Effects of Recombinant Human Thyrotropin Administration on 24-Hour Arterial Pressure in Female Undergoing Evaluation for Differentiated Thyroid Cancer

Objective. Thyroid-stimulating-hormone (TSH) receptors are expressed in endothelial cells. We investigated whether elevated TSH levels after acute recombinant TSH (rhTSH) administration may result in alterations in blood pressure (BP) in premenopausal women with well-differentiated thyroid carcinoma (DTC). Designs. Thirty euthyroid DTC female patients were evaluated by rhTSH stimulation test (mean age 40.4 ± 8.6 years). A 24 h ambulatory systolic and diastolic blood pressure (SBP, DBP) monitoring (24 hr ABPM) was performed on days 2-3(D2-3). TSH was measured on day 1(D1), day 3(D3), and day 5(D5). Central blood pressure was evaluated on D3. Twenty-three patients were studied 1-4 weeks earlier (basal measurements). Results. TSH levels were D1: median 0.2 mU/L, D3: median 115.0 mU/L, and D5: median 14.6 mU/L. There were no significant associations between TSH on D1 and D3 and any BP measurements. Median D5 office-SBP and 24 h SBP, DBP, and central SBP were correlated with D5-TSH ( < 0.04). In those where a basal 24 h ABPM had been performed median pulse pressure was higher after rhTSH-test ( = 0.02). Conclusions. TSH, when acutely elevated, may slightly increase SBP, DBP, and central SBP. This agrees with previous reports showing positive associations of BP with TSH

Effects of Recombinant Human Thyrotropin Administration on 24-Hour Arterial Pressure in Female Undergoing Evaluation for Differentiated Thyroid Cancer

Objective. Thyroid-stimulating-hormone (TSH) receptors are expressed in endothelial cells. We investigated whether elevated TSH levels after acute recombinant TSH (rhTSH) administration may result in alterations in blood pressure (BP) in premenopausal women with well-differentiated thyroid carcinoma (DTC). Designs. Thirty euthyroid DTC female patients were evaluated by rhTSH stimulation test (mean age 40.4 +/- 8.6 years). A 24 h ambulatory systolic and diastolic blood pressure (SBP, DBP) monitoring (24 hr ABPM) was performed on days 2-3(D2-3). TSH was measured on day 1(D1), day 3(D3), and day 5(D5). Central blood pressure was evaluated on D3. Twenty-three patients were studied 1-4 weeks earlier (basal measurements). Results. TSH levels were D1: median 0.2 mU/L, D3: median 115.0 mU/L, and D5: median 14.6 mU/L. There were no significant associations between TSH on D1 and D3 and any BP measurements. Median D5 office-SBP and 24 h SBP, DBP, and central SBP were correlated with D5-TSH (P < 0.04). In those where a basal 24h ABPM had been performed median pulse pressure was higher after rhTSH-test (P = 0.02). Conclusions. TSH, when acutely elevated, may slightly increase SBP, DBP, and central SBP. This agrees with previous reports showing positive associations of BP with TSH

Association Between Obesity and Mortality After Acute First-Ever Stroke The Obesity-Stroke Paradox

