The long-term recurrence risk of patients with unprovoked venous thromboembolism: an observational cohort study.

Essentials Long-term recurrence risk of venous thromboembolism (VTE) is uncertain. We performed a prospective cohort study of 839 patients with first unprovoked VTE. VTE recurrence risk is high, particularly in men with proximal thrombosis or pulmonary embolism. Sex and VTE site determine the recurrence risk and should be considered for patient counseling. SUMMARY: Background The long-term recurrence risk (ltRR) of venous thromboembolism (VTE) is uncertain. Objective To assess the ltRR of patients with first unprovoked VTE. Patients/methods Patients were classified into three categories: distal deep vein thrombosis (DVT), proximal DVT or pulmonary embolism (PE), that is, PE associated with DVT or isolated PE. Patients with major thrombophilia or antithrombotic therapy were excluded. The endpoint was recurrent symptomatic VTE. Results A total of 839 patients were followed for a median of 7.7 years. VTE recurred in 263 patients (31%). After 10 and 20 years, the cumulative ltRR was 32% (95% confidence interval [CI], 29-36) and 44% (95% CI, 38-49) with 3.9 (95% CI, 3.3-4.6) and 3.3 (95% CI, 2.7-4.0) events per 100 patient-years, respectively. The adjusted hazard ratio was 2.1 (95% CI, 1.4-3.2) and 2.1 (95% CI, 1.4-3.2) for patients with proximal DVT or PE compared with patients with distal DVT and was 2.1 (95% CI, 1.6-2.9) for men compared with women. At 10 years, 4.7 (95% CI, 3.8-5.8) events per 100 patient-years occurred in men with proximal DVT or PE, 2.4 (95% CI, 1.2-4.4) in men with distal DVT, 1.9 (95% CI, 1.2-2.8) in women with proximal DVT or PE and 0.9 (95% CI, 0.2-1.9) in women with distal DVT. Conclusion The ltRR of patients with first unprovoked VTE is high and dependent upon sex and VTE site.

Severity of chronic venous disorders and its relationship to the calf muscle pump.

BACKGROUND: To investigate the relationship between the calf muscle pump and the clinical severity of chronic venous disorders (CVD) and of venous function parameters. PATIENTS AND METHODS: 84 limbs in 44 patients underwent duplex scan and digital photoplethysmography (DPPG), the range of ankle movement was measured by digital goniometry and strength of calf muscles was determined by dynamometry. Limbs were allocated on the basis of clinical signs of CVD (according to the CEAP classification) into 4 groups: controls (no signs and symptoms of CVD): 34 limbs, C1/2: 24 limbs, C3/4: 16 limbs, C6: 10 limbs. RESULTS: A higher degree in clinical severity of CVD was related to shorter venous refilltime (VRT) and lower venous pump power (VPP) measured by DPPG. The strength of dorsiflexion was significantly reduced in group C6 compared to controls. There was a positive correlation between measurements of DPPG and the strength of dorsiflexion and also with total strength (p < 0.05). In limbs with pathological reflux (> 1 s) the strength of dorsiflexion, range of ankle plantarflexion movement and total range of ankle movement were significantly reduced compared to those without pathological reflux (p < 0,05). Strength of plantarflexion was significantly reduced in group C1/2 compared to control group (p < 0,05). CONCLUSIONS: Strength of dorsiflexion seems to be the main driving factor of normal venous flow and range of ankle movement is impaired in patients with pathological venous reflux. Further prospective studies should clarify if additional strengthening of ankle dorsiflexors should be included in well established venous training programs.

Potential of mid-infrared spectroscopy to aid the triage of patients with acute chest pain.

