Anna De Fazio

Hypertriglyceridemia and the apolipoprotein CIII gene locus: lack of association with the variant insulin response element in Italian school children

Hypertriglyceridemia is a common metabolic disorder with a major inherited component. In some individuals the condition is suspected to occur as a result of overproduction of apolipoprotein (apo)CIII, a major constituent of triglyceride-rich lipoproteins. Population studies have established an association with the apoCIII gene but the identity of the causal mutation remains unknown. In the present study we have examined a series of six 5′ polymorphic nucleotides (G–935 to A, C–641 to A, G–630 to A, deletion of T–625, C–482 to T, and T–455 to C) that lie within the promoter region of the apoCIII gene for evidence of possible involvement in disease susceptibility. The polymorphic nucleotides at positions –455 and –482 reside within a negative insulin-response element. We show, in a community-based sample of 503 school children, that a DNA polymorphism (S2 allele) within the 3′-noncoding region of the apoCIII gene was associated with elevated apoCIII and triglyceride levels, but that the polymorphic nucleotides of the promoter were not. In addition, no obvious effect of any extended apoCIII promoter haplotype on plasma apoCIII or triglyceride levels, over and above that conferred by the presence of the S2 polymorphic nucleotide, was detected. These results demonstrate that none of the 5′ apoCIII polymorphisms can account for the association of the apoCIII gene locus with hypertriglyceridemia and, moreover, owing to linkage disequilibrium, raise the possibility that the region conferring susceptibility maps downstream, rather than upstream, of the apoCIII gene promoter sequences.

Differences of regional coronary flow reserve assessed by adenosine thallium-201 scintigraphy early and six months after successful percutaneous transluminal coronary angioplasty or stent implantation

This study assesses regional coronary flow reserve using adenosine thallium-201 scintigraphy early and 6 months after angiographically successful percutaneous transluminal coronary angioplasty (PTCA) or stent implantation. Seventeen consecutive men with a significant isolated left anterior descending coronary artery stenosis were scheduled for repeat coronary angiography and adenosine-planar thallium-201 scintigraphy within 24 hours and 6 months after successful PTCA (n = 8) or stent implantation (n = 9). After background subtraction, left ventricular segmental uptake was semiquantitatively assessed on thallium images. The perfusion defect severity was scored from 0 (normal) to 3. Coronary angiograms were analyzed using an automated edge contour detection computer analysis system. Data are expressed as mean value +/- 1 SD, and proportions as percentage. The residual narrowing was 17 +/- 8% after PTCA and 9 +/- 2% after stent implantation (p = 0.02). Twenty-four hours after the procedure, hypoperfused segments were detected in all patients (100%) and in 4 patients (44%) (p = 0.05), respectively. The total number of hypoperfused segments was greater after PTCA than after stent implantation (16 [40%] vs 7 [16%], p = 0.001, respectively) as was the perfusion defect severity (4.4 +/- 3.1 vs 1 +/- 1.2, p = 0.006). Six months after the procedure, 3 of the 5 patients who had undergone PTCA without restenosis still had reversible perfusion defects. None of the stent-treated patients had restenosis or reversible perfusion defects (p = 0.05). Among PTCA-treated patients without restenosis, the total number of hypoperfused segments and the perfusion defect severity were 9 of 25 (36%) and 0.8 +/- 0.8, respectively. Thus, a regional reduction in coronary flow reserve, occasionally observed early after successful stent implantation, is probably due to a transient alteration of small coronary vessels, as was also supported by the absence of perfusion defects 6 months after the procedure. The more severe impairment of regional coronary flow reserve observed early after successful PTCA is probably also due to angiographic underestimation of the residual stenosis, as suggested also by the persistence of reversible perfusion defects 6 months after the procedure in a few patients.

Risk factors in schoolchildren associated with a family history of unheralded myocardial infarction or uncomplicated stable angina in male relatives.