Background and Purpose-Limited data exist concerning obesity and survival in patients after acute stroke. The objective of this study was to investigate the association between obesity and survival in patients with acute first-ever stroke. Methods-Patients were prospectively investigated based on a standard diagnostic protocol over a period of 16 years. Evaluation was performed on admission, at 7 days, at 1, 3, and 6 months after discharge, and yearly thereafter for up to 10 years after stroke. The study patients were divided into 3 groups according to body mass index (BMI): normal weight (<25 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese (>= 30 kg/m(2)). Overall survival during follow-up was the primary end point. The secondary end point was the overall composite cardiovascular events over the study period. Results-Based on our inclusion criteria, 2785 patients were recruited. According to BMI, 1138 (40.9%) patients were of normal weight, 1113 (41.0%) were overweight, and 504 (18.1%) were obese. NIHSS score on admission (mean, 11.28 +/- 8.65) was not different among the study groups. Early (first week) survival in obese (96.4%; 95% CI, 94.8%-97.9%) and overweight patients (92.8%; 95% CI, 91.2%-94.4%) was significantly higher compared to that of normal-weight patients (90.2%; 95% CI, 88.4%-92.0%). Similarly, 10-year survival was 52.5% (95% CI, 46.4%-58.6%) in obese, 47.4% (95% CI, 43.5%-51.3%) in overweight, and 41.5% (95% CI, 39.7%-45.0%) in normal-weight patients (log-rank test = 17.7; P < 0.0001). Overweight (HR, 0.82; 95% CI, 0.71-0.94) and obese patients (HR, 0.71; 95% CI, 0.59-0.86) had a significantly lower risk of 10-year mortality compared to normal-weight patients after adjusting for all confounding variables. Conclusions-Based on BMI estimation, obese and overweight stroke patients have significantly better early and long-term survival rates compared to those with normal BMI. (Stroke. 2011;42:30-36.

Embolic Strokes of Undetermined Source in the Athens Stroke Registry An Outcome Analysis

Background and Purpose-Information about outcomes in Embolic Stroke of Undetermined Source (ESUS) patients is unavailable. This study provides a detailed analysis of outcomes of a large ESUS population. Methods-Data set was derived from the Athens Stroke Registry. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group criteria. End points were mortality, stroke recurrence, functional outcome, and a composite cardiovascular end point comprising recurrent stroke, myocardial infarction, aortic aneurysm rupture, systemic embolism, or sudden cardiac death. We performed Kaplan-Meier analyses to estimate cumulative probabilities of outcomes by stroke type and Cox-regression to investigate whether stroke type was outcome predictor. Results-2731 patients were followed-up for a mean of 30.5 +/- 24.1months. There were 73 (26.5%) deaths, 60 (21.8%) recurrences, and 78 (28.4%) composite cardiovascular end points in the 275 ESUS patients. The cumulative probability of survival in ESUS was 65.6% (95% confidence intervals [CI], 58.9%-72.2%), significantly higher compared with cardioembolic stroke (38.8%, 95% CI, 34.9%-42.7%). The cumulative probability of stroke recurrence in ESUS was 29.0% (95% CI, 22.3%-35.7%), similar to cardioembolic strokes (26.8%, 95% CI, 22.1%-31.5%), but significantly higher compared with all types of noncardioembolic stroke. One hundred seventy-two (62.5%) ESUS patients had favorable functional outcome compared with 280 (32.2%) in cardioembolic and 303 (60.9%) in large-artery atherosclerotic. ESUS patients had similar risk of composite cardiovascular end point as all other stroke types, with the exception of lacunar strokes, which had significantly lower risk (adjusted hazard ratio, 0.70 [95% CI, 0.52-0.94]). Conclusions-Long-term mortality risk in ESUS is lower compared with cardioembolic strokes, despite similar rates of recurrence and composite cardiovascular end point. Recurrent stroke risk is higher in ESUS than in noncardioembolic strokes

Left atrial diameter thresholds and new incident atrial fibrillation in embolic stroke of undetermined source

Background and purpose: We analyzed consecutive patients with embolic stroke of undetermined source (ESUS) from three prospective stroke registries to compare the prognostic performance of different LAD thresholds for the prediction of new incident AF. Methods: We calculated the sensitivity, specificity, positive prognostic value (PPV), negative prognostic value (NPV) and Youden’s J-statistic of different LAD thresholds to predict new incident AF. We performed multivariate stepwise regression with forward selection of covariates to assess the association between the LAD threshold with the highest Youden’s J-statistic and AF detection. Results: Among 675 patients followed for 2437 patient-years, the mean LAD was 38.5 +/- 6.8 mm. New incident AF was diagnosed in 115 (17.0%) patients. The LAD threshold of 40mm yielded the highest Youden’s J-statistic of 0.35 with sensitivity 0.69, specificity 0.66, PPV 0.27 and NPV 0.92. The likelihood of new incident AF was nearly twice in patients with LAD > 40 mm compared to LAD <= 40 mm (HR:1.92, 95%CI:1.24-2.97, p = 0.004). The 10-year cumulative probability of new incident AF was higher in patients with LAD>40 mm compared to LAD <= 40 mm (53.5% and 22.4% respectively, log-rank-test: 28.2, p< 0.001). The annualized rate of stroke recurrence of 4.0% in the overall population did not differ significantly in patient above vs. below this LAD threshold (HR:0.96, 95%CI:0.62-1.48, p = 0.85). Conclusions: The LAD threshold of 40 mm has the best prognostic performance among other LAD values to predict new incident AF after ESUS. The diagnostic yield of prolonged cardiac rhythm monitoring in patients with LAD <= 40 mm seems low; therefore, such patients may have lower priority for prolonged cardiac monitoring

