Metabolic syndrome and chronic simvastatin therapy enhanced human cardiomyocyte stress before and after ischemia-reperfusion in cardio-pulmonary bypass patients.

Metabolic syndrome (MetS) is a set of metabolic alterations including high levels of low-density lipoprotein (LDL), which increase the risk of cardiomyopathy often leading to surgery. Despite inducing myopathy, statins are widely used to lower LDL. Cardiopulmonary bypass (Cpb) causes oxidative stress and metabolic injury, altering mitochondrial expression (Grp75) and endoplasmic reticulum (Grp78) chaperones, apoptotic enzymes (Bcl2 family) and increasing cardiomyocyte lipid/lipofuscin storage. We believe that cardiomyocytes from patients with MetS may be more sensitive to surgical stress, in particular after simvastatin therapy (MetS+Stat). The study group included ten patients with MetS, ten patients with Mets+Stat and ten healthy subjects. Myocardial biopsies were obtained both before and after-Cpb. Grp75, Grp78, Bax, Bcl2, lipids, lipofuscin and fibrosis were evaluated by immuno/histochemistry. MetS cardiomyocytes had higher Grp75, Bax, fibrosis and lipofuscin. MetS+Stat had lower Grp75 and higher Grp78 expressions, high Bax, fewer fibrosis and higher lipofuscin content. Cpb did not vary the fibrosis and lipids/lipofuscin content, although it influenced the chaperones and Bax expression in all groups. These changes were more profound in patients with MetS and even more so in patients with MetS+Stat. The results suggest that MetS and MetS+Stat cardiomyocytes were more highly stressed after-Cpb. Interestingly, simvastatin caused high stress even before-Cpb.

Interaction of homocysteine and conventional predisposing factors on risk of ischaemic stroke in young people: consistency in phenotype-disease analysis and genotype-disease analysis.

BACKGROUND AND OBJECTIVES: Whether the association between mild hyperhomocysteinaemia and ischaemic stroke is the consequence of a predisposing genetic background or is due to the confounding influence of established predisposing factors remains to be determined. METHODS: Plasma total homocysteine (tHcy) concentration and the distribution of the C677T genotypes of the methylenetetrahydrofolate reductase gene (MTHFR) were compared in 174 consecutive patients with stroke aged <45 years and 155 age and sex-matched controls. The effect of conventional risk factors on the relationship between phenotype-disease and genotype-disease was analysed by two-way and three-way interaction analysis and by the classification and regression trees (CART) model. RESULTS: tHcy concentrations were markedly higher in patients with ischaemic stroke (median 11.9 micromol/l, range 2.0-94.0) than in controls (median 9.8 micromol/l, range 4.7-49.6). An increased risk was also associated with the TT677 genotype (odds ratio (OR) 1.98; 95% confidence interval (CI) 1.04 to 3.78) and with the T allele (1.40; 95% 1.03 to 1.92) of the MTHFR gene. A differential effect of Hcy levels on risk of stroke was observed according to the distribution of environmental-behavioural risk factors, with a stronger influence in the subcategory of people with hypertension and smokers (OR 24.8; 95% CI 3.15 to 196). A comparable environmental-dependent TT677 MTHFR genotype-stroke association was observed in the genotype-disease analysis. CONCLUSIONS: A consistency of phenotype-disease analysis and genotype-disease analysis is indicated by analysing specific subcategories of patients, defined by the distribution of established risk factors. The assumption that the Hcy-stroke relationship is unlikely due to a reverse-causality bias is indirectly supported by our data.

Polymorphisms of the interleukin-1beta gene affect the risk of myocardial infarction and ischemic stroke at young age and the response of mononuclear cells to stimulation in vitro.

OBJECTIVE: To investigate the role of interleukin-1beta (IL-1beta) gene polymorphisms as a link between inflammation, coagulation, and risk of ischemic vascular disease at young age. METHODS AND RESULTS: A total of 406 patients with myocardial infarction (MI) at young age, frequency-matched for age, sex, and recruitment center, with 419 healthy population-based controls and 134 patients with ischemic stroke at young age, matched by age and sex, with 134 healthy population-based controls, were studied. Subjects carrying the TT genotype of the -511C/T IL-1beta polymorphism showed a decreased risk of MI (odds ratio [OR], 0.36; 95% CI, 0.20 to 0.64) and stroke (OR, 0.32; 95% CI, 0.13 to 0.81) after adjustment for conventional risk factors. In both studies, the T allele showed a codominant effect (P=0.0020 in MI; P=0.021 in stroke). Mononuclear cells from volunteers carrying the T allele showed a decreased release of IL-1beta and a decreased expression of tissue factor after stimulation with lipopolysaccharide compared with CC homozygotes. The presence of a monoclonal antibody against IL-1beta during cell stimulation resulted in a marked reduction of tissue factor activity expression. CONCLUSIONS: -511C/T IL-1beta gene polymorphism affects the risk of MI and ischemic stroke at young age and the response of mononuclear cells to inflammatory stimulation.

