Long-term outcomes of elderly patients with CYP2C9 and VKORC1 variants treated with vitamin K antagonists.

Essentials The long-term effects of VKORC1 and CYP2C9 variants on clinical outcomes remains unclear. We followed 774 patients ≥65 years with venous thromboembolism for a median duration of 30 months. Patients with CYP2C9 variants are at increased risk of death and non-major bleeding. Patients with genetic variants have a slightly lower anticoagulation quality only. SUMMARY: Background The long-term effect of polymorphisms of the vitamin K-epoxide reductase (VKORC1) and the cytochrome P450 enzyme gene (CYP2C9) on clinical outcomes remains unclear. Objectives We examined the association between CYP2C9/VKORC1 variants and long-term clinical outcomes in a prospective cohort study of elderly patients treated with vitamin K antagonists for venous thromboembolism (VTE). Methods We followed 774 consecutive patients aged ≥ 65 years with acute VTE from nine Swiss hospitals for a median duration of 30 months. The median duration of initial anticoagulant treatment was 9.4 months. The primary outcome was the time to any clinical event (i.e. the composite endpoint of overall mortality, major and non-major bleeding, and recurrent VTE. Results Overall, 604 (78%) patients had a CYP2C9 or VKORC1 variant. Three hundred and thirty-four patients (43.2%) had any clinical event, 119 (15.4%) died, 100 (12.9%) had major and 167 (21.6%) non-major bleeding, and 100 had (12.9%) recurrent VTE. After adjustment, CYP2C9 (but not VKORC1) variants were associated with any clinical event (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.08-1.66), death (HR, 1.74; 95% CI, 1.19-2.52) and clinically relevant non-major bleeding (sub-hazard ratio [SHR], 1.39; 95% CI, 1.02-1.89), but not with major bleeding (SHR, 1.03; 95% CI, 0.69-1.55) or recurrent VTE (SHR, 0.95; 95% CI, 0.62-1.44). Patients with genetic variants had a slightly lower anticoagulation quality. Conclusions CYP2C9 was associated with long-term overall mortality and non-major bleeding. Although genetic variants were associated with a slightly lower anticoagulation quality, there was no relationship between genetic variants and major bleeding or VTE recurrence.

Association between thyroid dysfunction and venous thromboembolism in the elderly: a prospective cohort study.

BACKGROUND: Venous thromboembolism (VTE) and subclinical thyroid dysfunction (SCTD) are both common in elderly patients. SCTD has been related to a hypercoagulable state and an increased thromboembolic risk. However, prospective data on the relationship between SCTD and VTE are lacking. OBJECTIVES: To investigate the relationship between SCTD and recurrent VTE (rVTE), all-cause mortality, and thrombophilic biomarkers. Patients Elderly patients with VTE were studied. METHODS: In a prospective multicenter cohort, thyroid hormones and thrombophilic biomarkers were measured 1 year after acute VTE, as both may be influenced by acute thrombosis. We defined subclinical hypothyroidism (SHypo) as elevated thyroid-stimulating hormone (TSH) levels (4.50-19.99 mIU L(-1) ), and subclinical hyperthyroidism (SHyper) as TSH levels of < 0.45 mIU L(-1) , both with normal free thyroxine levels. Outcomes were incidence of rVTE and overall mortality during follow-up starting after the 1-year blood sampling. RESULTS: Of 561 participants (58% with anticoagulation), 6% had SHypo and 5% had SHyper. After 20.8 months of mean follow-up, 9% developed rVTE and 10% died. The rVTE incidence rate was 7.2 (95% confidence interval [CI] 2.7-19.2) per 100 patient-years in SHypo participants, 0.0 (95% CI 0.0-7.6) in SHyper participants, and 5.9 (95% CI 4.4-7.8) in euthyroid participants. In multivariate analyses, the sub-hazard ratio for rVTE was 0.00 (95% CI 0.00-0.58) in SHyper participants and 1.50 (95% CI 0.52-4.34) in SHypo participants as compared with euthyroid participants, without increased levels of thrombophilic biomarkers. SHyper (hazard ratio [HR] 0.80, 95% CI 0.23-2.81) and SHypo (HR 0.99, 95% CI 0.30-3.29) were not associated with mortality. CONCLUSION: In elderly patients, SHyper may be associated with lower rVTE risks. SHypo showed a non-statistically significant pattern of an association with rVTE, without increased mortality or differences in thrombophilic biomarkers.

