Single administration of vildagliptin attenuates postprandial hypertriglyceridemia and endothelial dysfunction in normoglycemic individuals.

Postprandial hypertriglyceridemia impairs endothelial function and plays an important role in the development of atherosclerosis. The aim of the present study was to examine the postprandial effects of the dipeptidyl peptidase-4 inhibitor vildagliptin and the α-glucosidase inhibitor voglibose on endothelial dysfunction and lipid profiles following a single administration. A randomized cross-over trial using 11 normoglycemic individuals was performed. The postprandial effects of a single administration of vildagliptin (50 mg) or voglibose (0.3 mg) on endothelial function were analyzed using brachial artery flow-mediated dilation (FMD) and lipid profiles during fasting and 1.5 and 3 h after an oral cookie-loading test. Compared with voglibose, vildagliptin significantly suppressed postprandial endothelial dysfunction, (%FMD, -1.6±0.9 vildagliptin vs. -4.0±0.7 voglibose; P=0.01) and the postprandial incremental increase in the triglyceride level (28±18 vildagliptin vs. 51±26 mg/dl voglibose; P=0.01) 3 h after a cookie-loading test. In addition, vildagliptin significantly increased the levels of glucagon-like peptide-1 compared with voglibose 3 h after a loading cookie test (4.4±0.6 vs. 2.9±0.7 pmol/l, respectively; P=0.04). No significant differences in the levels of glucose, apolipoprotein B-48, glucagon or insulin were observed between vildagliptin and voglibose treatments. In conclusion, a single administration of vildagliptin attenuated postprandial endothelial dysfunction and postprandial hypertriglyceridemia, suggesting that vildagliptin may be a promising antiatherogenic agent.

Protective effect of eicosapentaenoic acid on insulin resistance in hyperlipidemic patients and on the postoperative course of cardiac surgery patients: the possible involvement of adiponectin.

Accumulated studies have shown that ω-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) have protective roles against inflammatory responses such as hyperlipidemia, diabetes mellitus (DM) and cardiovascular diseases. Here we examined the effects of administering EPA to hyperlipidemic patients and other patients undergoing cardiac surgery to determine whether this treatment would increase plasma EPA levels and to clarify the association between EPA treatment and adiponectin production in hyperlipidemic patients. We also assessed the effect of preoperative EPA administration on postoperative adverse events such as postoperative atrial fibrillation (POAF) and postoperative infection in the cardiac surgery patients. The EPA administration significantly increased the serum EPA concentrations in both patient populations (p＜0.001). In the hyperlipidemic patients, the EPA administration significantly increased plasma adiponectin levels (p＜0.05), accompanied by a decrease in insulin resistance designated by the HOMA-IR (homeostasis model assessment of insulin resistance) score (p＜0.05) and Hs-CRP (high sensitivity C-reactive protein) value (p＜0.05). In the cardiac surgery patients, no significant effect of EPA on cardiac adverse events such as POAF was observed. However, our results clearly demonstrated that both the neutrophil-to-lymphocyte ratio and the 2nd-line antibiotic requirement in the EPA group were significantly decreased compared to the untreated control group (p＜0.05). We suggest that EPA administration may exert anti-inflammatory effects in patients with hyperlipidemia and in those undergoing cardiac surgery, possibly through an increase in plasma adiponectin levels.

Relationship between activin A level and infarct size in patients with acute myocardial infarction undergoing successful primary coronary intervention.

