Associations of metabolically healthy obesity with prevalence and progression of coronary artery calcification: Results from the Heinz Nixdorf Recall Cohort Study.

BACKGROUND AND AIMS: There is controversy on the potentially benign nature of metabolically healthy obesity (MHO), i.e., obese persons with few or no metabolic abnormalities. So far, associations between MHO and coronary artery calcification (CAC), a measure of subclinical atherosclerosis, have mainly been studied cross-sectionally in Asian populations. We assessed cross-sectional and longitudinal MHO CAC associations in a Caucasian population. METHODS AND RESULTS: In the Heinz Nixdorf Recall Study, a population-based cohort study in Germany, CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. For cross-sectional and longitudinal analyses, we included 1585 participants free of coronary heart disease at baseline, with CAC measurements at baseline and at follow-up, and with either normal weight (BMI 18.5-24.9 kg/m2) or obesity (BMI ≥30.0 kg/m2) at baseline. We used four definitions of MHO. In our main analysis, we defined obese persons as metabolically healthy if they met ≤1 of the NCEP ATP III criteria for the definition of the metabolic syndrome - waist circumference was not taken into account because of collinearity with BMI. Persons with MHO had a higher prevalence of CAC than metabolically healthy normal weight (MHNW) persons (prevalence ratio = 1.59 (95% confidence interval 1.38-1.84) for the main analysis). Persons with MHO had slightly larger odds of CAC progression than persons with MHNW (odds ratios ranged from 1.17 (0.69-1.99) to 1.48 (1.02-2.13) depending on MHO definition and statistical approach). CONCLUSION: Our analyses on MHO CAC associations add to the evidence that MHO is not a purely benign health condition.

Association of dietary patterns with five-year degree and progression of coronary artery calcification in the Heinz Nixdorf Recall study.

BACKGROUND AND AIMS: As a modifiable lifestyle factor, diet is hypothesized to play an important role in the progression of atherosclerosis. The aim of this study was to explore associations of comprehensive dietary patterns derived by cluster analysis with degree and progression of coronary artery calcification (CAC) over five years of follow-up. METHODS AND RESULTS: In the population-based Heinz Nixdorf Recall study, 3718 participants (45-75 years; 47.6% men) without coronary heart disease completed a food frequency questionnaire at baseline. Five distinct dietary patterns were identified using cluster analysis: "Health-conscious", "Traditional German/Less alcohol", "Mediterranean-like", "Western" and "Animal fat/Alcohol" (used as reference). CAC was measured using electron-beam computed tomography at baseline and five years later. CAC after five years was predicted based on sex- and age-specific baseline percentiles. After comparing observed and predicted CAC Scores, CAC progression was classified as slow, expected, or rapid. Compared to "Animal fat/Alcohol" diet, a "Mediterranean-like" diet was associated with a relative risk (RR) for a rapid CAC progression in both sexes (men: 0.61; 95%-confidence interval [95%-CI]: 0.41; 0.90; women: 0.59; 95%-CI: 0.45; 0.78). Furthermore, reduced RRs were observed in women with a "Health-conscious" and a "Traditional German/Less alcohol" diet (0.63; 95%-CI: 0.47; 0.84, respectively 0.69; 95%-CI: 0.52; 0.90). No association was observed for a "Western" diet for both sexes. Similar results were revealed for degree of CAC. CONCLUSION: The study results support the hypothesis that a "Mediterranean-like" diet is associated with a lower CAC-progression and lower degree of CAC in men and women.

Sunitinib Efficacy in Patients with Advanced pNET in Clinical Practice.

