[Clarification of dizziness in old age : Interdisciplinary diagnostic process]. / Schwindelabklärung im Alter : Interdisziplinärer diagnostischer Prozess.

The clinical symptom dizziness encompasses a broad range of complaints. The prevalence among older adults is high. Over the course of 1 year 50% of people over 80 years old, 30% of those between 70-80 years old and 20% between 60-70 years old contact a physician as a result of dizziness. The diagnostic process has to be well organized. The medical history and clinical examination are frequently underestimated but in many cases are crucial. Extensive investigations should only be carried out in cases of a firmly suspected diagnosis. A good interdisciplinary cooperation can positively influence the diagnostic process. The awareness of red flags also helps to detect emergency patients with dizziness. This article discusses the differential diagnosis of dizziness in older adults and provides appropriate recommendations for the diagnostic process.

[Polyneuropathy in older individuals]. / Polyneuropathie im Alter.

The peripheral nervous system is subject to changes during the aging process, e.g., deep tendon reflexes decrease, as proprioception does. In contrast, polyneuropathies have to be distinguished from age-associated changes as independent diseases with etiologies similar to those in younger ages. Incidence of polyneuropathies is reported about 118/100,000, the overall prevalence in the general population is estimated to be about 1% and rises to up to 7% in the elderly. Etiology includes metabolic disorders, primary inflammatory polyneuropathies, systemic disorders and vasculitic neuropathies. Due to the age-specific increase of the prevalence of certain etiologies, neuropathies associated with diabetes, malignancy, and monoclonal gammopathies are even more common in older patients. However, the proportion of cryptogenic neuropathies, e.g. neuropathies without obvious cause, increases also with age. In older age, polyneuropathies additionally impair mobility and increase the risk of falling, thus the assessment of functional abilities is mandatory. It is essential to try to identify the underlying cause by a systematic approach including history, clinical investigation, neurophysiological and lab exams. Treatment of polyneuropathies is based on therapy of underlying conditions and requires management of neuropathic pain in the majority of cases. Physiotherapy and rehabilitation target pain relief and sustaining activities of daily living.

Sarcopenia and osteoporosis are interrelated in geriatric inpatients.

BACKGROUND: Sarcopenia and osteoporosis share an underlying pathology and reinforce each other in terms of negative outcomes. OBJECTIVE: To evaluate the extent of concomitance of sarcopenia as defined by the European Working Group on Sarcopenia in Older People (EWGSOP) and osteoporosis as defined by the World Health Organization (WHO) in geriatric inpatients and their relationship to nutritional and functional status. MATERIAL AND METHODS: A cross-sectional analysis of geriatric inpatients from the sarcopenia in geriatric elderly (SAGE) study. Measurements included dual X­ray absorptiometry for bone mineral density and appendicular muscle mass; gait speed and hand grip strength, the Barthel index, body mass index (BMI) and the mini nutritional assessment short form (MNA-SF). RESULTS: Of the 148 patients recruited for SAGE, 141 (84 women, 57 men; mean age 80.6 ± 5.5 years) had sufficient data to be included in this ancillary investigation: 22/141 (15.6%) were only osteoporotic, 19/141 (13.5%) were only sarcopenic and 20/141 (14.2%) osteosarcopenic (i.e. both sarcopenia and osteoporosis). The prevalence of osteoporosis was higher in sarcopenic than in non-sarcopenic individuals (51.3% vs. 21.6%, p < 0.001). Sarcopenic, osteoporotic and osteosarcopenic subjects had a lower BMI, MNA-SF, handgrip and gait speed (p < 0.05) than the reference group (those neither osteoporotic nor sarcopenic, n = 80). The Barthel index was lower for sarcopenic and osteosarcopenic (p < 0.05) but not for osteoporotic (p = 0.07) subjects. The BMI and MNA-SF were lower in osteosarcopenia compared to sarcopenia or osteoporosis alone (p < 0.05) while there were no differences in functional criteria. CONCLUSION: Osteoporosis and sarcopenia are linked to nutritional deficits and reduced function in geriatric inpatients. Co-occurrence (osteosarcopenia) is common and associated with a higher degree of malnutrition than osteoporosis or sarcopenia alone.

