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Biomedical subjects

Yehuda Adler

Publications and source records attributed to Yehuda Adler.

At least 19 recordsLinked to original sources
PubMed2006

Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level.

OBJECTIVE: Adiponectin is adipose-specific secretory protein and acts as anti-diabetic and anti-atherosclerotic molecule. We previously found peroxisome proliferators response element in adiponectin promoter region, suggesting that peroxisome proliferator-activated receptor (PPAR) ligands elevate adiponectin. Fibrates are known to be PPARalpha ligands and were shown to reduce risks of diabetes and cardiovascular disease. Effect of fibrates on adiponectin has not been clarified, whereas thiazolidinediones enhance adiponectin. Thus, we explored the possibility and mechanism that fibrates enhance adiponectin in humans, mice, and cells. METHODS AND RESULTS: Significant increase of serum adiponectin was observed in bezafibrate-treated subjects compared with placebo group in patients enrolled in The Bezafibrate Infarction Prevention study. Higher baseline adiponectin levels were strongly associated with reduced risk of new diabetes. Fibrates, bezafibrate and fenofibrate, significantly elevated adiponectin levels in wild-type mice and 3T3-L1 adipocytes. Such an effect was not observed in PPARalpha-deficient mice and adipocytes. Fibrates activated adiponectin promoter but failed to enhance its activity when the point mutation occurred in peroxisome proliferators response element site and the endogenous PPARalpha was knocked down by PPARalpha-RNAi. CONCLUSIONS: Our results suggest that fibrates enhance adiponectin partly through adipose PPARalpha and measurement of adiponectin might be a useful tool for searching subjects at high risk for diabetes.

Adipocytes↗
PubMed2006

Calcification of the thoracic aorta by spiral computed tomography among hypertensive patients: associations and risk of ischemic cerebrovascular events.

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.

Aged↗
PubMed2006

Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic options beyond statins.

Lowering of low-density lipoprotein cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is clearly efficacious in the treatment and prevention of coronary artery disease. However, despite increasing use of statins, a significant number of coronary events still occur and many of such events take place in patients presenting with type 2 diabetes and metabolic syndrome. More and more attention is being paid now to combined atherogenic dyslipidemia which typically presents in patients with type 2 diabetes and metabolic syndrome. This mixed dyslipidemia (or "lipid quartet"): hypertriglyceridemia, low high-density lipoprotein cholesterol levels, a preponderance of small, dense low-density lipoprotein particles and an accumulation of cholesterol-rich remnant particles (e.g. high levels of apolipoprotein B)--emerged as the greatest "competitor" of low-density lipoprotein-cholesterol among lipid risk factors for cardiovascular disease. Most recent extensions of the fibrates trials (BIP - Bezafibrate Infarction Prevention study, HHS - Helsinki Heart Study, VAHIT--Veterans Affairs High-density lipoprotein cholesterol Intervention Trial and FIELD--Fenofibrate Intervention and Event Lowering in Diabetes) give further support to the hypothesis that patients with insulin-resistant syndromes such as diabetes and/or metabolic syndrome might be the ones to derive the most benefit from therapy with fibrates. However, different fibrates may have a somewhat different spectrum of effects. Other lipid-modifying strategies included using of niacin, ezetimibe, bile acid sequestrants and cholesteryl ester transfer protein inhibition. In addition, bezafibrate as pan-peroxisome proliferator activated receptor activator has clearly demonstrated beneficial pleiotropic effects related to glucose metabolism and insulin sensitivity. Because fibrates, niacin, ezetimibe and statins each regulate serum lipids by different mechanisms, combination therapy--selected on the basis of their safety and effectiveness - may offer particularly desirable benefits in patients with combined hyperlipidemia as compared with statins monotherapy.

Clofibric Acid↗
PubMed2006

Long-term effect of bezafibrate on pancreatic beta-cell function and insulin resistance in patients with diabetes.