Physical activity and risk of bleeding in elderly patients taking anticoagulants.

BACKGROUND: Although the possibility of bleeding during anticoagulant treatment may limit patients from taking part in physical activity, the association between physical activity and anticoagulation-related bleeding is uncertain. OBJECTIVES: To determine whether physical activity is associated with bleeding in elderly patients taking anticoagulants. PATIENTS/METHODS: In a prospective multicenter cohort study of 988 patients aged ≥ 65 years receiving anticoagulants for venous thromboembolism, we assessed patients' self-reported physical activity level. The primary outcome was the time to a first major bleeding, defined as fatal bleeding, symptomatic bleeding in a critical site, or bleeding causing a fall in hemoglobin or leading to transfusions. The secondary outcome was the time to a first clinically relevant non-major bleeding. We examined the association between physical activity level and time to a first bleeding by using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. RESULTS: During a mean follow-up of 22 months, patients with a low, moderate, and high physical activity level had an incidence of major bleeding of 11.6, 6.3, and 3.1 events per 100 patient-years and an incidence of clinically relevant non-major bleeding of 14.0, 10.3, and 7.7 events per 100 patient-years, respectively. A high physical activity level was significantly associated with a lower risk of major bleeding (adjusted sub-hazard ratio 0.40, 95% confidence interval 0.22-0.72). There was no association between physical activity and non-major bleeding. CONCLUSIONS: A high level of physical activity is associated with a decreased risk of major bleeding in elderly patients receiving anticoagulant therapy.

Risk of falls and bleeding in elderly patients with acute venous thromboembolism.

OBJECTIVE: Whether or not a high risk of falls increases the risk of bleeding in patients receiving anticoagulants remains a matter of debate. METHODS: We conducted a prospective cohort study involving 991 patients ≥ 65 years of age who received anticoagulants for acute venous thromboembolism (VTE) at nine Swiss hospitals between September 2009 and September 2012. The study outcomes were as follows: the time to a first major episode of bleeding; and clinically relevant nonmajor bleeding. We determined the associations between the risk of falls and the time to a first episode of bleeding using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. RESULTS: Four hundred fifty-eight of 991 patients (46%) were at high risk of falls. The mean duration of follow-up was 16.7 months. Patients at high risk of falls had a higher incidence of major bleeding (9.6 vs. 6.6 events/100 patient-years; P = 0.05) and a significantly higher incidence of clinically relevant nonmajor bleeding (16.7 vs. 8.3 events/100 patient-years; P < 0.001) than patients at low risk of falls. After adjustment, a high risk of falls was associated with clinically relevant nonmajor bleeding [subhazard ratio (SHR) = 1.74, 95% confidence interval (CI) = 1.23-2.46], but not with major bleeding (SHR = 1.24, 95% CI = 0.83-1.86). CONCLUSION: In elderly patients who receive anticoagulants because of VTE, a high risk of falls is significantly associated with clinically relevant nonmajor bleeding, but not with major bleeding. Whether or not a high risk of falls is a reason against providing anticoagulation beyond 3 months should be based on patient preferences and the risk of VTE recurrence.

Multicentre validation of the Geneva Risk Score for hospitalised medical patients at risk of venous thromboembolism. Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE).

