Risk factors for contrast induced nephropathy: a study among Italian patients.

This study aimed to make a profile of patients at highest risk of developing contrast induced nephropathy (CIN) in order to take appropriate prevention measures. 591 patients undergoing coronary procedures were divided into two groups: patients with (CIN-group) and without (no-CIN) an increase in creatinine level equal or more than 25% from baseline values within 24-48 h after the coronary procedure. All patients underwent an accurate anamnesis, objective exam, hematochemical measurements, and diagnostic exams. The results of this study while confirming that, average age (p = 0.01), diabetes mellitus (p < 0.0001), base line renal insufficiency (p = 0.0001), diuretic therapy (p = 0.002), higher contrast doses (p = 0.01), are associated with a higher risk of contrast-induced nephropathy, also demonstrated that both clinical (p = 0.01) and subclinical (p < 0.0001) atherosclerosis, and higher preprocedural high sensitive C-reactive protein levels (hs- CRP) (p = 0.02) are risk factors for CIN.

Takotsubo cardiomiopathy after acute diarrhea.

Takotsubo cardiomyopaty is a recently described syndrome characterized by transient left ventricular dysfunction, mimicking an acute coronary syndrome and usually precipitated by a physical or emotional stress. We report the first case of Takotsubo cardiomyopathy after acute diarrhea in a man. It may be argued that severe diarrhea in predisposed individuals may cause an acute stress resulting in increased sympathetic activity leading to this syndrome. Probably the relationship between the adrenergic system and the heart is more complex than general thought and the stimuli which favor an autonomic imbalance and precipitate the syndrome are very disparate in clinical practice.

Analysis of N-terminal pro-B-type natriuretic peptide in patients with acute coronary syndromes.

BACKGROUND: The N-terminal portion of brain natriuretic peptide (NT-proBNP) has been identified as an indicator of prognosis in different cardiovascular diseases. The objective of this study was to determine the utility of measuring plasma NT-proBNP levels in patients with acute coronary syndromes. METHODS AND RESULTS: We studied 66 patients admitted in our division for acute coronary syndromes. Patients underwent a venous blood sample within 24 h from the admission to determine NT-proBNP levels. Increasing plasma levels of NT-proBNP (in tertiles) was associated with a greater history of hypertension and current smoking, whereas biochemical parameters were associated with higher level of creatine kinase-MB mass, cardiac troponin I, and renal insufficiency. We detected correlations between the values of NT-proBNP and several variables; positive correlations were found between the values of NT-proBNP and creatinine (r=+0354; P=0.0024), cardiac troponin I levels (r=0320; P=0.0111), and creatine kinase-MB mass values (r=0261; P=0.035). An interesting result of our study was a significantly longer hospitalization in those patients belonging to the third tertile compared with those belonging to the first one (P=0.02). Finally, we showed a higher N-terminal brain natriuretic peptide level in patients with poor outcome during the hospitalization (left-ventricular systolic dysfunction, recurrent ischemic events, or death) compared with those who did not (3204+/-1841 vs. 836+/-1136, P=0.003). CONCLUSION: Measurement of B-type natriuretic peptide provides predictive information during the hospitalization in patients with acute coronary syndromes.

TLR2 and age-related diseases: potential effects of Arg753Gln and Arg677Trp polymorphisms in acute myocardial infarction.

Inflammation is a key component of immune system. It is involved in both defense and pathophysiological events maintaining the dynamic homeostasis of host organism. Its function is controlled by innate immunity genes. Both their polymorphisms and environmental conditions give rise to different phenotypes in human population. Proinflammatory genotype may be beneficial in early life but not in old people. With advancing age, indeed, it increases the vulnerability and the intensity to inflammatory reactions responsible for the chronic inflammatory diseases, such as atherosclerosis and myocardial infarction (MI). Several studies have looked for detecting a genetic risk profile that might allow a pharmacogenomic approach to prevent and treat age-related diseases such as MI. We have evaluated the possible association between two polymorphisms of TLR2 gene-Arg677Trp and Arg753Gln-and MI. However, we found no association between TLR2 polymorphisms and MI.

