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Background: The CHA2DS2-VASc score has been recommended for the assessment of thromboembolic risk in patients with atrial fibrillation. Data regarding the association between the pre-admission CHA2DS2-VASc score and the outcome of patients with stroke and TIA are scarce. We aimed to assess the predictive value of pre-admission CHA2DS2-VASc score for early risk stratification of patients with acute cerebrovascular event., Methods: The study group consisted of 8309 patients (53% males, mean age of 70±13.3years) with acute stroke and TIA included in the prospective National Acute Stroke Israeli (NASIS) registry. The two-primary end-points were in-hospital mortality and severe disability at discharge. We divided the study population into 4 groups according to their pre-admission CHA2DS2-VASc score (0-1, 2-3, 4-5, >5)., Results: Following a multivariate analysis odds ratios (OR) for all-cause mortality increased for CHA2DS2-VASc score >1 (OR=2.1 95% CI=1.2-3.6, OR=1.8 95% CI=1.1-3.2, OR=1.8 95% CI 1.1-3.3, for patients with CHA2DS2-VASc score of 2-3, 4-5 and >5, respectively, p<0.001). OR for severe disability (mRS 4-5) at discharge increased significantly in direct association with the CHA2DS2-VASc score (OR=1.55 95% CI=1.14-2.12, OR=2.42 95% CI=1.8-3.3, OR=3 95% CI 2.19-4.27, for patients with CHA2DS2-VASc score of 2-3, 4-5 and >5, respectively as compared with 0-1, p<0.001). Each 1-point increase in the CHA2DS2-VASc score was associated with a 21% increase in the risk for severe disability., Conclusions: High-risk pre-admission CHA2DS2-VASc score among patients with acute cerebrovascular events is associated with higher in-hospital mortality and severe disability at discharge., (Copyright © 2017. Published by Elsevier B.V.)

Background: The importance of gender as an independent risk factor for poor outcome is not clear. We examined gender differences in patients' characteristic, management and outcome at discharge and 3-months after acute stroke in a national hospital-based registry., Methods: Data were derived from the triennial two-month national Acute Stroke Israeli Registry (Feb-March 2004, March-April 2007, April-May 2010). Unselected patients in all Israeli hospitals (n = 28) were included. Outcome at 3-month was assessed in a sub-sample. Logistic regression models were used in the study of gender as an independent risk factor for poor outcome., Results: In total, 5034 patients (88.5% ischemic stroke, 9.6% ICH and 1.9% undetermined stroke) were included, of them 2285 (45.4%) women. Follow-up at 3-month was completed for 1040 patients, 41.9% women. Women showed higher rates of cardiovascular risk factors in-hospital death (p = 0.007) and poor functional outcome (p < 0.0001). Following adjustment for age, prior disability, NIHSS, prior stroke and risk factors, risk estimates (ORs, 95%CI) for women compared to men were 0.72 (0.55-0.96) for in-hospital death, 1.03 (0.83-1.29) for discharge to a nursing home or death, and 1.01 (0.86-1.20) for disability. Poor outcomes at 3-month were significantly more common in women; however, adjusted risk estimates were not significantly increased: OR 0.95 (95%CI 0.50-1.81) for death at 3-months, 1.41 (0.99-2.01) for Barthel Index ≤ 60, 1.24 (0.90-1.72) for dependency and 0.88 (0.55-1.39) for living in a nursing home or death., Conclusion: Gender-differences in risk of death and poor functional outcome after stroke are mainly explained by dissimilarities in patients' characteristics and stroke severity., (© 2013.)

