Effects of switching statins on achievement of lipid goals: measuring effective reductions in cholesterol using rosuvastatin therapy (MERCURY I) study

Background

In a multinational trial (4522IL/0081), we assessed the effects of switching to low doses of rosuvastatin from commonly used doses of atorvastatin, simvastatin, and pravastatin on low-density lipoprotein cholesterol (LDL-C) goal achievement in high-risk patients.

Methods

Hypercholesterolemic patients (n = 3140) with coronary heart disease, atherosclerosis, or type 2 diabetes were randomized to open-label rosuvastatin 10 mg, atorvastatin 10 or 20 mg, simvastatin 20 mg, or pravastatin 40 mg for 8 weeks. Patients either remained on these treatments for another 8 weeks or switched treatments from atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg to rosuvastatin 10 mg or from atorvastatin 20 mg to rosuvastatin 10 or 20 mg. The primary efficacy measure was the proportion of patients reaching the Joint European Societies' LDL-C goal (<116 mg/dL) at week 16. For measures of cholesterol goal achievement, treatment arms were compared using logistic-regression analysis.

Results

Significant improvement in LDL-C goal achievement was found for patients who switched to rosuvastatin 10 mg, compared with patients who remained on atorvastatin 10 mg (86% vs 80%, P < .05), simvastatin 20 mg (86% vs 72%, P < .0001), and pravastatin 40 mg (88% vs 66%, P < .0001), and between patients switched to rosuvastatin 20 mg and those who remained on atorvastatin 20 mg (90% vs 84%, P < .01). Similar results were found for achievement of the European combined LDL-C and total cholesterol goals and National Cholesterol Education Program Adult Treatment Panel III LDL-C goals. All statins were well tolerated over 16 weeks.

Conclusions

We demonstrated that switching to a more efficacious statin is an effective strategy to improve lipid goal achievement in patients requiring lipid-lowering therapy.     

Achieving LDL cholesterol, non-HDL cholesterol, and apolipoprotein B target levels in high-risk patients: Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapY (MERCURY) II

Background

National Cholestesrol Education Program Adult Treatment Panel III guidelines for patients at a high risk of coronary heart disease set a low-density lipoprotein cholesterol (LDL-C) target of <100 mg/dL. This target can be difficult to attain with diet and current therapy.

Methods

In a 16-week multinational trial, 1993 high-risk patients were randomized to rosuvastatin 20 mg, atorvastatin 10 mg, atorvastatin 20 mg, simvastatin 20 mg, or simvastatin 40 mg for 8 weeks. Patients either remained on starting treatment or switched to lower or milligram-equivalent doses of rosuvastatin for 8 more weeks.

Results

At 16 weeks, more patients achieved their LDL-C target by switching to rosuvastatin 10 mg than staying on atorvastatin 10 mg (66% vs 42%, P < .001) or simvastatin 20 mg (73% vs 32%, P < .001). Changing to rosuvastatin 20 mg brought more patients to their LDL-C target than staying on atorvastatin 20 mg (79% vs 64%, P < .001) or simvastatin 40 mg (84% vs 56%, P < .001). More very high risk patients achieved an LDL-C target of <70 mg/dL when changed to rosuvastatin from atorvastatin or simvastatin (within-arm comparisons P < .01). More hypertriglyceridemic patients (triglycerides ≥200 mg/dL) met LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B targets by changing to rosuvastatin. Switching to rosuvastatin produced greater reductions in LDL-C, total cholesterol, non-HDL-C, apolipoprotein B, and lipid ratios. All treatments were well tolerated, with no differences among treatment groups in skeletal muscle, hepatic, or renal toxicity.

Conclusion

Rosuvastatin 10 or 20 mg is an effective and safe therapeutic option for high-risk patients to achieve their lipid and apolipoprotein targets.     

Efficacy and safety of rosuvastatin and atorvastatin in patients with hypercholesterolemia and a high risk of coronary heart disease: a randomized, controlled trial

Background

This double-blind, multicenter, randomized trial compared rosuvastatin and atorvastatin for reducing low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia and a high risk of coronary heart disease.