A total of 1,429 serum samples from 389 consecutive patients with acute chest pain were analyzed with the goal to aid the rapid diagnosis of acute myocardial infarction. To the best of our knowledge this is the largest and most comprehensive study on mid-infrared spectroscopy in cardiology. We were able to identify those signatures in the mid-infrared spectra of the samples, which were specific to either acute myocardial infarction or chest pain of other origin (angina pectoris, oesophagitis, etc). These characteristic spectral differences were used to distinguish between the cause of the donor's acute chest pain using robust linear discriminant analysis. A sensitivity of 88.5% and a specificity of 85.1% were achieved in a blind validation. The area under the receiver operating characteristics curve amounts to 0.921, which is comparable to the performance of routine cardiac laboratory markers within the same study population. The biochemical interpretation of the spectral signatures points towards an important role of carbohydrates and potentially glycation. Our studies indicate that the "Diagnostic Pattern Recognition (DPR)" method presented here has the potential to aid the diagnostic procedure as early as within the first 6 hours after the onset of chest pain.

Persistent sciatic artery: an uncommon cause of intermittent claudication.

Persistent sciatic artery (PSA) is a rarely seen variation of the lower limb vessels. Anatomically the PSA is the continuation of internal iliac arteries. It follows the sciatic nerve from the sciatic foramen to the level of the knee. We report our experience with conservative therapy in a patient with complete occlusion of a PSA. A 54-year-old man with typical symptoms of intermittent claudication on the left limb was referred to our Department. After clinical examination Doppler and duplex sonography were performed. Angiography showed bilateral PSA. On the left side the PSA was occluded. The patient received 20 intravenous courses of prostaglandin E1 for 4 weeks, followed by oral anticoagulation with phenprocoumon for life (INR: 2.5-3.5). After 3 years therapy he does not show any typical symptoms of intermittent claudication or limb ischemia. This case shows that conservative therapy may be effective. However, it has to be emphasised that this approach requires frequent clinical and duplex sonography follow-up every 3 to 6 months with oral anticoagulation.

C-reactive protein 3' UTR +1444C>T polymorphism in patients with spontaneous venous thromboembolism.

OBJECTIVE: Data on C-reactive protein (CRP) as a risk indicator of venous thromboembolism are conflicting. A recent study reported higher CRP levels in homozygous carriers of a novel CRP gene polymorphism at the 3' UTR (CRP +1444C>T). We investigated, whether homozygosity for CRP +1444C>T is associated with an increased risk of spontaneous venous thromboembolism (VTE). METHODS AND RESULTS: CRP +1444C>T genotype and plasma levels were assessed in 128 patients with deep venous thrombosis (DVT, 70 females/58 males), 105 with pulmonary embolism (PE, 58 females/47 males) and 122 healthy individuals (60 females/62 males). CRP +1444TT was significantly associated with increased CRP plasma levels in healthy individuals. CRP +1444TT was more frequent (14%) among controls than DVT patients (9%, p=0.26) or PE patients (6%, p=0.05), respectively. No significant deviation from Hardy-Weinberg equilibrium was observed in patients (p=0.8) or controls (p=0.3), respectively. CRP +1444C>T was not significantly associated with CRP levels in patients with VTE. CONCLUSIONS: Homozygous carriers of the CRP 3' UTR +1444C>T polymorphism do not have a significantly increased risk of VTE. Our data support the assumption that a clinically relevant association between CRP and VTE is missing.

The post-thrombotic syndrome: risk factors and impact on the course of thrombotic disease.

