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Biomedical subjects

Yehuda Adler

Publications and source records attributed to Yehuda Adler.

At least 37 records · Page 2Linked to original sources

Pretreatment with corticosteroids attenuates the efficacy of colchicine in preventing recurrent pericarditis: a multi-centre all-case analysis.

AIMS: Effective prevention of recurrent pericarditis remains an important yet elusive goal. Corticosteroid therapy often needs to be continued for a prolonged period and causes severe side effects. We performed a multi-centre all-case analysis to investigate the efficacy of colchicine in preventing subsequent relapses of pericarditis, and addressed the hypothesis that pretreatment with corticosteroids may attenuate the beneficial effect of colchicine. METHODS AND RESULTS: One hundred and forty published and unpublished cases of patients treated with colchicine after at least two relapses of pericarditis were aggregated from European centres. Of those, 119 were included in the study group. Only 18% of the patients had relapses under colchicine therapy, and 30% after its discontinuation. There were significantly more relapses among male patients after colchicine treatment (36 vs. 17%, P=0.046), and those with previous corticosteroid treatment (43 vs. 13%, P=0.02). Multivariate logistic regression analysis identified previous corticosteroid therapy (OR 6.68, 95% CI: 1.65-27.02) and male gender (OR 4.20, 95% CI: 1.16-15.21) as independent risk factors for recurrence following colchicine therapy. CONCLUSION: Treatment with colchicine is highly effective in preventing recurrent pericarditis, while pretreatment with corticosteroids exacerbates and extends the course of recurrent pericarditis.

Adolescent↗

Cognitive functions in severe congestive heart failure before and after an exercise training program.

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.

Adult↗

Impact of left ventricular filling properties on the benefit of exercise training in patients with advanced chronic heart failure secondary to ischemic or nonischemic cardiomyopathy.

This study examined left ventricular (LV) filling properties and exercise hemodynamics noninvasively before and after an exercise training program in patients with chronic heart failure (HF). Although exercise training did not improve LV filling properties in patients with advanced HF, LV filling properties determined the hemodynamic benefit attainable from exercise in this patient group.

Chronic Disease↗

Peroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease.

BACKGROUND: Recent studies have shown that type 2 diabetes is preventable by both lifestyle interventions and medications that influence primary glucose metabolism. Whether pharmacological interventions that influence primary lipid metabolism can also delay development of type 2 diabetes is unknown. The goal of this study was to evaluate the effect of the peroxisome proliferator-activated receptor ligand bezafibrate on the progression of impaired fasting glucose phase to type 2 diabetes in patients with coronary artery disease over a 6.2-year follow-up period. METHODS AND RESULTS: The study sample comprised 303 nondiabetic patients 42 to 74 years of age with a fasting blood glucose level of 110 to 125 mg/dL (6.1 to 6.9 mmol/L). The patients received either 400 mg bezafibrate retard (156 patients) or placebo (147 patients) once a day. No patients were using statins, and use of ACE inhibitors, which also reduce diabetes incidence, was relatively low. During follow-up, development of new-onset diabetes was recorded in 146 patients: in 80 (54.4%) from the placebo group and 66 (42.3%) from the bezafibrate group (P=0.04). The mean time until onset of new diabetes was significantly delayed in patients on bezafibrate compared with patients on placebo: 4.6+/-2.3 versus 3.8+/-2.6 years (P=0.004). Multivariate analysis identified bezafibrate treatment as an independent predictor of reduced risk of new diabetes development (hazard ratio, 0.70; 95% CI, 0.49 to 0.99). Other significant variables associated with future overt type 2 diabetes in patients with impaired fasting glucose were total cholesterol level (hazard ratio, 1.22; 95% CI 1.0 to 1.51) and body mass index (hazard ratio, 1.10; 95% CI, 1.05 to 1.16). CONCLUSIONS: Bezafibrate reduces the incidence and delays the onset of type 2 diabetes in patients with impaired fasting glucose. Whether the combination of bezafibrate with other recommended drugs for secondary prevention (statins and ACE inhibitors) would be as efficacious as suggested by our results remains to be determined.

Aged↗

Oral antidiabetic therapy in patients with heart disease. A cardiologic standpoint.

