Biomedical subjects
Publications and source records attributed to M Lanti.
Explore the source record for details and available documents.
BACKGROUND: The relationships of body mass index and skinfold thickness to all-causes mortality during a 10-year follow-up were assessed in 8,341 men and 1,100 women ages 30-69 years from different Italian population samples. RESULTS: Among men, both univariate and multivariate analyses showed a clear-cut parabolic (inverse J-shaped) relationship, whose left branch became less steep after the exclusion of smokers, people carrying severe diseases at entry, those who died during the first 5 years, or all of them. The minimum risk was almost always located around 28 units of body mass index, and it decreased to smaller levels of body mass index when the exclusions were adopted. The analysis of skinfold thickness showed similar but less clear-cut results. Among women, due to the limited number of fatal events, the analysis was unable to show any clear relationship of body mass index or skinfold thickness to all-causes mortality. The multivariate analysis showed a similar parabolic relationship of body mass index to all-causes mortality. The estimated multivariate risk of death broken down into five quintiles was unrelated to the mean level of body mass index for each quintile. From the multivariate model it was estimated that an excess of 10 kg in body weight (above the body mass index corresponding to the minimum risk level and everything else being equal) carries the same excess of risk produced by 5 mm Hg of systolic blood pressure or by less than 5 cigarettes smoked per day. CONCLUSION: These results suggest that high levels of obesity indicators are only slightly associated with an excess mortality and that overweight and obesity are health hazards only if they are accompanied by an elevation of other risk factors, mainly of blood pressure.
A pool of two Italian rural population samples made up of 1,712 men aged 40-59 at entry was studied in 1960 and than followed up for 25 years. The multivariate analysis of the first major coronary event using the Cox model showed, in men aged 40-59, 45-64 and 50-69, the significant predictive role of age, systolic blood pressure, serum cholesterol and cigarette smoking, but not of body mass index, without marked differences attributable to the aging process. Changes in systolic blood pressure, serum cholesterol and cigarette smoking occurring between year 0, 5 and 10 of follow-up, as defined by two different indicators, increased significantly the predictability of coronary events occurring between years 10 and 25 of follow-up when added to the model including the baseline factors. It is inferred that increases and decreases (even of relative nature) of the three major risk factors around the entry levels are associated with higher and lower levels of coronary risk in the 15 years after the changes have occurred.
BACKGROUND AND PURPOSE: The present investigation was aimed at evaluating the incidence and prediction of a first major cerebrovascular (fatal or nonfatal) event. METHODS: The study population included the two Italian rural samples of the Seven Countries Study (namely, Montegiorgio and Crevalcore), accounting for a total of 1,712 men aged 40-59 years at entry and followed up for mortality and morbidity for 25 years. A number of individual variables measured at baseline, at the fifth year, and at the tenth year of follow-up and possibly related to cerebrovascular events were considered. Of the 1,709 subjects free from major cerebrovascular events at entry 171 developed a first major cerebrovascular event, but for the multivariate Cox model analysis only 1,572 subjects and 152 events were employed due to some exclusions for missing data. RESULTS: Systolic blood pressure, indexes of respiratory function (protective), and physical activity at work (protective) demonstrated significant predictive roles for all ages and all lengths of follow-up considered. Other factors (presence of arrhythmias, presence of arcus senilis, and skinfold thickness [protective]), significantly contributed to the prediction, but in only some models. Time-related changes in systolic blood pressure significantly improved the prediction of cerebrovascular events. CONCLUSIONS: The multivariate prediction performed in this report allowed the validation of three risk factors (systolic blood pressure, respiratory function indexes, and physical activity at work) whose predictive powers remain stable with aging. The need for further studies specifically aimed at discriminating hemorrhagic from thrombotic events is suggested.