BACKGROUND: The post-thrombotic syndrome (PTS) is a frequent complication of deep vein thrombosis (DVT). Patients with recurrent ipsilateral DVT have an increased risk of PTS; other risk factors are unknown. OBJECTIVES: To establish risk factors of PTS and its impact on venous thrombotic disease. PATIENTS: We prospectively followed 406 patients after a first symptomatic DVT for a median of 60 months. Patients with recurrent DVT, a natural inhibitor deficiency, the lupus anticoagulant, cancer, long-term anticoagulation, an observation time < 18 months and DVT-recurrence prior PTS-assessment were excluded. Study outcomes were occurrence of PTS and recurrent symptomatic DVT. RESULTS: PTS was assessed after 44 +/- 23 months (mean +/- SD) using a clinical classification score. PTS developed in 176 of 406 patients (43.3%). Severe PTS was rare (1.4%). Proximal DVT was the strongest risk factor of PTS [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3-3.7]. Male gender (OR 1.6, 95% CI 1.0-2.8) and elevated D-dimer levels (OR 1.9, 95% CI 1.0-3.9) were weaker risk factors. Factor V Leiden, factor II G20210A or high factor VIII did not confer an increased risk of PTS. At 4 years, the cumulative probability of recurrence was 7.4% (95% CI 3.2-11.7) among patients with PTS when compared with 1.6% (95% CI 0-3.5; P < 0.02) among patients without PTS. The risk of recurrence was 2.6-fold (95% CI 1.2-5.9) increased when PTS was present. CONCLUSIONS: Proximal DVT, male gender, and high D-dimer levels are independently associated with the development of PTS in patients with a first DVT. Patients with PTS have an increased risk of recurrent venous thromboembolism.

The risk of recurrent venous thromboembolism among patients with high factor IX levels.

High factor IX (FIX) is a risk factor of deep vein thrombosis. The impact of high FIX on the risk of recurrent venous thrombosis is unknown. We prospectively followed 546 patients after anticoagulation for a first spontaneous venous thromboembolism. Patients with a natural coagulation inhibitor deficiency, lupus anticoagulant or cancer were excluded. At 3 years, the likelihood of recurrence was 23% among patients with high FIX (exceeding the 75th percentile) compared with 11% among patients with lower levels. Among patients with high FIX, the relative risk of recurrence was 2.2 (95% CI: 1.3-3.6) before and was 1.6 (95% CI: 1.0-2.8) after adjustment for age, gender, duration of anticoagulation, FV Leiden, FII G20210A, high FVIII and hyperhomocysteinemia. Compared with patients with low factor IX (< 138 IU dL(-1)) and low FVIII (

Oral anticoagulation in older patients with vascular or cardiovascular diseases. Aged over 70 years: same risk? Same benefit?

AIM: The purpose of the study was to assess patients aged over 70 years and younger patients for possible differences in several aspects concerning anticoagulant therapy. METHODS: Two-hundred and twenty-three patients with anticoagulant treatment for an average duration of 2.6 years at an angiologic outpatient clinic were subdivided into 2 groups (above 70 years n=114; below 70 years n=109). The 2 groups were compared with regard to patient-specific data, treatment-related and compliance parameters as well as complications. RESULTS: The group of older patients included a higher number of female patients, presented with a less favorable risk profile and revealed tendency or significance in showing better compliance data. No differences were found for the incidence of bleeding complications, while recurrences were more frequent in patients below the age of 70 years. Treatment-related parameters reflecting quality and stability of anticoagulant therapy (standard deviation of international ratio (INR), frequency of laboratory controls) represent predictors of bleeding risk being of more critical importance than the age of the patient. Recurrent events also showed correlation with same relevant parameters. Younger patients undergoing the same intensity of treatment for similarly distributed indications show a higher rate of recurrences. CONCLUSION: The lower recurrence rate in older patients is consistent with the observation that anticoagulant therapy is more profitable in elderly with atrial fibrillation. Since older patients being treated with the same therapy intensity for comparable periods of time showed no higher bleeding risk than that seen for younger patients, we believe that there is no need for specific guidelines for older patients provided treatment is carefully monitored and controlled.

[Effects of terazosine and atenolol on serum lipids in essential hypertension]. / Effekte von Terazosin und Atenolol auf die Serumlipide bei essentieller Hypertonie.