Methods

After a 6-week dietary lead-in period, patients with LDL-C levels ≥160 and <250 mg/dL and triglyceride levels ≤400 mg/dL were randomly assigned to 24 weeks' treatment in 1 of 3 groups, each with forced dose titrations at 12 and 18 weeks. Starting and titrated doses for each group were rosuvastatin 5, 20, and 80 mg (n = 127); rosuvastatin 10, 40, and 80 mg (n = 128); and atorvastatin 10, 40, and 80 mg (n = 128).

Results

At 24 weeks, LDL-C was reduced significantly more with 80 mg rosuvastatin (combined rosuvastatin group) than with atorvastatin 80 mg (60% vs 52% [P < .001]). At 12 weeks, rosuvastatin 5 and 10 mg reduced LDL-C significantly more than atorvastatin 10 mg (40% [P < .01], 47% [P < .001] vs 35%). At 18 weeks, LDL-C reductions were also significantly greater in both rosuvastatin groups than in the atorvastatin group (52% [P < .01], 59% [P < .001] vs 47%). Consequently, more patients receiving rosuvastatin achieved LDL-C goals. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apolipoproteins B and A-I, and all lipid ratios were more favorably modified by rosuvastatin at 24 weeks (P < .01). Effects of the 2 agents on triglycerides were similar.

Conclusions

Rosuvastatin was more efficacious than atorvastatin in modifying lipids in patients with hypercholesterolemia and a high coronary heart disease risk.     

Comparison of the dose-response relationships of 2 lipid-lowering agents: a Bayesian meta-analysis

Background

Comparing the dose-response of a new drug to that of a previously studied drug can aid in understanding their relative potencies. Two dose-finding studies addressed the effect of a new drug, rosuvastatin, on its ability to decrease low-density lipoprotein cholesterol (LDL-C) levels. One of these studies included 2 doses of atorvastatin, and substantial additional information is available in the literature about the effect of atorvastatin on LDL-C level lowering.

Methods

The 2 dose-finding studies of rosuvastatin considered otherwise healthy patients who had hypercholesterolemia. Comparable studies of atorvastatin were identified via a MEDLINE search in December 1999. Multiple reviewer consensus identified 15 of 41 studies on atorvastatin published since 1996 that met these selection criteria: reporting of LDL-C level change from baseline at least 6 weeks after treatment initiation, doses administered, and treatment group sizes. Eligible populations had clinical evidence of hypercholesterolemia. We excluded studies with patients who had severe illness or a previous history of transplantation. Data extraction of the mean, sample sizes, and SDs (or CIs) by dose was carried out independently by multiple reviewers. We combined the results from the various studies with Bayesian hierarchical modeling and analyzed them with Markov chain Monte Carlo techniques.

Results

Combining this study and literature results substantially increased the power to compare the dose-response relationships of rosuvastatin and atorvastatin. Rosuvastatin reduced LDL-C level by an estimated 10 to 17 percentage points more than atorvastatin when both were given at the same dose. Approximately one quarter of the dose of rosuvastatin achieved about the same magnitude of LDL-C level reduction as atorvastatin at dosages as high as 80 mg. This finding does not imply a 4-fold difference in efficacy overall and specifically does not describe the results at higher dosage levels.

Conclusions

Bayesian meta-analysis of results from related studies allows the comparison of the dose-response relationships of 2 drugs, better estimates of a particular dose-response relationship within an individual study, and the expression of relative benefits (of dose and drug) in terms of probabilities. Explicitly comparing a study’s results with historical data using Bayesian meta-analysis allows clinicians to view the study in the larger context of medical research.     

Relationship between advanced glycation end products and increased lipid peroxidation in semen of diabetic men

Aims

Majority of diabetic male patients have disturbances in their reproductive systems. However, the mechanisms underlying these disturbances are largely unknown. Since advanced glycation end products (AGE) have a key role in oxidative stress and cell damage in diabetic complications, we hypothesize that AGEs may be involved sperm lipid peroxidation.

Methods

Total AGEs in seminal plasma of 32 diabetic and 35 non-diabetic men was determined by spectrofluorimetric method and carboxy methyl lysine (CML) level was assayed using ELISA. Contents of lipid peroxidation in sperm and seminal plasma were determined by thiobarbituric acid reaction. Total antioxidant capacity (TAC) was measured by a colorimetric assay.