Sunitinib treatment leads to improvement in progression-free survival in patients with advanced pancreatic neuroendocrine tumours (pNETs). However, limited data exist regarding the effectiveness, safety and tolerability in clinical practice. We present the results of the first detailed pNET cohort analysis since sunitinib was approved. Patients with advanced, differentiated pNET treated with sunitinib were retrospectively analysed. All patients had progressive disease before start of sunitinib treatment. Twenty-one patients, with a median age of 64 years (range 28-78), were included in this study. Nineteen patients could be analysed for treatment effectiveness. Twelve (57%) patients exhibited either a partial response (1 patient) or stable disease (11 patients) according to the RECIST criteria. The median progression-free survival was 7.0 months (95% CI 3.0-12.0); the probability of being event-free at 6 months was 52.6% (95% CI 28.4-72.1). Potential influencing factors as Ki-67 index, age or duration of disease did not show significant correlations with the response to sunitinib therapy. Considering the differences in patients' characteristics, sunitinib in daily practice showed effectiveness parameters similar to the phase III trial.

Progression of coronary artery calcification by cardiac computed tomography.

The presence and extent of coronary artery calcification (CAC) is established in primary prevention since the CAC score is the single best predictor of future cardiovascular events. While CAC progresses with increasing age, individual CAC progression can be estimated based on the subject's age, gender, and CAC percentile at first examination. To date, several algorithms and methods for the definition of CAC progression are available in the literature. Increased CAC progression is associated with traditional cardiovascular risk factors including hypertension, diabetes, and smoking status. Also, lipid-lowering therapy may influence the progression of CAC. Epicardial adipose tissue is a further cardiovascular risk marker that may lead to intensified CAC progression if its volume increases. In terms of clinical implications, initial data suggest that extensive CAC progression is linked to worse outcome; however, further studies are needed to establish this relationship and to define appropriate time intervals between repetitive examinations. This review article gives an overview of the existing literature with an emphasis on various definitions of CAC progression, predictors of increased CAC progression, as well as clinical implications.

B-type natriuretic peptide predicts stroke of presumable cardioembolic origin in addition to coronary artery calcification.

BACKGROUND AND PURPOSE: B-type natriuretric peptide (BNP) is a marker of cardiac dysfunction that is released from myocytes in response to ventricular wall stress. Previous studies suggested that BNP predicts stroke events in addition to classical risk factors. It was suggested that the BNP-associated risk results from coronary atherosclerosis or atrial fibrillation. METHODS: Three thousand six hundred and seventy five subjects from the population-based Heinz Nixdorf Recall study (45-75 years; 47.6% men) without previous stroke, coronary heart disease, myocardial infarcts, open cardiac valve surgery, pacemakers and defibrillators were followed up over 110.1 ± 23.1 months. Cox proportional hazards regressions were used to examine BNP as a stroke predictor in addition to vascular risk factors (age, gender, systolic blood pressure, low-density lipoprotein, high-density lipoprotein, diabetes, smoking), renal insufficiency, atrial fibrillation/known heart failure and coronary artery calcification. RESULTS: Eighty-nine incident strokes occurred (80 ischaemic, 9 hemorrhagic). Subjects suffering stroke had significantly higher BNP values at baseline than the remaining subjects [26.3 (Q1; Q3 = 12.9; 51.0) vs. 17.4 (9.4; 31.4); P < 0.001]. In a multivariable regression, log10 BNP was an independent stroke predictor [hazard ratio 1.96, 95% confidence interval (CI) 1.13-3.41; P = 0.017] in addition to age (1.24 per 5 years, CI 1.04-1.49; P = 0.016), systolic blood pressure (1.25 per 10 mmHg, CI 1.14-1.38; P < 0.001), smoking (2.05, CI 1.24-3.39; P = 0.005), atrial fibrillation/heart failure (2.25, CI 1.05-4.83; P = 0.037) and computed-tomography-based log10 (coronary artery calcification + 1) (1.47, CI 1.15-1.88; P = 0.002). Log10 BNP predicted stroke in men but not women, both in subjects ≤65 and >65 years. In subsequent analyses, BNP discriminated the incidence of cardioembolic stroke (P for trend = 0.001), but not stroke of macroangiopathic (P = 0.555), microangiopathic (P = 0.809) or unknown (P = 0.367) origin. CONCLUSIONS: BNP predicts presumable cardioembolic stroke independent of coronary calcification.