Five types of oral antihyperglycemic drugs are currently approved for the treatment of diabetes: biguanides, sulfonylureas, meglitinides, glitazones, and alpha-glucosidase inhibitors. The cardiovascular effects of the most commonly used antidiabetic drugs in these groups are briefly reported, in an attempt to improve knowledge and awareness regarding their influences and potential risks when treating patients with coronary artery disease (CAD). Regarding biguanides, gastrointestinal disturbances such as diarrhea are frequent, and the intestinal absorption of group B vitamins and especially folate is impaired during chronic therapy. This deficiency may lead to increased plasma homocysteine levels which, in turn, accelerate the progression of vascular disease due to adverse effects on platelets, clotting factors, and endothelium. The existence of a graded association between homocysteine levels and overall mortality in patients with CAD is well established. In addition, metformin may lead to lethal lactic acidosis, especially in patients with clinical conditions that predispose to this complication, such as heart failure or recent myocardial infarction. Sulfonylureas avoid ischemic preconditioning. During myocardial ischemia, they may prevent the opening of the ATP-dependent potassium channels, impeding the necessary hyperpolarization that protects the cell by blocking calcium influx. Meglitinides may exert similar effects, due to their analogous mechanism of action. During treatment with glitazones, edema has been reported in 5% of patients, and these drugs are contraindicated in diabetics with NYHA class III or IV cardiac status. The long-term effects of alpha-glucosidase inhibitors on morbidity and mortality rates and on diabetic micro- and macrovascular complications are yet unknown. The combined sulfonylurea/metformin therapy reveals additive effects on mortality. It is concluded that(1) four of the five oral antidiabetic drug groups present proven or potential cardiac hazards;(2) these hazards are not mere "side effects", but are deeply rooted in the drugs' mechanism of action;(3) current data indicate that the combined glibenclamide/metformin therapy seems to present special risk and should be avoided in the long-term management of type 2 diabetics with proven CAD; and(4) customized antihyperglycemic pharmacological approaches should be investigated for optimal treatment of diabetic patients with heart disease.

Administration, Oral↗

Spiral computed tomography evidence of close correlation between coronary and thoracic aorta calcifications.

UNLABELLED: Coronary calcium (CC) is invariably associated with coronary atherosclerosis and can be diagnosed noninvasively by fast spiral computed tomography (dual slice mode) (CT). Calcium is often deposited in the aorta as well, but the pathogenesis, correlates and clinical implications of calcification of the aorta are not yet elucidated. A possible association between the presence of CC and thoracic aorta calcification, as detected by spiral CT, has not been investigated yet. The goal of the present work was to examine by spiral CT whether an association exists between the presence of CC and thoracic aorta calcification in patients with high risk for atherosclerotic development. Four hundred and five patients with at least two risk factors for atherosclerosis were included (212 men and 193 women, age ranged 52-79 years). All underwent chest CT for CC and aortic calcification scoring. Calcifications' thickness of > or =5 mm was considered advanced. CC was documented in 294 patients (170 men, 124 women; mean age 66 +/- 6 years, range 55-78 years). The non-CC group (control) included 111 patients (42 men, 69 women; mean age 64 +/- 6 years, range 52-79 years). Significant differences were found between CC group and control for the presence of ascending aorta calcification (69% versus 36%, P < 0.001), and advanced calcification of > or =5mm (17% versus 4%, P < 0.001). Significant differences were also found between groups regarding the presence of descending aorta calcification (60% versus 38%, P < 0.001), and number of consecutive slices with calcification (18.8 +/- 12.4 versus 10.7 +/- 8.7, P < 0.01). We identified age (in decades) (OR 1.9, 95% CI 1. 2-3.0, P < 0.001), gender (female) (OR 0.4, 95% CI 0.2-0.6, P < 0.001), and thoracic aorta calcification (OR 2.9, 95% CI 1.7-5.0, P < 0.001) as the independent variables significantly associated with CC. Only age [odds ratio (OR) 3.05, 95% confidence interval (CI) 1.86-5.01, P < 0.001] and CC (OR 2.53, 95% CI 1.26-5.08, P = 0.006) were identified as independent variables for the prediction of thoracic aorta calcification. CONCLUSIONS: Our study demonstrated a strong association of CC and calcification of the thoracic aorta on spiral CT.

Aged↗

Aortic valve calcification in hypertensive patients: prevalence, risk factors and association with transvalvular flow velocity.

