Fulvia Seccareccia

The Gln-Arg192 Polymorphism of Human Paraoxonase Gene Is Not Associated With Coronary Artery Disease in Italian Patients

Serum paraoxonase (PON) is an HDL-bound enzyme protecting LDL from oxidation. A common polymorphism of the paraoxonase gene (PON1) involving a Gln-to-Arg interchange at position 192 has been demonstrated to modulate PON activity toward paraoxon, a nonphysiological substrate; Arg192 (allele B) is associated with higher activity than Gln192 (allele A). This polymorphism has been proposed as a genetic marker of risk for coronary artery disease (CAD). However, the relationships between codon 192 PON1 genotypes, coronary atherosclerosis, and the occurrence of myocardial infarction (MI) are still controversial. PON1 genotypes were determined in 472 consecutive subjects (>40 years old) who underwent coronary angiography. CAD (>50% stenosis) was detected in 310 subjects (CAD+); 162 subjects with <10% stenosis served as controls (CAD-). We also evaluated 204 randomly selected individuals as population controls. PON1 genotypes were determined by PCR and AlwI restriction enzyme digestion. Frequencies of alleles A and B were 0. 70 and 0.30 in angiographically assessed subjects and 0.73 and 0.27 in population controls, respectively (chi2=2.0; P<0.3). Distribution of PON1 genotypes in CAD+ were not significantly different from those in CAD- (chi2=2.10; P<0.3). Similarly, no differences were observed in the subgroup of CAD+ with MI nor in that at higher oxidative risk (smokers and/or diabetics). After controlling for other coronary risk factors, no association was found between PON1 alleles and the presence of CAD. PON1 AA genotype was associated with reduced concentration of apolipoprotein B-containing triglyceride-rich lipoproteins. This study did not provide evidence of a significant association between codon 192 PON1 genotypes and coronary atherosclerosis in Italian patients. However, it did confirm that the PON1 low-activity allele is associated with a less atherogenic lipid profile.

Heart Rate as a Predictor of Mortality: The MATISS Project

OBJECTIVES This study sought to verify the independent role of heart rate in the prediction of all-cause, cardiovascular, and noncardiovascular mortality in a low-risk male population. METHODS In an Italian population-based observational study, heart rate was measured in 2533 men, aged 40 to 69 years, between 1984 and 1993. Data on cardiovascular risk factors were collected according to standardized procedures. Vital status was updated to December 1997. RESULTS Of 2533 men followed up (representing 24,457 person-years), 393 men died. Age-adjusted death rates for 5 heart rate levels showed increasing trends. The adjusted hazard rate ratios for each heart rate increment were 1.52 (95% confidence interval [CI] = 1.29, 1.78) for all-cause mortality, 1.63 (95% CI = 1.26, 2.10) for cardiovascular mortality, and 1.47 (95% CI = 1.19, 1.80) for noncardiovascular mortality. Relative risks between extreme levels were more than 2-fold for all endpoints considered. CONCLUSIONS Heart rate is an independent predictor of cardiovascular, noncardiovascular, and total mortality in this Italian middle-aged male population.

Transcatheter aortic valve implantation versus surgical aortic valve replacement for severe aortic stenosis: Results from an intermediate risk propensity-matched population of the Italian OBSERVANT study