Three cohorts of men aged 40-59 at entry examination were enrolled between 1962 and 1964 in the Serbian section of the Seven Countries Study of Cardiovascular Diseases. They were a sample in the rural village of Velika Krsna (n = 511), the workers in an agro-industrial cooperative in the city of Zrenjanin (n = 516), and the University professors of Belgrade (n = 536). At entry examination and then after 5 and 10 years, some cardiovascular risk factors were measured while the follow-up for mortality and causes of death was continued for 25 years. The 25 year standardized death rates from coronary heart disease (CHD) were higher in Zrenjanin (177 per 1000) and lower in Belgrade (118) and Velika Krsna (122). The multivariate prediction of CHD mortality by the Cox model in the lumped samples showed significant coefficients for age, body mass index, systolic blood pressure and cigarette consumption. The coefficient of serum cholesterol did not reach a statistically significant level. An unknown but significantly protective factor was identified for the Belgrade sample, likely bound to the higher social class of this group. Changes of systolic blood pressure in the first 10 years of follow-up were positively and highly related to the deaths occurred in the subsequent 15 years. The three population groups showed, between year 0 and year 10 follow-up, large increases in mean levels of blood pressure and mainly of serum cholesterol (+30 mg/dl in Velika Krsna; +36 mg/dl in Belgrade and +61 mg/dl in Zrenjanin). The sample in Zrenjanin started from intermediate levels (168.7 mg/dl) but attained the greatest increase and reached the highest CHD death rate in 25 years.
Nine population samples of mean aged 40-59, for a total of 1777 individuals drawn from nine health units, were examined in 1978-79 for the measurement of some risk factors possibly related to total mortality. The analysis evaluated the possible relationship between blood pressure levels and smoking habits measured in the population samples and the official death rates covering the period 1980-82 in the health units from which the samples were drawn. The analysis was conducted in a direct way but also by the help of a risk function linking blood pressure and smoking habits as obtained from another Italian population sample. The cograduation test between mean blood pressure in the nine areas and total mortality was 0.58 (linear correlation 0.57); the cograduation test was -0.70 for non-smokers, 0.62 for ex-smokers, 0.50 for present smokers (linear correlation of -0.27, 0.29 and 0.14 respectively). The death rates estimated by the risk function (Cox model) tended to overestimate the death rates from 5 to 64% (average 36.3%). The cograduation test between expected and observed death rates was 0.56 (linear correlation coefficient 0.66). Some limitations of this pilot study are largely explained by the small size of the sample and by the need to use a risk function provided by another population sample.
The study was aimed at comparing the effects of dobutamine (dob) and dopamine (dop) on isotonic contraction and rhythmicity of isolated guinea-pig papillary muscles (in oxygenated Tyrode at 37 degrees C), by taking into account: 1) the rate of stimulation (50% above the diastolic threshold) at 5 fixed periods: (RR: 1600, 1200, 1000, 800 and 400 ms); 2) 7 log concentrations (logC) of the index amine (from 10(-9) to 10(-3) M). To this end, a dose-relation protocol which explored the effects of all 5 RR and 7 logC was designed and 15 adult female Guinea-pigs (250 to 350 g) were randomized to either the dob (n = 8) or the dop (n = 7) arm. This enabled a total of 525 sets of data to be analyzed: in 38 sets (7.2%) premature contractions (CP) were coded. CP were sustained (freq: > 3) in 25 of these latter 38 sets (4.8%). Compared to the basal state, the amplitude (AMP%) and the log of percent amplitude (logAMP%) and time to peak (TP%) changes of the isotonic (Gould transducer) twitch were calculated along with the log of this latter variable (logTP%). AMP%, log AMP%, TP% and logTP% were linearly correlated with logC at all RR. In the range 1600-400 RR, for both amines, significant linear correlations (magnitude of 0.15 > r < magnitude of 0.70, 0.001 > p < 0.022) were seen for plots of AMP%, logAMP% and TP%:steeper correlations were observed for dop. This was confirmed in multivariate analysis (BMDP-9R) whereby AMP%, logAMP%, TP%, logTP%, CP, and freqCP were dependent variables and coded variables were included to either define the type of treatment (dop versus dob) or logC. In these analyses, logC (t > 11) and dop (t > magnitude of 3) might be used to explain (0.28 > r2 < 0.42, 0.00001 > p < 0.0025) AMP% and logAMP%, meaning that a different inotropic (isotonic) efficacy exists between these 2 amines, at all logC. On the other hand, when CP and freqCP were coded, explanatory variables were AMP% and logAMP% (4.86 > t < 6.95, 0.06 > r2 < 0.09, p < 0.00001), but not the variable used to code the type of treatment (dob versus dop).(ABSTRACT TRUNCATED AT 400 WORDS)