Results

Total AGEs were found significantly higher in seminal plasma of diabetic men than non-diabetic group (p < 0.001) whereas no significant differences in seminal plasma CML values between two groups was observed. Moreover, sperm and seminal plasma lipid peroxidation were significantly higher in diabetic subjects than non-diabetic men and a significantly lower TAC was detected in diabetic group compare to non-diabetics.

Conclusions

These results showed an increment in AGEs in seminal plasma of diabetic subjects and may suggest a key role for glycation process and increased oxidative stress in reproductive system dysfunction.     

Anti-endothelial and anti-neuronal effects from auto-antibodies in subsets of adult diabetes having a cluster of microvascular complications

Aims

To test autoantibodies from subsets of diabetes with painful neuropathy, maculopathy and nephropathy for effects in neurons.

Methods

Protein-A eluates from plasma of 27 diabetic and 19 age-matched controls were tested for effects on endothelial cell survival, and neurite outgrowth in rat pheochromocytoma PC12 cells. Painful diabetic neuropathy or control autoantibodies were compared for binding to PC12-derived heparan sulfate proteoglycans. The mechanism of the effects from pathologic autoantibodies was investigated by changes in intracellular calcium in endothelial cells, whole cell current in neurons, or using the Rho kinase inhibitor Y27632.

Results

Autoantibodies from diabetic patients with maculopathy, nephropathy, and painful neuropathy (n = 5) caused significantly greater mean inhibition of neurite outgrowth (p < 0.005) than diabetic or control patients with fewer or no complications (n = 30). Painful diabetic autoantibodies (3 μg/mL) bound neuronal heparan sulfate proteoglycan (HSPG) more than autoantibodies from diabetic or control subjects without painful neuropathy (p < .0001). Inhibition of PC12 neurite outgrowth by the painful neuropathy antibodies was completely prevented by 1 μM concentrations of Y27632.

Conclusion

These results suggest anti-endothelial and anti-neuronal effects from auto-antibodies in a subset of diabetic patients with a cluster of microvascular complications.     

Relationship between oxidative stress and apoptotic markers in lymphocytes of diabetic patients with chronic non healing wound

Aims

Hyperglycemia causes generation of free radicals which leads to oxidative stress and apoptosis in various cells. The present study was undertaken to investigate the correlation between oxidative stress and apoptotic markers in lymphocytes of diabetic patients with chronic non healing wounds.

Methods

Thirty healthy, thirty uncontrolled type 2 diabetes mellitus (T2DM) and thirty uncontrolled T2DM with chronic, non healing, neuropathic diabetic foot patients were included in this study. Indices of oxidative stress inside the lymphocyte lysate were estimated by measuring content of superoxide dismutase (SOD), Catalase, Glutathione and malonaldialdehyde (MDA). Protein expression studies of pro and anti apoptotic markers were carried out to elucidate their possible involvement in diabetic context.

Results

SOD and MDA activity was significantly higher in the lymphocytes of diabetic patients having chronic, non healing diabetic wound as compared with healthy (p < 0.001); whereas catalase and GSH activity was significantly reduced (p < 0.001) in the same group. Expressions of pro apoptotic markers (Caspase-3, Fas and Bax) were significantly higher whereas reduced expression of anti-apoptotic marker (Bcl-2) were obtained in lymphocytes of diabetic and non diabetic individuals.

Conclusions

Hyperglycemia confers pro apoptotic manifestations which are mostly through altered indices of oxidative stress within lymphocytic milieu.     

N-terminal Pro brain natriuretic peptide is a reliable biomarker of reduced myocardial contractility in patients with lamin A/C gene mutations

Background

Recently, concerns have been raised about a possible lack of sensitivity of biomarkers to detect left ventricular (LV) dysfunction in patients with myopathies. We examined the ability of the N-terminal brain natriuretic peptide (NT-proBNP) to detect LV or right ventricular (RV) dysfunction in patients with lamin A/C (LMNA) gene mutations.

Methods

We prospectively measured plasma NT-proBNP in consecutive patients with documented LMNA mutations and age-sex matched controls. All patients underwent standard echocardiography implemented by pulsed tissue-Doppler echocardiography (TDE).

