Relationship between B-type natriuretic peptide levels and ventilatory response during cardiopulmonary exercise test in patients with chronic heart failure.

AIM: Aim of the study was to evaluate if brain natriuretic peptide (BNP) levels, a cardiac neurohormone well correlated with prognosis in chronic heart failure (CHF), are associated with enhanced ventilatory response to exercise, in ambulatory patients with intermediate peak oxygen uptake (PVO2). METHODS: Resting BNP was measured in 129 consecutive stable CHF patients with mild to moderate heart failure (90% New York Heart Association (NYHA) class II or III) and intermediate (10-18 mL/kg/min) PVO2, assessed during cardiopulmonary exercise test. Mean (SD) left ventricular ejection fraction (EF) and pulmonary systolic pressure (PAP) were 41 +/- 3% and 47 +/- 14 mmHg, respectively. The enhanced ventilatory response to exercise (EVR) was assessed as a slope of the relation between minute ventilation and carbon dioxide production (VE/VCO2 slope) > 35. RESULTS: Thirty-three over 129 patients (26%) had EVR. Mean BNP plasma level was 394 +/- 347 pg/mL. A significant correlation between BNP and EVR (r = 0.310; p < 0.01), was observed. In the logistic multivariate model, a BNP plasma level > 100 pg/mL had an independent predictive value for EVR (95% IC 1.68 to 10.5, Odds Ratio 4.23, p = 0.02). We found a significant correlation between BNP and PAP (r = 0.390; p < 0.001), and between PAP and EVR (r = 0.511; p < 0.01). CONCLUSIONS: In CHF patients with intermediate PVO2, plasma BNP is clearly related to the enhanced ventilatory response to exercise. In this subset, BNP levels could represent an effective alternative tool for the clinical assessment in patients with unreliable cardiopulmonary exercise test.

Influence of contractile reserve and inducible ischaemia on left ventricular remodelling after acute myocardial infarction.

OBJECTIVE: To assess the relative influence of contractile reserve and inducible ischaemia on subsequent left ventricular volume changes after myocardial infarction. DESIGN: Left ventricular end diastolic and end systolic index volumes were calculated prospectively at discharge and at six months in 143 patients referred for early postinfarction dobutamine stress echocardiography. On the basis of their responses to this test, patients were divided into three groups: scar (n = 48; group 1); contractile reserve (n = 36; group 2); inducible ischaemia (n = 59; group 3). RESULTS: At six months, the left ventricular end diastolic index volume decreased in group 2 (mean (SD), -3.9 (9.4) ml/m2) and increased in both group 1 (+2.8 (10.6) ml/m2, p = 0.009 v group 2) and group 3 (+7.5 (11.4) ml/m2, p < 0.0001 v group 2). The end systolic index volume decreased in group 2 (-4.9 (7.3) ml/m2) and increased in both group 1 (+1.3 (8.3) ml/m2, p = 0.0015 v group 2) and group 3 (+2.8 (8.9) ml/m2, p = 0.0002 v group 2). In multivariate analysis, the contractile reserve (hazard ratio 0.19, 95% confidence interval (CI) 0.14 to 0.47), inducible ischaemia (5.86, 95% CI 1.54 to 29.7), and end systolic index volume at discharge (1.04, 95% CI 0.99 to 1.11) were independent predictors of an increase in end diastolic index volume of > or = 15 ml/m2 at six months. CONCLUSIONS: Contractile reserve and inducible ischaemia, as detected by early dobutamine stress echocardiography, identify patients with differences in long term left ventricular remodelling after acute myocardial infarction.

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.

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.

[Smoking and prevention of cardiovascular diseases in Italy. Research Group of the Cardiovascular Epidemiologic Observatory]. / Fumo e prevenzione delle malattie cardiovascolari in Italia. Gruppo di Ricerca dell'Osservatorio Epidemiologico Cardiovascolare.

BACKGROUND: Cigarette smoking is one of the most important risk factors for chronic diseases. Major epidemiological studies provide consistent evidence that cardiovascular risk is 3-fold among smokers compared to non-smokers, incidence increases with the number of cigarettes smoked daily and cardiovascular risk is less among subjects who have stopped smoking. METHODS: To support evidence of a time decreasing trend of smoking habits in Italy, data from two observational studies carried out in different Italian regions, the RIFLE Project (1978-1987), the Cardiovascular Epidemiological Observatory (1998), and data collected from the "Multiscopo" ISTAT Investigation on Italian families (1980-1997) have been analyzed. RESULTS: During the 1950's, the prevalence of smokers among adult men was about 80%, it decreased to 50% in the 1980's and now is about 30-40%. Contemporarily, the prevalence of smokers among adult women has increased, from 17% in the 1980's to 23% nowadays. The habit is more common in Central-Southern Italy compared to the North and is less frequent among married subjects, and male graduates. Learned women smoke more than those who have not received any education. Men begin smoking at 17-18 years, and this trend seems to have remained stable; on the contrary, women have changed their habits and now start smoking at 17 years compared to 25-30 in previous generations. Almost all smokers would like to stop smoking, more than 60% have tried at least once, but on average have lasted only for about 1 year. Passive smoking exposure varies from 1 hour in Northern Italy to 2 hours in the South. CONCLUSIONS: Although smoking habits, at least in men, reveal a decreasing trend, about 30-40% of adult men continue to smoke. Preventive intervention, especially focused on the younger generations, could be useful to contrast this attitude at an early stage.