There is a need to validate risk assessment tools for hospitalised medical patients at risk of venous thromboembolism (VTE). We investigated whether a predefined cut-off of the Geneva Risk Score, as compared to the Padua Prediction Score, accurately distinguishes low-risk from high-risk patients regardless of the use of thromboprophylaxis. In the multicentre, prospective Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE) cohort study, 1,478 hospitalised medical patients were enrolled of whom 637 (43%) did not receive thromboprophylaxis. The primary endpoint was symptomatic VTE or VTE-related death at 90 days. The study is registered at ClinicalTrials.gov, number NCT01277536. According to the Geneva Risk Score, the cumulative rate of the primary endpoint was 3.2% (95% confidence interval [CI] 2.2-4.6%) in 962 high-risk vs 0.6% (95% CI 0.2-1.9%) in 516 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.5% vs 0.8% (p=0.029), respectively. In comparison, the Padua Prediction Score yielded a cumulative rate of the primary endpoint of 3.5% (95% CI 2.3-5.3%) in 714 high-risk vs 1.1% (95% CI 0.6-2.3%) in 764 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.2% vs 1.5% (p=0.130), respectively. Negative likelihood ratio was 0.28 (95% CI 0.10-0.83) for the Geneva Risk Score and 0.51 (95% CI 0.28-0.93) for the Padua Prediction Score. In conclusion, among hospitalised medical patients, the Geneva Risk Score predicted VTE and VTE-related mortality and compared favourably with the Padua Prediction Score, particularly for its accuracy to identify low-risk patients who do not require thromboprophylaxis.

Glucose control during a driving training in patients with type 1 and type 2 diabetes mellitus - a randomised, controlled trial.

AIM: To investigate the effect of prolonged acute mental stress by means of a driving training on glucose control in patients with type 1 and type 2 diabetes mellitus. METHODS: 39 patients with insulin-treated diabetes (18 type 1, 21 type 2 diabetes) were exposed to mental stress by means of a 2 h-driving training. The training session started 15 min after intake of a standard meal. Blood glucose, blood pressure, heart rate, salivary cortisol, and subjective stress perception were monitored in regular intervals and compared to a control day. RESULTS: On the stress testing day, blood pressure rose from 142/86±16/9 mmHg to 162/95±22/11 mmHg (p<0.001), heart rate from 72±11 bpm to 86±16 bpm (p<0.001) and subjective stress perception from 1.4±0.6 to 4.7±2.5 points (p<0.001). Salivary cortisol concentrations increased from a median of 5.1 nmol/l (Interquartile Range (IQR) 3.5-7.5 nmol/l) at baseline to 7.7 nmol/l (IQR 4.7-12.8 nmol/l, p<0.001), all these measurements remained stable on the control day. Glucose control showed no significant difference on the stress testing day compared to the control day (mean difference over time=0.22 mmol/l, 95%-CI -1.5 to +1.9 mmol/l, p=0.794). A multivariate linear regression and correlation analysis showed no association of demographic characteristics (diabetes type, age, body mass index (BMI), diabetes duration, HbA1c), objective or subjective stress parameters with the course of glucose concentrations during the driving training. CONCLUSIONS: Although a 2 h-driving training causes increased subjective and objective stress parameters, glucose control is maintained in patients with insulin-treated diabetes.

Prospective, multicenter validation of prediction scores for major bleeding in elderly patients with venous thromboembolism.

BACKGROUND: The Outpatient Bleeding Risk Index (OBRI) and the Kuijer, RIETE and Kearon scores are clinical prognostic scores for bleeding in patients receiving oral anticoagulants for venous thromboembolism (VTE). We prospectively compared the performance of these scores in elderly patients with VTE. METHODS: In a prospective multicenter Swiss cohort study, we studied 663 patients aged ≥ 65 years with acute VTE. The outcome was a first major bleeding at 90 days. We classified patients into three categories of bleeding risk (low, intermediate and high) according to each score and dichotomized patients as high vs. low or intermediate risk. We calculated the area under the receiver-operating characteristic (ROC) curve, positive predictive values and likelihood ratios for each score. RESULTS: Overall, 28 out of 663 patients (4.2%, 95% confidence interval [CI] 2.8-6.0%) had a first major bleeding within 90 days. According to different scores, the rate of major bleeding varied from 1.9% to 2.1% in low-risk, from 4.2% to 5.0% in intermediate-risk and from 3.1% to 6.6% in high-risk patients. The discriminative power of the scores was poor to moderate, with areas under the ROC curve ranging from 0.49 to 0.60 (P = 0.21). The positive predictive values and positive likelihood ratios were low and varied from 3.1% to 6.6% and from 0.72 to 1.59, respectively. CONCLUSION: In elderly patients with VTE, existing bleeding risk scores do not have sufficient accuracy and power to discriminate between patients with VTE who are at a high risk of short-term major bleeding and those who are not.