BACKGROUND: Only a few studies have evaluated the efficacy of alpha-blocking agents in combination with other classes of antihypertensive agents, especially in patients not adequately controlled by monotherapy. As alpha-blockers have an additional beneficial effect on serum lipids, it seems reasonable to use them instead of beta-blockers or diuretics in insufficiently treated hypertensive patients with hyperlipidemia. MATERIALS AND METHODS: All patients with insufficient blood pressure control with either a calcium channel blocker or an ACE inhibitor and evidence of hyperlipidemia (total serum cholesterol > 5.69 mmol/L) were included into an open, randomized and prospective study to evaluate the effects of terazosin and atenolol on lipid profile in hypertensive patients. The patients received either terazosin (n = 26; dose 1 to 10 mg) or atenolol (n = 28; dose 25 to 100 mg). Blood pressure was assessed by 24-hour ambulatory blood pressure measurement and serum lipids were evaluated at the time of inclusion and 12 weeks later. RESULTS: Blood pressure was similar after 12 weeks of treatment (atenolol: 129 (9)/75 (7) mm Hg; terazosin: 128 (11)/75 (9) mm Hg) and total cholesterol was significantly reduced after 12 weeks of treatment (atenolol: Diff 0-12 weeks: 7.29 (1.32) versus 6.62 (1.14 mmol/L, p = 0.006; terazosin: 7.34 (0.93) versus 6.67 (0.85) mmol/L, p = 0.002). In the terazosin group, HDL-cholesterol increased and triglycerides decreased significantly (Diff 0-12 weeks: HDL-chol: 1.55 (0.31) versus 1.63 (0.44) mmol/L, p = 0.04; TG: 1.93 (1.17) versus 1.34 (0.64) mmol/L, p = 0.03). Comparing both groups a significant difference was found with regard to HDL-cholesterol and triglycerides (atenolol versus terazosin: HDL-chol: -0.05 (0.12) versus +0.08 (0.1) mmol/L, p = 0.04; TG: -0.18 (0.61) versus--0.59 (0.6), p = 0.03). CONCLUSIONS: The alpha-blocker terazosin is as effective as atenolol when combined with either an ACE inhibitor or a calcium-channel blocker as a part of a multidrug regimen to achieve sufficient blood pressure control. In addition, terazosin is superior to atenolol with regard to the effect on the lipid profile of hypertensive and hyperlipidemic patients and seems therefore a reasonable alternative to beta-blockers in hypertensive patients with hyperlipidemia.

Double-blind, randomised, placebo controlled low level laser therapy study in patients with primary Raynaud's phenomenon.

BACKGROUND: No causal treatment of primary Raynaud's phenomenon is available due to its unclear aetiology. Low level laser therapy (LLLT) is applied in a multitude of medical conditions often without sufficient evidence of efficacy and established mechanisms. To asses the effect of this therapy in patients with primary Raynaud's phenomenon a randomised, double blind, placebo controlled cross over study was designed. PATIENTS AND METHODS: Absolute and relative frequency and intensity of vasospastic attacks during three weeks of either LLLT or placebo therapy and results of infrared thermography before onset and at the end of both therapy sequences were evaluated in 15 patients with primary Raynaud's phenomenon. RESULTS: Frequency of Raynaud's attacks was not significantly affected by low level laser therapy. Compared to placebo a significantly lower intensity of attacks during laser irradiation was observed, but no transfer effect occurred. Additionally the mean temperature gradient after cold exposure was reduced after laser irradiation, while the number of fingers showing prolonged rewarming was unaffected. CONCLUSION: Though further studies are necessary to confirm these results we could demonstrate for the first time in a double blind placebo controlled clinical trial that low laser therapy is a potential candidate for an effective therapy of Raynaud's phenomenon, although effects seem to be of short duration.

Clinical application of rapid quantitative determination of cardiac troponin-T in an emergency department setting.