Results

Twenty-three patients were included (10 males, mean age 39.2 ± 18.9 years);10 had previous atrial arrhythmias, 8 had been implanted with cardioverter defibrillator for primary prevention of sudden death, 5 patients were of NYHA class II and 18 of NHYA class I. Sinus rhythm was recorded in all. NT-proBNP was increased in LMNA patients versus controls (123 ± 229 versus 26 ± 78 pg/ml, p = 0.0004); 7 patients had depressed LV and/or RV contractility. Patients with reduced LV or RV contractility had increased mean NT-proBNP (341 ± 1032 pg/ml versus 80 ± 79 pg/ml in patients with normal myocardial contractility, p = 0.004). Receiver-operating-characteristics analysis shows that NT-proBNP reliably detected depressed contractility (area under the curve 0.889 [0.697-1.000]). Sensitivity and specificity were 88% and 83% respectively, applying manufacturer's recommended cut-off concentration of 125 pg/ml.

Conclusion

NT-proBNP reliably detected the presence of reduced LV/RV contractility in LMNA patients.     

Elevated micronuclei frequency in type 2 diabetes with high glycosylated hemoglobin

Aim

The role of oxidative damage to DNA due to hyperglycemia is well known. In the current study we have evaluated the induction of micronuclei due to increased glycosylation in type 2 diabetes.

Methods

Forty-nine subjects divided into two groups of normoglycemic controls and type 2 diabetic cases were recruited in the study. Whole blood was cultured and micronuclei were scored in all the cases. This was correlated with age, sex, blood glucose levels and glycosylated hemoglobin.

Results

Age and sex matched diabetic patients had an increased micronuclei frequency in response to elevated glycosylation of hemoglobin (R² = 0.229, p = 0.037) compared to normoglycemic subjects.

Conclusion

The increased glycosylation seems to induce oxidative damage in the DNA of the diabetic patients, which manifests as an increased micronuclei frequency. This has a potential to be used as a biomarker for subsequent diabetic complications.     

Influence of age, gender, and race on the efficacy of adding ezetimibe to atorvastatin vs. atorvastatin up-titration in patients at moderately high or high risk for coronary heart disease

Background

Age, gender, and race are factors that influence atherosclerotic coronary heart disease (CHD) risk and may conceivably affect the efficacy of lipid-altering drugs.

Methods

Post hoc analysis of two multicenter, 6-week, double-blind, randomized, parallel-group trials assessed age (< 65 and ≥ 65 years), gender, and race (white, black, and other) effects on atorvastatin plus ezetimibe versus up-titration of atorvastatin in hypercholesterolemic patients with CHD risk. High CHD risk subjects with low-density lipoprotein (LDL) cholesterol levels ≥ 70 mg/dL (~ 1.81 mmol/L) during stable atorvastatin 40 mg therapy were randomized to atorvastatin 40 mg plus ezetimibe 10 mg, or up-titrated to atorvastatin 80 mg. Moderately high CHD risk subjects with LDL cholesterol levels ≥ 100 mg/dL (~ 2.59 mmol/L) with atorvastatin 20 mg were randomized to atorvastatin 20 mg plus ezetimibe 10 mg, or atorvastatin 40 mg.

Results

Although some variability existed, age, gender, and race subgroups did not substantially differ from the entire patient population with regard to lipid-altering findings. Ezetimibe plus atorvastatin produced greater percent reductions in LDL cholesterol, total cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B than up-titration of atorvastatin for all subgroups. HDL cholesterol and apolipoprotein AI changes were small and variable.

Conclusion

Treatment efficacy in age, gender, and race subgroups did not substantially differ from the entire study population. Ezetimibe combined with atorvastatin generally produced greater incremental reductions in LDL cholesterol and several other key lipid parameters compared with doubling the atorvastatin dose in hypercholesterolemic patients with high or moderately high CHD risk. These results suggest that co-administration of ezetimibe with statins is a useful therapeutic option for treatment of dyslipidemia in differing patient populations.     

Type 2 diabetes risk in persons with dysglycemia: the Framingham Offspring Study

Aims

Detection of risk of type 2 diabetes mellitus (T2DM) among adults with dysglycemia.

Methods

We used a nested case-cohort prospective design to estimate risk of new diabetes (diabetes treatment or FPG ≥7.0 mmol/L) among 1004 Framingham Heart Study Offspring with baseline dysglycemia [fasting plasma glucose (FPG) 5.4-6.9 mmol/L and/or 2-h post glucose load level 7.8-11.0 mmol/L]. Using clinical characteristics previously shown to predict incident T2DM, we used logistic regression to estimate odds ratios (OR), p-values for predictors, and assessment of model discrimination.