OBJECTIVES The aim of this study was to compare risk factors for coronary atherosclerosis in children with a family history of unheralded myocardial infarction or uncomplicated stable angina. BACKGROUND In patients with unheralded myocardial infarction, coronary atherosclerosis might have a greater tendency to cause acute coronary occlusion than in patients with uncomplicated stable angina, suggesting the possibility of different risk factors in these two groups of patients. METHODS Serum lipid levels were compared in children with a family history of unheralded myocardial infarction (236 children) or uncomplicated stable angina (48 children) or no family history of ischemic heart disease (613 children). RESULTS Mean (+/- 1 SD) total serum cholesterol was higher in children with a family history of myocardial infarction than in control subjects (161 +/- 28 vs. 154 +/- 25 mg%, p < 0.01). In children with a family history of stable angina, mean total serum cholesterol (159 +/- 25 mg%) was similar to that in children with family history of myocardial infarction. High density lipoprotein cholesterol and apolipoprotein A-I were higher in children with family history of stable angina than in children with family history of myocardial infarction and control subjects (69 +/- 18 vs. 61 +/- 13 and 60 +/- 13 mg%, p < 0.01; 143 +/- 23 vs. 130 +/- 18 and 129 +/- 18 mg%, p < 0.01, respectively). In children with a family history of myocardial infarction, the low density/high density lipoprotein cholesterol ratio was significantly higher than in control subjects (1.53 +/- 0.64 vs. 1.44 +/- 0.56, p < 0.05). Conversely, in children with a family history of stable angina, this ratio (1.24 +/- 0.51) was significantly lower (p < 0.05) than in control subjects. CONCLUSIONS Risk factors for coronary athersclerosis in children with a family history of unheralded myocardial infarction are different from those in children with a family history of uncomplicated stable angina. Higher levels of apolipoprotein A-I early in life might reduce the risk of acute coronary syndromes.

Peak exercise left ventricular performance in normal subjects and in athletes assessed by first-pass radionuclide angiography

The role of Frank-Starling law of the heart in determining the increase in cardiac output during exercise in humans is still controversial (e.g., the mechanisms responsible for the enhancement of left ventricular [LV] filling during the shortened diastolic interval). Ten weight lifters, 12 swimmers and 12 sedentary subjects who underwent maximal upright bicycle exercise testing were studied. First-pass radionuclide angiography was performed both at rest and at peak exercise using a multicrystal gamma camera. Compared with resting values, heart rate and cardiac index at peak exercise increased by 101 +/- 16 beats/min (p less than 0.001) and 6.7 +/- 2.8 liters/min/m2 (p less than 0.001) in weight lifters, by 96 +/- 9 beats/min (p less than 0.001) and 9.5 +/- 2 liters/min/m2 (p less than 0.001) in swimmers, and by 103 +/- 9 beats/min (p less than 0.001) and 7.3 +/- 1.8 liters/min/m2 (p less than 0.001) in sedentary subjects. Stroke volume increased by 20.5 +/- 9.8 ml/m2 (p less than 0.001) in swimmers only. End-diastolic volume at peak exercise did not change in weight lifters and in swimmers; it decreased by 8.2 +/- 8.6 ml/m2 (p less than 0.01) in sedentary subjects. A significant correlation was found between the decrease in end-systolic volume and the increase in peak rapid filling rate at peak exercise in all 3 groups (r = 0.65, p less than 0.05 in weight lifters; r = 0.59, p less than 0.05 in swimmers; r = 0.67, p less than 0.05 in sedentary subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of Cardiovascular Events by Inflammatory Markers in Patients Undergoing Carotid Stenting