Modeling premature occurrence of acute coronary syndrome with atherogenic and thrombogenic risk factors and gene markers in extended families.

BACKGROUND: The interaction between genetic and environmental risk factors in determining premature cardiovascular events has been largely investigated in case-control association studies. By contrast, few family based analyses have been performed so far. PATIENTS/METHODS: From a series of 2936 subjects aged 45-64, we selected probands who died for a premature (<50 years) ischemic heart disease (IHD) and with at least one family member with a history of IHD also occurring under the age of 50. Ninety-four families from 32 pedigrees including 296 subjects were identified. In this population, we analyzed the relationship between background risk factors [age, gender, the G1691A polymorphisms of factor V gene, the C677T polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, the 844ins68bp polymorphisms of the cystathionine-beta-synthase (CBS) gene, and the apolipoprotein E (APOE) polymorphisms] and environmental risk factors, both atherogenic (smoke, hypertension, diabetes, dyslipidemia, obesity) and thrombogenic (smoke, homocysteine, fibrinogen) by a Markov block-recursive modeling approach. RESULTS: None of the studied polymorphisms had an independent direct effect on the risk of IHD. As opposed to atherogenic factors, thrombogenic factors (homocysteine and fibrinogen) turned out to be possible mediators of the indirect effect of the MTHFR gene on IHD risk (OR: 1.30; 95% CI: 1.01-1.69, for every 8 mm increase in plasma levels of homocysteine in TT-carriers compared with CT/CC-carriers (OR: 1.11; 95% CI: 1.01-1.22), for every 20 g L(-1) increase in plasma levels of fibrinogen in TT-carriers compared with CT/CC-carriers). CONCLUSION: Plasma levels of homocysteine and fibrinogen may be interpreted as intermediate factors mediating the effect of predisposing genes on the risk premature cardiovascular disease.

Homocysteine levels are associated with the severity of peripheral arterial disease in Type 2 diabetic patients.

BACKGROUND: Homocysteine levels are positively associated with the risk of cardiovascular disease. They might be determined by both MTHFR677C-->T polymorphisms and folate or B-vitamin status. OBJECTIVES: To investigate the possible association between plasma homocysteine levels and its genetic or environmental determinants and either the presence or the severity of peripheral arterial disease (PAD), in Type 2 diabetic patients. METHODS: From a cohort of 944 patients with Type 2 diabetes, 135 patients with PAD were selected, and frequency-matched for age and sex with 219 Type 2 diabetic control patients without macrovascular complications. According to the increasing severity of the disease, patients were divided into PAD1 (only diffuse calcifications of the arteries without any stenosis or occlusion), PAD2 (one or two stenosis or occlusions) and PAD3 (three or more). RESULTS: Homocysteine levels were similar in control and case patients (10.3 micromol L-1 vs. 10.7 micromol L-1, P = 0.53); however, a significant increase was found in PAD3 patients: odds ratio = 2.77 (95% confidence interval 1.14, 6.72) for patients with homocysteine levels above the median vs. those under the median in multivariate analysis. Although all significantly associated with homocysteine levels, neither MTHFR genotype nor folic acid or vitamin B12 levels were associated with severity of PAD. A significant interaction (P < 0.05) was found between folic acid and MTHFR polymorphism in determining the levels of homocysteine. CONCLUSIONS: In Type 2 diabetes, homocysteine was associated with the angiographic severity of PAD, but neither the genotypes nor vitamin levels contributed to this association.

Echo-phonocardiographic evaluation of the Björk-Shiley mitral prosthesis.

Ninety patients were studied with combined echophonocardiography after Björk-Shiley disc prosthetic mitral valve replacement. They were evaluated every 6 months (mean follow-up 6 years). Nine cases of left ventricular (LV) failure and 6 cases of prosthetic malfunction (5 paravalvular leaks and 1 thrombosis) were detected; 1 case was confirmed at necropsy and the other 5 cases were surgically verified and repaired. The following measures of prosthetic malfunction were evaluated: opening and closing velocity, maximal amplitude of the prosthesis, septal motion 6 months after operation, LV diastolic diameter, protodiastolic hump, variations during same record of the interval between aortic valve closure sound to the phono and mitral valve opening to the echo, and interval between aortic valve closure sound and maximal excursion of the LV posterior wall. All measures studied were useful for detecting prosthetic malfunction, but 2 are more useful in individual cases: variations of the interval between second heart sound and mitral valve opening and the interval between the aortic valve closure sound and LV posterior wall motion. These 2 intervals also allow discrimination between normal function, prosthetic malfunction and LV failure.