[Usefulness of coronary angiography with multidetector computed tomography in the evaluation of aorto-coronary bypass patency]. / Utilità dell'angiografia coronarica eseguita mediante tomografia computerizzata multidetettore nel controllo della pervietà del bypass aortocoronarico.

BACKGROUND: Coronary angiography is actually the gold standard to visualize coronary artery bypass graft patency and to detect bypass stenoses. However, it is an invasive examination that makes use of X-ray emission and it may lead to deleterious effects even at low dosage. Therefore, it is still needed a non-invasive examination with good diagnostic accuracy for the follow-up of patients with coronary artery bypass grafts. The aim of this study was to evaluate the diagnostic accuracy of a 40-row multidetector computed tomography scanner for the assessment of bypass surgery versus coronary angiography. METHODS: Twenty-six consecutive patients (20 male, 6 female, mean age 65 years) and a total number of 68 coronary bypass grafts (25 arterial and 43 venous grafts, 111 anastomoses) were examined by 40-row multidetector computed tomography. RESULTS: It was possible to analyze coronary artery bypass graft patency for every patient. At coronary angiography 23 patients showed bypass stenoses or occlusion: 19 of them were correctly diagnosed by computed tomography (sensitivity 84%, specificity 100%). In particular, computed tomography showed a sensitivity of 90% and a specificity of 100% for coronary artery bypass grafts, whereas it showed a sensitivity of 88% and a specificity of 94% for anastomoses. CONCLUSIONS: On the basis of the results of our study, computed tomography is a valuable tool for assessing coronary artery bypass graft patency in patients with clinical suspect of coronary occlusion.

Peripheral atherosclerosis is associated with the occurrence of restenosis after percutaneous coronary intervention.

INTRODUCTION: The aim of our study was to evaluate, in patients with proven coronary artery disease (CAD) and treated with elective percutaneous coronary intervention (PCI), whether the coexistence of asymptomatic carotid and femoral atherosclerotic lesions would provide prognostic information in terms of occurrence of restenosis. METHODS: We studied 104 patients with CAD (M/F=77/27), mean age 60.5+/-9 years. All patients were treated with elective PCI. After PCI the suspicion of restenosis was confirmed by coronary angiography. All patients underwent ultrasound duplex scan of carotid and femoral-popliteal-tibial axis to detect atherosclerotic lesions. According to ultrasound results, patients were classified as normal, with increased intima-media thickness (IMT) or with asymptomatic plaque (AP). If carotid and femoral lesions coexisted (together with coronary ones) patients were considered to have multifocal atherosclerosis. RESULTS: About 90% of the patients had carotid lesions: 40% had carotid IMT and 50% AP. Femoral lesions were found in 72% of the population and in 41% there was an increased IMT and in 21% an increased AP. Prevalence of restenosis after PCI was 12.5%. Patients with restenosis had a significantly higher prevalence of asymptomatic carotid and/or femoral lesions than those without restenosis. The occurrence of restenosis was independently associated with the detection of carotid, femoral and multifocal atherosclerosis. CONCLUSION: The detection of carotid and/or peripheral atherosclerotic lesions in patients with CAD who underwent PCI may be a marker of increased risk. We believe that investigating these areas, by echo-Doppler duplex scanning, may be a cost-effective strategy in the work-up before elective PCI. It may allow identification of high-risk subgroups of patients, and enable the planning of patient-tailored therapeutic strategies and follow-up.

[Forty-slice multidetector computed tomography for non-invasive diagnostic approach to coronary artery disease]. / Approccio diagnostico non invasive con tomografia computerizzata multidetettore a 40 strati per lo studio della malattia aterosclerotica coronarica.