OBJECTIVE To assess whether inflammatory markers predict atherosclerotic disease activity after carotid treatment in patients with severe carotid stenosis and nonsignificant coronary artery disease undergoing carotid stenting. PATIENTS AND METHODS From March 1, 2004, to September 30, 2005, a total of 55 consecutive patients (mean ± SD age, 69±8.3 years; 26 men) with severe carotid stenosis and nonsignificant coronary artery disease were treated with carotid stent implantation. Patients were followed up for a period of 5 years for the occurrence of cardiovascular events. RESULTS A significant correlation between quantitative analysis of debris entrapped in the filters and inflammatory markers was found. Moreover, the number of particles per filter, the total particles area, and the mean particle axis per filter were significantly higher in patients with clinical events at the follow-up compared with patients without events (87 vs 32, P=.006; 50,118.7 vs 17,782, P=.002; 33.9 vs 30.2, P=.03). At 5-year follow-up we recorded cardiovascular or neurologic events in 11 of the 55 patients (20%). Higher preprocedural levels of high-sensitivity C-reactive protein, interleukin 6 soluble receptor, and interleukin 6 were significantly associated with clinical events at follow-up (P<.001, P=.05, and P=.02, respectively). In particular high-sensitivity C-reactive protein measured at 24 and 48 hours after carotid stenting showed a significant correlation with clinical events (P=.001). Also preprocedural intracellular adhesion molecule 1 and circulating vascular cell adhesion molecule 1 blood concentrations were significantly correlated with a worse prognosis at follow-up (P=.04 and P=.03, respectively). CONCLUSION In patients with severe carotid stenosis and nonsignificant coronary artery disease, inflammation is associated with atherosclerotic disease activity and a worse prognosis. Interleukin 6, interleukin 6 soluble receptor, intracellular adhesion molecule 1, vascular cell adhesion molecule 1, and high-sensitivity C-reactive protein levels at baseline and 24 and 48 hours after carotid stenting are predictive of neurologic and cardiovascular events at follow-up.

Percutaneous Repair of Post-myocardial Infarction Ventricular Septal Rupture

Post-myocardial infarction ventricular septal rupture (VSR) is one of the most serious complications occurring in patients with ST elevation myocardial infarction. Although surgical repair with concurrent coronary artery bypass grafting (CABG) is considered the treatment of choice, it carries a very high morbidity and mortality rates. For this reason, surgical approach to all patients might not be reasonable, in particular when patients are critically ill or with multiple comorbidities. Percutaneous interventional approach appears to be safe and effective in patients with a chronic VSR or treated for a residual shunt after initial surgical closure. Immediate primary transcatheter closure in acute setting may also be considered an alternative and effective strategy in selected patients ensuring greater effectiveness and fewer complications compared to surgery. The timing of surgical or percutaneous intervention is critical: the presence of cardiogenic shock and closure in the acute phase after VSR diagnosis are important risk factors of mortality. Due to the high mortality rate, the use of percutaneous occluders has been investigated as an alternative approach. The treatment with dedicated device is in general successful with few procedure-related complications. This strategy is a less invasive alternative to surgical approach; however it needs to be applied on a case-by-case basis.

Difficult Cases and Complications from the Catheterization Laboratory: Left Atrial Appendage Closure Step-By-Step

A 68-year-old man with hypertension, dyslipidemia, chronic kidney disease, and history of hemorrhagic stroke was admitted to our hospital because of atrial fibrillation (AF). After transesophageal echocardiography (TEE) that excluded the presence of left atrial appendage (LAA) thrombus, he underwent electrical cardioversion with sinus rhythm restoration. Nevertheless, he presented at 1-month follow-up visit with atrial fibrillation. Due to the history of hemorrhagic stroke and the subsequent contraindication to anticoagulation therapy, he was identified as a candidate to percutaneous closure of LAA. TEE was performed before the procedure to rule out the presence of LAA thrombus and to assess the dimensions and the morphology of the LAA. The procedure was performed under general anesthesia and TEE guidance. After transseptal puncture of the fossa ovalis, a 22-mm Amplatzer Cardiac Plug (ACP) (AGA, St. Jude Medical) device was advanced in the LAA through a dedicated delivery system (12-Fr Amplatzer TorqVue 45 × 45 Delivery Sheath – AGA, St. Jude Medical). Once the correct implanting zone was localized, the device was released under fluoroscopic and echocardiographic guidance. A check for pericardial effusion at the end of the procedure was done by transthoracic echo (TTE). The patient was discharged the day after the procedure with long-term therapy with a daily 100-mg aspirin and 75-mg clopidogrel for 3 months. Endocarditis antibiotic prophylaxis was also recommended for at least 6 months (Figs. 19.1, 19.2, 19.3, 19.4, 19.5, 19.6, 19.7, 19.8, and 19.9).