Prospective comparison of clinical prognostic scores in elder patients with a pulmonary embolism.

BACKGROUND: The Geneva Prognostic Score (GPS), the Pulmonary Embolism Severity Index (PESI) and its simplified version (sPESI) are well-known clinical prognostic scores for a pulmonary embolism (PE). OBJECTIVES: To compare the prognostic performance of these scores in elderly patients with a PE. PATIENTS AND METHODS: In a multicenter Swiss cohort of elderly patients with venous thromboembolism, we prospectively studied 449 patients aged ≥ 65 years with a symptomatic PE. The outcome was 30-day overall mortality. We dichotomized patients as low vs. higher risk in all three scores using the following thresholds: GPS scores ≤ 2 vs. > 2, PESI risk classes I-II vs. III-V and sPESI scores 0 vs. ≥ 1. We compared 30-day mortality in low- vs. higher-risk patients and the areas under the receiver-operating characteristic curve (ROC). RESULTS: Overall, 3.8% of patients (17/449) died within 30 days. The GPS classified a greater proportion of patients as low risk (92% [413/449]) than the PESI (36.3% [163/449]) and the sPESI (39.6% [178/449]) (P < 0.001 for each comparison). Low-risk patients based on the sPESI had a mortality of 0% (95% confidence interval [CI] 0-2.1%) compared with 0.6% (95% CI 0-3.4%) for low-risk patients based on the PESI and 3.4% (95% CI 1.9-5.6%) for low-risk patients based on the GPS. The areas under the ROC curves were 0.77 (95% CI 0.72-0.81), 0.76 (95% CI 0.72-0.80) and 0.71 (95% CI 0.66-0.75), respectively (P = 0.47). CONCLUSIONS: In this cohort of elderly patients with PE, the GPS identified a higher proportion of patients as low risk but the PESI and sPESI were more accurate in predicting mortality.

Cardiac troponin testing and the simplified Pulmonary Embolism Severity Index. The SWIss Venous ThromboEmbolism Registry (SWIVTER).

A low simplified Pulmonary Embolism Severity Index (sPESI), defined as age ≤80 years and absence of systemic hypotension, tachycardia, hypoxia, cancer, heart failure, and lung disease, identifies low-risk patients with acute pulmonary embolism (PE). It is unknown whether cardiac troponin testing improves the prediction of clinical outcomes if the sPESI is not low. In the prospective Swiss Venous Thromboembolism Registry, 369 patients with acute PE and a troponin test (conventional troponin T or I, highly sensitive troponin T) were enrolled from 18 hospitals. A positive test result was defined as a troponin level above the manufacturers assay threshold. Among the 106 (29%) patients with low sPESI, the rate of mortality or PE recurrence at 30 days was 1.0%. Among the 263 (71%) patients with high sPESI, 177 (67%) were troponin-negative and 86 (33%) troponin-positive; the rate of mortality or PE recurrence at 30 days was 4.6% vs. 12.8% (p=0.015), respectively. Overall, risk assessment with a troponin test (hazard ratio [HR] 3.39, 95% confidence interval [CI] 1.38-8.37; p=0.008) maintained its prognostic value for mortality or PE recurrence when adjusted for sPESI (HR 5.80, 95%CI 0.76-44.10; p=0.09). The combination of sPESI with a troponin test resulted in a greater area under the receiver-operating characteristic curve (HR 0.72, 95% CI 0.63-0.81) than sPESI alone (HR 0.63, 95% CI 0.57-0.68) (p=0.023). In conclusion, although cardiac troponin testing may not be required in patients with a low sPESI, it adds prognostic value for early death and recurrence for patients with a high sPESI.

Long-term anticoagulation treatment for acute venous thromboembolism in patients with and without cancer. The SWIss Venous ThromboEmbolism Registry (SWIVTER) II.