BACKGROUND: Multidetector computed tomography coronary angiography (MDCT-CA) is a non-invasive technique that clearly shows coronary anatomy and correctly identifies plaque location and morphology. In this study we assessed diagnostic accuracy of MDCT-CA in detectiong significant stenosis in patients with clinically relevant coronary tree disease. METHODS: . Fifty patients (38 males, 12 females, mean age 60.9 +/- 9.2 years) with atypical chest pain, stable or unstable angina pectoris, or non-ST-elevation myocardial infarction underwent MDCT-CA (Brilliance 40, Philips Medical Systems, Cleveland, OH, USA) within 3 days before diagnostic conventional coronary angiography. Inclusion criteria were sinus rhythm, heart rate <70 b/min, and ability to hold breath for more than 12 s. Exclusion criteria were known intolerance to contrast medium, serum creatinine >2 mg/dl, pregnancy, respiratory insufficiency, unstable clinical conditions, and severe heart failure. Beta-blockers were administered if heart rate was >70 b/min. To synchronize arrival of the contrast bolus (Iomeron 400, Bracco, Milan) in the coronary arteries with the start of the scan the bolus-tracking technique was used. Diagnostic accuracy was evaluated per segment, per vessel, and per patient. RESULTS: Mean heart rate during examination was 61.9 +/- 6.2 b/min; 618 segments were evaluated. The assessment was impaired by respiratory artifacts only in 1 patient (2%). MDCT-CA showed good sensitivity, specificity, and positive and negative predictive values in detecting significant coronary artery stenosis (94, 94, 91, and 96% per segment; 91, 97, 95, and 92% per vessel; 100, 100, 100, and 100% per-patient, respectively). CONCLUSIONS: Forty-slice MDCT-CA showed a good diagnostic capability in detecting significant coronary artery stenosis in patients referred to our institution for suspected or known significant coronary artery disease.

PECAM-1/CD31 in infarction and longevity.

Inflammation has recently proven to be associated with the pathogenesis of atherosclerosis and inflammatory genes are good candidates for the risk of developing atherosclerosis. The early phase of atherosclerosis involves the recruitment of inflammatory cells from the circulation and their transendothelial migration. This process is mainly mediated by cellular adhesion molecules, which are expressed by the vascular endothelium and by circulating leukocytes in response to several inflammatory stimuli. Adhesion of circulating cells to the arterial surface is among the first detectable events in atherogenesis. Cellular adhesion molecules, expressed by the vascular endothelium and by circulating leukocytes, mediate cell recruitment and their transendothelial migration. Platelet endothelial cellular adhesion molecule-1 (PECAM-1/CD31), involved in this migration, has been associated with the developmental course of atherosclerosis. Studies have investigated an association between coronary heart disease (CHD) and single nucleotide polymorphisms (SNP) located in functionally important domains of the PECAM-1/CD31 gene, with contrasting results. In particular, we previously analyzed for the following PECAM-1/CD31 SNP: Val125Leu, Asn563Ser, and Gly670Arg. The frequency of the Gly670Arg polymorphism was significantly higher in patients with myocardial infarction (MI), whereas the frequencies of the other two SNP (Leu125Val and Ser563Asn) were not significantly different between patients and controls. To check the validity of our results, we have analyzed the distribution of these SNP in centenarian men (age >99) from our homogeneous Sicilian population, since our previous studies have demonstrated that alleles associated with MI susceptibility are not included in the genetic background favoring longevity. We showed, as regard to polymorphisms of PECAM-1/CD31, that there were no significant differences between male patients affected by MI, male controls, and male centenarians. According to our hypothesis present results seemingly do not support a role for these SNP in conferring the susceptibility to MI at least in this Italian population.

Alpha1-antitrypsin heterozygosity plays a positive role in attainment of longevity.