Consequences of applying the new EWGSOP2 guideline instead of the former EWGSOP guideline for sarcopenia case finding in older patients.

INTRODUCTION: we examined the consequences of applying the new EWGSOP2 algorithm for sarcopenia screening instead of the former EWGSOP algorithm (EWGSOP1) in geriatric inpatients. METHODS: the dataset of our formerly published Sarcopenia in Geriatric Elderly (SAGE) study includes 144 geriatric inpatients (86 women, 58 men, mean age 80.7±5.6 years) with measurements of gait speed, handgrip strength and appendicular muscle mass by dual x-ray absorptiometry (DXA). We analysed the agreement between EWGSOP and EWGSOP2 algorithms in identifying patients as sarcopenic/non-sarcopenic. Differences in the distribution sarcopenic vs. non-sarcopenic were assessed by Chi²-test. RESULTS: sarcopenia prevalence according to EWGSOP1 (41 (27.7%)) was significantly higher than with EWGSOP2 (26(18.1%), p<0.05). The sex-specific sarcopenia prevalence was 22.1% (EWGSOP1) and 17.4% (EWGSOP2), respectively, for women (difference not significant) and 37.9% vs. 19.4% for men (p<0.05%). The overall agreement in classifying subjects as sarcopenic/non-sarcopenic was 81.25% (81.4% for women, 81.0% for men). However, among the 41 sarcopenia cases identified by EWGSOP1, only 20 (48.8%) were diagnosed with sarcopenia by EWGSOP2 (9/19 w (47.4%), 11/22 m (50.0%)). Ten of 19 women (52.6%) and 11 of 22 men (50.0%) diagnosed with sarcopenia by EWGSOP1 were missed by EWGSOP2, while 6 of 15 women (40.0%) and 0 of 11 men (0.0%) were newly diagnosed. DISCUSSION: there is a substantial mismatch in sarcopenia case finding according to EWGSOP1 and EWGSOP2. The overall prevalence and the number of men diagnosed with sarcopenia are significantly lower in EWGSOP2. While the absolute number of women identified as sarcopenic remains relatively constant, the overlap of individual cases between the two definitions is low.

Quantifying appendicular muscle mass in geriatric inpatients: Performance of different single frequency BIA equations in comparison to dual X-ray absorptiometry.

BACKGROUND: Quantification of skeletal muscle mass is mandatory for diagnosing sarcopenia, a highly prevalent geriatric syndrome. While dual energy X-ray absorptiometry (DXA) is the reference method in a clinical context, bioimpedance analysis (BIA) is more readily applicable on a broad scale. Recently BIA equations for the prediction of appendicular skeletal muscle mass in higher age groups have been published, but data on their performance in geriatric inpatients are lacking. METHODS: In 144 geriatric inpatients (86 women and 58 men, mean age 80.7 ± 5.6 years) appendicular skeletal muscle mass was predicted by 4 different BIA equations and measured by DXA. Results were compared by linear regression analysis and Bland Altmann plots. The agreement with DXA in classifying subjects to have normal or reduced muscle mass was calculated for the BIA based approaches. RESULTS: The 4 BIA equations showed only minor differences in regression analysis, but major differences in mean error (range -0.98 kg to + 0.19 kg in women and -2.47 kg to -0.58 kg in men). Considering regression parameters and mean error, the equation of Scafoglieri et al. performed best, resulting in an agreement with DXA of more than 83%. Sensitivity to detect subjects with reduced muscle mass was <70% in the whole group for all BIA equations. CONCLUSION: The BIA equation of Scafoglieri et al. performs best in geriatric inpatients, with more than 83% of subjects classified correctly as having normal or reduced muscle mass compared to DXA. Low sensitivity to detect subjects with reduced muscle mass in geriatric inpatients remains a limitation of BIA.

[Pain and pain-assessment in nursing homes : Results of the OSiA study]. / Schmerz und Schmerzerfassung in Altenpflegeheimen : Ergebnisse der OSiA-Studie.