[Distribution of carotid intima media thickness in men and women with and without coronary heart disease. Cross-sectional data of the Heinz Nixdorf Recall Study]. / Verteilung der karotidalen Intima-Media-Dicke bei Männern und Frauen mit und ohne koronare Herzerkrankung : Querschnittsdaten aus der Heinz Nixdorf Recall Studie.

PURPOSE: The aim of this study was to introduce population-based sex and age-stratified distributions of carotid intima media thickness (CIMT), to compare fixed cut-off and percentile values for subjects with and without known coronary heart disease (CHD) and to describe CIMT percentiles. METHODS: Between 2000 and 2003, a total of 4,814 subjects aged 45-75 years were recruited into the Heinz Nixdorf recall study (HNR). Ultrasound examination of extracranial arteries was performed and the CIMT was measured manually over a distance of 1 cm proximal to the bulb in the common carotid artery (CCA). Both sides were measured and the average of the right and left artery were calculated (mean CIMT). RESULTS: The CIMT was measured for 1,749 men and 1,802 women without prevalent CHD and 177 men and 50 women with prevalent CHD. Mean CIMT values were higher in men compared to women (men 0.71 ± 0.14 mm vs. women 0.65 ± 0.11 mm, p ≤ 0.0001) and in subjects with CHD compared to those without (men with and without CHD: 0.76 ± 0.14 mm and 0.70 ± 0.14 mm, p ≤ 0.0001, respectively; women with and without CHD: 0.73 ± 0.15 mm and 0.64 ± 0.11 mm, p ≤ 0.0001, respectively). In men the mean CIMT increased from 0.62 ± 0.10 mm in the youngest (45-49 years old) up to 0.79 ± 0.13 mm in the highest age group (≥ 70 years) (0.57 ± 0.08 mm up to 0.71 ± 0.12 mm in women, p ≤ 0.0001 for both). CONCLUSIONS: Compared to international studies similar CIMT distributions were found in this study using both continuous and percentile distributions. However, lower CIMT values were observed in older participants, which can be explained by exclusion of carotid plaque formation in CIMT measurements.

Dose-escalated radiotherapy with PET/CT based treatment planning in combination with induction and concurrent chemotherapy in locally advanced (uT3/T4) squamous cell cancer of the esophagus: mature results of a phase I/II trial.

BACKGROUND: This prospective phase I/II trial assessed feasibility and efficacy of dose-escalated definitive chemoradiation after induction chemotherapy in locally advanced esophageal cancer. Primary study endpoint was loco-regional progression-free survival at 1 year. METHODS: Eligible patients received 2 cycles of induction chemotherapy with irinotecan, folinic acid and 5-fluorouracil weekly and cisplatin every 2 weeks (weeks 1-6, 8-13) followed by concurrent chemoradiation with cisplatin and irinotecan (weeks 14, 15, 17, 18, 20). Radiotherapy dose escalation was performed in three steps (60 Gy, 66 Gy, 72 Gy) using conventional fractionation, planning target volumes were delineated with the aid of 18F-FDG-PET/CT scans. During follow-up, endoscopic examinations were performed at regular intervals. RESULTS: Between 09/2006 and 02/2010, 17 patients were enrolled (male/female:13/4, median age: 59 [range 48-66] years, stage uT3N0/T3N1/T4N1: 4/12/1). One patient progressed during induction chemotherapy and underwent surgery. Of 16 patients treated with definitive chemoradiotherapy, 9 (56%) achieved complete response after completion of chemoradiation. One-, 2-, 3- and 5-year overall survival rates (OS) were 77% [95%CI: 59-100], 53% [34-83], 41% [23-73], and 29% [14-61], respectively. Loco-regional progression-free survival at 1, 3, and 5 years was 59% [40-88], 35% [19-67], and 29% [14-61], corresponding cumulative incidences of loco-regional progressions were 18% [4-39%], 35% [14-58%], and 41% [17-64%]. No treatment related deaths occurred. Grade 3 toxicities during induction therapy were: neutropenia (41%), diarrhoea (41%), during combined treatment: neutropenia (62%) and thrombocytopenia (25%). CONCLUSIONS: Dose-escalated radiotherapy and concurrent cisplatin/irinotecan after cisplatin/irinotecan/5FU induction chemotherapy was tolerable. The hypothesized phase II one-year loco-regional progression free survival rate of 74% was not achieved. Long-term survival compares well with other studies on definitive radiotherapy using irinotecan and cisplatin but is not better than recent trials using conventionally fractionated radiotherapy ad 50 Gy with concurrent paclitaxel or 5FU and platinum compound. Trial registration The present trial was registered as a phase I/II trial at the EudraCT database: Nr. 2005-006097-10 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-006097-10/DE ) and authorized to proceed on 2006-09-25.