Genes involved in cardiovascular diseases (CVD) play an opposite role in human longevity. The alpha1-antitrypsin (AAT) is a serine-protease inhibitor required for the prevention of proteolytic tissue damage, by neutrophil elastase. The role of AAT in CVD has not been definitively assessed and its effect on longevity has not yet fully been studied. To clarify these points, we have studied the distribution of AAT allele variants in 3 cohorts: 127 young patients affected by acute myocardial infarction (AMI), 255 young controls and 143 centenarians from Sicily. The Z allele frequency was most frequent in centenarians (13.3%), intermediate in healthy young controls (3.1%) and less frequent in AMI patients (1.2%) (P = 0.0000001). The heterozygous MZ genotype was significantly over represented in centenarians (38/143) and under represented in AMI patients (3/127) with intermediate values in young controls (16/255) (P = 0.0000001). After adjustment for well-recognized AMI risk factors, the MZ genotype still predicted a significant negative risk factor for developing AMI in the Sicilian population. Thus, our data show a positive role of MZ heterozygosity in attainment of successful ageing linked to the positive effects of this genotype versus the cardiovascular ischemic diseases.

Persistence of the altered polymorphonuclear leukocyte rheological and metabolic variables after 12 months in juvenile myocardial infarction.

Acute myocardial infarction (AMI) is associated with an elevated polymorphonuclear leukocyte (PMN) count and a PMN rheological impairment. In this study we evaluated two major rheological aspects (membrane fluidity and cytosolic Ca2+ concentration) in a group of young adults with AMI. We enrolled 41 AMI patients (39 men and 2 women; mean age 41.0 +/- 4.0 years), who were examined 5-10 days after AMI (T1) and 12 months later (T2). The membrane fluidity was obtained labelling granulocytes with the fluorescent probe 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and considering the degree of fluorescence polarization, inversely correlated to the membrane lipid fluidity. The cytosolic Ca2+ content was obtained marking PMN cells with the fluorescent probe Fura-2AM and considering the ratio between the Fura 2-Ca2+ complex and the unchelated Fura 2 fluorescence intensity. Both parameters were evaluated at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA) at the concentration of 4.5 muM, prolonged for 5 and 15 minutes. At T1 the PMN membrane fluidity and cytosolic Ca2+ content in AMI patients were respectively decreased and increased in comparison with control group. At T2 the membrane fluidity was not any more different from control subjects, but there was also a further increase in cytosolic Ca2+ content. In vitro, PMN activation caused no significant variation of these parameters in the control group, while in AMI patients membrane fluidity significantly decreased and cytosolic Ca2+ content increased not only during the initial stage, but also after 12 months. The long-term functional alteration of PMN cells observed in young adults with AMI confirms the role of these cells in the inflammatory response following AMI. In the light of these data, the use of molecules able to modulate granulocyte activity, such as calcium channel blockers or pentoxifylline, should be reconsidered in myocardial infarction, together with the usual pharmacological treatment.

Opposite role of pro-inflammatory alleles in acute myocardial infarction and longevity: results of studies performed in a Sicilian population.

The major trait characterizing offspring in centenarians is a reduction in the prevalence of cardiovascular disease. Because a pro-inflammatory genotype seems to contribute significantly to the risk of coronary heart disease, alleles associated with disease susceptibility would not be included in the genetic background favoring longevity, as suggested by our previous studies on inflammatory cytokines. To confirm whether genotypes of inflammatory molecules play an opposite role in atherosclerosis and longevity, we are studying the role of other proinflammatory alleles, such as pyrin and CCR5, in acute myocardial infarction and longevity. The results support the hypothesis that the genetic background favoring cardiovascular diseases is detrimental to longevity. In addition, they suggest that the centenarian genetic background may be useful for investigating genetic key components of age-associated diseases that are characterized by a multifactorial etiology.

Association between +1059G/C CRP polymorphism and acute myocardial infarction in a cohort of patients from Sicily: a pilot study.