In patients with acute cancer-associated thrombosis, current consensus guidelines recommend anticoagulation therapy for an indefinite duration or until the cancer is resolved. Among 1,247 patients with acute venous thromboembolism (VTE) enrolled in the prospective Swiss Venous Thromboembolism Registry (SWIVTER) II from 18 hospitals, 315 (25%) had cancer of whom 179 (57%) had metastatic disease, 159 (50%) ongoing or recent chemotherapy, 83 (26%) prior cancer surgery, and 63 (20%) recurrent VTE. Long-term anticoagulation treatment for >12 months was more often planned in patients with versus without cancer (47% vs. 19%; p<0.001), with recurrent cancer-associated versus first cancer-associated VTE (70% vs. 41%; p<0.001), and with metastatic versus non-metastatic cancer (59% vs. 31%; p<0.001). In patients with cancer, recurrent VTE (OR 3.46; 95%CI 1.83-6.53), metastatic disease (OR 3.04; 95%CI 1.86-4.97), and the absence of an acute infection (OR 3.55; 95%CI 1.65-7.65) were independently associated with the intention to maintain anticoagulation for >12 months. In conclusion, long-term anticoagulation treatment for more than 12 months was planned in less than half of the cancer patients with acute VTE. The low rates of long-term anticoagulation in cancer patients with a first episode of VTE and in patients with non-metastatic cancer require particular attention.

PROCAM-, FRAMINGHAM-, SCORE- and SMART-risk score for predicting cardiovascular morbidity and mortality in patients with overt atherosclerosis.

BACKGROUND: The predictive value of PROCAM, FRAMINGHAM, SCORE and SMART-score to estimate the cardiovascular risk in patients with overt atherosclerosis had never been assessed. PATIENTS AND METHODS: 96 consecutive patients with clinically evident atherosclerosis (coronary, cerebrovascular, peripheral artery and renovascular disease) were enrolled in this preliminary observational study. At baseline, medical history and blood chemistry were obtained. Sonographic measurement of the intima-media thickness (IMT) in the common carotid artery was performed and risk estimations according to the above listed risk scores were calculated. During a 6 year follow-up the occurrence of cardiovascular death, acute coronary syndrome and stroke was assessed. RESULTS: Mean (±SD) risk-scores were 10.9±2.5, range 6-17 (SMART); 18.9±18.2%; range 0.2-94.1% (PROCAM); 21.4±13.1%, range 4-56% (FRAMINGHAM); and 4.8±3.9%, range 0.4-15.3% (SCORE). Mean IMT was 0.84±0.14 mm, range 0.51-1.20 mm. All scores correlate significantly with each other (r>0.321; p<0.01), but only SMART-score correlated significantly with baseline IMT(r=0.372; p<0.001). Within the median follow-up of 73 months, a cardiovascular endpoint was observed in 36 (42%) patients. The AUC (95% confidence interval) for SMART-risk-score predicting a cardiovascular event was 0.67 (0.54-0.77; p<0.02); for PROCAM 0.60 (0.47-0.73; p=n.s.); for FRAMINGHAM 0.56 (0.43-0.69; p=n.s.); and for SCORE 0.60 (0.46-0.73; p=n.s.). Cox regression analysis showed a relative risk for a cardiovascular event per additional SMART score point of 1.15 (95% CI 1.01-1.30 p=0.03). CONCLUSIONS: PROCAM-, FRAMINGHAM- and SCORE-risk score seem to be barely useful in a secondary prevention setting. In patients with overt atherosclerosis, the cardiovascular risk seems to be better assessed by means of the SMART score.

Clinical predictors of prophylaxis use prior to the onset of acute venous thromboembolism in hospitalized patients SWIss Venous ThromboEmbolism Registry (SWIVTER).