Development and longitudinal validation of the overall benefit of analgesia score: a simple multi-dimensional quality assessment instrument.

BACKGROUND: The goal of this study was to develop and validate the overall benefit of analgesic score (OBAS), which assesses pain intensity and the opioid-related adverse effects. METHODS: The score was developed and validated in four trials (n=1470 patients). Data from randomized trial I were used to develop the OBAS (factor analysis). Data from randomized trial II were used to compare the resolution of rofecoxib's analgesic effects between OBAS and pain scores. Randomized trial III (spine surgery) was conducted to evaluate prospectively the reliability of the OBAS and to compare its resolution of analgesic treatment with the opioid-related symptom distress scale (OR-SDS) and the modified brief pain inventory short form (m-BPI-sf). Trial IV was conducted to evaluate in patients with a moderate-to-high level of postoperative pain (after major abdominal surgery) the relation of OBAS and pain scores for patients' satisfaction with analgesic therapy. RESULTS: The seven-item OBAS yielded a higher resolution of analgesic treatment effects than pain scores, the OR-SDS and m-BPI-sf. The OBAS has a fair inter-rater reliability (concordance correlation of 0.71 c) and is more sensitive (P=0.03) in indicating the delivery of opioid boluses than the dedicated OR-SDS. The OBAS, but not pain scores at rest or pain scores during movement, explained significant variance in patients' satisfaction with postoperative pain therapy. CONCLUSIONS: The OBAS is a simple, multi-dimensional quality assessment instrument to measure patients' benefit from postoperative pain therapy. Opioid symptom distress, pain relief, and patients' satisfaction are combined in a reliable and valid tool.

Residential exposure to traffic is associated with coronary atherosclerosis.

BACKGROUND: Long-term exposure to fine-particulate-matter (PM2.5) air pollution may accelerate the development and progression of atherosclerosis. We investigated the associations of long-term residential exposure to traffic and fine particulate matter with the degree of coronary atherosclerosis. METHODS AND RESULTS: We used baseline data on 4494 participants (age 45 to 74 years) from the German Heinz Nixdorf Recall Study, a population-based, prospective cohort study that started in 2000. To assess exposure differences, distances between residences and major roads were calculated, and annual fine particulate matter concentrations, derived from a small-scale dispersion model, were assigned to each address. The main outcome was coronary artery calcification (CAC) assessed by electron-beam computed tomography. We evaluated the association between air pollution and CAC with logistic and linear regression analyses, controlling for individual level risk factors of coronary atherosclerosis. Compared with participants living >200 m away from a major road, participants living within 50, 51 to 100, and 101 to 200 m had odds ratios of 1.63 (95% CI, 1.14 to 2.33), 1.34 (95% CI, 1.00 to 1.79), and 1.08 (95% CI, 0.85 to 1.39), respectively, for a high CAC (CAC above the age- and gender-specific 75th percentile). A reduction in the distance between the residence and a major road by half was associated with a 7.0% (95% CI, 0.1 to 14.4) higher CAC. Fine particulate matter exposure was associated with CAC only in subjects who had not been working full-time for at least 5 years. CONCLUSIONS: Long-term residential exposure to high traffic is associated with the degree of coronary atherosclerosis.