Inflammation plays a role in all the phases of atherosclerosis, and increased production of the acute-phase reactant, C-reactive protein (CRP), predicts future cardiovascular events. Furthermore, CRP has been claimed to play a role in the pathogenesis of atherosclerosis; therefore, CRP polymorphisms might be associated with acute myocardial infarction (AMI). We have analyzed male patients affected by AMI and healthy age-related male controls from Sicily for +1059G/C CRP single-nucleotide polymorphism (SNP). There was a significantly higher frequency of +1059C SNP (P = 0.0008; OR 3.86) in patients compared to controls. CRP serum levels were significantly higher in C+ healthy subjects rather than in C- subjects (P = 0.0075). The results of the present pilot case-control study performed in a homogeneous caucasoid population suggest that +1059C CRP gene SNP is associated with AMI. In any case, the results of the present study should add to the growing body of evidence on the role of pro-inflammatory genotypes in unsuccessful aging, determining susceptibility to immune-inflammatory diseases such as coronary heart disease.

Role of the pyrin M694V (A2080G) allele in acute myocardial infarction and longevity: a study in the Sicilian population.

A proinflammatory genotype seems to contribute significantly to the risk of developing coronary heart disease (CHD). Conversely, the susceptibility alleles to inflammatory disease should be infrequent in the genetic background favoring longevity. In fact, in a modern environment, attainment of longevity is facilitated by an anti-inflammatory status. To evaluate whether inflammatory alleles of pyrin, the gene responsible for familial Mediterranean fever (FMF) may play an opposite role in CHD and in longevity, we examined three FMF-associated mutations, M694V (A2080G), M694I (G2082A), and V726A (T2177C), encoded by the FMF gene (MEFV) in 121 patients affected by acute myocardial infarction (AMI), in 68 centenarians, and in 196 age-matched controls from Sicily. None of the Sicilian subjects studied carried the V726A and the M694I FMF-related mutations. The proinflammatory M694V (A2080G) mutation was the only one we found, which was over-represented significantly in CHD patients and under-represented in oldest old, and intermediate values were in healthy, young controls. After adjustment for well-recognized AMI risk factors, the M694V allele still predicted a significant risk to develop AMI. So, according to these results, we suggest that carrying the proinflammatory M694V pyrin allele may increase the risk to develop AMI. Conversely, the wild-type pyrin genotype may predispose to a greater chance to live longer in a modern environment with reduced pathogen load and improved control of severe infections by antibiotics. All these data indicate a strong relationship among inflammation, genetics, CHD, and longevity.

Role of proinflammatory alleles in longevity and atherosclerosis: results of studies performed on -1562C/T MMP-9 in centenarians and myocardial infarction patients from Sicily.

Centenarians are characterized by marked delay or escape from age-associated diseases that cause mortality at earlier ages. Jointly, atherosclerosis and its complications, such as myocardial infarction (AMI), significantly contribute to mortality in the elderly. Inflammation is a key component of atherosclerosis and inflammatory genes are good candidates for the risk of the development of atherosclerosis. Genetic traits contribute to the risk of AMI and allelic variations in inflammatory genes should boost the risk of disease. If proinflammatory genotypes significantly contribute to the risk of AMI, alleles associated with disease susceptibility should not be included in the genetic background favoring longevity. Hence, genotypes of natural immunity should play an opposite role in atherosclerosis and longevity. Metalloproteinase (MMPs) are involved in tissue remodeling and therefore play a remarkable role in inflammation-based disease. MMPs are a family of Zn(2+)-dependent enzymes with proteolytic activity against connective tissue proteins such as collagens, proteoglycans, and elastin, which appear to play important roles in the development and progression of the atherosclerotic lesion. There is evidence indicating a role played by the MMPs in the weakening of atherosclerotic plaque which predisposes to lesion disruption. In this study we performed a genetic study on -1562C/T MMP-9 single nucleotide polymorphism (SNP) in order to discern a possible role in AMI. We analyzed the distribution of this SNP in 115 AMI patients, 123 controls, and 34 centenarians from Sicily. We found no significant differences in the genetic distribution and allelic frequency of -1562C/T MMP-9 SNP between the studied groups. The present results are not in agreement with our previous findings, strengthening our hypothesis that genetic background protection against cardiovascular disease is a relevant component of the longevity trait, at least in the generation of Italian male centenarians under study. However, present results do not exclude that differential expression of MMP-9 playing an opposite role in AMI and longevity because other kinds of regulation might be more relevant than those linked to the SNP under study.