Objectives: The objective of this study is to examine the association between perceived hardships and long-term stroke mortality among a large cohort of middle-aged men., Background: Unlike cardiovascular morbidity and mortality, much less is known about the relationship between psychosocial factors and risk of stroke., Methods: A cohort of 10,059 men aged ≥ 40 years at study inclusion that were tenured civil servants or municipal employees were followed for mortality over a median of 28.1 years (IQR 18.9-34.3). During follow-up 6528 (64.9%) men died, 665 of stroke and 1769 of coronary heart disease (CHD). A composite score of perceived hardships was calculated based on a structured psychosocial questionnaire filled at baseline, assessing domains of work, family, and finance. Cox proportional hazard models were used adjusting for traditional risk factors and socio-economic status., Results: At baseline, subjects with higher hardship scores were slightly older, smoked more cigarettes, had higher prevalence of CHD, lower systolic blood pressure, higher anxiety levels and lower socio-economic status. Compared with the bottom tertile, the middle (HR 1.26, 95% CI 1.04-1.53) and top tertiles of the hardship score (HR 1.33, 95% CI 1.07-1.64) exhibited higher risk of stroke mortality (P for trend=0.008), while no significant association was found with long-term mortality from CHD. The magnitude of the association was comparable to that of diabetes (HR 1.30, 95% CI 1.02-1.66)., Conclusion: Perceived hardships measured at midlife in a large cohort of apparently healthy men independently predict stroke mortality over long-term follow-up., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Atrial fibrillation (AF) is a major risk factor of ischemic stroke. We tested whether the adoption of the CHADS(2) score in clinical guidelines has impacted treatment strategies for stroke prevention, and examined how AF affects stroke outcome., Methods: In the setting of two national surveys [National Acute Stroke Israeli Surveys; all patients hospitalized for stroke in Israel during February-March 2004, and March-April 2007] data of patients with and without AF were analyzed with respect to patient characteristics, use of anticoagulation, stroke severity, clinical course, and long-term outcome., Results: Of 3040 patients with acute ischemic stroke, 586 patients (19%) had a history of AF. Severe strokes on admission were significantly more frequent in patients with AF, as was the proportion of total anterior circulation strokes. Ischemic stroke associated with AF predicted poor outcome at discharge (adjusted OR 1.56; 95%CI 1.24-1.96) and higher mortality rates throughout follow-up. Among patients with a CHADS(2) score ≥ 2 prior to the index stroke and without known contraindications, 41% received anticoagulation. This proportion increased to only 62% after the index stroke, even after excluding patients with severe disability and no significant increase between 2004 and 2007 was detectable. Increasing age, in-hospital infectious complications, and unfavorable functional status at discharge were independently associated with decreased likelihood of receiving anticoagulation., Conclusions: In deviation from current recommendations and in spite of the introduction of CHADS(2) criteria, anticoagulation for stroke prevention remains underutilized, despite the particularly poor outcome of strokes associated with AF., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Background: A number of reports controversially describe the influence of cholesterol level and lipid-lowering treatment (LLT) on the progression of coronary calcium (CC). We tested the hypothesis that long-term changes in serum cholesterol (CL) would affect the progression of CC., Methods: The study population comprised 510 patients with stable angina pectoris, mean age of 63 ± 9 years. At baseline 372 patients received statin and/or fibrate (LLT group) while 138 patients did not (No-LLT at baseline group). Spiral CT every 24 months was used to track the progression of CC over a median 5.6 year follow-up., Results: CL decreased during follow-up in both groups, but more pronouncedly in patients with LLT. The changes in total calcium score (TCS) were similar in both groups (p=0.3). Changes in CL during follow-up were not associated with CC: TCS increased by 501 ± 63 from baseline in the 1st (upper) quartile, and by 350 ± 44, 403 ± 41 and 480 ± 56 in the 2nd, 3rd, and 4th quartiles of CL longitudinal changes (p = 0.2), respectively. Baseline TCS and its changes were not correlated with baseline CL and its changes. New calcified lesions were diagnosed in 132 (28.2%) out of the 467 patients available for this analysis, without significant difference between groups (p=0.4). Multivariate analysis demonstrated that only baseline TCS (p < 0.001), body mass index (p = 0.007) and age (p = 0.006) were independent predictors for the TCS changes., Conclusions: Longitudinal CL changes do not seem to have a measurable effect on the rate of progression of CC., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Calcium is often deposited in the aorta, but the associations and clinical implications of calcification of the aorta have not yet been elucidated., Methods: In a prospective cohort of 455 hypertensive patients with at least 1 additional risk factor for atherosclerosis that underwent dual slice spiral computed tomography of the chest for assessment of arterial calcification (mean age 65.7+/-5.8, range 52-80 years, 48% female), we assessed for calcifications of the ascending and descending aorta and their association with the risk of subsequent ischemic cerebrovascular events during 3-year follow-up., Results: Calcification of the ascending or descending aorta was present in 342 (75%) patients (60% calcification of the ascending aorta and 56% of the descending aorta). The main associations of calcification of the thoracic aorta were increasing age and the presence of coronary calcification, mitral annulus calcification, and aortic valve calcification. In a logistic regression model the main predictors of ischemic cerebrovascular events (n=27) during follow-up were the presence of severe calcification (thickness of > or = 5 mm) of the descending aorta (OR 4.9, 95%CI 1.8 to 13.5) and cigarette smoking (OR 2.8, 95%CI 1.1 to 6.7)., Conclusions: Calcification of the thoracic aorta is highly prevalent among women and men with hypertension, is age-related, and correlates with calcification of the coronary arteries and heart valves. Only severe calcification of the descending aorta is associated with subsequent ischemic cerebrovascular events, suggesting that calcification of the thoracic aorta is a marker of the burden of vascular disease.