Embolic Stroke of Undetermined Source and Detection of Atrial Fibrillation on Follow-Up: How Much Causality Is There?

Background: There is increasing debate whether atrial fibrillation (AF) episodes during follow-up in patients with embolic stroke of undetermined source (ESUS) are causally associated with the event. AF-related strokes are more severe than strokes of other etiologies. In this context, we aimed to compare stroke severity between ESUS patients diagnosed with AF during follow-up and those who were not. We hypothesized that, if AF episodes detected during follow-up are indeed causally associated with the index event, stroke severity in the AF group should be higher than the non-AF group. Methods: Dataset was derived from the Athens Stroke Registry. ESUS was defined by the Cryptogenic Stroke/ESUS International-Working-Group criteria. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score. Cumulative probabilities of recurrent stroke or peripheral embolism in the AF and non-AF ESUS groups were estimated by Kaplan-Meier analyses. Results: Among 275 ESUS patients, AF was detected during follow-up in 80 (29.1%), either during repeated electrocardiogram monitoring (18.2%) or during hospitalization for stroke recurrence (10.9%). NIHSS score was similar between the two groups (5 [2-13] versus 5 [2-14], P = .998). More recurrent strokes or peripheral embolisms occurred in the AF group compared with the non-AF group (42.5% versus 13.3%, P = .001). Conclusions: Stroke severity is similar between ESUS patients who were diagnosed with AF during follow-up and those who were not. Given that AF-related strokes are more severe than strokes of other etiologies, this finding challenges the assumption that the association between ESUS and AF detected during follow-up is as frequently causal as regarded

Prevalence and Overlap of Potential Embolic Sources in Patients With Embolic Stroke of Undetermined Source

Background-We aimed to assess the prevalence and degree of overlap of potential embolic sources (PES) in patients with embolic stroke of undetermined source (ESUS). Methods and Results-In a pooled data set derived from 3 prospective stroke registries, patients were categorized in >= 1 groups according to the PES that was/were identified. We categorized PES as follows: atrial cardiopathy, atrial fibrillation diagnosed during follow-up, arterial disease, left ventricular disease, cardiac valvular disease, patent foramen ovale, and cancer. In 800 patients with ESUS (43.1% women; median age, 67.0 years), 3 most prevalent PES were left ventricular disease, arterial disease, and atrial cardiopathy, which were present in 54.4%, 48.5%, and 45.0% of patients, respectively. Most patients (65.5%) had >1 PES, whereas only 29.7% and 4.8% of patients had a single or no PES, respectively. In 31.1% of patients, there were >= 3 PES present. On average, each patient had 2 PES (median, 2). During a median follow-up of 3.7 years, stroke recurrence occurred in 101 (12.6%) of patients (23.3 recurrences per 100 patient-years). In multivariate analysis, the risk of stroke recurrence was higher in the atrial fibrillation group compared with other PES, but not statistically different between patients with 0 to 1, 2, or >= 3 PES. Conclusions-There is major overlap of PES in patients with ESUS. This may possibly explain the negative results of the recent large randomized controlled trials of secondary prevention in patients with ESUS and offer a rationale for a randomized controlled trial of combination of anticoagulation and aspirin for the prevention of stroke recurrence in patients with ESUS