Results

At the end of 7 years follow-up there were 118 incident T2DM cases. In a model that included age, sex, elevated blood pressure or blood pressure treatment, lipid-lowering treatment and elevated triglycerides, we found the following additional characteristics to be independently associated with new T2DM: parental history of diabetes (OR 2.28, p = 0.004); excess adiposity (BMI ≥ 30 kg/m² or waist circumference ≥101.6 cm) (OR 2.04, p = 0.0005), and low HDL-C [<1.0 (men) or <1.3 mmol/L (women)] (OR 2.77, p < 0.0001). The multivariable C-statistic for this model was 0.701, and with glycemic category information included, c = 0.751.

Conclusions

The key non-glycemic traits that predicted later T2DM in adults with dysglycemia were parental history of diabetes, excess adiposity and low HDL-C.     

Serum asymmetric dimethylarginine levels in diabetic patients with neuropathy

Objective

The goal of our study was to evaluate the role of asymmetric dimethylarginine (ADMA) in patients with diabetic neuropathy.

Materials and methods

In this study, 58 diabetic patients and 26 healthy volunteers were included. In both groups ADMA measurements were performed together with other biochemical examinations. Nerve conduction studies and Neuropathy Symptom Score (NSS) were administered to the diabetic patients.

Results

ADMA levels were found significantly higher in diabetic patients compared to the control group (p = 0.0001). However, ADMA levels were not statistically significant between diabetic patients with neuropathy and without neuropathy (p = 0.86 and p = 0.47).

Conclusion

These results demonstrate that there is not any significant relationship between ADMA and diabetic neuropathy.     

The achievement of target cholesterol level differs between coronary heart disease and diabetic patients

Background

Guidelines recommend that LDL-C level should be < 100 mg/dl among diabetes mellitus (DM) and coronary heart disease (CHD) patients.

Objective

To evaluate how patients with DM and CHD differ in attaining the target level and to examine the association between goal achievement, demographic and clinical parameters.

Methods

The study was conducted in Maccabi Healthcare Services, the second largest health maintenance organization in Israel. All patients with DM (n = 54,261), CHD (n = 24,083) or DM and CHD (n = 15,370) who were listed in the computerized database and had at least one LDL-C level measurement between January 1, 2007 and July 15, 2008 were eligible. The percentage of patients who attained LDL-C level < 100 mg/dl and its association with demographic and clinical parameters were analyzed.

Results

The rate of reaching the LDL-C target level was higher among the CHD and CHD and DM patients than DM ones (67% vs. 57% vs. 50%, p < 0.001, respectively). Male gender; 5th socioeconomic status quintile; underlying disease i.e. CHD, CHD and DM; high statins compliance; and revascularization by percutaneous coronary intervention predicted for reaching target level. DM; absence of renal function evaluation; hospitalizations; HbA1C > 7% or missing its measurements had a negative predictive value.

Conclusions

The rate of reaching LDL-C target level should be increased in all high risk patients, mainly diabetic ones. Efforts should include educational programs to physicians and patients regarding the importance, the need to adhere and to intensify the cholesterol lowering treatment.     

Glyburide increases risk in patients with diabetes mellitus after emergent percutaneous intervention for myocardial infarction — A nationwide study

Background

Sulfonylureas have been linked to an increased cardiovascular risk by inhibition of myocardial preconditioning. Whether individual sulfonylureas affect outcomes in diabetic patients after emergent percutaneous coronary intervention for myocardial infarction is unknown.

Methods

All Danish patients receiving glucose-lowering drugs admitted with myocardial infarction between 1997 and 2006 who underwent emergent percutaneous coronary intervention were identified from national registers. Multivariable Cox proportional hazards models were used to analyze the risk of cardiovascular mortality and morbidity associated with sulfonylureas.

