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Biomedical subjects

Michael Motro

Publications and source records attributed to Michael Motro.

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

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

Tracking coronary calcification and atherosclerotic lesions in patients with stable angina pectoris undergoing nifedipine therapy.

AIMS: The objective of the Coronary Calcification (CC) study was to determine in patients with chronic symptomatic coronary artery disease, if, in addition to standard therapy, nifedipine GITS, relative to placebo, would arrest or slow down the progression of calcium or the development of new atherosclerotic lesions in the coronary arteries. METHODS AND RESULTS: The CC study was part of the ACTION trial. Multi-slice computerized tomography was used to measure and track the progression of CC. Five hundred and eighteen patients were included in this study. The changes in calcium score from baseline every 24 months, over a period of between 4.5 and 6 years, were similar in the nifedipine and placebo treatment groups (p = 0.8). Compared to placebo, more patients in the nifedipine group (71 vs. 60%) were free of new calcified atherosclerotic lesions during follow-up(p = 0.095). CONCLUSION: Nifedipine GITS was not effective in slowing down the progression of calcium in advanced atherosclerotic plaques in patients with stable angina pectoris. Although statistically not significant, Nifedipine demonstrated a trend in slowing down the development of new atherosclerotic lesions.

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

Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate.

BACKGROUND: Development of insulin resistance (IR) may be important in the pathogenesis of both metabolic syndrome and type 2 diabetes mellitus. Few data are available regarding the short-term efficacy of the peroxisome proliferator-activated receptor ligand bezafibrate on IR, and its long-term effect is unknown. The present analysis aimed to investigate the effect of bezafibrate on IR in patients with coronary artery disease enrolled in the Bezafibrate Infarction Prevention Study. METHODS: Metabolic and inflammatory parameters were analyzed from stored frozen plasma samples obtained from patients who completed a 2-year, randomized, double-blind, placebo-controlled study. The homeostatic indexes of IR (HOMA-IRs) were calculated according to the homeostasis model of assessment. RESULTS: Both the patients taking bezafibrate (n = 1262) and those taking placebo (n = 1242) displayed similar baseline characteristics. The HOMA-IRs significantly correlated at baseline and during follow-up with glucose (r = 0.35 and 0.31, respectively) and triglycerides (r = 0.16 and 0.19, respectively). In a subgroup of 351 patients with diabetes, HOMA-IR at baseline was 88% higher than in their counterparts with normal glucose levels (P<.001). In the placebo group, during follow-up there was a significant 34.4% rise in HOMA-IR. In contrast, in the bezafibrate group there was only a nonsignificant 6.6% change in HOMA-IR. The intergroup differences in percentage changes of HOMA-IR were in favor of bezafibrate (P<.001). CONCLUSIONS: In patients with coronary artery disease enrolled in our study, as represented by the placebo group, HOMA-IR increased over time. During the 2 years of the follow-up, bezafibrate significantly attenuated this process.

Aged↗
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

Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons.

There are three peroxisome proliferator-activated receptors (PPARs) subtypes which are commonly designated PPAR alpha, PPAR gamma and PPAR beta/delta. PPAR alpha activation increases high density lipoprotein (HDL) cholesterol synthesis, stimulates "reverse" cholesterol transport and reduces triglycerides. PPAR gamma activation results in insulin sensitization and antidiabetic action. Until recently, the biological role of PPAR beta/delta remained unclear. However, treatment of obese animals by specific PPAR delta agonists results in normalization of metabolic parameters and reduction of adiposity. Combined treatments with PPAR gamma and alpha agonists may potentially improve insulin resistance and alleviate atherogenic dyslipidemia, whereas PPAR delta properties may prevent the development of overweight which typically accompanies "pure" PPAR gamma ligands. The new generation of dual-action PPARs--the glitazars, which target PPAR-gamma and PPAR-alpha (like muraglitazar and tesaglitazar) are on deck in late-stage clinical trials and may be effective in reducing cardiovascular risk, but their long-term clinical effects are still unknown. A number of glitazars have presented problems at a late stage of clinical trials because of serious side-effects (including ragaglitazar and farglitazar). The old and well known lipid-lowering fibric acid derivative bezafibrate is the first clinically tested pan--(alpha, beta/delta, gamma) PPAR activator. It is the only pan-PPAR activator with more than a quarter of a century of therapeutic experience with a good safety profile. Therefore, bezafibrate could be considered (indeed, as a "post hoc" understanding) as an "archetype" of a clinically tested pan-PPAR ligand. Bezafibrate leads to considerable raising of HDL cholesterol and reduces triglycerides, improves insulin sensitivity and reduces blood glucose level, significantly lowering the incidence of cardiovascular events and new diabetes in patients with features of metabolic syndrome. Clinical evidences obtained from bezafibrate-based studies strongly support the concept of pan-PPAR therapeutic approach to conditions which comprise the metabolic syndrome. However, from a biochemical point of view, bezafibrate is a PPAR ligand with a relatively low potency. More powerful new compounds with pan-PPAR activity and proven long-term safety should be highly effective in a clinical setting of patients with coexisting relevant lipid and glucose metabolism disorders.

Bezafibrate↗
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

Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome.