Nicorandil (N) increases potassium conductance in vascular smooth muscle and so induces vasodilation; N also dose-dependently reduces action potential duration (APD). However, it is unclear whether increased potassium conductance, and concomitant APD shortening, might be arrhythmogenic, particularly when myocardial ischemia (where potassium efflux is increased) concurs. Data on the anti-arrhythmic effectiveness of N have also been published: N reduced the spontaneous discharge of sino-atrial node and so reduced heart rate, both in vitro and man. On the other hand, among other vasodilators, cicletanine (C) has been reported to increase potassium conductance, an effect which was advocated to explain its antiarrhythmic potency. In the present investigation the direct myocardial effects of N were compared to those following C in 63 experiments (from 13 Guinea-pigs), using atrial strips (containing sino-atrial node) superfused in 1-compartment bath with normal Tyrode's solution. Using glass microelectrodes, standard electrophysiologic variables were recorded (APA, RMP, APD50%, Vmax) in spontaneously beating atrial tissue, either in Tyrode, dimethyl-sulfoxide (DMSO 1:100, as solvent), C 10(-5) M (in DMSO 1:100), and N 10(-3) M (in DMSO 1:100), whose respective perfusion periods (15 min) were randomized, always following 15 min of washout with Tyrode. Only N was tested in experiments of both 15 and 30 min duration.(ABSTRACT TRUNCATED AT 250 WORDS)
The relationship of indicators of obesity, such as the body mass index (BMI) and the skinfold thickness in some areas (SKIN) to all causes mortality have been analyzed in three italian epidemiological studies. They are the Seven Countries Study--italian areas conducted on 2480 men at entry and followed-up for 25 years; the Brisighella study conducted on 1123 men and 1100 women aged 30-69 and followed-up for 15 years; and the NFR study in Rome conducted on 3395 men aged 46-66 and followed-up of 6.5 years. The univariate analysis concerning the BMI for various age groups, the two sexes, and variable periods of follow-up has almost systematically showed a parabolic inverted J shaped relationship with minimal levels of risk for BMI values of 27-29 units. However this was not the case for the women group and for the oldest men where no clear relationship was found. The analysis concerning the SKIN provided similar but less clear-cut results. The multivariate analysis has confirmed the parabolic relationship of BMI to all causes mortality even in the presence of other 4-5 covariates. The left branch of risk is higher than the right one and its slope could be reduced, although not completely, by the exclusion of heavy smokers, of those who died within the first 5 years of follow-up, of those who were carriers of severe diseases at entry examination.(ABSTRACT TRUNCATED AT 250 WORDS)
We have investigated (multivariate Cox's model) the relative risk of stable excitation-conduction block (ECB) in right ventricular myocardial strips (2 x 5 x 1 mm) from 26 female guinea-pigs, bathed in a 2-compartment chamber (3 ml) on the anterior side of which modified Tyrode's solution (K+ 12 mM, HCO3- 9 mM, pH 7 +/- 0.05, pO2 80 +/- 10 mmHg and absence of glucose) is supraperfused (stimulation rate: 450 ms; wire in the posterior compartment), thus enabling simulation of electrophysiologic changes seen during acute myocardial ischemia. Using glass microelectrodes, action potential amplitude (APA), durations (APD50 and 90%), resting membrane potential (RMP) and upstroke velocity (Vmax) are investigated. The hypothesis was tested of prostacyclin and histamine involvement in the genesis of ischemia-induced ECB in this model. Either a weak prostacyclin stimulator (cicletanine 10(-5) M, IPSEN, Paris, F, in DMSO 1:100; n = 16) or a potent prostacyclin generation blocker (indomethacin 10(-5) M, Sigma, in DMSO 1:100; n = 10) and either DMSO alone (1:100; n = 16) or a specific histaminergic H1 receptor antagonist (terfenadine 10(-5) M, Sigma, in DMSO 1:100; n = 10) were supraperfused using a randomization scheme. Each animal was used twice and either a first or a second occlusion (supraperfusing the modified Tyrode's solution for 30 min) period was performed and the randomized substances were supraperfused, thus enabling obtention of n = 52 experiments for analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
