Aldosterone, mortality, and acute ischaemic events in coronary artery disease patients outside the setting of acute myocardial infarction or heart failure.

BACKGROUND: Recent studies have demonstrated that aldosterone levels measured in patients with heart failure or acute myocardial infarction (MI) are associated with long-term mortality, but the association with aldosterone levels in patients with coronary artery disease (CAD) outside these specific settings remains unknown. In addition, no clear mechanism has been elucidated to explain these observations. The present study was designed to evaluate the relationship between the level of aldosterone and the risk of death and acute ischaemic events in CAD patients with a preserved left ventricular (LV) function and no acute MI. METHODS AND RESULTS: In 799 consecutive CAD patients referred for elective coronary angioplasty measurements were obtained before the procedure for: aldosterone (median = 25 pg/mL), brain natriuretic peptide (BNP) (median = 35 pg/mL), hsC-reactive protein (median = 4.17 mg/L), and left ventricular ejection fraction (mean = 58%). Patients with acute MI or coronary syndrome (ACS) who required urgent revascularization were not included in the study. The primary endpoint, cardiovascular death, occurred in 41 patients during a median follow-up period of 14.9 months. Secondary endpoints-total mortality, acute ischaemic events (acute MI or ischaemic stroke), and the composite of death and acute ischaemic events-were observed in 52, 54, and 94 patients, respectively. Plasma aldosterone was found to be related to BMI, hypertension and NYHA class, and inversely related to age, creatinine clearance, and use of beta-blockers. Multivariate Cox model analysis demonstrated that aldosterone was independently associated with cardiovascular mortality (P = 0.001), total mortality (P = 0.001), acute ischaemic events (P = 0.01), and the composite of death and acute ischaemic events (P = 0.004). Reclassification analysis, using integrated discrimination improvement (IDI) and net reclassification improvement (NRI), demonstrated incremental predictive value of aldosterone (P < 0.0001). CONCLUSION: Our results demonstrate that, in patients with CAD but without heart failure or acute MI, the level of aldosterone is strongly and independently associated with mortality and the occurrence of acute ischaemic events.

Metabolic syndrome and collateral vessel formation in patients with documented occluded coronary arteries: association with hyperglycaemia, insulin-resistance, adiponectin and plasminogen activator inhibitor-1.

AIMS: The metabolic syndrome (MS) is associated with an increased cardiovascular risk. Patients with the MS have endothelial dysfunction, decreased circulating adiponectin, and a high expression of angiogenic inhibitors such as plasminogen activator inhibitor-1 (PAI-1). We hypothesized that such patients, in the event of a coronary occlusion, might exhibit a less developed collateral circulation. METHODS AND RESULTS: Three hundred and eighty-seven consecutive patients with at least one coronary occlusion of a major coronary vessel at diagnostic angiography were prospectively enrolled. Collateral development was graded with validated angiographic methods. The MS was defined according to the ATP-III definition. Fasting glucose, adiponectin, insulin concentrations, and PAI-1 were measured at the time of angiography. MS was associated with less developed collateral vessels (P = 0.005). In multivariable analysis adjusting for potential confounding factors including the duration of coronary occlusion (P = 0.0001), fasting glycaemia (P = 0.0007), low adiponectin concentration (P = 0.01), insulin-resistance (HOMA-IR; P = 0.01), high circulating PAI-1 concentration (P = 0.01), and hypertension (P = 0.008) were independently associated with poor coronary collateral vessel development. CONCLUSION: This study shows that in patients with coronary occlusion, collateral circulation is impaired in patients with the MS. This association is partly related to fasting glycaemia and to key parameters linked to insulin resistance.

Comparison of Immediate With Delayed Stenting Using the Minimalist Immediate Mechanical Intervention Approach in Acute ST-Segment-Elevation Myocardial Infarction: The MIMI Study.

BACKGROUND: Delayed stent implantation after restoration of normal epicardial flow by a minimalist immediate mechanical intervention aims to decrease the rate of distal embolization and impaired myocardial reperfusion after percutaneous coronary intervention. We sought to confirm whether a delayed stenting (DS) approach (24-48 hours) improves myocardial reperfusion, versus immediate stenting, in patients with acute ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS AND RESULTS: In the prospective, randomized, open-label minimalist immediate mechanical intervention (MIMI) trial, patients (n=140) with ST-segment-elevation myocardial infarction ≤12 hours were randomized to immediate stenting (n=73) or DS (n=67) after Thrombolysis In Myocardial Infarction 3 flow restoration by thrombus aspiration. Patients in the DS group underwent a second coronary arteriography for stent implantation a median of 36 hours (interquartile range 29-46) after randomization. The primary end point was microvascular obstruction (% left ventricular mass) on cardiac magnetic resonance imaging performed 5 days (interquartile range 4-6) after the first procedure. There was a nonsignificant trend toward lower microvascular obstruction in the immediate stenting group compared with DS group (1.88% versus 3.96%; P=0.051), which became significant after adjustment for the area at risk (P=0.049). Median infarct weight, left ventricular ejection fraction, and infarct size did not differ between groups. No difference in 6-month outcomes was apparent for the rate of major cardiovascular and cerebral events. CONCLUSIONS: The present findings do not support a strategy of DS versus immediate stenting in patients with ST-segment-elevation infarction undergoing primary percutaneous coronary intervention and even suggested a deleterious effect of DS on microvascular obstruction size. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01360242.