Alterations in forearm vascular reactivity in patients with septic shock.

Patients with septic shock are haemodynamically unstable and suffer from vasodilation. Studying the human forearm vascular bed in patients with septic shock, we tested the hypothesis that the responses to regionally infused endothelium-(in)dependent vasodilators and vasoconstrictors are uniformly impaired. Forearm blood flow (FBF, venous occlusion plethysmography) and brachial arterial pressure were determined to calculate forearm vascular resistance (FVR) in eight consecutive sedated, mechanically ventilated patients with septic shock (APACHE II Score range 21-34, SOFA Score 11-16) and 11 healthy volunteers. Despite increased baseline FBF in patients with septic shock (6.1 (SD 1.5) ml x min(-1) x (100 ml of tissue)(-1) compared to 4.7 (1.4) in volunteers) the significant decreases in FVR seen in response to exogenous nitric oxide (nitroprusside) and acetylcholine did not differ between groups. However, compared to volunteers, mitigation of endogenous nitric oxide production by a low dose of N(G)-methyl-L-arginine acetate (L-NMMA) caused a significant increase (+6.7 mmHg x min x ml(-1)) in septic patients. Regional vasoconstriction in response to phenylephrine (FVR: +9.9 vs +30.7 mmHg x min x ml(-1) in controls) and angiotensin II (FVR: +9.0 vs +67.4 mmHg x min x ml(-1)) was markedly impaired. In contrast, vasopressin, in dosages evoking no vasoconstriction in volunteers, induced a significant increase in FVR in septic patients (+10.0 mmHg x min x ml(-1)). In the forearm of patients with septic shock, vasoconstriction by alpha1- and angiotensin II receptor agonists is selectively impaired, whereas the vasoconstrictor response to vasopressin is exaggerated. These findings exclude a generalised impairment of vasomotor activity in patients with septic shock and provide a rationale for vasopressin administration.

Mediterranean diet has no effect on markers of inflammation and metabolic risk factors in patients with coronary artery disease.

OBJECTIVE: Mediterranean diet is associated with decreased levels of inflammatory markers and metabolic risk factors in epidemiologic studies and recent trials on patients with metabolic syndrome. Given the recent improvements in medical treatments, it is unclear if such beneficial effects are also present in patients with coronary artery disease (CAD). We therefore investigated the effect of Mediterranean diet on markers of inflammation and metabolic risk factors in patients with treated CAD. DESIGN: Randomized, controlled trial. SUBJECTS: A total of 101 patients (59.4+/-8.6 years, 23% female) with established and treated CAD (80% statins). INTERVENTIONS: Participants were assigned to a Mediterranean diet group (MG; n=48) with a 1-year program of 100 h of education, or to a written advice-only group (AG; n=53). Before and after intervention, we measured serum high-sensitivity C-reactive protein (hs-CRP), fibrinogen, fasting insulin, homocysteine, serum lipids and plasma fatty acids. RESULTS: The Mediterranean diet program increased the intakes of fish, fruits/vegetables and moderately of canola/olive oil and increased plasma concentrations of long-chain n-3 polyunsaturated fatty acids in the MG. Median hs-CRP and mean fibrinogen, homocysteine, fasting insulin, triglycerides and serum cholesterols remained unchanged in both groups. CONCLUSIONS: Adoption of a Mediterranean diet by patients with medically treated CAD has no effect on markers of inflammation and metabolic risk factors. SPONSORSHIP: Alfried Krupp Foundation, Essen, Germany.

Comparison of electron microscopy, enzyme-linked immunosorbent assay, solid-phase radioimmunoassay, and indirect immunofluorescence for detection of human rotavirus antigen in faeces.