BACKGROUND: We investigated clinical predictors of appropriate prophylaxis prior to the onset of venous thromboembolism (VTE). METHODS: In 14 Swiss hospitals, 567 consecutive patients (306 medical, 261 surgical) with acute VTE and hospitalization < 30 days prior to the VTE event were enrolled. RESULTS: Prophylaxis was used in 329 (58%) patients within 30 days prior to the VTE event. Among the medical patients, 146 (48%) received prophylaxis, and among the surgical patients, 183 (70%) received prophylaxis (P < 0.001). The indication for prophylaxis was present in 262 (86%) medical patients and in 217 (83%) surgical patients. Among the patients with an indication for prophylaxis, 135 (52%) of the medical patients and 165 (76%) of the surgical patients received prophylaxis (P < 0.001). Admission to the intensive care unit [odds ratio (OR) 3.28, 95% confidence interval (CI) 1.94-5.57], recent surgery (OR 2.28, 95% CI 1.51-3.44), bed rest > 3 days (OR 2.12, 95% CI 1.45-3.09), obesity (OR 2.01, 95% CI 1.03-3.90), prior deep vein thrombosis (OR 1.71, 95% CI 1.31-2.24) and prior pulmonary embolism (OR 1.54, 95% CI 1.05-2.26) were independent predictors of prophylaxis. In contrast, cancer (OR 1.06, 95% CI 0.89-1.25), age (OR 0.99, 95% CI 0.98-1.01), acute heart failure (OR 1.13, 95% CI 0.79-1.63) and acute respiratory failure (OR 1.19, 95% CI 0.89-1.59) were not predictive of prophylaxis. CONCLUSIONS: Although an indication for prophylaxis was present in most patients who suffered acute VTE, almost half did not receive any form of prophylaxis. Future efforts should focus on the improvement of prophylaxis for hospitalized patients, particularly in patients with cancer, acute heart or respiratory failure, and in the elderly.

Intima-media thickness and carotid resistive index: progression over 6 years and predictive value for cardiovascular events.

PURPOSE: Intima-media thickness (IMT) of the common carotid artery and the resistive index (RI) of the internal carotid artery correlate with the degree of atherosclerosis and are predictors of cardiovascular morbidity and mortality. Limited or no data are available about long-term predictive values and the progression of the two markers themselves. MATERIALS AND METHODS: 145 patients with at least one cardiovascular risk factor or clinically manifest atherosclerosis were included. At enrollment and after 36 and 74 months, duplex sonographic measurements of IMT CCA and RI ICA were performed. During follow-up, the occurrence of cardiovascular events (cardiovascular death, myocardial infarction, stroke) was assessed. RESULTS: At baseline, IMT was 0.79 +/- 0.16 mm and RI 0.66 +/- 0.08. Log-rank analysis showed a continuous increase in the risk of a cardiovascular event with an increasing range of IMT (p = 0.011) and RI (p = 0.006). IMT progression in patients with low versus high atherosclerotic burden (as defined by SMART score < or =7 points and > 7 points) differs significantly (32 +/- 83 microm versus 95 +/- 125 microm; p < 0.002). IMT progression was even more pronounced in patients suffering a cardiovascular event (141 +/- 105 microm versus 54 +/- 111 microm; p < 0.001). No significant RI ICA progression could be detected during follow-up in any group (patients with low vs. high atherosclerotic burden 0.00 +/- 0.06 versus 0.00 +/- 0.04; p = n. s.; patients with vs. without cardiovascular event 0.00 +/- 0.05 versus 0.01 +/- 0.03; p = n. s.). CONCLUSION: Our results confirm the predictive value for cardiovascular events of RI and IMT in long-term follow-up. In contrast to RI, IMT increases over six years, above all in patients suffering a cardiovascular event. The results suggest that IMT is suitable for cardiovascular risk prediction as well as for progression measurements, while RI cannot be recommended for progression measurements. The effect of drug therapy on RI needs further clarification.

Quantitative d-dimer levels and the extent of venous thromboembolism in CT angiography and lower limb ultrasonography.