BACKGROUND: Adequate and sufficient data on pain in nursing home residents is still lacking in Austria. This study intends to gather and increase available data on pain and pain assessment as well as identify potential improvement possibilities. STUDY PARTICIPANTS AND METHODS: Using a cross-sectional design, 425 residents from 12 Austrian nursing homes were recruited. The selected homes were selected as a cluster sample from 29 homes operated by one carrier. Pain assessment of cognitively intact as well as cognitively impaired residents was conducted using questionnaires, observation, and medical record examination. RESULTS: Pain prevalence was dependent on type of resident and ranged between 37.9 and 73.1 %. Sensitivity of the proxy assessment instruments varied between 47.7 and 87.7 %. Overall, 81 % of residents with daily recurring pain have been pain sufferers for at least one year. Between 40 and 68 % do not disclose their pain or consider their pain as being a part of aging. CONCLUSION: Our data on pain indicate a definite need for action. Accurately detecting pain requires reliable and resident-adapted means of assessment. Varying prevalence, specificity, and sensitivity numbers indicate the need for further research.

[Measuring gait velocity in the elderly with a gait analysis system and a 10-meter walk test. A comparison]. / Gehgeschwindigkeit bei älteren Patienten im Ganganalysesystem und 10-Meter-Gehtest. Ein Vergleich.

BACKGROUND: Gait disorders are common in the elderly, compromising quality of life and increasing the risk for falls. Mobility and fall risk assessment usually includes measurement of gait velocity. Computerized gait analyses are able to measure additional gait parameters. MATERIALS AND METHODS: This study addressed the question whether elderly patients (n=66) change their self-selected gait speed when walking on a computerized platform compared to a 10-m walk test. A second aim was to compare gait velocity, gait parameters, and clinical measurements (TUG, POMA) in subgroups of patients with a history of a fall (n=27) vs. without a history of a fall (n=39). RESULTS: Our results demonstrate that gait velocity was significantly reduced in the subgroup of fallers, but not in the group of nonfallers. Moreover, other gait parameters and the clinical tests differed significantly between fallers and nonfallers. DISCUSSION: A possible explanation could be the visual requirements of the test environment, which may influence the walking speed in terms of a dual-task paradigm in those participants with mobility problems.

[Delirium: an interdisciplinary challenge]. / Delir : Eine interdisziplinäre Herausforderung.

Delirium, the acute deterioration of cognitive function and attention, is the most frequent mental disorder in elderly. Its correct diagnosis and adequate management are of crucial importance for the patient's health and functional outcome. First of all, one has to be aware of the possibilities of preventing this complex, potentially life-threatening problem, which means recognizing the patient at risk, avoiding environmental stress and causal factors (i.e., anticholinergic medication) in cognitively impaired patients, and timely reaction to prodromal symptoms. Causal therapy (i.e., treatment of the causal condition and/or eliminating the precipitating situation) is imperative. It must be accompanied by nursing and environmental measures and, if necessary, by antipsychotic and/or sedating symptomatic treatment.

Three-question dementia screening. Development of the Salzburg Dementia Test Prediction (SDTP).

BACKGROUND: To date, short dementia screenings are often limited by poor specificity or still take too much time with respect to the restricted resources of primary care physicians and the increasing number of dementia disorders. As a new instrument, the three-question dementia screening (SDTP, Salzburg Dementia Test Prediction) should be compared with the eight-item screening of Chen et al. and the CERAD battery (Consortium to Establish a Registry for Alzheimer's Disease), focusing on specificity and economy of time. MATERIALS AND METHODS: We tested 404 patients (243 women). The mean age of the subjects was 80.1 years (SD = 6.8) for men and 83.2 years (SD = 6.0) for women. The mean Mini-Mental State Examination (MMSE) score was 21.9 (SD = 5.8) for men and 21.1 (SD = 6.3) for women. Artificial neural networks (ANNs) were used to find a mathematical model that allows the total MMSE to be predicted with only three questions of the MMSE. This is achieved by multiplying the outcome of the three best predictor questions with a weighting coefficient, which was delineated by using ANNs. RESULTS: The Salzburg Dementia Test Prediction (SDTP) had a sensitivity of 94% (95% CI: 87-97%) for screening of possible dementia, when the MMSE (MMSE < 25/30) was used as the reference test method and 96% when the CERAD was used. The specificity was 68% (95% CI: 57-77%) if the MMSE was used and 70% if the whole test battery (CERAD) was used, which is as sensitive as and more specific than the eight-item screening. CONCLUSION: The SDTP is a time-saving instrument for screening of dementia, which is as sensitive as and more specific than the eight-item screening of Chen et al. and provides a prediction of the MMSE with high accuracy.