BACKGROUND: A consistent relationship between metabolic syndrome (MS) and myocardial infarction (MI) has been demonstrated. We evaluated the effect of bezafibrate retard, a fibric acid derivative, on the incidence of MI in patients with MS enrolled in the Bezafibrate Infarction Prevention (BIP) study. METHODS: Patients who displayed at least 3 of the following 5 risk factors were considered to have MS: (1) a fasting glucose level of 110 mg/dL (6.11 mmol/L); (2) a triglyceride level of 150 mg/dL (1.70 mmol/L); (3) a high-density lipoprotein cholesterol level less than 40 mg/dL (<1.04 mmol/L) in men or less than 50 mg/dL (<1.30 mmol/L) in women; (4) a systolic blood pressure of 130 mm Hg or diastolic blood pressure of 85 mm Hg; and (5) a body mass index of 28.0 kg/m(2). The study sample for this post hoc subgroup analyses comprised 1470 patients aged 42 to 74 years. The patients received either 400 mg of bezafibrate retard (740 patients) or placebo (730 patients) once a day. The mean follow-up period was 6.2 years for events and 8.1 years for mortality data. RESULTS: New MI was recorded in 193 patients: 82 (11.1%) of the 740 patients in the bezafibrate group vs 111 (15.2%) of the 730 patients in the placebo group (P = .02). Bezafibrate was associated with a reduced risk of any MI and nonfatal MI with hazard ratios (HRs) of 0.71 (95% confidence interval [CI], 0.54-0.95) and 0.67 (95% CI, 0.49-0.91), respectively. The cardiac mortality risk tended to be lower in patients taking bezafibrate (HR, 0.74; 95% CI, 0.54-1.03). In 575 patients with augmented features of MS (4-5 risk factors), the remarkable strengthening of cardiac mortality reduction when taking bezafibrate (HR, 0.44; 95% CI, 0.25-0.80) should be noted. CONCLUSION: Bezafibrate reduces the incidence of MI in patients with MS during long-term follow-up.

Adult↗
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

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↗
PubMed2005

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↗
PubMed2005

Coronary artery calcium measurement with multi-detector row CT and low radiation dose: comparison between 55 and 165 mAs.

PURPOSE: To prospectively compare the results of coronary artery calcium (CAC) measurements obtained with 55- and 165-mAs electrocardiographically gated multi-detector row computed tomography (CT). MATERIALS AND METHODS: Institutional clinical study review board approval and written informed consent were obtained. Fifty-one consecutive subjects (mean age, 59 years +/- 10) were scanned consecutively by using 165 and 55 mAs. For each examination, the number of lesions, total calcium score (TCS) calculated with Agatston algorithm (130-HU threshold), and calcium mass (in milligrams) were measured. Noise was measured by averaging 1 standard deviation of the CT attenuation values in five consecutive transverse sections of the ascending aorta. Paired t test and Pearson correlation were used to compare measurements between the examinations. RESULTS: By using 55 mAs, CAC was detected (TCS > 0) in all 33 subjects in whom CAC was initially detected with 165 mAs. The mean values of CAC measures with 165 and 55 mAs, respectively, were as follows: number of lesions, 6.2 +/- 9.6 and 6.1 +/- 9.4; TCS, 123 +/- 223 and 126 +/- 225; and calcium mass, 23.25 mg +/- 43 and 24.25 mg +/- 44 (P value was not significant for all parameters). Significant high correlation was found between the two methods for all measures (r > 0.90, P < .01). Similar results were obtained with analysis by coronary vessel. Image noise was 9.3 HU +/- 2.1 with 165 mAs and 14.7 HU +/- 3.9 with 55 mAs (P < .001), with a parallel decrease in the volume CT dose index from 12 to 4 mGy. CONCLUSION: Radiation dose can be reduced (eg, 55 mAs) for CAC detection and measurement at multi-detector row CT and provides results comparable to those obtained with 165 mAs.

Adult↗
PubMed2004

Accelerated progression of coronary calcification: four-year follow-up in patients with stable coronary artery disease.

PURPOSE: To prospectively assess the 4-year progression rate of coronary artery calcium (CAC) in patients with clinically stable coronary artery disease (CAD) with multi-detector row computed tomography (CT). MATERIALS AND METHODS: The study group consisted of 382 consecutive patients. All underwent baseline dual-sector spiral CT, and CT was repeated at 2 and 4 years later. Progression of CAC was assessed with measurement of the increase in total calcium score (TCS) and with repeated-measures analysis and multivariate linear regression models. Logistic regression model was used to predict incidence of new lesions. RESULTS: Eighty-seven percent (333 of 382) of the study group were men, with mean age of 65 years +/- 11, and 13% (49 of 382) were women, with mean age of 68 years +/- 11. The average TCS increased after 4 years by sixfold from baseline in the 1st quartile, and by four-, two- and 1.5-fold in the 2nd, 3rd, and 4th quartiles of baseline TCS (P <.01), respectively. Multiple linear regression analysis included age; sex; natural logarithm of baseline TCS; history of hypertension, diabetes mellitus, current smoking, hypercholesterolemia, and lipid-lowering therapy with cholesterol synthesis enzyme inhibitor (statin); and family history of premature CAD. Results demonstrated that natural logarithm of baseline TCS and history of current smoking were independent predictors of the 4th-year natural logarithm of TCS levels (R(2) = 0.85, P <.001). New lesions were diagnosed in 56 (15%) patients. History of statin therapy (odds ratio = 0.35; 95% confidence interval [CI]: 0.16, 0.77; P <.01), age with an increment of 5 years (odds ratio = 0.76; 95% CI: 0.64, 0.90; P =.01), and natural logarithm of baseline TCS (odds ratio = 0.73; 95% CI: 0.62, 0.86; P <.01) were independent predictors for new calcific lesions during 4 years. CONCLUSION: Accelerated progression of CAC during 4 years was found in clinically stable patients with CAD.

Aged↗
PubMed2004

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↗
PubMed2004

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↗