BACKGROUND: The important role of the "nonobstructive" aortic valve calcification (AVC) in cardiovascular morbidity and mortality has recently been emphasized. The present work had two goals: (1) to analyze the prevalence and factors determining the extent of AVC in hypertensive patients; (2) to investigate a possible association between the extent of AVC and flow velocity across the aortic valve. METHODS: This was a prospective study performed in a university hospital. The sample included 263 consecutive patients (139 men and 124 women), mean age 65+/-6, who underwent echo-Doppler. The upper quartile of peak flow velocity across the aortic valve (>130 mm/s in our population) was defined as augmented flow velocity. RESULTS: There were 31 (12%) patients in the advanced AVC group and 122 (46%) without any calcified deposits (the no AVC group). The remaining 110 (42%), who did not meet criteria for advanced AVC, comprised the trivial AVC group. Peak flow velocity was significantly higher in patients with advanced vs. trivial AVC and no AVC groups: 135+/-45, 116+/-23 and 113+/-23 cm/s, respectively; p=0.0002. Prevalence of augmented transvalvular aortic flow was significantly higher (p=0.01) among patients with advanced AVC (41.9%) vs. trivial (20.9%) and no AVC (20.5%). Multivariate analyses identified age as the only independent variable associated with advanced AVC [OR 1.6 (CI 1.2-2.3), 5 years increment]. Advanced AVC and female gender were identified as independent variables for augmented transvalvular aortic flow with OR 2.9 (CI 1.3-6.4) and 2.5 (CI 1.4-4.6), respectively. CONCLUSIONS: Prevalence of AVC among hypertensive patients is high and clearly age-related. Female gender and advanced (but not trivial) AVC are associated with augmented aortic transvalvular peak flow. Our results stress the role of protruding calcium deposits in augmentation of rest flow velocity across the aortic valve regardless of visible restriction of leaflet opening.

Age Factors↗

Ischemic preconditioning: nearly two decades of research. A comprehensive review.

The phenomenon of "ischemic preconditioning" has been recognized for almost two decades. In experimental animals and humans, a brief period of ischemia has been shown to protect the heart from more prolonged episodes of ischemia, and reduce the degree of impaired ventricular function or subsequent damage. Ischemic preconditioning is classified into two distinct components: the classic early preconditioning and the delayed or late preconditioning, each with its own biologic mechanism of adaptation. A comprehensive understanding of these mechanisms and application to clinical scenarios has the promise of providing unique opportunities, particularly regarding the development of preconditioning mimetic agents. Administration of these mimetic drugs or procedures could potentially advance the use of preconditioning as a therapeutic tool and/or preventive factor for cardiovascular disease.

Animals↗

Is hypoglycaemia a marker for increased long-term mortality risk in patients with coronary artery disease? An 8-year follow-up.

BACKGROUND: No information is available regarding the association between low plasma glucose levels and cause-specific and all-cause mortality in patients with coronary artery disease (CAD). We aimed to investigate the relationship between hypoglycaemia and all-cause, cardiovascular and cancer mortality in a large population of patients with CAD. DESIGN: Patients were recruited from the BIP (Bezafibrate Infarction Prevention) registry, a secondary prevention prospective multicentre randomized, placebo-controlled, double-blind trial aimed to assess the efficacy of bezafibrate in reduction of coronary events. METHODS: The study included 14,670 CAD patients aged 45-74, divided into six groups: (1) hypoglycaemic (up to 69 mg/dl); (2) low normal (70-79 mg/dl); (3) euglycaemic (80-109 mg/dl); (4) impaired fasting glucose (IFG) (110-125 mg/dl); (5) borderline diabetics (126-139 mg/dl); (6) diabetics (> or 140 mg/dl). RESULTS: Patients comprised 131 with hypoglycaemia (0.9%), 731 with low normal glucose (5%), 9308 euglycaemic (63.4%), 1577 with IFG (10.7%), 617 borderline diabetics (4.2%) and 2306 diabetics (15.7%). Over a mean 8-year follow-up, crude all-cause mortality was higher in both diabetic (31.8%) and hypoglycaemic groups (25.2%) as compared with euglycaemics (14.9%; P<0.0001); CAD mortality was higher in diabetic and borderline groups (17.8 and 13.3%, respectively, versus 7.9% in euglycaemics; P<0.0001). The highest prevalence of cancer mortality was documented in the hypoglycaemic group (6.1 versus 2.9% in euglycaemics; P<0.02). Actuarial survival curves showed the lowest mortality in euglycaemic and low normal groups; the highest was seen in diabetic and hypoglycaemic patients. Intermediate values were found in borderline and IFG patients. After adjustment for variables, a significantly higher mortality rate was seen in hypoglycaemics when compared with euglycaemics (P<0.0001). Hypoglycaemia was identified as a predictor of increased all-cause and cancer mortality with a hazard ratio (HR) of 1.84 [95% confidence interval (CI) 1.29-2.61] and 2.26 (95% CI 1.12-4.57), respectively, but not of increased CAD mortality, with HR 1.30 (95% CI 0.73-2.29). CONCLUSIONS: Over a mean 8-year follow-up, hypoglycaemia emerges as a marker for substantially increased all-cause and cancer mortality among patients with CAD presenting with low fasting glucose levels.