BACKGROUND Few studies have yielded information on comparative effectiveness of transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR) procedures in a real-world setting. The aim of this analysis is to describe procedural and post-procedural outcomes in a TAVI/SAVR intermediate risk propensity-matched population. METHODS OBSERVANT is an observational prospective multicenter cohort study, enrolling AS patients undergoing SAVR or TAVI. Propensity score method was applied to analyze procedural and post-procedural outcomes. Pairs of patients with the same probability score were matched (caliper matching). RESULTS The unadjusted enrolled population (N=2108) comprises 1383 SAVR patients, 602 transarterial-TAVI patients and 123 transapical-TAVI patients. Matched population comprised a total of 266 patients (133 patients for each group). A relatively low risk population was selected (mean logistic EuroSCORE 9.4 ± 10.4% vs 8.9 ± 9.5%, SAVR vs TAVI; p=0.650). Thirty-day mortality was 3.8% for both SAVR and TAVI (p=1.000). The incidence of stroke (1.5% SAVR and 0.0% TAVI; p=0.156) and myocardial infarction (0.8% SAVR and 0.8% TAVI; p=1.000) was not statistically different between groups, whereas a higher requirement for blood transfusion was reported across the surgical cohort (49.6% vs 36.1%; p=0.026). A higher incidence of major vascular damage (5.3% vs. 0.0%; p=0.007) and pacemaker implantation(0.8% vs 12.0%; p=0.001) were reported in the TAVI group. CONCLUSIONS Patients undergoing transcatheter and surgical treatment of severe aortic stenosis are still extremely distinct populations. In the relatively low-risk propensity-matched population analyzed, despite similar procedural and 30-day mortality, SAVR was associated with a higher risk for blood transfusion, whereas TAVI showed a significantly increased rate of vascular damage, permanent AV block and residual aortic valve regurgitation.

Inter-cohort differences in coronary heart disease mortality in the 25-year follow-up of the seven countries study

Sixteen cohorts of men aged 40–59 years at entry were examined with the measurement of some risk factors and then followed-up for mortality and causes of death for 25 years. These cohorts were located in the USA (1 cohort), Finland (2), the Netherlands (1), Italy (3), the former Yugoslavia (5), Greece (2), and Japan (2), and included a total of 12,763 subjects.Large differences in age-adjusted coronary heart disease (CHD) death rates were found, with extremes of 45 per 1000 in 25 years in Tanushimaru, Japan, to 288 per 1000 in 25 years in East Finland. In general, higher rates were found in the US and Northern European cohorts as compared to the Southern European and Japanese cohorts. However, during the last 10 years of follow-up large increases of CHD death rates were found in some Yugoslavian areas. Out of 5 measured entry characteristics treated as age-adjusted levels (serum cholesterol, systolic blood pressure, cigarette smoking, body mass index and physical activity at work), only serum cholesterol was significant in explaining cohort differences in CHD death rates.Over 50% of the variance in CHD death rates in 25 years was accounted for by the difference in mean serum cholesterol. This association tended to decline with increasing length of follow-up, but this was due to the great changes in mean serum cholesterol in the two Jugoslavian cohorts of Velika Krsna and Zrenjanin. When these two cohorts were excluded the association increased with time.Changes in mean serum cholesterol between year 0 and 10 helped in explaining differences in CHD death rates from year 10 onward.It can be concluded that this study suggests that mean serum cholesterol is the major risk factor in explaining cross-cultural differences in CHD.

Seven Countries Study. First 20-Year Mortality Data in 12 Cohorts of Six Countries

Out of the original 16 cohorts in the Seven Countries Study on Cardiovascular Diseases, 12 population samples in six countries have reached the 20 year follow-up deadline. Data on mortality became fully available for a total of 8287 men aged 40-59 at entry examination (two cohorts in Finland, one in the Netherlands, three in Italy, two in Yugoslavia, two in Greece, and two in Japan). Death rates from CHD as well as from all causes follow the traditional falling north to south trend (18 fold between the extremes for CHD; 2.7 fold for total mortality). The differences in all causes mortality are, however, largely accounted for by the variation in CHD mortality. The mean entry levels of serum cholesterol and representative levels of the consumption of saturated fats, mono-unsaturated fats, poly-unsaturated fats and carbohydrates explain a large proportion of inter-cohort difference in CHD mortality (81% for saturated fats). By applying the proportional hazards model to the pools of national cohorts, with CHD deaths as end-point and five risk factors as covariates, only age and mean blood pressure are universally significant predictors of fatal events. Cholesterol, smoking habits, body mass index and physical activity play some part but not in all the pools. Age and mean blood pressure are also the only universal risk factors for all causes of death.