OBJECTIVES: We analysed the clinical use of Troponin-T compared to creatine kinase MB in a non-trauma emergency department setting. BACKGROUND: A newly established single specimen quantitative Troponin T assay allows the clinical application of this parameter. METHODS. Five-hundred Troponin T tests were provided for use by emergency physicians who could combine them with the routine laboratory tests without restriction as to the indication or number of tests per patient. The number of tests per patient, time frame, final diagnosis and additional clinical information gained were recorded. All patients were followed for at least 6 months to verify the diagnosis and to assess the occurrence of cardiac events (nonfatal AMI or cardiac death). The ability of Troponin T and creatine kinase MB tests to predict cardiac events within 6 months were compared. RESULTS: The 500 Troponin T tests were used in 249 patients (median two tests per patient (range 1-5)) within 41 days. The final diagnosis revealed coronary heart disease in 85, non-coronary heart disease in 39, non-cardiac chest pain in 86 and other diagnoses in 39 of the patients. In 14 patients with an elevated creatine kinase MB, myocardial damage could safely be ruled out by a negative Troponin T, in six patients with a normal creatine kinase MB minor myocardial damage could be detected by a positive Troponin T. During follow up 28 cardiac events were recorded. Troponin T had a significantly higher specificity, positive predictive value and proportion of correct prediction for cardiac events within 6 months compared to creatine kinase MB. CONCLUSIONS: Troponin T has proved to be an useful method for diagnosing myocardial damage in routine clinical use in the non-trauma emergency department.

[Aneurysm of the popliteal vein]. / Aneurysma der V. poplitea.

Venous aneurysms are a rare pathology. The possible complications are rupture, thrombosis and subsequently pulmonary embolism. The case of a 54-year-old male is reported, who was admitted on the suspicion of pulmonary embolism to our department. This suspicion was confirmed by scintigraphy and computed tomography. Further examination by colour coded duplex sonography showed an aneurysm of the popliteal vein in clinically asymptomatic legs, as a possible cause of the pulmonary embolism. The finding was confirmed phlebographically. After successful surgical treatment of the aneurysm the patient got an anticoagulation therapy for 6 months. In the case of thromboembolism the entire venous system can be affected. Therefore an examination of the peripheral veins should be carried out whenever there is an occurrence of pulmonary embolism.

Recalibration of the point-of-care test for CARDIAC T Quantitative with Elecsys Troponin T 3rd generation.

The rapid troponin T assay CARDIAC T Quantitative was recalibrated using Elecsys Troponin T 3rd Generation as a new reference method. This paper presents the method comparisons at six centres using the new reference method. Method comparison between CARDIAC T Quantitative versus Elecsys Troponin T 3rd Generation were performed using 319 samples from patients with acute coronary syndromes. The quality of the CARDIAC T Quantitative was controlled by a daily single determination of CARDIAC Control Troponin T, and for the Elecsys Troponin T 3rd Generation, the Elecsys controls were included in each run. The results for the control materials for the CARDIAC T Quantitative were between 93% and 107% of the target values. The CV ranged from 7% to 16%. From the regression analysis, according to Bablok and Passing (y=1.07x) and the Bland and Altman plot, the bias between CARDIAC T Quantitative and Elecsys Troponin T 3rd Generation is from +6% to +7%. The correlation coefficient is 0.93, and a 3x3 comparison of the clinical efficiency yielded 92% clinical concordance between CARDIAC T Quantitative and Elecsys Troponin T 3rd Generation. In conclusion, CARDIAC T Quantitative was in good agreement with the reference and calibration method Elecsys Troponin T 3rd Generation.

Different patterns of angioedema in patients with and without angiotensin-converting enzyme inhibitor therapy.