Influence of the pericardium on right and left ventricular filling in the dog.

We compared the influence of the pericardium on left and right ventricular (LV, RV) filling by measuring LV and RV pressures and segment lengths (SL, LV free wall, and RV inflow and outflow tracts) in six open-chest, pentobarbital sodium-anesthetized dogs before and after pericardiectomy. End-diastolic pressure (EDP) was varied by partial caval occlusion and dextran infusion. At each site the ln EDP-SL relation was fitted by linear regression and characterized by its slope and 1-Torr EDP intercept. The slope and 1-Torr intercept of the LV ln EDP-SL relation changed variably after pericardiectomy, but in each dog a change occurred that shifted this relation downward. In contrast, the RV inflow tract slope invariably decreased significantly after pericardiectomy, whereas its intercept was unchanged in all but one dog. The RV outflow tract results were similar to the inflow tract but less consistent. By the use of the raw EDP-SL data points, we calculated that the absolute contribution of the pericardium to EDP (i.e., the effective pericardial surface pressure) was similar at the three sites. However, as EDP values increased the proportional contribution of the pericardium to right ventricular end-diastolic pressure (RVEDP) increased, whereas that to left ventricular end-diastolic pressure (LVEDP) remained relatively constant. As a result, at the higher EDP values tested, the pericardium was responsible for a larger proportion of RVEDP than LVEDP.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of leisure time and working activity on principal risk factors and relative interactions in active middle-aged men.

DESIGN: This study was designed to evaluate, in a cohort of 1039 middle-aged men, the interaction between the duration and intensity of physical activity performed either during leisure time (competitive sports, walking, cycling) or work, and principal coronary disease risk factors. METHOD: A cohort of subjects aged 45-64 years were recruited in 1993. Subjects included both individuals who were physically active and those who were sedentary, and were age-matched. RESULTS: Leisure time physical activity was inversely related to levels of total cholesterol, triglycerides, and fibrinogen, and to diastolic and systolic blood pressure. High-density lipoprotein cholesterol level was directly related to leisure time activity. Working activity, even if strenuous, was not related to risk profile. Leisure time activity did not favorably influence lipid levels in smokers, obese subjects or those with known dyslipidemia. CONCLUSIONS: This study further reinforces the use of continuous diet and drug treatment in dyslipidemic subjects and in smokers, who have to refrain from smoking if they are to benefit fully from the effects of physical activity.

Bioavailability and related heart function index of digoxin capsules and tablets in cardiac patients.

A loading dose of digoxin (750 microgram) in two commercial formulations was administered to 14 patients with heart disease according to a crossover design. One formulation consisted of soft gelatin capsules containing a solution of digoxin; the other formulation was compressed tablets. All parameters investigated, i.e., serum peak height, time of the peak, area under the serum level--time curve (AUC), and area above the Q--S2I (electromechanical systole) decrease (obtained from polycardiographic evaluation), showed better bioavailability of digoxin capsules than tablets, averaging 36.3%. The better bioavailability of digoxin capsules than tablets seems to be more evident in heart disease patients than that encountered previously in healthy subjects. The AUC and the area above the Q-S2I decrease were linearly correlated only with digoxin capsules.

Effects of changes in intravascular volume on atrial size and plasma levels of immunoreactive atrial natriuretic peptide in uremic man.

To study the trigger for the release of atrial natriuretic peptide (ANP) in man, we measured the atrial areas (AA) by 2-D echocardiography, the total blood volume (TBV) by 131I-serum albumin and plasma immunoreactive ANP (i-ANP) concentrations by radioimmunoassay, after prior plasma extraction, for 10 dialyzed uremic patients. Measurements were made when the patients were volume-loaded or volume-depleted by isoosmotic ultrafiltration and again 48 h later, when they were again volume-loaded. Analysis of plasma extracts by high-performance gel permeation chromatography revealed that the greatest amount of the i-ANP fraction was a peptide eluting like human synthetic alpha-ANP. Ultrafiltration consistently decreased the TBV, while spontaneous regain of body-fluids caused TBV to rise to pre-ultrafiltration levels. Changes in TBV were closely related in time to changes in both right (RAA) and left (LAA) atrial area and in plasma i-ANP concentrations. Significant direct relationships were found between TBV and RAA, TBV and i-ANP and between both LAA and RAA and i-ANP. Furthermore, the decreases and the increases in TBV, RAA and LAA were closely correlated with changes in i-ANP. Multiple regression analysis, however, revealed that the changes in plasma i-ANP were mainly related to the changes in RAA, with little or no relationship to the changes in TBV or LAA. These findings are evidence for a positive feed-back between the level of intravascular filing volume, extent of atrial distention and amount of i-ANP released into the blood stream.