Serum cotinine as a marker of environmental tobacco smoke exposure in epidemiological studies : the experience of the MATISS project

To describe serum cotinine levels in a rural Italian population and to examine its usefulness as an epidemiologic biomarker of nicotine exposure, cross-sectional data collected in 1993 for the MATISS Project (2098 men and 1352 women, aged 20–79 years) were used. The study population consisted of 977 current smokers, 882 nonsmokers reporting exposure to environmental tobacco smoke (ETS) and 1520 nonsmokers reporting no ETS exposure. Mean values of serum cotinine measured by radioimmunoassay for never smokers, ex-smokers and current smokers (including four categories of cigarette consumption), and for categories of ETS exposure in all nonsmokers were calculated. In univariate analysis, there was a positive association between self-reported nicotine exposure and serum cotinine levels in all groups. Using self-reported status as truth, sensitivity and specificity for various cotinine cutoff points were estimated to distinguish nonsmokers from smokers. The value of 15 ng/mL represented the best combined levels of sensitivity (95%) and specificity (96%). Using this cutoff point, the overall misclassification rate for self-reported nonsmokers was 2.1% and about two times greater for the more vs. the less educated. In multivariate analysis, reported ETS exposure among nonsmokers was significantly associated with serum cotinine even after adjusting for age, socio-demographic and behavioural factors, though the strength of the association was not strong. In conclusion, serum cotinine represents a reliable epidemiological marker of nicotine intake and may be helpful when studying ETS exposure. Improved information collection is needed to reduce misclassification among nonsmokers and enhance our understanding of the relationship between ETS and cotinine measures.

Twenty-five-year prediction of stroke deaths in the seven countries study: the role of blood pressure and its changes.

BACKGROUND AND PURPOSE This report explores the prediction of long-term stroke mortality in cohorts of the Seven Countries Study. METHODS Sixteen cohorts of men aged 40 to 59 years at entry were examined at years 0, 5, and 10, with mortality follow-up through 25 years. RESULTS Stroke death rates in 25 years were high in rural Serbia, Croatia, and Japan; intermediate in Italy, Greece, and urban Serbia; and low in Finland, the Netherlands, and the United States. Age and blood pressure were powerful predictors of 25-year stroke mortality in almost all cohorts and countries. Proportional hazards regression coefficients were .0232 increase in stroke death hazard per millimeter of mercury (t=14.60) for systolic blood pressure and .0409 (t=13.41) for diastolic blood pressure. Moderate blood pressure increases from low usual levels were associated with lower stroke mortality rates in years 10 to 25. Increases of blood pressure starting from high usual levels were associated with increased rates of stroke mortality. Systolic blood pressure was associated with stroke mortality at given levels of diastolic pressure, but diastolic blood pressure was not predictive of stroke mortality at given levels of systolic blood pressure. CONCLUSIONS Associations of systolic and diastolic blood pressure with stroke mortality were similar in cultures with different stroke mortality rates. Increases in blood pressure were associated with subsequent excess stroke mortality only in those who started from high usual levels; this study finds lower stroke risk in those men whose blood pressure increased moderately from low usual levels. Diastolic blood pressure is not independently associated with stroke risk in these populations.

A Simple Risk Tool (the OBSERVANT Score) for Prediction of 30-Day Mortality After Transcatheter Aortic Valve Replacement

Risk stratification tools used in patients with severe aortic stenosis have been mostly derived from surgical series. Although specific predictors of early mortality with transcatheter aortic valve replacement (TAVR) have been identified, the prognostic impact of their combination is unexplored. We sought to develop a simple score, using preprocedural variables, for prediction of 30-day mortality after TAVR. A total of 1,878 patients from a national multicenter registry who underwent TAVR were randomly assigned in a 2:1 manner to development and validation data sets. Baseline characteristics of the 1,256 patients in the development data set were considered as candidate univariate predictors of 30-day mortality. A bootstrap multivariate logistic regression process was used to select correlates of 30-day mortality that were subsequently weighted and integrated into a scoring system. Seven variables were weighted proportionally to their respective odds ratios for 30-day mortality (glomerular filtration rate <45 ml/min [6 points], critical preoperative state [5 points], New York Heart Association class IV [4 points], pulmonary hypertension [4 points], diabetes mellitus [4 points], previous balloon aortic valvuloplasty [3 points], and left ventricular ejection fraction <40% [3 points]). The model showed good discrimination in both the development and validation data sets (C statistics 0.73 and 0.71, respectively). Compared with the logistic European System for Cardiac Operative Risk Evaluation in the validation data set, the model showed better discrimination (C statistic 0.71 vs 0.66), goodness of fit (Hosmer-Lemeshow p value 0.81 vs 0.00), and global accuracy (Brier score 0.054 vs 0.073). In conclusion, the risk of 30-day mortality after TAVR may be estimated by combining 7 baseline clinical variables into a simple risk scoring system.

