Faculty Bibliography

OBJECTIVES: Hypoadiponectinemia is associated with coronary artery disease (CAD). Pioglitazone has been shown to increase levels of adiponectin in diabetic patients. We sought to assess whether administration of pioglitazone to patients with CAD and without diabetes would affect plasma adiponectin levels and endothelial function. METHODS: Seventeen patients with stable CAD and without evidence of diabetes were treated for 12 weeks with pioglitazone hydrochloride 30 mg daily. Adiponectin levels and endothelium-dependent flow-mediated vasodilation (ED-FMD) measurements were obtained pretreatment, posttreatment, and after a 12-week washout period. RESULTS: Treatment with pioglitazone increased adiponectin levels from an average of 10.6 to 21.1 microg/ml (P=0.001) and improved ED-FMD from 4.45 to 8.43% (P=0.001). CONCLUSION: Treatment with pioglitazone increased plasma adiponectin levels and improved ED-FMD in patients with stable CAD and no evidence of diabetes or insulin resistance

CONTEXT: No antidiabetic regimen has demonstrated the ability to reduce progression of coronary atherosclerosis. Commonly used oral glucose-lowering agents include sulfonylureas, which are insulin secretagogues, and thiazolidinediones, which are insulin sensitizers. OBJECTIVE: To compare the effects of an insulin sensitizer, pioglitazone, with an insulin secretagogue, glimepiride, on the progression of coronary atherosclerosis in patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, multicenter trial at 97 academic and community hospitals in North and South America (enrollment August 2003-March 2006) in 543 patients with coronary disease and type 2 diabetes. INTERVENTIONS: A total of 543 patients underwent coronary intravascular ultrasonography and were randomized to receive glimepiride, 1 to 4 mg, or pioglitazone, 15 to 45 mg, for 18 months with titration to maximum dosage, if tolerated. Atherosclerosis progression was measured by repeat intravascular ultrasonography examination in 360 patients at study completion. MAIN OUTCOME MEASURE: Change in percent atheroma volume (PAV) from baseline to study completion. RESULTS: Least squares mean PAV increased 0.73% (95% CI, 0.33% to 1.12%) with glimepiride and decreased 0.16% (95% CI, -0.57% to 0.25%) with pioglitazone(P = .002). An alternative analysis imputing values for noncompleters based on baseline characteristics showed an increase in PAV of 0.64% (95% CI, 0.23% to 1.05%) for glimepiride and a decrease of 0.06% (-0.47% to 0.35%) for pioglitazone (between-group P = .02). Mean (SD) baseline HbA(1c) levels were 7.4% (1.0%) in both groups and declined during treatment an average 0.55% (95% CI, -0.68% to -0.42%) with pioglitazone and 0.36% (95% CI, -0.48% to -0.24%) with glimepiride (between-group P = .03). In the pioglitazone group, compared with glimepiride, high-density lipoprotein levels increased 5.7 mg/dL (95% CI, 4.4 to 7.0 mg/dL; 16.0%) vs 0.9 mg/dL (95% CI, -0.3 to 2.1 mg/dL; 4.1%), and median triglyceride levels decreased 16.3 mg/dL (95% CI, -27.7 to -11.0 mg/dL; 15.3%) vs an increase of 3.3 mg/dL (95% CI, -10.7 to 11.7 mg/dL; 0.6%) (P < .001 for both comparisons). Median fasting insulin levels decreased with pioglitazone and increased with glimepiride (P < .001). Hypoglycemia was more common in the glimepiride group and edema, fractures, and decreased hemoglobin levels occurred more frequently in the pioglitazone group. CONCLUSION: In patients with type 2 diabetes and coronary artery disease, treatment with pioglitazone resulted in a significantly lower rate of progression of coronary atherosclerosis compared with glimepiride. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00225277