It is unclear whether sudden or nonsudden death can be predicted independently from other risk factors for coronary artery disease (CAD). Therefore, this investigation was undertaken to measure 12-lead QRS voltage sum, a recently proposed (Am J Cardiol 1985;55:485-494) index of left ventricular (LV) hypertrophy, and its ability to predict either subsequent sudden (less than 2 hours) or nonsudden CAD death during 20 to 23 years of follow-up in 1,588 middle aged men (40 to 61 years old) from 2 cohorts of the Italian section of the Seven Countries Study who were free of demonstrable CAD (at entry examination in 1962). The Sokolow-Lyon and the modified Sokolow-Lyon indexes, 2 standard electrocardiographic methods to detect LV hypertrophy were also measured and compared. During follow-up, 67 patients died suddenly and 87 died a nonsudden CAD death. In the Cox proportional-hazards model, age, mean blood pressure, heart rate, body mass index, cholesterol, physical activity, smoking habit, ST-T alterations (Minnesota codes 4.1 to 4.3 together with 5.1 to 5.3) and the 3 electrocardiographic indexes, all measured at the time of enrollment into the study, were included. The 12-lead QRS voltage sum retained significant and independent relation to sudden death (t = 2.00); Sokolow-Lyon index entered the Cox solution for nonsudden CAD death but the association was inverse (t = -2.10). ST-T alterations were significantly associated only with nonsudden CAD death (t = 2.19). Thus, in addition to several known risk factors, measurement of 12-lead QRS voltage sum in middle-aged men without clinical evidence of heart disease may help identify subjects at an increased risk of sudden death; nonsudden CAD death is predicted by Sokolow-Lyon index and by ST-T alterations. The usefulness of these indexes needs to be tested in different populations.
In 60 randomized dogs the effects of epoprostenol infusion (100 ng/kg/min) on ischemia-induced premature ventricular contractions (PVCs), ventricular tachycardia (VT), ventricular flutters and ventricular fibrillation were studied. The circumflex coronary artery occlusion canine model of sudden death was used. The results demonstrate different effects of epoprostenol on ischemia-induced ventricular arrhythmias: 1) both postischemic (7 of 30 vs 15 of 30, p = 0.0298) and postreperfusion (5 of 23 vs 8 of 15, p = 0.0492) ventricular fibrillations were prevented in epoprostenol dogs with an improvement of the global survival rate (18 of 30 vs 7 of 30, p = 0.0019) as compared to controls; 2) in epoprostenol treated dogs a significantly increased incidence of non lethal arrhythmias-including ventricular flutters that occurred in 12 of 30 dogs vs 4 of 30 in controls (p = 0.0195)--was observed; 3) a positive correlation between the percent diastolic pressure fall 10 min after the start of epoprostenol infusion and the number of non lethal arrhythmias was noted. However, hemodynamic effects of the compound, suggesting an oxygen sparing action, did not preclude the antifibrillatory effectiveness. Thus, the antifibrillatory and antiarrhythmic effects of epoprostenol after circumflex coronary artery occlusion and reperfusion in dogs seem independent from one another.
In 881 middle-aged men from one Italian cohort of the Seven Countries Study, QT and RR intervals were measured in lead 2 from resting ECGs (25 mm/sec) and fitted separately with 10 mathematically different QT prediction formulas. The relative accuracy of fit to data was assessed from the minimum mean-squared residual and the minimum Akaike Information Criterion values. Using the Minnesota code, 588 men had normal (group 1) and 293 had abnormal (group 2) ECGs. A better fit to QT-RR data by all formulas was observed in group 1, compared with group 2. Among one-parameter equations in both groups, the cubic root Fridericia's formula is better suited to fit the data than the Bazett's square root or other formulas. The former compares favorably with multiparameter equations or with the inverse relation and gives the best fit in group 2. Thus the cubic root equation might be more accurate than the square root or several complex formulas for correcting measured QT intervals for cardiac cycle length in middle-aged men.