OBJECTIVE: Development of insulin resistance (IR) and the progressive failure of the pancreatic beta-cell function (BCF) may be important in the pathogenesis of type 2 diabetes. Influence of peroxisome proliferator-activated receptors ligand bezafibrate on BCF and IR in patients with diabetes is unknown. The present study was aimed to investigate the long-term effect of bezafibrate on these parameters in diabetic patients enrolled in the Bezafibrate Infarction Prevention (BIP) Study. METHODS: Metabolic and inflammatory parameters were analyzed from stored frozen plasma samples obtained from 351 diabetic patients (168 treated by bezafibrate and 183 by placebo) who completed a 2-year of randomized, double-blind, placebo-controlled study period. The homeostatic indexes of BCF (HOMA-BCF) and IR (HOMA-IR) were calculated according to the homeostasis model of assessment. RESULTS: Both groups displayed similar baseline characteristics. During follow-up, in the placebo group there was 28% rise of HOMA-IR (p<0.001). In contrast, HOMA-IR in patients in the bezafibrate group did not change (p=0.99). The intergroup differences in HOMA-IR percentage changes were in favor of bezafibrate (p=0.01). HOMA-BCF values have significantly decreased by 13.9% (p=0.04) in patients of placebo group, whereas in patients of bezafibrate group HOMA-BCF was stable during follow-up and its alterations (-2.9%) were non-significant (p=0.59). CONCLUSIONS: Diabetic patients from the placebo group demonstrated a progressive declining of BCF and an increasing of IR over 2 years of follow-up. These longitudinal changes were attenuated when patients used bezafibrate.

Aged↗
PubMed2006

Long-term outcomes in difficult-to-treat patients with recurrent pericarditis.

Patients with many recurrences of acute pericarditis are commonly alarmed by the fear of constriction. We studied their long-term outcome and the possible presence of systemic diseases. Sixty-one Italian patients (36 men) were followed for an average of 8.3 years according to a predefined protocol, including testing for autoimmune diseases and familial Mediterranean fever. Symptomatic pericarditis lasted from 1 to 43 years (mean 5.4 years). Fifty-two patients had been referred to us after failure of previous therapies, including steroids. We observed 378 attacks with a mean of 1.6 per patient per year and 156 hospital admissions. Thirteen patients had a post-cardiac injury syndrome. In 43 (70.5%), the pericarditis remained idiopathic, whereas we made a new diagnosis of rheumatoid arthritis in 1 and of Sjogren's syndrome in 4 patients, but in these patients pericarditis represented the dominant clinical manifestation. Cardiac tamponade occurred during the initial attacks in 4 patients (6.5%) but never recurred. Pleural effusions were present during the first attack in 22 patients (36.0%) and liver involvement in 5 (8%). No patients developed constrictive pericarditis. Echocardiographic examination produced no evidence of chronic myocardial disease. Response to therapy was good. Thirty-one patients (50.8%) are in sustained remission, without any therapy; their total observation period has averaged 10.3 years. In idiopathic patients, antinuclear antibodies were present in 56.2% and anti-Ro/SSA in 8.3%. Mutations linked to familial Mediterranean fever were absent. In conclusion, in this large series of difficult patients with recurrent acute pericarditis and a very long follow-up, the long-term prognosis is good.

Acute Disease↗
PubMed2006

C-reactive protein as a predictor of incident ischemic stroke among patients with preexisting cardiovascular disease.

BACKGROUND AND PURPOSE: C-reactive protein (CRP) has emerged as an important predictor of cardiovascular disease, but there are few prospective data on its association with risk of ischemic stroke in patients at high risk. METHODS: We examined the association between CRP levels and subsequent risk of incident ischemic stroke among 2979 patients with stable coronary heart disease included in a controlled clinical trial (Bezafibrate Infarction Prevention) that assessed the efficacy of bezafibrate, a fibric acid derivative, versus placebo for secondary prevention. CRP was measured by a high-sensitivity assay in plasma samples collected before randomization and again at the second follow-up year of an overall mean follow-up of 6.2 years. RESULTS: Risk of ischemic stroke per 1000 person-years increased from 4.1% for baseline CRP in the lowest tertile (<2.3 mg/L; n=982) to 5.9% for levels at the middle tertile (2.3 to 5.4 mg/L; n=1013) and 10.5% for CRP levels at the upper tertile (>5.4 mg/L; n=984; P<0.001). With adjustment for potential confounders, baseline CRP levels in the top versus bottom tertile were associated with a 2.16-fold increased hazard (95% CI, 1.32 to 3.53) for ischemic stroke, and CRP levels measured after 2 years were associated with a hazard ratio of 2.43 (95% CI, 1.30 to 4.57). The risk of an incident ischemic stroke did not differ between the bezafibrate group compared with the placebo group regardless of baseline CRP levels. CONCLUSIONS: These findings, based on a large prospective study, demonstrate the risk prediction for incident ischemic stroke conferred by CRP levels in patients at high risk.

Aged↗
PubMed2006

Long-term versus intermediate-term supervised exercise training in advanced heart failure: effects on exercise tolerance and mortality.