Background: Exercise intolerance is a widespread and serious problem in chronic heart failure (CHF) patients. However, the impact of a supervised exercise and rehabilitation program on exercise tolerance and cardiac performance in severe CHF patients has not yet been fully investigated., Methods: Of 56 consecutive patients with severe CHF (New York Heart Association functional class III, Stage D) 44 underwent a hospital-based supervised 18-week, cardiac exercise and rehabilitation program (exercise group), and 12 did not (control group). Cardiac performance was assessed by a 6-minute walk test, peak exercise VO(2), exercise duration time, resting and immediate post peak exercise stroke index (SI), cardiac index (CI) and systemic vascular resistance (SVR), before and after exercise., Results: Both groups were comparable regarding baseline clinical characteristics. Post exercise training, functional and hemodynamic parameters improved significantly in the exercise group compared to controls. A highly significant interaction between the groups and change was found in the 6-minute walk test (p<0.001), exercise test duration (p<0.001), METs during exercise (p<0.001), immediate post peak exercise CI (0.016), delta peak VO(2) (p=0.028), and immediate post peak exercise SVR (p=0.045)., Conclusions: A hospital-based supervised exercise and rehabilitation program significantly improves functional and hemodynamic parameters in severe CHF patients, and may partially contribute to better physical conditioning detected in these patients after exercise training.

Aim: To date there have been no studies exploring the effects of long-term versus intermediate-term and short-term supervised exercise training program in patients with severe chronic heart failure (CHF) on optimal medical therapy. We assessed exercise tolerance and mortality in CHF patients undergoing long- versus intermediate-term exercise training (ET)., Methods: Forty-two consecutive severe CHF patients (New York Heart Association functional class III) were referred for a supervised exercise and cardiac rehabilitation program and were followed-up for 3 years: 20/42 (48%) patients discontinued ET after intermediate-term period of 1.6+/-0.8 years (Group A, intermediate-term ET), and 22/42 (52%) remained on the ET program for 3.0+/-0.3 years (Group B, long-term ET). Exercise duration, 6-min walked distance and metabolic equivalents (METs) assessed by modified Bruce protocol were recorded before, 4.5 months after, and 3 years after initiation of ET., Results: Both groups were comparable regarding age, gender, prevalence of ischemic etiology, mean ejection fraction and medications. Risk factors for ischemic heart disease were similar, except for the prevalence of diabetes, which was higher in Group A compared to Group B (11/20 versus 5/22, p=0.03). Significantly more Group A patients died after ET discontinuation (4/20 versus 0/22, p=0.01). At the end of follow-up a significant improvement could be seen in Group B patients compared to A in exercise duration, 6-min walked distance and metabolic equivalents (p<0.01 for all)., Conclusions: Higher survival rate was observed in severe CHF patients undergoing long-term versus intermediate-term exercise training. Long-term supervised exercise training is safe and improves exercise tolerance in these patients.

Background: CD40 ligand (CD40L) is a trimeric, transmembrane protein of the tumor necrosis factor family and together with its receptor CD40 is an important contributor to the inflammatory processes that lead to atherosclerosis, plaque destabilization, and thrombosis., Methods: In order to assess the association between serum concentrations of CD40 ligand (CD40L) and risk of future ischemic stroke and coronary events among patients with chronic CHD, we obtained baseline serum samples from patients (n = 3090) with chronic CHD enrolled in a secondary prevention trial. With a prospective nested case-control design, we measured baseline CD40L concentration in sera of patients who subsequently developed myocardial infarction, sudden cardiac death or ischemic stroke during follow-up (cases, n = 233) and in 233 age- and gender-matched pairs without any subsequent cardiovascular events., Results: Relative odds for recurrent cardiovascular events per one natural log unit difference of CD40L were 0.97 (95%CI, 0.82-1.16). No increase in relative odds for recurrent cardiovascular events was observed per increasing quartiles of CD40L concentrations. In analysis for individual end-points, different trends of risks were observed beyond the 95 percentile for ischemic stroke (OR 2.22; 95%CI, 0.46-12.5) and for recurrent coronary events (OR 0.35; 95%CI, 0.07-1.37), but falling short of statistical significance., Conclusion: High serum concentrations of CD40L were not associated with increased risk of ischemic stroke or coronary events in patients with chronic coronary heart disease.