[Management and therapy of atrial fibrillation in geriatric patients]. / Management und Therapie des Vorhofflimmerns beim geriatrischen Patienten.

Among geriatric patients, atrial fibrillation is the most common cardiac arrhythmia. In patients over 80 years of age, the prevalence rises to approximately 10%. Atrial fibrillation is associated with serious health implications, including a 2-fold increase in mortality risk and a 5-fold increase in stroke risk. In contrast to these facts, the current guidelines on the management of atrial fibrillation of the European Society of Cardiology (ESC) contain only a short paragraph on these patients. Many relevant clinical aspects go without any comment. Thus, the purpose of our paper is to discuss those special needs of geriatric patients and their physicians which are not mentioned in the guidelines of the ESC. In our review, we discuss rhythm versus rate control, oral anticoagulation, outcome, prevention, falls, adherence, polypharmacy, dementia, nursing home patients, frailty, and geriatric assessment in consideration of geriatric patients. An extended search of the literature on Pubmed served as the basis for this review. Individual aspects of each geriatric patient should be considered when managing these complex patients; however, the complexity of each case must not lead to an individualized therapy that is not in accordance with current guidelines and the literature. A large number of papers which help us to answer most of the clinical questions regarding the management of trial fibrillation in geriatric patients have already been published.

Thrombolytic therapy for acute stroke in Austria: data from the Safe Implementation of Thrombolysis in Stroke (SITS) register.

BACKGROUND: We aimed at determining the safety and efficacy of IV alteplase in Austrian versus non-Austrian centres as documented in the Internet-based registers Safe Implementation of Thrombolysis for Stroke - MOnitoring STudy (SITS-MOST) and - International Stroke Thrombolysis Register (SITS-ISTR). METHODS: We analysed patient data entered in the registers SITS-MOST and SITS-ISTR in the period December 2002 to 15 November 2007. RESULTS: Compared to the non-Austrian cohort (n=15153), the Austrian cohort (n=896) was slightly older [median, interquartile range (IQR): 70, 60-77 years vs. 69, 60-76 years, P=0.05] and included more women (44.6% vs. 41.0%, P=0.03). Austrian patients had a significantly shorter stroke onset-to-treatment time (OTT; median, IQR: 135, 105-160 min vs. 145, 115-170 min, P<0.0005). Symptomatic intracerebral haemorrhages were observed in 1.6% of Austrian and 1.7% of non-Austrian patients (P=0.82). At 3 months, 50.8% of Austrian and 53.0% of non-Austrian patients were independent (P=0.23), but death was less frequent in Austrian patients (12.1% vs. 14.9%, P=0.03). Multivariate analyses adjusted for demographic and baseline characteristics confirmed lower mortality at 3 months in the Austrian cohort (odds ratio 0.81, 95% confidence intervals 0.71-0.92, P=0.001). Longer OTT was associated with increased mortality at 3 months, with a hazard ratio of 1.02 (95% CI 1.01-1.03; P=0.005) for each 10-min increase in OTT. CONCLUSIONS: The implementation of intravenous alteplase for acute stroke has been safe and efficacious in Austrian centres. OTT and mortality were significantly lower in Austrian patients compared to non-Austrian SITS centres.

[Consensus statement "Dementia 2010" of the Austrian Alzheimer Society]. / Konsensusstatement "Demenz 2010" der Osterreichischen Alzheimer Gesellschaft.

The Austrian Alzheimer Society developed evidence-based guidelines based on a systematic literature search and criteria-guided assessment with subsequent transparent determination of grades of clinical recommendation. The authors evaluated currently available therapeutic approaches for the most common forms of dementia and focused on diagnosis and pharmacological intervention, taking into consideration the situation in Austria. The purpose of these guidelines is the rational and cost-effective use of diagnostic and therapeutic measures in dementing illnesses. Users are physicians and all other providers of care for patients with dementia in Austria.