BACKGROUND: Activin A, a member of the transforming growth factor-beta cytokine family, has been suggested to have a role in inflammation. We examined the serum level of activin A in patients with acute myocardial infarction (AMI) undergoing successful primary percutaneous coronary intervention (PCI). METHODS: The subjects were 30 AMI patients, 20 stable angina pectoris (AP) patients and 20 normal subjects. The serum levels of activin A in AMI patients were measured before PCI and on days 1, 2, 7, and 14. RESULTS: Activin A levels before PCI in AMI patients (557+/-255 pg/ml) showed a significantly higher value than those in AP patients (364+/-159 pg/ml) and control subjects (316+/-144 pg/ml). Increased serum activin A level before PCI was decreased on day 2, and then gradually re-elevated on days 7 and 14. The serum activin A level before PCI was correlated with log-transformed peak creatine kinase (CK) as a surrogate of infarct size (r=0.48, p=0.008). Stepwise multiple regression analysis demonstrated that the serum activin A level before PCI was an independent predictor of peak CK. CONCLUSIONS: The serum activin A level, increased in AMI, was positively correlated with peak CK and CK-MB levels which are measures of infarction size.

Coronary pressure measurement to identify the lesion requiring percutaneous coronary intervention in equivocal tandem lesions.

OBJECTIVES: No reliable methods are available for determining application of percutaneous coronary intervention for treatment of equivocal tandem lesions. We investigated whether coronary pressure measurement is useful for determining the lesion that requires percutaneous coronary intervention in tandem lesions. METHODS: We measured coronary pressure in 72 consecutive patients with tandem lesions. Myocardial fractional flow reserve (FFRmyo) was obtained as the ratio of coronary pressure distal to the lesion/aortic pressure under maximal hyperemia. If the FFRmyo across the tandem lesions was >or=0.75, we deferred percutaneous coronary intervention for the lesion. When the tandem lesions showed FFRmyo<0.75, percutaneous coronary intervention was performed on the lesion that showed angiographically higher stenosis. When FFRmyo was <0.75 after one-lesion percutaneous coronary intervention, this intervention was carried out on the remaining lesion. RESULTS: We deferred percutaneous coronary intervention for 26 patients (36.1%), and performed percutaneous coronary intervention in 46 patients (63.8%). We performed percutaneous coronary intervention for one lesion in 19 patients (26.4%) and for both lesions in 27 patients (37.5%). Among patients in whom percutaneous coronary intervention was deferred, only two patients (7.7%) required target lesion revascularization during the follow-up period. This rate was not higher than that in the 46 patients who underwent percutaneous coronary intervention for one or two lesions (six patients, 13.0%). Similarly, the target lesion revascularization in lesions with initially deferred percutaneous coronary intervention (5.6%, 4/71 lesions) was not higher than that in lesions with percutaneous coronary intervention (15.1%, 11/73 lesions). Major cardiac events, cardiac death and acute myocardial infarction, did not occur in patients with deferred percutaneous coronary intervention and in those with percutaneous coronary intervention during the follow-up period. CONCLUSION: Our results clearly showed that coronary pressure measurement was clinically useful for identifying equivocal tandem lesions requiring percutaneous coronary intervention.

Nicorandil reduces the incidence of minor cardiac marker elevation after coronary stenting.

BACKGROUND: Minor cardiac marker elevation after percutaneous coronary intervention has long-term prognostic significance. We examined whether nicorandil, a nicotinamide-nitrate ester, reduces the incidence of minor cardiac marker elevation after coronary stenting. METHODS: Patients (n=192) undergoing coronary stenting were randomly assigned to receive nicorandil (nicorandil group, n=91) or vehicle (control group, n=101). Nicorandil (2 mug/kg/min, intravenously) was administered immediately after the patients were transferred into the catheterization laboratory and continued for 6 h. We measured the serum concentrations of creatine kinase isoenzyme MB (CK-MB) before, immediately after, and 6, 12, and 24 h after the procedure, and those of cardiac troponin T (cTnT) 24 h after the procedure. RESULTS: There was no significant difference in clinical background between the 2 groups. The nicorandil group showed a significantly lower incidence of CK-MB elevation (>1x upper limit of control range, 20 IU/l) than the control group (8.8% vs 21.8%, p<0.05). The levels of serum CK-MB in the nicorandil group were significantly lower than those in the control group (13.4+/-5.7 vs 16.5+/-9.7 IU/l, p<0.01). Similarly, the nicorandil group showed a significantly lower incidence of cTnT elevation [>1x (0.1 ng/ml) or >2x (0.2 ng/ml)] upper limit of control range than the control group (14.3% vs 26.7%, p<0.05, or 7.7% vs 17.8%, p<0.05). Serum cTnT levels were also significantly lower in the nicorandil group than in the control group (0.05+/-0.10 vs 0.15+/-0.36 ng/ml, p<0.05). CONCLUSIONS: The results demonstrated that nicorandil reduces minor cardiac marker elevation after coronary stenting.