Results

A total of 926 patients were included and 163 (17.6%) patients died during the first year of which 155 (16.7%) were cardiovascular deaths. The most common treatment was sulfonylureas which were received by 271 (29.3%) patients, and 129 (13.9%) received metformin. Cox proportional hazard regression analyses adjusted for age, sex, calendar year, comorbidity and concomitant pharmacotherapy showed an increased risk of cardiovascular mortality (hazard ratio [HR] 2.91, 95% confidence interval [CI] 1.26-6.72 ; p = 0.012), cardiovascular mortality and nonfatal myocardial infarction (HR 2.69 , 95% CI 1.21-6.00; p = 0.016), and all-cause mortality (HR 2.46, 95% CI 1.11-5.47; p = 0.027), respectively, with glyburide compared to metformin.

Conclusions

Glyburide is associated with increased cardiovascular mortality and morbidity in patients with diabetes mellitus undergoing emergent percutaneous coronary intervention after myocardial infarction. Early reperfusion therapy is the mainstay in modern treatment of myocardial infarction and the time may have come to discard glyburide in favour of sulfonylureas that do not appear to confer increased cardiovascular risk.     

Effect of metformin on oxidative stress, nitrosative stress and inflammatory biomarkers in type 2 diabetes patients

Aim

Advanced research has radically changed both diagnosis and treatment of diabetes during last three decades; a number of classes of oral antidiabetic agents are currently available for better glycemic control. Present study aims to evaluate the effect of metformin on different stress and inflammatory parameters in diabetic subjects.

Methods

208 type 2 diabetes patients were randomly assigned for metformin and placebo.

Results

Reactive oxygen species generation, advanced oxidation protein products (179.65 ± 13.6, 120.65 ± 10.5 μmol/l) and pentosidine (107 ± 10.4, 78 ± 7.6 pmol/ml) were found to be reduced by metformin treatment compared to placebo. On the other hand metformin administration enhanced total thiol and nitric oxide level (p < 0.05). But nutrient level (Mg⁺², Ca⁺²) in plasma was not altered by the treatment. Significant restoration of C reactive protein (p < 0.05) was noticed after metformin therapy. Metformin administration also improved Na⁺K⁺ATPase activity (0.28 ± 0.08, 0.41 ± 0.07 μmol Pi/mg/h) in erythrocyte membrane.

Conclusions

This study explores that metformin treatment restores the antioxidant status, enzymatic activity and inflammatory parameters in type 2 diabetic patients. Metformin therapy improves the status of oxidative and nitrosative stress altered in type 2 diabetes. This study unfolds the cardio protective role of metformin as an oral hypoglycemic agent.     

Ten-year incidence of diabetic retinopathy and macular edema. Risk factors in a sample of people with type 1 diabetes

Aims

To determine the 10-year incidence of diabetic retinopathy (DR) and macular edema (DME), and its relationship with its risk factors in a sample of type 1 diabetes mellitus.

Methods

A total of 334 patients without diabetic retinopathy at baseline underwent a 10-year prospective study, the risk factors included: age, gender, diabetes duration, HbA1c, LDL-C, HDl-C, TC/HDL-C ratio, ApoA1, ApoB, ApoB/ApoA1 ratio, and triglycerides were recorded. Risk factors for diabetic macular edema (DME) were also recorded.

Results

The 10-year incidence of any DR was 35.90%, and 11.07% developed DME. The risk factors for DR and DME were: diabetes duration, high glycosylated level, and arterial hypertension, and overt nephropathy was well correlated with DME. The lipid study demonstrated that ApoB/ApoA1 ratio was significant for any DR [HRR: 0.594 (0.416-0.848), p = 0.01], and DME [HRR: 0.601 (0.433-0.894), p = 0.009]. The TC/HDL ratio was only significant for DME [HRR: 0.624 (0.440-0.886), p = 0.008]; other lipids values were not significant for any groups studied.

Conclusions

In the present study, the ApoB/ApoA1 ratio was significant to the 10-year incidence of diabetic retinopathy and to macular edema; and the TC/HDL ratio was significant to a 10-year incidence of macular edema.     

Role of quantitative chest perfusion computed tomography in detecting diabetic pulmonary microangiopathy

Aims

Aim of the study was to determine the role of perfusion chest computed tomography (pCT) in evaluation of pulmonary diabetic angiopathy.

Methods

18 never-smoking patients (10 diabetic patients and 8 healthy controls) underwent chest high resolution CT (HRCT) and then pCT scanning. In both groups, blood tests, biochemical analysis, fibrinogen, HbA_1c, spirometry, diffusion capacity for carbon monoxide (DLCO) and body pletysmography were performed.Following parameters of pulmonary perfusion have been analysed: blood volume (BV), blood flow (BF), mean transit time (MTT), time to peak (TTP) and permeability surface (PS).