Four techniques were compared for their practicability, speed, and sensitivity for the detection of human rotavirus. Radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) were found to be the most sensitive means of identifying rotavirus, and, once processed, up to 40 specimens could be examined daily. Electron microscopy, although less sensitive than these techniques, had the advantage of being able to detect other viral agents present in faecal extracts. Indirect immunofluorescence failed to detect rotavirus as often as the other three methods. In laboratories where routine examination of faecal specimens from patients with gastroenteritis is required, ELISA and RIA are useful alternatives to electron microscopy.

The detection of hepatitis B surface antigen by radioimmunoassay.

A comparative study was performed to assess the sensitivity and specificity of counterimmunoelectrophoresis (CIEP) and radioimmunoassay (RIA) for the detection of hepatitis B surface antigen. The 8,823 sera examined included selected reference panels and sera collected from populations with low, moderate and high rates of chronic antigen carriage. Overall, hepatitis B surface antigen was detected in 265 sera by CIEP and in 376 by RIA. As well as detecting 46.4% additional positives, the RIA test detected all CIEP-positive sera; i.e., there were no false negative results. However, 150 sera (1.8% of the total tested) gave a positive result by RIA which was not repeatable on retesting. The explanation for this phenomenon appeared to lie in inadequate washing of the antibody-coated tubes.

Plasma levels of immunoinhibitory cytokines interleukin-10 and transforming growth factor-beta in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Cardiovascular surgery with extracorporeal circulation causes a systemic inflammatory response, which can lead to organ failure and increased postoperative morbidity. Advances in knowledge about the interactions between markers of cellular and humoral immunity involved in the inflammatory response to cardiopulmonary bypass (CPB) may reduce the deleterious effects and improve the outcome for patients undergoing cardiac surgery. METHODS: To determine the release of immunoinhibiting cytokines during CPB, we measured plasma levels of interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) in 30 patients undergoing elective coronary artery bypass grafting. Arterial blood samples were collected at eight time points before, during and after CPB, using a standardized ELISA-technique. RESULTS: Plasma IL-10 and TGF-beta increased significantly after weaning off CPB (P < 0.05) and peaked respectively at time of skin closure (IL-10, 308 +/- 180 pg/ml; TGF-beta, 1860 +/- 906 pg/ml; mean peak +/-S.D.). Postoperatively, 6 h, IL-10 decreased to 19.8 +/- 9.8 pg/ml (P < 0.05) and TGF-beta decreased to 1133 +/- 547 pg/ml (P < 0.05). CONCLUSIONS: Both cytokines are major immunoregulatory factors with negative influence on T cell-mediated immunologic response. The significantly elevated levels at the end of CPB indicate that IL-10 and TGF-beta may be important factors of immunologic dysregulation following CPB.

Identification of lorazepam and sildenafil as examples for the application of LC/ionspray-MS and MS-MS with mass spectra library searching in forensic toxicology.

A mass spectra (MS) library using in-source collision induced dissociation (ESI-CID) as well as a tandem-mass spectra (MS-MS) library with product ion spectra of drugs has recently been developed with a triple-quadrupole ionspray mass spectrometer [1,2]. For the ESI-CID MS library, single-quadrupole mode and for the MS-MS library triple-quadrupole mode have been used. These mass spectra libraries were applied successfully for the general-unknown screening for drugs and metabolites in serum and urine with liquid-chromatography-mass spectrometry (LC-MS) using a PE/SCIEX API 365 with a turboionspray source. As examples, the identification of lorazepam and lorazepam-glucuronide in a serum extract and the identification of sildenafil and alkyloxidated sildenafil in urine are presented here.

Cardiac risk in patients with treatment naïve, first-line medically controlled and first-line surgically cured acromegaly in comparison to matched data from the general population.