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.

Exercise Therapy↗
PubMed2006

Interleukin-6 and the risk of future cardiovascular events in patients with angina pectoris and/or healed myocardial infarction.

The aim of this study was to evaluate the prognostic value of interleukin-6 (IL-6) for myocardial infarction (MI) and mortality in a population with stable coronary artery disease (CAD) during a mean period of 6.3 years. IL-6 is a major proinflammatory cytokine of acute phase response; elevated levels are associated with worse prognosis in unstable angina and after acute MI. However, data regarding its long-term prognostic value in stable CAD are limited and controversial. A nested case-control study design was used. Of 3,090 patients with stable CAD, 129 with an adequate blood sample for IL-6 and who reached the end points (MI or sudden death) were randomly selected. Each case was 1:1 matched with 129 controls (alive at the end of the study and free of cardiovascular events) according to age, gender, and treatment. Of the 129 cases, 113 had a MI as the initial event, and for the other 16 the initial event was sudden death. There were 8 patients who first had a MI and later died suddenly. IL-6 was significantly higher in cases (2.34 pg/ml) than in controls (1.65 pg/ml) (p = 0.0004). IL-6 was significantly correlated with C-reactive protein (r = 0.2, p = 0.002); a borderline significance was also found for fibrinogen (r = 0.11, p = 0.07). Each increase of 1 pg/ml in IL-6 was associated with a 1.70 (range 1.23 to 2.45) increased relative odds of subsequent MI or sudden death. Events rate per 1,000 patients-years for the 5 quintiles of IL-6 were 72.26, 89.61, 79.76, 142.53, and 181.08, respectively (p <0.0001). A significantly higher risk in the upper quintile was found (odds ratio, 3.44; 95% confidence interval 1.57 to 8.13). In conclusion, elevated IL-6 levels are strongly associated with future cardiac events and mortality in a population with stable CAD during a long-term follow-up.

Aged↗
PubMed2006

CD40 ligand and risk of ischemic stroke or coronary events in patients with chronic coronary heart disease.

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.

Biomarkers↗
PubMed2005

Smoking and development of type 2 diabetes in patients with decreased functional capacity.

OBJECTIVE: Data regarding the possible contribution of cigarette smoking to development of type 2 diabetes are scarce and inconclusive. Patients with impaired functional capacity and diminished physical activity are prone to develop new diabetes. However, the role of smoking on diabetes incidence among these patients has not been specifically investigated. The present study was aimed to evaluate the association between cigarette smoking and development of type 2 diabetes in patients with coronary artery disease and decreased functional capacity over a 6.2-year follow-up period. METHODS: The study sample comprised 630 nondiabetic patients aged 45-74 years, with a fasting blood glucose of <126 mg/dl and with impaired functional capacity (New York Heart Association functional class II and III). The sample was classified into two groups: 1) non smokers (never and past smokers pooled together)--552 patients and 2) current smokers--78 patients. RESULTS: Smokers were younger but they had a relatively unfavorable lipid profile (with respect to apolipoproteins A, triglyceride and HDL-cholesterol levels). No significant differences between the groups were found for weight, body mass index, total cholesterol and blood pressure. During the follow-up, development of new diabetes was recorded in 98 patients: in 80 (14.5%) non smokers and in 18 (23.1%) smokers, p=0.05. Among the non smokers, there were no significant differences in diabetes incidence between 357 past smokers and 195 never smokers: respectively, 48 (13.4%) and 32 (16.4%), p=0.34. In addition, all-cause mortality among the smokers (23.1%) was significantly higher than in non smokers (12.7%), p=0.01. Multivariate analysis identified current smoking as an independent predictor of increased risk of new diabetes development with a hazard ratio of 1.94 (95% confidence interval 1.16-3.25). CONCLUSIONS: Current smoking was associated with an independent two-fold increased risk for development of type 2 diabetes in patients with impaired functional capacity.

Aged↗
PubMed2005

Usefulness of helical computed tomography in detection of mitral annular calcification as a marker of coronary artery disease.

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.

Aged↗
PubMed2005

Statins research unfinished saga: desirability versus feasibility.