Supraventricular Extrasystoles on Standard 12-lead Electrocardiogram Predict New Incident Atrial Fibrillation after Embolic Stroke of Undetermined Source: The AF-ESUS Study

Background: The diagnosis of covert atrial fibrillation (AF) remains a major challenge to guide secondary prevention of patients with embolic stroke of undetermined source (ESUS). Aims: We analyzed consecutive ESUS patients from 3 prospective stroke registries to assess whether the presence of supraventricular extrasystoles (SVE) on standard 12-lead electrocardiogram (ECG) is associated with the detection of AF (primary outcome), stroke recurrence and death (secondary outcomes) during follow-up. Methods: We measured the number of SVEs in all available ECGs of patients hospitalized for ESUS. Multivariate stepwise regression with forward selection of covariates assessed the association between SVE (classified in 4 groups according to their number per 10 seconds of ECG: no SVE, >0-1SVEs, >1-2SVEs, and >2SVEs) and outcomes during follow-up. The Kaplan-Meier product limit method estimated the 10-year cumulative probabilities of outcomes in each SVE group. We calculated the negative prognostic value (NPV) of the presence of any SVE to predict new AF, defined as the probability that AF will not be detected during follow-up if there is no SVE. Results: Among 853 ESUS patients followed for 2857 patient-years (median age: 67 years, 43.0% women), 226 (26.5%) patients had at least 1 SVE at the standard 12-lead ECGs performed during hospitalization. AF was detected in 125 (14.7%) of patients in the overall population during follow-up: 8.9%, 22.5%, 28.1%, and 48.3% in patients with no SVE, greater than 0-1SVE, greater than 1-2SVE and greater than 2SVE respectively. In multivariate regression analysis, compared to patients with no SVEs, the corresponding hazard-ratios were 1.80 [95% confidence intervals (95%CI):1.06-3.05], 2.26 (95%CI:1.28-4.01) and 3.19 (95%CI:1.93-5.27). The NPV of the presence of any SVE for the prediction of new AF was 91.4%. There was no statistically significant association of SVE with the risk of ischemic stroke recurrence and death. Conclusions: In ESUS patients without SVEs during hospitalization, the probability that AF will not be detected during a follow-up of 3.4 years is more than 91%

External Performance of the HAVOC Score for the Prediction of New Incident Atrial Fibrillation

Background and Purpose-The HAVOC score (hypertension, age, valvular heart disease, peripheral vascular disease, obesity, congestive heart failure, coronary artery disease) was proposed for the prediction of atrial fibrillation (AF) after cryptogenic stroke. It showed good model discrimination (area under the curve, 0.77). Only 2.5% of patients with a low-risk HAVOC score (ie, 0-4) were diagnosed with new incident AF. We aimed to assess its performance in an external cohort of patients with embolic stroke of undetermined source. Methods-In the AF-embolic stroke of undetermined source dataset, we assessed the discriminatory power, calibration, specificity, negative predictive value, and accuracy of the HAVOC score to predict new incident AF. Patients with a HAVOC score of 0 to 4 were considered as low-risk, as proposed in its original publication. Results-In 658 embolic stroke of undetermined source patients (median age, 67 years; 44% women), the median HAVOC score was 2 (interquartile range, 3). There were 540 (82%) patients with a HAVOC score of 0 to 4 and 118 (18%) with a score of >= 5. New incident AF was diagnosed in 95 (14.4%) patients (28.8% among patients with HAVOC score >= 5 and 11.3% among patients with HAVOC score 0-4 [age- and sex-adjusted odds ratio, 2.29 (95% CI,1.37-3.82)]). The specificity of low-risk HAVOC score to identify patients without new incident AF was 88.7%. The negative predictive value of low-risk HAVOC score was 85.1%. The accuracy was 78.0%, and the area under the curve was 68.7% (95% CI, 62.1%-73.3%). Conclusions-The previously reported low rate of AF among embolic stroke of undetermined source patients with low-risk HAVOC score was not confirmed in our cohort. Further assessment of the HAVOC score is warranted before it is routinely implemented in clinical practice