INTRODUCTION: Coronary risk factors in patients with acromegaly after first-line transsphenoidal surgery (TSS) or first-line somatostatine analogue (SSA) treatment have rarely been examined. Aim of this study was an evaluation of cardiovascular risk factors and left ventricular hypertrophy (LVH) in 3 different patient groups with treatment naïve, active (ACT), first-line medically controlled (MED) and first-line surgically treated (SUR) acromegaly and a calculation of the Framingham Weibull Risk Score (FS). DESIGN: Retrospective comparative matched case-control study. PATIENTS & METHODS: 40 acromegalic patients (cases aged 45-74 years, 23 men) were matched with respect to age and gender to 200 controls from the general population. 13 patients had treatment-naïve acromegaly (ACT), 12 patients were SSA treated (MED) and 15 patients were operated by TSS (SUR). Coronary risk factors were assessed after 12 months of treatment by interviews and direct laboratory measurements. Only patients normalized for IGF-I in MED and SUR group were included. FS and odds ratios (OR) from multiple conditional logistic regression (matched for age and gender, adjusted for BMI) were calculated. RESULTS: Compared to matched controls ACT patients had higher HbA1c levels (6.9±1.4 vs. 5.5±0.7% (p<0.0001)) and an increased prevalence of left ventricular hypertrophy (LVH) (30.8 vs. 3.2% (p=0.007). MED and SUR groups were similar for gender, age, disease duration and IGF-I levels at diagnosis. Compared to matched controls, MED patients had a significantly increased diastolic blood pressure (89±9 vs. 79±11 mmHg (p=0.001), prevalence of LVH (41.7 vs. 1.7% (p<0.0001), prevalence of diabetes mellitus (33.3 vs. 10.0% (p=0.03)), higher HbA1c levels (6.8±1.3 vs. 5.5±0.7% (p=0.0005)) and a higher FS (21.2±9.7 vs. 12.4±7.7% (p=0.002), OR 1.11 [1.02-1.21] (p=0.01)) while in the SUR group only higher prevalences of LVH (40.0 vs. 4.1% (p<0.0001)) and HbA1c levels (6.4±1.2 vs. 5.5±0.8% (p=0.006)) were found compared to controls. CONCLUSION: When comparing treatment naive, medically treated and surgically cured patients with acromegaly to age- and gender-matched subjects from the general population, we have found an increased cardiovascular risk in patients at 12 months after first-line SSA treatment but not in patients after first-line surgery.

[Functional activity of autonomous adenoma in Germany]. / Funktionelle Aktivität fokaler Schilddrüsenautonomien in Deutschland.

BACKGROUND: The American (ATA) and the European Thyroid Association (ETA) recommend a thyroid scintiscan for the detection of a suspected autonomy only when serum thyrotropin (TSH) levels are low or suppressed. If ultrasound reveals a thyroid nodule > 1.0 cm and TSH is normal, a fine-needle biopsy is recommended without a preceding scintiscan as the next step. The aim of this prospective study was to evaluate the incidence of reduced or suppressed TSH in 100 autonomous adenoma > 1.0 cm and to clarify, if normal TSH does substantially exclude a focal autonomy. When the study was conducted no data of German patients were available. PATIENTS AND METHODS: An unselected group of 496 patients with a nodular goiter was continuously screened by scintiscan in order to detect 100 autonomous adenoma > 1.0 cm for the study. The following investigations were carried out: ultrasound, scintiscan and laboratory tests (fT3, fT4, TSH, TPO-antibodies). The reference range of TSH was 0.4 to 4.0 µU/ml. RESULTS: 21% of patients (100/476) with a nodular goiter had a focal autonomy. 32 % (32/100) of autonomous adenoma revealed a reduced (< 0.4 µU/ml) or completely suppressed TSH, while in 68 % (68/100) normal TSH level were found. CONCLUSION: In Germany autonomous adenoma are still frequent (21 % of all thyroid nodules). Most of them (68 %) reveal normal TSH levels. Our data demonstrate, that there is no relevant connection between TSH level and autonomous adenoma detected by scintiscan. In most cases, TSH is not able to discriminate, whether a nodule is autonomous or not. Biopsy of undetected autonomous nodules should not be performed, as they often show cytological features of follicular neoplasias. In thyroid nodules > 1.0 cm a scintiscan should routinely be performed in primary diagnostics to avoid unnecessary fine-needle biopsy of autonomous adenoma.