Background: Congestive heart failure is associated with cognitive impairment, particularly of attentional skills. We assessed, in a hypothesis-generating study, the effect of an exercise training program on cognitive functions among patients with severe congestive heart failure., Methods: Patients with severe congestive heart failure (n=20; New York Heart Association functional class III; left ventricular ejection fraction < or =35%) were evaluated before and following a standardized and supervised exercise training program (x2/week for 18 weeks; exercise group), while 5 additional patients did not undergo an exercise training program (control group). A battery of cognitive tests was used to assess cognitive functions. Physical performance was assessed by the 6-min walk test and the modified Bruce exercise test, cardiac index and systemic vascular resistance using thoracic electrical bioimpedance, and cerebral vasomotor reactivity to hypercapnia by means of the breath-holding index using transcranial Doppler., Results: Time of completion of the trail making A (105+/-116 to 75+/-52; p=0.02) and B (169+/-100 to 119+/-65; p=0.002) tests, and of the Stroop part A (40+/-13 to 37+/-13; p=0.04) was shorter in patients completing the exercise training program, but not in control patients, while the other neuropsychological measures remained unchanged in both groups. Cerebral vasomotor reactivity to hypercapnia remained diminished (breath-holding index 0.64+/-0.27 vs. 0.68+/-0.37) despite significant improvements in exercise capacity (6-min walk test 308+/-87 to 423+/-91 m, p<0.001; modified Bruce exercise test 5.6+/-3.8 to 9.8+/-3.4 min, p<0.001)., Conclusions: Patients with severe congestive heart failure undergoing an exercise training program improve in some measures of cognitive functions that are limited to general attention and psychomotor speed. Based on these preliminary findings, further evaluations are designed within the framework of a larger controlled clinical trial.

Background: Mitral annulus calcification (MAC) may be a form of atherosclerosis. The goal of the present work was to investigate whether helical CT can determine the presence of MAC and to clarify its possible association with coronary artery disease (CAD) in elderly patients., Design and Methods: Three hundred and twenty-nine consecutive elderly patients (165 men and 164 women, age range 60-79 years) underwent double helical CT of the heart to determine MAC and coronary calcifications (CC) according to a previously described protocol., Results: MAC was documented in 60 patients (25 men, 35 women; mean age 69 +/- 4.5 years, range 60-78 years). The non-MAC group (control) included 269 patients (140 men, 129 women; mean age 67 +/- 4.6 years, range 60-79 years). Age was the only risk factor which had significant association with MAC (p = 0.01). A significant difference was found between MAC and control group for mean total CC score and advanced CC (total CC > 300) (323 +/- 565 vs. 184 +/- 429, p = 0.033 and 30% vs. 16%, p = 0.017, respectively). A significant difference was also found between groups for the prevalent proven CAD (30% vs. 16%, p = 0.008). Stepwise logistic regression analysis identified age [odds ratio (OR) 3.3, 95% confidence interval (CI) 1.7-6.4, p < 0.001)], gender (male) (OR 3.1, 95% CI 1.6-6.0, p = 0.001), and MAC (OR 2.4, 95% CI 1.2-5.0, p = 0.016) as the independent variables significantly associated with CAD. The independent variables significantly associated with advanced CC (TCS > 300) were MAC (OR 2.6, 95% CI 1.3-5.2, p = 0.005), gender (male) (OR 2.3, 95% CI 1.2-4.2, p = 0.012) and age (OR 1.9, 95% CI 1.0-3.7, p = 0.052)., Conclusions: Our study demonstrated the usefulness of helical computed tomography in the detection of mitral annular calcification as an additional marker of prevalent CAD. However, the diagnostic significance of the MAC detection is relatively minor and should not be considered as a direct proof for coronary atherosclerosis.

Aim: To evaluate the association between previous exposure to Chlamydia pneumoniae and future coronary risk in patients with coronary heart disease., Methods: A prospective, nested, case-control design was used. The patient sample was derived from a trial study of bezafibrate for the treatment of coronary heart disease. Anti-Chlamydia pneumoniae antibodies (IgG and IgA) in the baseline sera of 136 patients who had coronary events during follow-up (mean 6.2 years) were compared with those in 136 age- and gender-matched patients from the same trial without subsequent coronary events., Results: Mean titers of IgG and IgA antibodies were similar in cases and controls. The relative odds of future coronary events in patients who were seropositive at baseline were 1.0 (95% CI, 0.54-1.84) for IgG and 0.74 (95% CI, 0.41-1.31) for IgA. The relative odds did not change after adjustment for multiple confounding variables. The risk of future coronary events did not increase with increasing anti-Chlamydia pneumoniae antibody titers., Conclusions: Prior exposure to Chlamydia pneumoniae in patients with chronic coronary heart disease is not associated with increased risk of recurrent coronary events.