Are plasma VEGF and its soluble receptor sFlt-1 atherogenic risk factors? Cross-sectional data from the SAPHIR study.

AIMS: Vascular endothelial growth factor (VEGF) is a potent hypoxia-regulated angiogenic factor. Its soluble receptor soluble (s)Flt-1 binds VEGF with high affinity inhibiting the angiogenic function of VEGF. The role of circulating VEGF in atherosclerosis is unclear. METHODS AND RESULTS: In 909 healthy subjects (511 male, 398 female) from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) we determined fasting plasma VEGF and sFlt-1 concentration, cardiovascular risk factors and carotid atherosclerosis. VEGF levels were lower and sFlt-1 levels higher in men than in women. VEGF and sFlt-1 showed a positive correlation. In the entire population VEGF correlated positively with age, BMI, insulin resistance, white blood cell and platelet count, C-reactive protein (CRP) and carotid intima media thickness (IMT). After adjustment for age, VEGF showed a weak positive correlation with BMI, liver enzymes, CRP and platelet count in males. In females VEGF correlated negatively with LDL-cholesterol and positively with insulin resistance and platelet count. After adjustment for age, no significant correlation with carotid atherosclerosis could be detected. CONCLUSION: Plasma VEGF and sFlt-1 are only weakly correlated with cardiovascular risk factors, suggesting that circulating VEGF levels do have only a minor impact on the development of atherosclerosis.

MMP-9 haplotypes and carotid artery atherosclerosis: an association study introducing a novel multicolour multiplex RealTime PCR protocol.

BACKGROUND: Among other matrix metalloproteinases (MMPs), gelatinase B (MMP-9) is discussed to be associated with the pathogenesis of vascular diseases. Two single nucleotide polymorphisms (SNPs) of the MMP-9 gene, C-1562T in the promoter region and a G/A transition in exon 6 (R + 279Q), have been addressed in previous association studies which, however, produced conflicting results. MATERIAL AND METHODS: A novel multiplex RealTime PCR protocol for the fast and simultaneous detection of both polymorphisms is presented, which was used for genotyping 1737 participants of a prospective study investigating genetic factors influencing the progression of atherosclerosis. RESULTS: Haplotype analysis revealed -1562C/+279Q as the major haplotype in this population. Allelic distribution of the C-1562T polymorphism was consistent with data published for similar cohorts; however, we found that R + 279Q allelic distribution appears to vary significantly among Caucasian populations. Considering clinical data available from 1487 participants, we found significant associations between the presence of atherosclerotic plaque and the CA-haplotype in men (P = 0.028, phi = 0.08), and between the AG variant of exon 6 and common carotid artery intima-media thickness (CIMT) in women (P = 0.004, Eta(2) = 0.019). CONCLUSIONS: In summary, our results demonstrate associations of MMP-9 genotypes with different stages of carotid atherosclerosis.

Comparison of different definitions of the metabolic syndrome.

BACKGROUND: The International Diabetes Federation (IDF) published a new definition of the metabolic syndrome (MetS). For this definition we compared frequency, concordance, clinical and laboratory stigmata and carotid atherosclerosis with those of the established definitions by the National Cholesterol Education Program (NCEP) and World Health Organization (WHO). MATERIALS AND METHODS: A total of 1518 subjects (943 men, 575 women) from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR), free of clinical atherosclerosis, were included in this study. To estimate insulin sensitivity two methods, i.e. homeostasis model assessment of insulin resistance (HOMA-IR) and the short insulin tolerance test, were employed. Carotid intima media thickness (IMT) and plaque extent were quantified for all subjects using high-resolution ultrasound. RESULTS: Prevalence of the MetS was 18.7% for men and 16.2% for women for the WHO definition, 18.9% and 17.0%, respectively, for the NCEP definition, and 25.8% and 19.5%, respectively, for the IDF definition. Concordance was lower between the definitions of WHO and IDF (< 50%) than between NCEP and IDF (> 67%). Compared to subjects identified by NCEP definition, subjects identified in excess by IDF (3.1-11.7%) showed less insulin resistance and lower IMT and plaque extent indistinguishable from MetS-free subjects. CONCLUSIONS: Our data suggest that the IDF definition includes subjects as MetS sufferers above these detected by NCEP or WHO, who exhibit considerably less insulin resistance and carotid atherosclerosis blurring the distinction between health and disease.