Comparison of dual-source and electron-beam CT for the assessment of coronary artery calcium scoring.

OBJECTIVE: Cardiac CT allows the detection and quantification of coronary artery calcification (CAC). Electron-beam CT (EBCT) has been widely replaced by high-end CT generations in the assessment of CAC. The aim of this study was to compare the CAC scores derived from an EBCT with those from a dual-source CT (DSCT). METHODS: We retrospectively selected 92 patients (61 males; mean age, 60.7 ± 12 years) from our database, who underwent both EBCT and DSCT. CAC was assessed using the Agatston score by two independent readers (replicates: 1, 2; 3=mean of reading 1 and 2). RESULTS: EBCT scores were on average slightly higher than DSCT scores (281 ± 569 vs 241 ± 502; p<0.05). In regression analysis R(2)-values vary from 0.956 (1) to 0.966 (3). We calculated a correction factor as EBCT=(DSCT+1)(1.026)-1. When stratifying into CAC categories (0, 1-99, 100-399, 400-999 and ≥1000), 79 (86%) were correctly classified. From those with positive CAC scores, 7 out of 61 cases (11%, κ=0.81) were classified in different categories. Using the corrected DSCT CAC score, linear regression analysis for the comparison to the EBCT results were r=0.971 (p<0.001), with a mean difference of 6.4 ± 147.8. Five subjects (5.4%) were still classified in different categories (κ=0.84). CONCLUSION: CAC obtained from DSCT is highly correlated with the EBCT measures. Using the calculated correction factor, agreement only marginally improved the clinical interpretation of results. Overall, for clinical purposes, face value use of DSCT-derived values appears as useful as EBCT for CAC scoring.

Association of coronary artery calcium and congestive heart failure in the general population: Results of the Heinz Nixdorf Recall study.

BACKGROUND: The main causes of congestive heart failure (CHF) are coronary artery disease (CAD) and arterial hypertension. Coronary artery calcification (CAC) evidencing coronary atherosclerosis may occur prior to clinical CAD. The aim of our study was to assess the association between CAC as a sign of subclinical CAD and CHF in a general unselected population. METHODS: Participants of the Heinz Nixdorf Recall Study without known CAD but with known CHF as defined by a physicians' diagnosis of CHF and dyspnea were identified. B-natriuretic peptide was measured and an exercise stress test was performed as possible. Cardiovascular risk factors and the EBCT-based CAC Agatston score were determined. RESULTS: Those 105/4,230 subjects (2.5%) with CHF (age 65 +/- 7 years, 44% males), had higher brain natriuretic peptide (BNP) levels (median BNP 36.8 [16.5-70.1] vs. 17.6 [9.5-31.7] pg/ml, p<0.01) and lower exercise capacity (108.7 +/- 39.4 vs. 130.0 +/- 40.7 W, p<0.01) than those without. CAC in subjects with CHF was significantly higher than in those without (median CAC 64.7 [8.5-312.3] vs. 11.6 [0-109.8], p<0.01). In univariate analysis, CAC-burden after logarithmic transformation according to log(2)(CAC + 1) showed a significant association with the presence of CHF (odds ratio (OR) (95% CI): 1.16 (1.1-1.23), p<0.0001). Adjustment for age and sex (OR 1.11 (1.04-1.18), p<0.001), additional Framingham risk score (OR 1.09 (1.02-1.16), p = 0.015), and additional cardiovascular medication (OR 1.07 (0.998-1.14), p = 0.058) attenuated this association. Age, systolic blood pressure, antihypertensive medication and increased body mass index also remained significantly associated with presence of CHF in the full multivariate model. CONCLUSION: The observed association between CAC and CHF in persons without clinically overt CAD is partly determined by risk factors that are involved in the natural history of both CAC and CHF. Whether CAC has a role to identify subjects at risk of future CHF remains to be determined using follow-up analyses.