Invasive and echocardiographic evaluation of non-Q myocardial infarction with isolated stenosis of descending anterior coronary artery.

Prognostic and clinical characteristics of acute myocardial infarction (AMI) can usually justify surgical and/or angioplastic approach if the residual ventricular function is still good. Multivessel disease frequently complicates results interpretation. We studied with 2D echocardiography and coronary angiography two groups of patients with one vessel stenosis located on anterior descending (AD) and previous AMI (means 19 days): 23 patients with spontaneous non-Q infarction (group 1), and 23 patients with Q infarction. Left ventricular function was better in group 1. Percent occlusion of AD was lower in group 1 and angiographic AD caliber was significantly higher. Differences between groups were much more evident in subgroups with proximal stenosis of AD: patients of non-Q subgroups had very good left ventricular function but frequently had post-AMI instable angina (88%). Our results underline the usefulness of aggressive diagnostic and therapeutic approach in non-Q AMI, because of higher amount of myocardium at risk.

Noninvasive evaluation of asymptomatic athletes with cardiac murmur.

The increasing number of amateur sportsmen enhances the need for a correct evaluation of subjects suspected of overt and mild cardiac disease. Out of 4000 athletes, 72 subjects were clinically preselected by the sport doctor during an annual routine examination. They were studied with mono and 2D echo, pulsed color (PW) and continuous wave Doppler. Five asymptomatic patients are reported with congenital or acquired valvular diseases.

Sudden dilatation of right ventricle in two patients with thrombosis of a mitral Björk valve detected by echocardiography: different aspects of acute and chronic overloads of the right ventricle in these patients.

Acute thrombotic obstruction of disc valve prosthesis is a rare but catastrophic event without an immediate correct diagnosis and precocious treatment (Amman et al., 1984; Assanelli et al., 1986; Copans et al., 1980; Mann et al., 1986; Gibson et al., 1974; Johnson et al., 1973; Ledain et al., 1986). That is the main reason it is important to consider each helpful sign in order to recognize such a situation. We detected an important dilatation of the right ventricle in two patients with different stages of thrombosis of mitral Björk, the first one had also a chronic dilatation of the right ventricle due to tricuspid regurgitation. The clinical and pathophysiological aspects of these unusual situations are described in this article.

Left ventricular dysfunction versus paravalvular leak in patients with mitral disc prostheses.

UNLABELLED: Left ventricular dysfunction and prosthesis malfunction are the main causes of hemodynamic deterioration following prosthetic mitral valve replacement. The aim of this study is to reassess the usefulness of a combined echo-phonocardiographic technique to differentiate these different situations in order to select medical or surgical treatment in patients with a mitral disc prosthesis. Two patient groups were studied. The first group consists of five patients with paravalvular leak (PL), surgically or pathologically verified. Second group: nine patients with left ventricular failure (LVF) and normal functioning prosthesis. The diastolic diameter of the left ventricle (LV) was significantly increased in the LVF group compared with the PL group. A protodiastolic hump was present in four cases of PL. The variability of the interval between A2 and the mitral valve opening (delta A2-MVO) was less than 30 msec in the LVF group and greater than 30 msec in the PL group. The interval between A2 and maximal LV posterior wall (A2-PW) exceeded 60 msec in the PL group and was shorter than 60 msec in the LVF group. IN CONCLUSION: the echo-phonocardiographic technique, especially when by using two newly proposed parameters, seems to be very useful to discriminate between PL and LVF.

Ejection phase indexes with apexcardiography. Comparison with echocardiographic and angiographic parameters.

The reliability of a new noninvasive method for evaluating ejection fraction and the mean velocity of circumferential fiber shortening by apexcardiography and carotid pulse tracing has been evaluated. Three groups of subjects were considered. Group 1: 30 normal subjects (mean age 43 years); Group 2: 34 patients with aortic valve disease (mean age 51 years); Group 3: 76 patients with coronary artery disease (mean age 50 years). The mechano-cardiographic tracing points were acquired by an ultrasonic digitizing system and compared with the same indexes measured from the ventriculogram. In 53 patients M-mode echocardiographic evaluations also were performed. The correlations between the apexcardiographic derived ejection phase indexes and the angiographic measurements were highly significant in all subjects and in each group of patients. The correlations between the ejection phase indexes determined by echocardiography and the same angiographic data were also significant, but the r-values were somewhat lower than those found between the apexcardiographic and angiographic parameters in the same patients. Our results have assessed the reliability of this new method and demonstrated that this noninvasive technique can be applied not only in coronary disease but also in aortic valve disease and in normal subjects. It can be concluded that the apexcardiographic evaluation of cardiac performance appears applicable to patients in whom a means of assessing and sequentially following ventricular function is indicated.