Brain perfusion SPECT in patients with mild cognitive impairment and Alzheimer's disease: comparison of a semiquantitative and a visual evaluation.

Due to the increasing importance of early recognition and differential diagnosis of dementias, cerebral perfusion scans using "single photon emission computed tomography" (SPECT) are increasingly integrated into the examination routine. The goal of this study was to check the diagnostic validity of SPECT scans of MCI- and DAT-patients, two subgroups out of 369 persons with etiologically unclear cognitive dysfunction, which underwent an assessment program for probable dementia including cognitive testing, cranial computed tomography, ultrasound, routine laboratory testing including vascular risk factors. After exclusion of patients with no or other forms of dementia we analyzed SPECT data of patients with mild cognitive impairment (MCI; n = 85) and dementia of the Alzheimer type (DAT; n = 78) in comparison with a healthy control group (n = 34).Visual assessment as well as a manual "regions of interest" (ROI) regionalization of the cortex were performed, whereby a ROI/cerebellum ratio was calculated as a semi-quantitative value. Association cortex areas were assessed regarding frontal, temporal, and parietal lobes of both hemispheres. When comparing the ratios of patients with DAT and controls, we found a statistically significant reduction of the cerebral perfusion in all measured cortex areas (p < 0.001). The comparison of patients with MCI with the selected control group also established a statistically significant difference in the cerebral perfusion for the evaluated cortex areas with the exception of the left hemispheric frontal and parietal cortex.A considerable number of the MCI patients showed an MMSE-score within the normal range, but with regard to the perfusion in the right hemispheric association cortex these patients also could be distinguished unambiguously from controls. Sensitivity levels found by visual assessment were at least as high as those found by the ROI method (pathological assessment: visual 49.4% vs. ROI 47.1% for MCI; visual 75.6% vs. ROI 73.1% for DAT). High experienced visual assessment of cerebral perfusion scans using SPECT provides an useful additional tool in diagnosis of cognitive impairment. The used semiquantitative ROI-method is nearly equivalent and does not depend on the experience of the investigator.

Relationship of QT interval duration with carotid intima media thickness in a clinically healthy population undergoing cardiovascular risk screening.

OBJECTIVES: To investigate the relationship between cardiac repolarization (QT interval duration) and intima media thickness (IMT) of the carotid arteries as surrogate measures of subclinical atherosclerosis. DESIGN: Prospective study with consecutive subjects enrolled in the SAPHIR program (Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk). SETTING: The analysis of the material was performed at the departments of medicine and neurology of a university hospital. SUBJECTS: The study cohort comprises a population-based sample of 1199 clinically healthy subjects (851 men and 348 women; age 39-66 years). Exclusion criteria were cardiovascular disease, diabetes, atrial fibrillation, bundle branch block and use of medication affecting QT interval duration. MAIN OUTCOME MEASURES: IMT of common (CCA) and internal carotid arteries (ICA) was measured by B-mode ultrasound. QT interval duration was determined in the resting 12-lead electrocardiogram by an automatic analysis program. The QT intervals were corrected for heart rate with five standard equations (QTc-Bazett, -Fridericia, -Framingham, -Hodges and -Rautaharju) and tested for their relationship with carotid IMT after adjustment for clinical and metabolic variables. Results. Females had higher heart rates than males (64 +/- 10 b min(-1) vs. 60 +/- 9 b min(-1), P <0.0005), with longer mean QT (410 +/- 28 ms vs. 404 +/- 28 ms, P=0.003) and QTc intervals in all correction formulae (P <0.0005). Significant correlations between QT/QTc and ICA IMT (r=0.14-0.16) were found in males. In the general linear model the association between QTc (except for Bazett) and ICA IMT remained significant after adjusting for age, BMI and further cardiovascular risk factors. In females the crude correlations between QT/QTc and ICA IMT were lower than those with CCA IMT. Only the correlation between uncorrected QT and CCA IMT (r=0.15, P=0.006) remained significant after adjustment for covariates. CONCLUSIONS: The results of the present study demonstrate that QT and QTc prolongation are in part associated with IMT of carotid arteries, which is an established risk marker of subclinical atherosclerosis. In men the data support the hypothesis of an association between QTc and ICA IMT. In women a statistically significant relationship was found between the uncorrected QT interval and CCA IMT. These findings suggest that differences in carotid IMT and ventricular repolarization between genders might be related to hormonal and nonhormonal effects.