BACKGROUND: There is convincing evidence for a causal relationship between angiotensin converting enzyme inhibitor (ACEI) therapy and angioedema, but the clinical features of the patients remain unclear. The aim of the study was to compare patterns of angioedema in patients under ACEI therapy and those without ACEI therapy. METHODS: One hundred and seventeen consecutive patients with angioedema treated in the emergency department of a 2000-bed tertiary care university hospital were included. A retrospective cohort study was performed, the exposure being ACEI therapy. The pattern of location of angioedema was the primary outcome measure. RESULTS: Of 117 patients with angioedema, 25 (21%) received ACEI therapy. In a multivariate logistic regression model, angioedema of the cheeks, eyelids or nose was independently negatively associated with ACEI therapy [adjusted odds ratio 0.13 (95% confidence interval 0.03 to 0.49), p = 0.003]. Higher age was also significantly associated with ACEI therapy [adjusted odds ratio 1.85 (95% confidence interval 1.23 to 2.80), p = 0.003]. Furthermore, a trend towards an independent negative association between a history of allergies and angioedema under ACEI therapy was seen. CONCLUSION: Patients with angioedema under ACE inhibitor therapy differ significantly from those receiving no ACEI therapy in terms of patterns of angioedema and age. The applicability of this observation as a tool for deciding whether to continue or terminate ACEI therapy requires prospective evaluation.

Directional coronary atherectomy: the Vienna experience.

BACKGROUND: Several multicenter trials have shown excellent results for directional coronary atherectomy (DCA) in a selected patient cohort. To prove the applicability of this method in daily clinical routine and a nonselected patient cohort, we analyzed 46 consecutive cases performed at our catheterization lab. METHODS: DCA was performed as a routine procedure in 45 suitable patients. Balloon dilatation or stent implantation postprocedure was accomplished only in case of unsatisfactory results. Quantitative coronary angiography was achieved pre- and postprocedure as well as at 6-month follow-up. RESULTS: Optimal atherectomy < 20% residual stenosis was reached in 24 (52%) of 46 target lesions and a residual stenosis < 50% in 46 (100%) lesions. Procedure-related complications occurred in three (6%) patients (one major complication, death, < 24 hours, 2%; two minor complications, pseudoaneurysm, 4%). The 6-month angiographic follow-up revealed a binary restenosis rate of 29% (n = 11). Ten out of 11 restenotic lesions required revascularization. When patients were stratified in two groups according to their preprocedural minimal lumen diameter (MLD), this parameter proved to be a very strong predictor of outcome. The percentage of restenosis was significantly higher in patients with an MLD > 1.60 mm compared to patients with a smaller MLD (54% vs 19.3%; P < 0.0001). Reference vessel diameter preprocedure did not differ significantly. CONCLUSIONS: Our study demonstrated that DCA is a suitable technique for the daily clinical routine, as the rates of complications and restenosis were similar to that in a highly selective patient cohort. Additionally, our study showed that patient selection should include preprocedural analysis of MLD in order to achieve optimal results. Therefore, atherectomy yielded comparable results to other conventional techniques and may be used instead of or in combination with them.

Out-of-hospital diagnosis of cerebral infarction versus intracranial hemorrhage.

OBJECTIVE: To establish a model based on clinical and anamnestic data easily available in the out-of-hospital setting, which facilitates the differential diagnosis between cerebral infarction and intracranial hemorrhage. DESIGN: Retrospective study that simulates a prospective approach. SETTING: Emergency Department of the University Hospital in Vienna, Austria. PATIENTS AND PARTICIPANTS: Data of 224 patients with either intracranial hemorrhage or cerebral infarction were prospectively collected. Uni-and multivariate analysis was performed to identify neurological symptoms and anamnestic data, which were associated with either intracranial hemorrhage or cerebral infarction. MEASUREMENTS AND RESULTS: Unilateral weakness or sensory loss was observed more frequently in patients with infarction compared to hemorrhage (69.8 % vs 11.9 %, P < 0.001). The frequency of patients with impaired level of consciousness was significantly higher in the hemorrhage group compared to the infarction group (59.3 % vs 3.8 %, P < 0.001). A multivariate logistic regression analysis showed that hypertension (OR = 0.31, 95 % CI = 0.12-0.76, P = 0.01), diabetes (OR = 0.17, 95% CI = 0.04-0.68, P = 0.01), and unilateral weakness or sensory loss (OR = 0.10, 95 % CI = 0.04-0.26, P < 0.001) were significantly associated with cerebral infarction. Impaired level of consciousness was significantly related to hemorrhage (OR = 13.41, 95 % CI = 3.92-45.91, P < 0.001). On the basis of the logistic regression analysis, we generated a scoring system for the out-of-hospital diagnosis between infarction and hemorrhage. The values of the score lay between -3 and +3. The probability of infarction increases when the score becomes negative, and the probability for hemorrhage increases when the score becomes positive. CONCLUSION: Our model is a useful guideline for the differential diagnosis between cerebral infarction and intracranial hemorrhage in the out-of-hospital setting, as it is based on easily available clinical and anamnestic parameters.