[Arterial blood pressure in a population of Italian clerical workers. Correlation with other coronary risk factors]. / Pression artérielle dans une population d'employés italiens. Corrélation avec d'autres facteurs de risque coronarien.

Distribution of arterial blood pressure and prevalence of hypertension have been reported in 172 subjects (568 males and 144 females), derived from screening of a bank clerks population. 99 subjects were found to be hypertensive: 46 (46.4 p. 100) were aware of being hypertensive, 24 (24.3 p. 100) resulted to be under treatment and only in 5 subjects blood pressure values were effectively controlled. The relationships between arterial blood pressure and some recognized or suspected coronary risk factors were also determined by multiple regression analysis. Age, heart rate, body mass index, glycemia after loading, turned out the variables most correlated with blood pressure. The multiple regression analysis showed that overall evaluation of coronary risk factors explained up to 21 p. 100 of the systolic blood pressure variation and to 17 p. 100 of diastolic pressure in male subjects, while for women the obtained values were 34 p. 100 and 24 p. 100 respectively. After a critical evaluation of different parameters able to affect arterial blood pressure, the difficult approach to hypertension preventive and therapeutic problems was emphasized.

Alcohol consumption among high school students and young athletes in north Italy.

Alcohol consumption was assessed among 366 male high school students and 330 young men playing in sports teams. On the average, the athletes drank less wine, beer and spirits than the students and reported fewer drunkenness episodes. The association of alcohol drinking with sporting activity and with some independent variables was estimated by logistic regression techniques, fitting models for ordinal or nominal response variables. Point estimates of the odds ratios and their confidence limits showed: 1) an inverse relationship between alcohol drinking and sporting activity, especially as regards the consumption of spirits; 2) a strong positive relationship of alcohol drinking with both experimental and regular smoking; 3) peer alcohol drinking (best friend's and girlfriend's drinking) was the strongest predictor of the participant's alcohol consumption.

Smoking habits and sporting activity among adolescents in north Italy.

A cross-sectional survey of the smoking habits of 330 17-19 year-old males practising physical activity as members of sports teams, and of 366 male students in the same age range was carried out in Brescia, North Italy. A total of 23.3% of the athletes and 30.9% of the students smoked at least one cigarette a week (chi 2 = 4.60, p less than 0.05), and 17.3% and 19.7% smoked at least one cigarette a day, respectively (chi 2 = 0.51; p greater than 0.05). The smoking athletes had on average 50.3 cigarettes/week and students 47.0 (t-test: 0.46; p greater than 0.05). No difference was found with respect to age at their first experience with smoking, while athletes began to smoke regularly before than students, proportionally (chi 2 for linear trend: 5.29, p less than 0.05). Sporting activity was negatively associated with current smoking by multiple logistic regression: the odds ratio of current smoking for athletes with respect to students was 0.5 (95% CI: 0.4-0.8). Among a set of social, environmental and behavioural variables, best friend's and girlfriend's smoking was the one most strongly associated with current smoking in both groups.

[Work, cardiopathy, and sports]. / Lavoro, cardiopatie e sport.

BACKGROUND: Heart disease is the main cause of early disability and premature death in Europe. Regular physical activity may prevent heart disease, diabetes, ictus, and obesity. Nevertheless, a certain resistance to a dynamic lifestyle, lack of free time, lack of motivation and other factors are frequently encountered. OBJECTIVES: To stress the importance of physical activity in the prevention of cardiovascular disease. METHODS: A literature review of the main risk factors for cardiovascular disease was carried out. RESULTS AND CONCLUSION: It has been shown that physical exercise is beneficial to the cardiovascular apparatus and to the bones and joints, by improving some metabolic parameters. Recent studies have shown that a personalized, moderate physical activity should be suggested for primary and secondary prevention, in particular for subjects with coronary artery disease and left ventricular dysfunction. An increase in sports activity and physical exercise at work and at school is recommended so as to improve quality of life and promote home rehabilitation. Some promising experience has already been made among workers and their families with excellent results, as shown by a follow-up period of three years.