Aged↗

Correlation between ST elevation and Q waves on the predischarge electrocardiogram and the extent and location of MIBI perfusion defects in anterior myocardial infarction.

BACKGROUND: The common electrocardiographic subclassification of anterior acute myocardial infarction (AMI) is not reliable in presenting the exact location of the infarct. We investigated the relationship between predischarge electrocardiographic patterns and the extent and location of perfusion defects in 55 patients with first anterior AMI. METHODS: Predischarge electrocardiogram was examined for residual ST elevations and Q waves which were correlated with technetium-99m-sestamibi function and perfusion scans. RESULTS: Patients with ST elevations in V2-V4 and Q waves in leads V3-V5 had worse global perfusion scores. Perfusion defects in the apex inferior segment were significantly less frequent in patients with Q waves in leads I and aVL (11% vs 54%, P = 0.027; and 22% vs 60%, P = 0.011, respectively). Patients with Q wave in aVF had more frequently involvement of the apex inferior segment (80% vs 40%; P = 0.035). Patients with Q wave in lead II had significantly more frequent perfusion defects in the inferior wall. ST elevation in V3 and V4 was associated with perfusion abnormalities of the infero-septal segments. ST elevation in V5 and V6 and Q wave in V5 were associated with regional perfusion defects in apical inferior segment (73% vs 30%, P = 0.002), extending into the mid inferior segment (55% vs 18%, P = 0.005 for Q wave in V5). Q wave in lead aVL is associated with less apical and inferior involvement. Q waves in leads II and aVF are a sign of inferior extension of the infarction. CONCLUSIONS: Residual ST elevation in leads V3 and V4 are more frequently associated with involvement of the apical-inferoseptal segment rather than the anterior wall. Residual ST elevation and Q waves in V5 are related to a more inferior rather than a lateral involvement.

Adult↗

[Post-pericardiotomy syndrome].

Postpericardiotomy syndrome (PPS) is a common complication of cardiac surgery. This syndrome is characterized by postoperative fever, pericarditis and laboratory findings that confirm inflammation. Over the past years, different studies were conducted in order to determine the etiology of PPS. Understanding the mechanisms that activate the inflammatory syndrome (possibly an autoimmune response) will contribute to the understanding of similar inflammatory processes and will guide towards an optimal method of treatment. This article reviews most of the studies on this topic that were published in the past 20 years.

Cardiac Surgical Procedures↗

Increased prevalence of left ventricular hypertrophy in hypertensive women with type 2 diabetes mellitus.

BACKGROUND: Left ventricular hypertrophy (LVH) is a powerful independent risk factor for cardiovascular morbidity and mortality among hypertensive patients. Data regarding relationships between diabetes and LVH are controversial and inconclusive, whereas possible gender differences were not specifically investigated. The goal of this work was to investigate whether gender differences in left heart structure and mass are present in hypertensive patients with type 2 diabetes. METHODS: Five hundred fifty hypertensive patients with at least one additional cardiovascular risk factor (314 men and 246 women, age 52 to 81, mean 66 +/- 6 years), were enrolled in the present analysis. In 200 (36%) of them--108 men and 92 women--type 2 diabetes mellitus was found upon enrollment. End-diastolic measurements of interventricular septal thickness (IVS), LV internal diameter, and posterior wall thickness were performed employing two-dimensionally guided M-mode echocardiograms. LVH was diagnosed when LV mass index (LVMI) was > 134 g/m2 in men and > 110 g/m2 in women. RESULTS: Mean LVMI was significantly higher among diabetic vs. nondiabetic women (112.5 +/- 29 vs. 105.6 +/- 24, p = 0.03). In addition, diabetic women presented a significantly higher prevalence of increased IVS thickness, LVMI and left atrial diameter on intra-gender comparisons. The age adjusted relative risk for increased LVMI in diabetics vs. nondiabetics was 1.47 (95% CI: 1.0-2.2) in females and only 0.8 (0.5-1.3) in males. CONCLUSION: Type 2 diabetes mellitus was associated with a significantly higher prevalence of LVH and left atrial enlargement in hypertensive women.