Use of an age-adjusted Doppler E/A ratio in patients with moderate to severe hypertension.

OBJECTIVE: To assess the ratio of early (E) to late atrial (A) mitral Doppler peak flow velocity (Doppler E/A ratio) before and after adjustment for age in patients with moderate to severe hypertension, in whom left ventricular diastolic dysfunction is an early finding. Mitral flow patterns can be used to assess diastolic filling characteristics, and the Doppler E/A ratio is the parameter most commonly used, although it is known to be strongly age dependent. There are no established normal values for this ratio. DESIGN: Retrospective data analysis. SETTING: A 2000-bed tertiary-care teaching hospital. PATIENTS: We studied 190 patients (99 women and 91 men; ages 55 +/- 13 years) with moderate to severe hypertension. INTERVENTIONS: The ratio of early (E) to late atrial (A) mitral Doppler peak flow velocity was measured. As this ratio depends on age, a Z score was calculated to control for this influence. The Z score is the standardized normal deviation of the mean, with a normal value of 0 +/- 2. MAIN OUTCOME MEASURES: Sensitivities and specificities for detecting an age-dependent reduction in Doppler E/A score (Z score less than -2) with a non-age-dependent Doppler E/A ratio (less than 1) were calculated. RESULTS: In 106 of the patients (56%) the Doppler E/A ratio was less than 1.0. Only nine patients (4.7%) had a Z score less than -2. The sensitivity of the Doppler E/A ratio threshold of 1.0 for detecting a Z score less than -2 was 0.89 and the specificity was 0.46. A Z score less than -2 was found only in patients younger than 45 years. CONCLUSIONS: The Doppler E/A ratio was reduced in a large proportion of our patients. However, after correction for age it was decreased in only 4.7% of these patients. The use of a single Doppler E/A ratio threshold value has a weak diagnostic power to detect age-independent changes in mitral flow patterns.

G-protein beta3 subunit gene (GNB3) polymorphism 825C-->T in patients with hypertensive crisis.

OBJECTIVE: The polymorphism 825C-->T in exon 10 of the gene GNB3 encoding the beta3 subunit of heterotrimeric guanine nucleotide binding regulatory proteins (G-proteins) results in a splicing variant (GNB3-s) in which the nucleotides 498-620 of exon 9 are deleted. The T allele has been shown to be overrepresented in patients with essential hypertension. Because GNB3-s may support the development of severe elevation of blood pressure, we hypothesized that GNB3 825C-->T may be present more frequently in patients with hypertensive crisis. DESIGN: Case control study. SETTING: Department of Emergency Medicine at the University Hospital of Vienna, Vienna, Austria. PATIENTS: A total of 174 patients admitted to an emergency department for treatment of hypertensive crisis diagnosed as suffering from essential hypertension. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were genotyped for the 825C-->T transition in GNB3. An equal number of age- and gender-matched normotensive, healthy individuals served as the control population. The allele frequency of 825C-->T in the GNB3 gene was 0.310 in patients with hypertensive crisis and 0.342 in the control group. There was no difference in genotype distribution and allele frequency between the patients and the age- and gender-matched control group or between the observed prevalence and the occurrence rate expected from the Hardy-Weinberg principle within each group. CONCLUSIONS: GNB3 825C-->T is not associated with the phenotype of hypertensive crisis in patients suffering from essential hypertension. Furthermore, our data do not support the concept that the 825C-->T transition in the GNB3 gene is associated with essential hypertension.