Drugs in the same class are generally thought to be therapeutically equivalent because of similar mechanisms of action (the so-called "class effect"). However, statins differ in multiple characteristics, including liver and renal metabolism, half-life, effects on several serum lipid components, bioavailability and potency. Some are fungal derivatives, and others are synthetic compounds. The percentage absorption of an oral dose, amount of protein binding, degree of renal excretion, hydrophilicity, and potency on a weight basis is variable. These differences may be even greater in diabetic patients, who may present diabetes-induced abnormalities in P450 isoforms and altered hepatic metabolic pathways. Thus, it is obvious that head-to-head comparisons between different statins are preferable than trial-to-trial comparisons. Such assessments are of utmost importance, especially in cases in which specific populations with a distinct lipid profile and altered metabolic pathways, like diabetics, are studied. It should be specially pinpointed that patients with metabolic syndrome and diabetes constitute also a special population regarding their atherogenic dyslipidemia, which is usually associated with low HDL-cholesterol, hypertriglyceridemia and predominance of small dense LDL-cholesterol. Therefore, these patients may benefit from fibrates or combined statin/fibrate treatment. This policy is not accomplished since in the real world things are more complex. Trials would require very large sample sizes and long-term follow-up to detect significant differences in myocardial infarction or death between two different statins. Moreover, the fact that new compounds are under several phases of research and development represents an additional drawback for performing the trials. Ideally, head-to-head trials regarding clinically important outcomes should be conducted for all drugs. Nonetheless, the desirability of performing such trials, which epitomize modern evidence-based medicine, is frequently superseded by the feasibility dictated by pragmatic and economic circumstances. In the latter case, in absence of solid systematic documentation of comparable health benefits and long-term safety, both researchers and practicing physicians should allude to the weight of scientific endorsement behind the arguments and seek for the possible strengths and weaknesses intrinsic to each specific study. In any case, conclusions based on surrogate endpoints cannot completely substitute head-to-head comparisons regarding patients' outcome.

Clinical Trials as Topic↗
PubMed2005

Effect of bezafibrate on incidence of type 2 diabetes mellitus in obese patients.

AIMS: To assess the effect of fibric acid derivative bezafibrate on incidence of type 2 diabetes in obese patients over a median 6.3 years follow-up period. METHODS AND RESULTS: The study sample comprised 339 non-diabetic obese patients (body mass index > or = 30.0 kg/m2) aged 42-74. Patients received either bezafibrate retard 400 mg (178 patients) or placebo (161 patients) once daily. Development of new diabetes was recorded in 98 patients: in 56 (37.0%) from the placebo group vs. 42 (27.1%) from the bezafibrate group, (P log-rank=0.01). The median time (interquartile range) until onset of new diabetes was significantly delayed in patients on bezafibrate when compared with those on placebo: 4.0 (2.1-5.0) vs. 2.0 (0.5-3.5) years, P=0.002. Multivariable analysis identified bezafibrate treatment as an independent predictor of reduced risk of new diabetes with hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.39-0.91]. Other significant variables associated with future overt type 2 diabetes in obese patients were triglycerides (50 mg/dL increment) with HR 1.15 (95% CI 1.02-1.28) and fasting glucose (10 mg/dL increment) with HR 2.27 (95% CI 1.83-2.81). CONCLUSION: Bezafibrate, when compared with placebo, reduced the incidence and delayed the onset of type 2 diabetes in obese patients over a long-term follow-up period.

Adult↗
PubMed2005

The anteroposterior pericardial sac diameter measured by echocardiography correlates with the volume of pericardial effusion and with effort dyspnea.

AIMS: To examine the value of the anteroposterior pericardial sac diameter (APD) for prediction of the volume of pericardial effusion. METHODS AND RESULTS: We measured the APD by echocardiography before 52 pericardiocentesis procedures and correlated it with the aspirate volume, etiology, symptoms, and clinical outcome. The volume of the aspirate ranged from 60 to 2300 ml (median 650 ml). The APD (range 8.0 cm-15.9 cm, median 12 cm) correlated well with the cubic root of the volume of the effusion [volume=(0.8APD-0.6)3, r2=0.533, p<0.01]. An APD>or=12 cm had a positive predictive value of 88% and a negative predictive value of 83% for effusion volume above the sample median (>or=650 ml) and a positive predictive value of 100% for effusion in the middle or upper aspirate volume tertiles. Effort dyspnea was more common among patients with APD>or=12.0 cm (n=13) than in those with APD<12.0 cm (n=11) (p=0.007). One-year survival after pericardiocentesis was closely related to the severity of the underlying etiology and was not influenced by the volume of the effusion before aspiration. CONCLUSIONS: The APD is a simple, valuable method for non-invasive prediction of pericardial fluid volume. A greater APD is associated with, and may explain, effort dyspnea.

Adult↗