Coronary pressure measurement to determine treatment strategy for equivocal left main coronary artery lesions.

It is often hard to select a treatment strategy for equivocal left main coronary artery (LMCA) disease. We investigated the usefulness of coronary pressure (CP) measurement for determining the treatment strategy in intermediate LMCA disease. We measured CP in 15 consecutive patients with equivocal LMCA disease (age 67.6 +/- 7.5 years, 14 males). Myocardial fractional flow reserve (FFRmyo) was obtained as the ratio of CP distal to the lesion/aortic pressure under maximal coronary dilation. Patients with FFRmyo > or = 0.75 and <0.75 received medical therapy and coronary artery bypass grafting (CABG), respectively, and were followed up for 32.5 +/- 9.7 (20-47) months. Eight patients received medical therapy and 7 patients underwent CABG in accordance with the FFRmyo criteria noted above. FFRmyo of the LMCA was 0.91 +/- 0.01 and 0.61 +/- 0.03 in patients who received medical and surgical therapy, respectively. Neither reference vessel diameter, minimal lumen diameter, nor percent diameter stenosis was significantly different between patients who received medical and surgical therapy. During the follow-up period, no patients with medical therapy showed symptoms due to the LMCA lesion. Similarly, 5 of 7 patients with CABG showed improvement of symptoms and the remaining 2 patients were hospitalized with congestive heart failure. No cardiac death was recorded in the patients with medical or surgical therapy. In conclusion, the present results clearly demonstrated that CP is clinically useful for determining the treatment strategy for equivocal LMCA lesions but coronary angiography is not.

Significant correlation of recruitable coronary collateral blood flow determined by coronary wedge pressure with ST-segment elevation during coronary occlusion.

OBJECTIVES: Quantitative assessment of coronary collateral blood flow can be archived by measuring coronary pressure. We studied the relationships between recruitable coronary collateral blood flow and electrocardiographic changes during percutaneous coronary intervention (PCI). METHODS: We measured coronary pressure during coronary occlusion with PCI in 119 patients with left anterior descending coronary artery stenosis. During balloon inflation, the electrocardiogram was continuously recorded. The ST-segment elevation in the most elevated lead was defined as MaxST and the sum of the maximal ST elevation in leads V2-V4 was defined as sumST. Fractional collateral flow (Qc/Q(N)) was calculated as the coronary wedge pressure divided by the mean aortic pressure. Myocardial ischemia was defined as an ST-segment shift >0.1 mV in any of the V2, V3 or V4 leads. RESULTS: A significant relationship between Qc/Q(N) and MaxST was observed (r=-0.455, P<0.0001). Similarly, Qc/Q(N) was significantly correlated with sumST (r=-0.477, P<0.0001). The receiver operating characteristic curve showed that a cut-off value of 0.27 for Qc/Q(N), with sensitivity of 71.4% and specificity of 76.2%, was an indicator of electrophysiologically sufficient recruitable coronary collateral blood flow for prevention of ischemia during coronary obstruction. Qc/Q(N) values during the first, second, third and fourth inflation were not significantly different. CONCLUSIONS: Qc/Q(N) could be clinically useful for determining whether there is electrophysiologically sufficient recruitable coronary collateral blood flow for prevention of ischemia during coronary obstruction. Repeat transient coronary occlusion during PCI did not lead to increased collateral blood flow.