Role of body mass index in the prediction of all cause mortality in over 62,000 men and women. The Italian RIFLE Pooling Project. Risk Factor and Life Expectancy.

STUDY OBJECTIVE: To evaluate the relation of body mass index (BMI) to short-term mortality in a large Italian population sample. DESIGN: Within the Italian RIFLE pooling project, BMI was measured in 47 population samples made of 32,741 men and 30,305 women ages 20-69 years (young 20-44, mature 45-69). Data on mortality were collected for the next six years. MAIN OUTCOME MEASURES: Age adjusted death rates in quintile classes of BMI and Cox proportional hazards models with six year all causes mortality as end point, BMI as covariate and age, smoking, systolic blood pressure as possible confounders were computed. Multivariate analysis was tested in all subjects and after the exclusion of smokers, early (first two years) deaths, and both categories. RESULTS: The univariate analysis failed to demonstrate in all cases a U or inverse J shaped relation. The Cox coefficients for the linear and quadratic terms of BMI proved significant for both young and mature women. The minimum of the curve was located at 27.0 (24.0, 30.0, 95% confidence limits, CL) and 31.8 (25.5, 38.2, 95% CL) units of BMI, for young and mature women respectively. Similar findings were obtained even when exclusion were performed. No relation was found for young men while for mature adult men only the model for all subjects retained significant curvilinear relation (minimum 29.3; 22.4, 36.2, 95% CL). CONCLUSION: These uncommon high values of BMI carrying the minimum risk of death seems to be in contrast with weight guidelines. A confirmation of these findings in other population groups might induce the consideration of changes in the suggested healthy values of BMI.

Prognostic Value of Dobutamine Echocardiography Early After Uncomplicated Acute Myocardial Infarction: A Comparison With Exercise Electrocardiography

OBJECTIVES This study sought to assess the relative prognostic power of dobutamine echocardiography and exercise electrocardiography after acute myocardial infarction. BACKGROUND The prognostic value of dobutamine echocardiography early after acute myocardial infarction has not yet been reported. METHODS One hundred seventy-eight patients (mean age 58 +/- 9 years) with a first uncomplicated acute myocardial infarction underwent predischarge dobutamine echocardiography (5 to 40 micrograms/kg body weight per min, plus atropine if needed) and symptom-limited bicycle exercise electrocardiography and were followed up for 17 +/- 13 months. Stress-induced dyssynergy and ST segment depression > 1 mm were considered criteria of positivity for dobutamine echocardiography and exercise electrocardiography, respectively. RESULTS Dobutamine echocardiography was positive in 83 patients and exercise electrocardiography in 60. At follow-up there were 5 deaths, 6 nonfatal myocardial infarctions (11 hard events) and 20 cases of unstable angina. Dobutamine echocardiography and exercise electrocardiography had similar negative predictive values both for all events (88% and 86%, respectively) and for hard events (98% and 95%, respectively). The hard events rate was significantly higher in patients with positive rather than negative dobutamine echocardiography (relative risk [RR] 5.15, 95% confidence interval [CI] 1.14 to 23.16), although there was no difference between patients with positive and negative exercise electrocardiograms. When Cox analysis was performed, dobutamine echocardiography had an independent prognostic value both for all events (RR 2.88, 95% CI 1.37 to 6.08) and for hard events (RR 6.56, 95% CI 1.42 to 30.46). CONCLUSIONS After uncomplicated acute myocardial infarction, dobutamine echocardiography and exercise electrocardiography have a similar high negative predictive value for both all events and hard events only. Positive dobutamine echocardiography, but not positive exercise electrocardiography, identifies a group of patients at higher risk of subsequent cardiac events.