Results

There were no statistically significant differences between groups in terms of age, sex, BMI, forced expiratory volume in one second (FEV₁), DLCO. Chest HRCT revealed no pathologies. Significantly higher values of chest pCT for BF (p = 0.05), BV (p = 0.05) and PS (p = 0.01) have been found in diabetics in comparison to controls. No differences were found in MTT.

Conclusions

Significant increase of perfusion parameters in diabetes seems to confirm pulmonary microangiopathy. The results indicate that further studies on application of pCT in diabetic patients may be beneficial for better understanding of lung microangiopathy, its diagnosing and monitoring.     

TIMI risk index and the benefit of enoxaparin in patients with ST-elevation myocardial infarction

Purpose

The purpose of the study was to evaluate the cause of death, risk of nonfatal complications, and relative outcomes with an enoxaparin versus unfractionated heparin strategy in ST-elevation myocardial infarction stratified using the Thrombolysis in Myocardial Infarction (TIMI) Risk Index (TRI).

Methods

We evaluated 30-day outcomes in 19,941 patients with ST-elevation myocardial infarction treated with fibrinolysis and unfractionated heparin or enoxaparin. Patients were categorized on the basis of prespecified ranges of the TRI [heart rate × (age/10)²/systolic blood pressure].

Results

There was a strongly graded increase in 30-day mortality with increasing TRI (1.2%-20.7%, P <.0001). The proportion of deaths due to mechanical causes (congestive heart failure, shock, and myocardial rupture) increased progressively with the TRI. There also was a significant positively graded association between the TRI and nonfatal heart failure or shock (0.4%-4.4%, P <.0001). In contrast, death resulting from recurrent ischemic events predominated in the lowest TRI group. The relative reduction in death/myocardial infarction with the enoxaparin strategy appeared inversely graded with the TRI. There was a 38% reduction in the lowest risk group (relative risk 0.62, 95% confidence interval 0.45-0.86) and a decrease in the relative benefit of enoxaparin with increasing risk index.

Conclusions

The TRI was a strong predictor of all-cause mortality in a broad population, with a positive association with the risk of death due to mechanical complications and an inverse association with deaths due to recurrent ischemia. The enoxaparin strategy was superior to unfractionated heparin in a majority of patients with ST-elevation myocardial infarction, except for the group at the highest risk for severe mechanical complications, in whom the 2 anticoagulant strategies showed similar results.     

Microangiopathy is independently associated with presence, severity and composition of carotid atherosclerosis in type 2 diabetes

Background and aims

Common mechanisms for the development of micro- and macroangiopathic diabetic complications have been suggested. We aimed to cross-sectionally investigate strength and characteristics of the association between carotid atherosclerosis and microangiopathy in type 2 diabetic patients.

Methods and results

Common carotid artery intima-media thickness (cIMT), carotid plaque (CP) type and degree of stenosis were evaluated by ultrasound, along with the determination of anthropometric parameters, HbA1c, lipid profile, assessment of diabetic retinopathy and nephropathy, in 662 consecutive patients with type 2 diabetes mellitus (T2DM). Patients were divided according to high/low cIMT, presence/absence of CP and of retinopathy and nephropathy. Patients with CP were older, more prevalently males, past smokers, had longer diabetes duration, significantly lower HDL cholesterol and more prevalent ischemic heart disease (all p < 0.05) as compared to those with cIMT < 1 mm. Microangiopathies were more prevalent in patients with CP than in those without. At multivariate logistic regression, factors independently associated with the presence of CP were age, past smoke, HDL cholesterol, retinopathy and retinopathy plus nephropathy. A significant independent correlation of CP stenosis with stage of retinopathy and nephropathy was found. Finally, echolucent CPs were associated with a lower prevalence of proliferative retinopathy than CP containing calcium deposits.

Conclusion

In T2DM, retinopathy, alone or in combination with nephropathy, is independently associated to CP, and severity of microangiopathy correlates with severity of carotid atherosclerosis. These observations, together with the different prevalence of proliferative retinopathy according to CP types, point to possible common pathogenic mechanisms in micro- and macrovascular complications.