BACKGROUND: We evaluated the diagnostic yield of multidetector-row CT angiography and determined the clot burden within pulmonary vasculature as a measure of pulmonary embolism (PE) severity at different d-dimer levels and pretest clinical probabilities. PATIENTS AND METHODS: 254 consecutive patients referred to CT pulmonary angiography for suspected PE after d-dimer testing were grouped into clinical probability classes using Wells' score, and the frequency of PE was determined. A score representing clot burden within pulmonary vasculature was calculated from the number of obstructed segmental arteries in CT scans in a partly differing group of 96 PE positive patients. RESULTS: The prevalence of PE increases with the d-dimer level (7% at d-dimer levels of 0.5-1 microg/ml, reaching 90% at d-dimer levels > 9 microg/ml; p < 0.001). D-dimer levels above 4 microg/ml are associated with a significantly higher clot burden in pulmonary arteries (median score 11 versus 5, and 53% versus 16% of patients in the subgroup with a score > 10 points; p < 0.001), and thrombus in a main pulmonary artery was detected more frequently (37% versus 9%, p = 0.003). Similar results were obtained for distal versus proximal deep venous thromboses, detected by ultrasonography of the lower limb in a separate group of 44 patients. CONCLUSIONS: High d-dimer levels are associated with an increased prevalence of CT radiographic findings indicating extended clinically severe PE or lower limb venous thrombosis.

[Conservative treatment of acute embolisms of the carotid bifurcation]. / Konservative Behandlung akuter embolischer Verschlüsse der Karotisbifurkation.

Embolic events of the carotid bifurcatin are a rare cause of cerebrovascular accidents. We observed two patients who showed a spontaneous recanalisation of an embolic occlusion of the extracranial vessels when treated with conservative procedure using heparin. Both patients had a near complete remission of the symptoms without impairment in their daily activities.

Comparison of carotid arterial resistive indices with intima-media thickness as sonographic markers of atherosclerosis.

UNLABELLED: Background and Purpose-The intima-media thickness (IMT) of the carotid artery is a (morphological) sonographic parameter that depends on the degree of atherosclerosis. In the renal arteries, the value of the (hemodynamic) resistive index (RI) is correlated with the severity of atherosclerosis. In contrast to the well-known IMT, no study has yet applied the carotid RI to estimate generalized atherosclerosis. METHODS: -The SMART atherosclerosis risk score was determined in 157 patients (94 men and 63 women; mean age 63 [range 19 to 80] years) with at least 1 vascular risk factor or a known vascular disease. Duplex sonography of the common carotid (CCA) and internal carotid artery (ICA) was then performed, with determination of IMT and RI. RESULTS: -The mean risk score of all patients was 8.8+/-3.5 (range 1 to 17), the mean IMT value in the CCA was 0.727+/-0.161 mm, the mean RI in CCA was 0.79+/-0.066, and the mean RI in ICA was 0.661+/-0.082. Highly significant correlations were found between the score and IMT CCA and the score and RI ICA (r=0.62, P:<0.0001 and r=0.55, P:<0.0001). The score-RI CCA correlation was much less marked (r=0.354, P:<0.0001). The intraobserver and interobserver agreement was less for IMT than for RI CCA and ICA. The areas under the curve of the receiver operating curves to distinguish between low-risk and high-risk patients resulted in values of 0.86, 0.81, and 0.69 for IMT, RI ICA, and RI CCA, respectively. CONCLUSIONS: -Although RI reflects the atherosclerotic process in an indirect manner, the correlation between the RI ICA and the SMART atherosclerosis score as well as the ability to distinguish between low- and high-risk patients are comparable to those of the well-known IMT.

Optimising the use of carotid duplex sonography.

AIM: We analysed factors influencing diagnostic yield and treatment and their potential for optimising the use of carotid duplex sonography (CDS). METHOD: Patients referred for CDS were divided into three groups: 1: high likelihood of carotid symptoms, 2: suspected presence of asymptomatic carotid lesions, 3: other indications. Clinical data, the grading of stenosis and the therapeutic consequences were analysed. The efficiency of diagnosis was tested with an algorithm. RESULTS: 344 patients were included. Groups 1, 2 and 3 contained > or = 1 pathological finding in the carotid or vertebral system in 68%, 86% and 55% respectively, whereas high-grade stenoses or occlusions of the internal carotid artery (ICA) were detected in 10.8%, 16% and 3.6% respectively. Age > 50, > 1 risk factor, carotid murmur and concomitant vascular disease were associated with a significantly higher diagnostic yield. Subsequent treatment in groups 1, 2 and 3 involved carotid thromboendarterectomy in 6.4%, 2% and 0.7% respectively and the start of treatment with a platelet aggregation inhibitor in 9%, 30% and 17% respectively. The optimisation algorithm would have saved 21% of CDS scans. CONCLUSION: Clinical pre-selection criteria determine the diagnostic yield of CDS. The potential for optimisation depends on the treatment regimen chosen for asymptomatic stenoses and secondary prophylaxis.