Journal Article↗

Prospective study of serum homocysteine and risk of ischemic stroke among patients with preexisting coronary heart disease.

BACKGROUND AND PURPOSE: Substantial evidence is accumulating suggesting that hyperhomocysteinemia may be a risk factor for ischemic stroke. Results of prospective studies are, however, conflicting, and the role of hyperhomocysteinemia in patients with preexisting atherosclerotic vascular disease is not clear. Our aim was to assess prospectively the risk of incident ischemic stroke conferred by serum total homocysteine among patients with preexisting stable coronary heart disease (CHD). METHODS: We obtained baseline fasting serum samples from patients with chronic CHD enrolled in the Bezafibrate Infarction Prevention (n=3090) secondary prevention study cohort. With a nested case-control design, we measured baseline total homocysteine concentration by a high-performance liquid chromatography-based method in sera (n=160) of matched case-control pairs: patients who developed ischemic stroke during a mean follow-up of 8.2 years (cases) and age- and sex-matched controls without subsequent cardiovascular events. RESULTS: An increase of 1 natural log unit in homocysteine concentration was associated with a >3-fold increase in relative odds of incident ischemic stroke (3.3; 95% CI, 1.2 to 10.2). Homocysteine concentrations at the highest quartile (>17.4 micromol/L) were associated with significantly higher odds of ischemic stroke compared with the lowest quartile in matched-pair analysis (3.1; 95% CI, 1.1 to 9.8) and after multivariable adjustments (4.6; 95% CI, 1.3 to 18.9). Adding fibrinogen or soluble intercellular adhesion molecule-1 concentrations, markers of inflammation, to the model did not attenuate this association. The linear trends across the quartiles were significant for all models (P<0.05). CONCLUSIONS: Serum total homocysteine concentration is a strong predictor for incident ischemic stroke among patients at increased risk because of chronic CHD. The graded association observed is independent of traditional risk factors or inflammatory markers and indicates the importance of serum homocysteine levels in patients with preexisting vascular disease.

Brain Ischemia↗

Functional class in patients with heart failure is associated with the development of diabetes.

PURPOSE: Recent reports suggest that decreased functional capacity in patients with heart failure may be associated with abnormalities in glucose metabolism. We followed patients with coronary artery disease who participated in the Bezafibrate Infarction Prevention study to determine the incidence of diabetes by baseline functional status during a 7.7-year follow-up. METHODS: The sample comprised 2616 nondiabetic patients aged 45 to 74 years with a fasting blood glucose level <7 mmol/L (126 mg/dL). They were divided into three groups by New York Heart Association (NYHA) criteria: class I (n = 1986 patients), class II (n = 518), and class III (n = 112). The detection of a fasting blood glucose level > or =7 mmol/L during follow-up was defined as the criterion for the development of diabetes. RESULTS: The study groups had similar demographic and clinical characteristics, except that patients with symptomatic heart failure (NYHA class II or III) were more likely to have angina. During follow-up, diabetes developed in 259 patients (13%) in NYHA class I, 76 (15%) in class II, and 22 (20%) in class III (P for trend = 0.05). At the last visit, patients in NYHA class III were twice as likely (17% [n = 19]) to have fasting blood glucose levels > or =7 mmol/L as those in NYHA class I (7.8% [n = 154]) or class II (8.7% [n = 45]) (P = 0.005). In a multivariate analysis, NYHA class III was associated with a 1.7-fold (95% confidence interval [CI]: 1.1 to 2.6) increase in the rate of development of diabetes, but NYHA class II was not (hazard ratio = 1.0; 95% CI: 0.8 to 1.3). CONCLUSION: Among patients with coronary artery disease, advanced heart failure (NYHA class III) is associated with a significantly increased risk of developing diabetes during a 6- to 9-year follow-up.

Age Distribution↗