Association between platelet glycoprotein Ib-alpha and myocardial infarction: results of a pilot study performed in male and female patients from Sicily.

Myocardial infarction (AMI) is a complex multifactorial disorder. Platelet adhesion and thrombosis are pivotal events in the development of atherosclerotic lesions. Occlusive thrombus is almost exclusively initiated by plaque rupture and adhesion of platelets to subendothelial von Willebrand factor (vWf) by its specific platelet receptor, the alpha-chain of glycoprotein (GP) Ib-IX-V complex of the human platelet-specific antigens (HPA). Two polymorphisms have been reported in the sequence of GPIb-alpha. The first, a C/T transition at nucleotide 1018 results in an amino acid dimorphism (Thr/Met) at residue 145 of GPIb-alpha, which is located within the vWF-binding domain of the receptor. The second is a T/C polymorphism in the Kozak sequence at position -5 from the initiator ATG. This affects the receptor density on the platelet surface. We assessed 1018 C/T and -5 T/C Kozak polymorphisms to see whether they are associated with AMI in homogeneous populations of Sicilian patients with AMI. To this end, we have analyzed the distribution of 1018 C/T and -5 T/C Kozak polymorphisms in 105 young Sicilian patients (<46 years) and 110 healthy age-related controls, by PCR-SSP and PCR-RFLP. Our results demonstrate no significant differences in the frequency of 1018 C/T and -5 T/C Kozak polymorphism between patients with AMI and controls. Stratifying by gender, there is no difference between male and female patients and control data. Thus, our results indicate that the HPA-2 polymorphisms are not associated with an increased risk for AMI at early onset (< 46 years) both in men and in women.

Two cases of tako-tsubo cardiomyopathy in Caucasians.

Tako-tsubo cardiomyopathy is a recently described disease characterized by chest pain, transient left ventricular dysfunction and specific electrocardiographic changes. The disease takes its name from the typical left apical ballooning observed at left ventriculogram. Tako-tsubo cardiomyopathy was first described by Sato in 1990. Since then sporadic cases were reported by Japanese authors, and only a few European publications are available. We describe 2 cases of patients affected by this syndrome.

Rupture of an aortic dissection into the right atrium in a patient with a previous aortic valve replacement: a case report.

We report the case of a 73-year-old man with a history of previous aortic valve replacement in 1990 and rupture of an aortic dissection into the right atrium. The patient was admitted to the emergency room because of chest pain, stopped not long after. The electrocardiogram did not show any signs of ischemia and myocardial enzymes were not increased. Transthoracic echocardiography revealed aortic root dilation (maximum diameter 60 mm) extended to the aortic arch, and the presence of a flow from the ascending aorta to the right atrium (evocative of a fistula between the two chambers). The aortic valvular prosthesis function was good. Transesophageal echocardiography confirmed an aorta-right atrium fistula. Cardiac catheterization did not show any luminal obstructions in the coronary arteries; there was a small shunt from the aorta to the right atrium. The ascending aorta and the aortic root were replaced with a Dacron graft. Right and left sinuses were reimplanted to the graft. The fistula was repaired with 4-0 pledgeted Prolene sutures. The surgeon's diagnosis was "type A aortic dissection in a patient with an ascending aorta aneurysm and an old ascending aorta-right atrium fistula".