BACKGROUND: The present study was undertaken to investigate the effect of statins plus omega-3 polyunsaturated fatty acids (PUFAs) on endothelial function and lipid profile in South Asians with dyslipidemia and endothelial dysfunction, a population at high risk for premature coronary artery disease. METHODS: Thirty subjects were randomized to rosuvastatin 10 mg and omega-3-PUFAs 4 g or rosuvastatin 10 mg. After 4 weeks, omega-3-PUFAs were removed from the first group and added to subjects in the second group. All subjects underwent baseline, 4-, and 8-week assessment of endothelial function and lipid profile. RESULTS: Compared to baseline, omega-3-PUFAs plus rosuvastatin improved endothelial-dependent vasodilation (EDV: -1.42% to 11.36%, p = 0.001), and endothelial-independent vasodilation (EIV: 3.4% to 17.37%, p = 0.002). These effects were lost when omega-3-PUFAs were removed (EDV: 11.36% to 0.59%, p = 0.003). In the second group, rosuvastatin alone failed to improve both EDV and EIV compared to baseline. However, adding omega-3-PUFAs to rosuvastatin, significantly improved EDV (-0.66% to 14.73%, p = 0.001) and EIV (11.02% to 24.5%, p = 0.001). Addition of omega-3-PUFAs further improved the lipid profile (triglycerides 139 to 91 mg/dl, p = 0.006, low-density lipoprotein cholesterol 116 to 88 mg/dl, p = 0.014). CONCLUSIONS: Combined therapy with omega-3-PUFAs and rosuvastatin improves endothelial function in South Asian subjects with dyslipidemia and endothelial dysfunction

BACKGROUND: No direct comparisons exist of the renal tolerability of the low-osmolality contrast medium iopamidol with that of the iso-osmolality contrast medium iodixanol in high-risk patients. METHODS AND RESULTS: The present study is a multicenter, randomized, double-blind comparison of iopamidol and iodixanol in patients with chronic kidney disease (estimated glomerular filtration rate, 20 to 59 mL/min) who underwent cardiac angiography or percutaneous coronary interventions. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2 to 5 days after receiving medications. The primary outcome was a postdose SCr increase > or = 0.5 mg/dL (44.2 micromol/L) over baseline. Secondary outcomes were a postdose SCr increase > or = 25%, a postdose estimated glomerular filtration rate decrease of > or = 25%, and the mean peak change in SCr. In 414 patients, contrast volume, presence of diabetes mellitus, use of N-acetylcysteine, mean baseline SCr, and estimated glomerular filtration rate were comparable in the 2 groups. SCr increases > or = 0.5 mg/dL occurred in 4.4% (9 of 204 patients) after iopamidol and 6.7% (14 of 210 patients) after iodixanol (P=0.39), whereas rates of SCr increases > or = 25% were 9.8% and 12.4%, respectively (P=0.44). In patients with diabetes, SCr increases > or = 0.5 mg/dL were 5.1% (4 of 78 patients) with iopamidol and 13.0% (12 of 92 patients) with iodixanol (P=0.11), whereas SCr increases > or = 25% were 10.3% and 15.2%, respectively (P=0.37). Mean post-SCr increases were significantly less with iopamidol (all patients: 0.07 versus 0.12 mg/dL, 6.2 versus 10.6 micromol/L, P=0.03; patients with diabetes: 0.07 versus 0.16 mg/dL, 6.2 versus 14.1 micromol/L, P=0.01). CONCLUSIONS: The rate of contrast-induced nephropathy, defined by multiple end points, is not statistically different after the intraarterial administration of iopamidol or iodixanol to high-risk patients, with or without diabetes mellitus. Any true difference between the agents is small and not likely to be clinically significant