[Tick-borne meningoencephalitis in Thurgau Canton: a clinical and epidiomological analysis]. / Die Frühsommer-Meningoenzephalitis im Kanton Thurgau: eine klinisch-epidemiologische Analyse.

BACKGROUND: Tick-borne meningo-encephalitis (TBE) is caused by a flavivirus species that is transmitted from rodents to humans by Ixodes ticks. The clinical picture of central nervous system involvement varies from febrile headache to lethal encephalitis. To date no specific treatment exists, although protective active immunisation is available. METHODS: We present the clinical and epidemiological data from 73 patients with TBE who acquired the infection in Canton Thurgau in the years 1996-1999. RESULTS: Canton Thurgau is a state in eastern Switzerland with a population of 230,000. Within the last five years the reported cases of TBE have increased more than threefold. The area where infectious tick bites were registered has expanded from the western to the eastern part and now encompasses the entire state. The risk of infection is clearly related to frequent activities in wooded areas, though outdoor activities not in forests also carry a considerable risk. In > 80% of the cases a postviral neurasthenic syndrome develops involving absence from work for two months on average. In the elderly and patients who present with encephalitic symptoms, a worse outcome with persistent neurological symptoms or even death has been observed. CONCLUSION: The increasing incidence of TBE, the expansion of infectious ticks to the east and high morbidity justify active immunisation against TBE on a broad scale in Canton Thurgau.

Duplex sonographic registration of age and diabetes-related loss of renal vasodilatory response to nitroglycerine.

BACKGROUND: Nitroglycerine effects dilatation of the vas afferens in the kidney by its active metabolite nitric oxide (NO). In diabetic nephropathy, NO appears to cause hyperfiltration and proteinuria. The aim of this study was to investigate the potential of duplex Doppler ultrasonography in recording changes in resistive indices following nitroglycerine and whether the extent of changes in diabetic nephropathy is reduced as a result of the arteriolar dilatation mediated by NO. METHODS: Fifty-three subjects made up three groups: group 1, 12 young healthy volunteers (5 male, 7 female, 28+/-6 years); group 2, 21 older healthy volunteers (7 male, 14 female, 62+/-8 years); group 3, 20 patients (13 male, 7 female, 56+/-18 years) with mild diabetic nephropathy. The resistive index (RI) was measured in the interlobar arteries before, and 1, 3 and 5 min after administration of 0.8 mg sublingual nitroglycerine. RESULTS: The initial RI of 0.592 decreased in group 1 by 10.8% (P<0. 01) after nitroglycerine, in group 2 the initial figure of 0.631 decreased by 5.9% (P<0.01), and in group 3 the initial figure of 0. 669 decreased by 3.4% (P<0.01). Initial RI values differed significantly between groups 1 and 3 (P<0.01) and groups 1 and 2 (P<0.01), as did values between all healthy volunteers (groups 1 and 2, n=33) and patients with nephropathy (P<0.005). The extent of DeltaRI differed significantly between groups 1 and 3 (P<0.01), 1 and 2 (P<0.02), and between all volunteers and group 3 (P<0.003). In groups 1 and 2 the initial RI was dependent on age (P<0.03), in group 3 on age and creatinine clearance (P<0.02 and P<0.05 respectively). DeltaRI correlated with age in the healthy subjects (P<0.01) and with duration of diabetes in diabetic nephropathy (P0. 03). CONCLUSIONS: Haemodynamic changes in renal perfusion caused by nitroglycerine can be detected using duplex ultrasonography. In healthy subjects, DeltaRI declines with increasing age. In diabetic nephropathy patients, the response to nitroglycerine is reduced. The increased initial RI in such patients suggests fixed arteriolar damage.