Associations of the UCP2 gene locus with asymptomatic carotid atherosclerosis in middle-aged women.

OBJECTIVE: Reactive oxygen species (ROS) contribute to atherogenesis. Uncoupling protein 2 (UCP2) reduces mitochondrial ROS generation and protects against the disease in animal models. A common -866G/A promoter polymorphism that has been associated with obesity and beta-cell function may also affect UCP2 gene expression in cells of the arterial wall. METHODS AND RESULTS: Genotype distributions of the -866G/A and of a 45nt-del/ins polymorphism in the 3'-untranslated region of the UCP2 gene were determined in 1334 participants of the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR). We observed a modest association of the -866G/A promoter polymorphism and 2-loci haplotypes with asymptomatic carotid atherosclerosis in female study participants. Functional studies revealed increased expression of the -866G wild-type allele in human umbilical vein endothelial cells and differentiated THP-1 cells. Electrophoretic mobility shift assay studies and antibody-interference assays performed with nuclear extracts of various cell lines showed binding of cell-type specific protein complexes to the region encompassing the -866 site and suggested involvement of hypoxia inducible factor 1alpha in the regulation of UCP2 gene expression in endothelial cells and macrophages. CONCLUSIONS: Our results suggest a role of UCP2 in atherogenesis as originally proposed from studies in animal and cell culture models.

Cholesteryl ester transfer protein TaqIB polymorphism and its relation to parameters of the insulin resistance syndrome in an Austrian cohort.

The cholesteryl ester transfer protein (CETP) is responsible for the exchange of triglycerides and cholesteryl esters between lipoprotein particles leading to an increased hepatic clearance of HDL-cholesteryl esters. A high CETP activity reduces serum HDL levels, whereas persons without CETP activity have high HDL levels. We investigated the association of the TaqIB CETP polymorphism and various parameters of the insulin resistance syndrome in a cross sectional population based study. We included 1029 persons without known cardiovascular disease or diabetes mellitus consecutively enrolled in our SAPHIR program (Salzburg Atherosclerosis Prevention program in persons with a High Infarction Risk). Numerous clinical and laboratory data were accomplished. Insulin sensitivity was measured by a short insulin tolerance test. The TaqIB CETP polymorphism was determined by PCR, TaqI restriction and electrophoresis. 35.2% were homozygous for the prevalence (B1B1), 46.7% were heterozygous (B1B2), and 18.1% homozygous for the absence (B2B2) of the restriction site. HDL cholesterol and apolipoprotein A1 were lower and small dense low-density lipoproteins (sdLDL) higher in B1B1 compared to B2B1 and B2B2 persons. In women, we found a significant interaction effect between CETP genotype and adiposity for HDL cholesterol. B1B1 women with a BMI and a waist circumference above the median had 9.7 mg/dl lower HDL than B1B2 and 9.1 mg/dl lower HDL than B2B2 women (P < 0.001). In men, no interaction effect but a marked genotype to HDL correlation was found. There was a high CETP effect on sdLDL detected in men (P = 0.001). B1B1 men had sdLDL in 36%, B1B2 in 24.6%, and B2B2 in only 14.5%. Men with adiposity and insulin resistance had twice as many sdLDL as insulin sensitive men. We found a significant sex specific effect of the TaqIB CETP polymorphism on the insulin resistance parameters HDL-cholesterol and sdLDL in an Austrian population based study.