OBJECTIVE: To test the hypothesis that pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, will improve endothelial function in non-diabetic subjects with coronary artery disease, we conducted a prospective study to evaluate the effect of this medication on the brachial artery vasomotor function and circulating markers of endothelial activation. METHODS: Baseline characteristics were collected. After initial endothelial function assessment, patients were treated with pioglitazone hydrochloride 30 mg daily. The medication was continued for 12 weeks and endothelial function was reassessed as well as the inflammatory markers. The study medication then was stopped, and all the tests were repeated 12 weeks later. RESULTS: Seventeen subjects completed all three-study phases. Mean age was 58 (range: 36-77 years). Compared with the baseline, the endothelium-dependent vasodilation improved significantly with the treatment (p < 0.001) from 4.4 +/- 3.9 to 8.4 +/- 4.1%, a relative increase of 91%. After withdrawal of treatment, the endothelium-dependent vasodilation returned towards baseline values. There was no change in endothelium-independent vasodilatation (12.27 +/- 6.35 to 13.9 +/- 9.23%, to 12.42 +/- 5.35%, p = 0.177). The urine asymmetric dimethlyarginine levels decreased significantly with the treatment, but also returned to the initial values after the wash-out period (1.27 +/- 0.5 micromol/ml to 0.97 +/- 0.3 micromol/ml to 1.34 +/- 0.5 micromol/ml, p = 0.017). No difference in the lipid profile, C-reactive protein, erythrocyte sedimentation rate, or fibrinogen levels was seen. CONCLUSION: Pioglitazone rapidly improves endothelial function in non-diabetic patients with coronary artery disease. This improvement is associated with a change in mean urinary asymmetric dimethylarginine levels, although a cause and effect cannot be determined from this investigation.

Bilateral stenting of the common iliac arteries via the radial access route, in the same setting, is presented in this case report. Radial access limits bleeding complications, avoids the crossover technique and allows same-day discharge

OBJECTIVE: Radial artery spasm remains a major complication of transradial coronary interventions. The aim of this study was to compare the efficacy of three different intra-arterial vasodilating cocktails in reducing the incidence of radial artery spasm in patients undergoing transradial coronary angiography. The secondary goal was to assess the predictors of arterial spasm in this large group of patients. METHODS: A total of 379 patients undergoing the procedure were randomly enrolled in 1 of 3 groups. Every patient in each of the 3 groups received intra-arterial heparin, lidocaine and diltiazem. Along with that, patients in Group A received nitroglycerin; patients in Group B received nitroprusside instead of nitroglycerin; and patients in Group C received both nitroglycerin and nitroprusside. A single experienced operator, blinded to the study drug, subjectively determined the presence of spasm. RESULTS: Of 379 patients, a total of 44 patients (11.6%) experienced spasm. The occurrence of spasm was similar, independent of the vasodilator cocktail used (Group A: 12.2%, Group B: 13.4%, Group C: 9.5%; p = 0.597). After multivariate analysis, the following variables were found to be independent predictors of spasm: radial artery diameter (RD)/height index (p = 0.005), RD/BSA index (p = 0.012), and sheath outer diameter (OD)/RD index (p = 0.024). CONCLUSION: In this prospective, randomized trial, the addition of a direct nitric oxide donor to nitroglycerin in an antispastic cocktail did not reduce the risk of spasm, and the use of nitroglycerin was found to be as effective as nitroprusside. Also, morphometric and mechanical factors play a significant role in predicting the occurrence of radial spasm. The sex of the patient, presence of diabetes, body surface area and smoking history appeared to play no role in predicting the occurrence of radial spasm

There is controversy concerning the prognostic significance of conduction delays that occur after aortic valve replacement (AVR). We retrospectively reviewed 389 consecutive patients who underwent AVR at our institution between April 1995 and March 1997. Adverse events were defined as the occurrence of complete atrioventricular block, syncope, or sudden cardiac death. Among 262 patients included in our database, 31 (11.8%) had a preoperative bundle branch block (BBB) and 41 (15.6%) developed new BBB postoperatively. At a mean follow-up of 54 months, the event rate was 1.6% (3 of 190) in patients with no BBB versus 17% (7 of 41, p = 0.0004) in patients who developed new BBB after surgery. There were 4 events (4 of 15 = 26.6%, p = 0.0006) in patients who developed new left BBB and 3 (3 of 26, 11.5%, p = 0.02) in those who developed new right BBB after AVR. There was also an increased adverse event rate in patients who had preoperative BBB (3 of 31, 9.7%, p = 0.037). By multivariate analysis, a new and persistent BBB acquired after surgery was the only independent predictor of adverse events during follow-up (odds ratio 8.85, p = 0.0004). The highest event rate was seen in patients who developed new left BBB and left axis deviation after surgery. Most events occurred during the first year of follow-up. A new and persistent BBB acquired after AVR is associated with an increased adverse event rate. This finding suggests that early prophylactic pacemaker implantation should be considered in these patients