothelfunktion mittels hochauflösendem Ultraschall.

UNLABELLED: The non-invasive evaluation of endothelial dysfunction with high-resolution ultrasound has become a widely accepted tool in determination of high-risk subjects for early atherosclerosis. Furthermore it is often used as intermediate outcome in intervention studies. AIM: We examined the influence of examiner experience on intra- and inter-individual variability in the measurement of flow-associated vasodilation (FAD) independent of automated analysis systems. METHOD: FAD was measured on two occasions in 7 and 8 subjects respectively (mean age 32 +/- 3 years) by two investigators after different prior training procedures with a 13 MHz linear transducer (LA14A, ESAOTE Biomedica). RESULTS: The intra-individual variability expressed as median absolute difference in the measurements of FAD was 1.1 % (range from 0.03 % to 3.2 %) for examiner one with an experience of more than 50 FAD measurements through former studies and 2.9 % (range from 1.6 % to 9.2 %) for examiner two with only 10 training examinations under supervision. By a further training period of two months, with an increase of examinations of additional 20 measurements by both examiners, the intra-observer variability could be dropped to 0.9 % (range from 0.03 % to 1.3 %) for examiner two (p = 0.0025) with no significant change for examiner one (median 0.6 % with a range from 0.14 % to 3.7 %). As expected, the inter-individual variability was not influenced by this further training (median 1.0 % with a range of 0.5 % to 3.6 % versus a median of 1.6 % with a range from 0.15 % to 7.5 %). CONCLUSION: 30 training measurements of FAD under supervision should be regarded as minimum requirement for valid determination of endothelial function. The reachable result for the intra-observer variability is thereby within the range of computed analysis systems.