A common variant of endothelial nitric oxide synthase (Glu298Asp) is associated with collateral development in patients with chronic coronary occlusions.

BACKGROUND: Experimental studies support an important role for endothelial nitric oxide synthase (eNOS) in the regulation of angiogenesis. In humans, a common polymorphism exists in the eNOS gene that results in the conversion of glutamate to aspartate for codon 298. In vitro and in vivo studies have suggested a decreased NOS activity in patients with the Asp298 variant. We hypothesized that a genetic-mediated decreased eNOS activity may limit collateral development in patients with chronic coronary occlusions. METHODS: We selected 291 consecutive patients who underwent coronary angiography and who had at least one chronic (>15 days) total coronary occlusion. Collateral development was graded angiographically using two different methods: the collateral flow grade and the recipient filling grade. Genomic DNA was extracted from white blood cells and genotyping was performed using previously published techniques. RESULTS: Collateral development was lower in patients carrying the Asp298 variant than in Glu-Glu homozygotes (collateral flow grade: 2.64 +/- 0.08 and 2.89 +/- 0.08, respectively, p = 0.04; recipient filling grade: 3.00 +/- 0.08 and 3.24 +/- 0.07, respectively, p = 0.04). By multivariable analysis, three variables were independently associated with the collateral flow grade: female gender, smoking, and the Asp298 variant (p = 0.03) while the Asp298 variant was the sole variable independently associated with the recipient filling grade (p = 0.03). CONCLUSION: Collateral development is lower in patients with the Asp298 variant. This may be explained by the decreased NOS activity in patients with the Asp298 variant. Further studies will have to determine whether increasing eNOS activity in humans is associated with coronary collateral development.

Pheochromocytoma unmasked by amisulpride and tiapride.

OBJECTIVE: To describe the unmasking of pheochromocytoma in a patient treated with amisulpride and tiapride. CASE SUMMARY: A 42-year-old white man developed acute hypertension with severe headache and vomiting 2 hours after the first doses of amisulpride 100 mg and tiapride 100 mg. Both drugs were immediately discontinued, and the patient recovered after subsequent nicardipine and verapamil treatment. Abdominal ultrasound showed an adrenal mass, and postoperative histologic examination confirmed the diagnosis of pheochromocytoma. DISCUSSION: Drug-induced symptoms of pheochromocytoma are often associated with the use of substituted benzamide drugs, but the underlying mechanism is unknown. In our case, use of the Naranjo probability scale indicated a possible relationship between the hypertensive crisis and amisulpride and tiapride therapy. CONCLUSIONS: As of March 24, 2005, this is the first reported case of amisulpride- and tiapride-induced hypertensive crisis in a patient with pheochromocytoma. Physicians and other healthcare professionals should be aware of this potential adverse effect of tiapride and amisulpride.

Serum hepatocyte growth factor levels predict long-term clinical outcome after percutaneous coronary revascularization.

AIMS: To evaluate, in patients referred for elective percutaneous coronary revascularization (PCR) without heparin pre-treatment, the relationship between baseline serum levels of the angiogenic growth factors, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), and clinical outcome. METHODS AND RESULTS: In 488 consecutive patients undergoing elective coronary angioplasty, hsC-reactive protein, HGF, and VEGF levels were measured before heparin administration. The primary endpoint, a composite of death and myocardial infarction, occurred in 44 patients at a median follow-up of 14.9 months. At baseline, VEGF levels were related to C-reactive protein levels and inversely related to age; HGF levels were related to C-reactive protein levels, diabetes, and recent clinical instability. In the univariate analysis, HGF had a significant positive relationship (P=0.003) with the primary endpoint. A similar trend was observed for VEGF (P=0.11). The only three variables significantly associated with the primary endpoint in the multivariable Cox model were HGF (P=0.004), C-reactive protein (P=0.007), and diabetes (P=0.04). CONCLUSION: Our results demonstrate that in patients, without heparin pre-treatment, referred for PCR, a high serum level of HGF is an independent predictor of clinical events during follow-up and is correlated with other surrogate measures of the activity of atherosclerosis.