To gain insight into the differences in antiarrhythmic potential of right vs left stellate ganglionectomy, 72 dogs were randomized to either unilateral stellectomy or second intercostal space thoracotomy and left circumflex coronary arteriovenous pedicle occlusion was performed, without vagotomy, a mean of 8 weeks later under anesthesia. The type and timing of ventricular ectopic beats, including both nonsustained and sustained ventricular tachycardia and ventricular fibrillation, were investigated. Several covariates, including postischemic electrocardiographic changes, were considered. Both right and left stellate ganglionectomy reduced the incidence of early (0 to 10 min) (p = .004 and p = .001, respectively) and total (0 to 60 min) (p = .009 and p = .008, respectively) ischemia-induced ventricular fibrillation, and improved outcome (p = .0013 and p = .0012, respectively). Early sustained ventricular tachycardia was similarly reduced (p = .02) in both stellectomized groups. By contrast, neither the type nor the time distribution of the other forms of ventricular arrhythmias differed significantly among the randomized groups. The multivariate Cox's regression model showed that ST segment elevation at 3 min postocclusion, unilateral stellate ganglionectomy (either right or left), sex, and weight were significant independent predictors of the incidence of ventricular fibrillation during the occlusion period. Lower ST segment elevation and reduced incidence of sustained ventricular tachycardia in the early postischemic period might explain improved outcome in stellectomized dogs by Cox analysis. The side of intervention (either stellectomy or sham operation) did not influence survival; however, left-sided interventions were more effective than right-sided ones. These results confirm the previously reported antifibrillatory effect of left and indicate like effects of right stellate ganglionectomy in a randomized experimental study.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We evaluated the incidence of hypertension over 5-10 years of follow-up in middle-aged men, 40-59 years at entry, selected from the Italian section of the Seven Countries Study. Out of the 2480 subjects, 852 were normotensive at entry [systolic blood pressure (SBP) less than 140 mmHg and diastolic blood pressure (DBP) less than 90 mmHg)], alive after 10 years and had been evaluated repeatedly after 5 and 10 years. After 5 years, 31.3% had developed borderline hypertension (140 less than or equal to SBP less than 160 and 90 less than or equal to DBP less than or equal to 95 mmHg) and 14.6% had developed definite hypertension (SBP greater than or equal to 160 mmHg or DBP greater than or equal to 95 mmHg). During the next 5 years, out of the 267 borderline hypertensives, 28.5% became definite hypertensives, while 29.6% reverted to normal blood pressure. Out of the 124 definite hypertensives, 46% remained in this category, while 34.7% became borderline hypertensives and 19.4% became normotensive. In men aged 60-69 years, less than 2% of hypertensives were being effectively treated and changes in body weight were closely related to blood pressure. In addition, out of 461 normotensive subjects who remained normotensive at the 5-year examination, 63.6% remained normotensive in the next 5 years also, while 28% developed borderline hypertension and only 8.4% moved into the definite hypertensive class. These data suggest that a normotensive subject aged 40-59 years has a 34.4% probability of remaining normotensive in the next 10 years.(ABSTRACT TRUNCATED AT 250 WORDS)
Multivariate analysis of survival using Cox's proportional hazards model demonstrates that several clinically measurable covariates are determinants of life-threatening arrhythmias following left circumflex coronary artery occlusion-reperfusion in 107 dogs. These are heart rate, ST segment elevation and mean aortic pressure immediately (3 min) following occlusion, and the presence of early (0-10 min) post-occlusion sustained ventricular tachycardia. The risk of occlusion-reperfusion ventricular fibrillation was determined according to Cox's solution based on ST segment elevation, thus enabling quantification of the role of cicletanine. Since cicletanine-treated dogs had reduced mean ST segment elevation at 3 min post-occlusion, lower incidence of early post-occlusion (0-10 min) sustained ventricular tachycardia, and increased endogenous production of prostacyclin, and the latter was inversely correlated with the level of ST segment elevation, it is concluded that such favourable effects on the ischaemic myocardium were contributory to the improved outcome in these experiments. These effects on the ischaemic myocardium obtained in spite of a hypotensive action in the experimental setting might be regarded as desirable and it is therefore suggested that they should be further investigated by pharmacodynamic studies in human subjects.