Independent value of tumor size and DNA ploidy for the prediction of disease progression in patients with organ-confined renal cell carcinoma.

BACKGROUND: Greater than 20% of patients with apparently localized renal cell carcinoma (RCC) present with disease progression after surgery. The objective of the current study was to improve the ability of clinicians to predict prognosis in patients with localized RCC. METHODS: The authors studied 154 patients with organ-confined RCC classified as pT1 to pT2-pN0-M0 who underwent radical nephrectomy. Follow-up ranged from 24-128 months (median, 72 months). Several morphologic parameters of the tumor were considered. DNA content was analyzed by flow cytometry and tumor size was determined from the surgical specimen. A Cox proportional hazards regression model was used to identify significant independent prognostic factors for disease progression. RESULTS: At 5 and 10 years of follow-up, disease free survival was found to be 87% and 86%, respectively. Univariate analysis revealed that DNA content, Furhman grade, and tumor size had a statistically significant predictive value for disease progression, whereas, with regard to grade, the difference was significant only between patients with Grade 3 tumors and all other patients with Grade 1-2 tumors (P < 0. 0001). Although DNA content was found to correlate with tumor size (P < 0.0001), multivariate analysis showed that these were the only significant independent predictors of disease progression. The sum of DNA content and tumor size therefore was considered to distinguish separate risk groups. For a patient with diploid RCC, the risk of progression increased from 4% if the tumor size was 3 cm to 43% if the tumor size was 10 cm. For a patient with nondiploid RCC, this risk was 32% if the tumor size was 3 cm, increasing to 99% for tumors measuring 10 cm. CONCLUSIONS: Stratification of organ-confined RCC according to tumor size and DNA content could possibly provide more information that could be useful in the selection of individuals with significantly different risks of disease progression.

The common mutations in the lipoprotein lipase gene in Italy: effects on plasma lipids and angiographically assessed coronary atherosclerosis.

The present study evaluated the role of the common lipoprotein lipase (LPL) mutations on the risk of dyslipidemia and coronary atherosclerosis in an Italian population. Cohorts of 632 patients undergoing coronary angiography, as well as 191 healthy controls, were screened by a combination of PCR and restriction enzyme digestion. In the pooled population, the frequencies of LPL D9N and N291S were 4.1%, with no homozygous carriers, whereas that of LPL S447X was 21% with 19.6% heterozygous and 1.4% homozygous carriers. Compared to non-carriers, LPL N291S carriers showed higher plasma triglycerides (TG) (p < 0.03) and increased risk of high TG phenotype (odds ratio [OR] 2.49, 95% Cl 1.06-5.81; p < 0.03). When this LPL mutation was associated with high body mass index (BMI) ( > 25 Kg/m2) or fasting, plasma insulin (> 10.6 mU ml(-1)) significantly reduced HDL-C levels were also observed. Carriers of the S447X mutation presented with higher HDL-C concentrations (p < 0.05) as compared to non-carriers; they also showed a significantly reduced risk of high TG/low HDL-C dyslipidemia (OR 0.34, 95%, Cl 0.12-0.99; p < 0.05). The favourable effect of the LPL S447X variant was even more pronounced in lean subjects and in those with low insulin levels. No significant influence on plasma lipids by the LPL D9N was observed. None of LPL variants was a significant predictor of angiographically assessed coronary atherosclerosis. At most, the risk was borderline, increased in N291S carriers and possibly decreased in S447X carriers.

A common mutation of the insulin receptor substrate-1 gene is a risk factor for coronary artery disease.

Insulin resistance is associated with increased risk of atherosclerosis. Insulin receptor substrate-1 (IRS-1) plays a key role in tissue insulin sensitivity. A common mutation (G972R) of the IRS-1 gene has been shown to impair IRS-1 function, and it has been associated with reduced insulin sensitivity and lipid abnormalities. This led us to investigate the role of the G972R mutation in predisposing individuals to coronary artery disease (CAD). The DNA of 318 subjects with angiographically documented coronary atherosclerosis (>50% stenosis) and 208 population control subjects was analyzed for the presence of the G972R mutation. This mutation was detected by nested polymerase chain reaction and BstNI restriction enzyme digestion. The frequency of the G972R mutation was significantly higher among patients with CAD than controls (18. 9% versus 6.8%, respectively; P<0.001). After controlling for other coronary risk factors, the relative risk of CAD associated with the G972R mutation was 2.93 (95% CI 1.30 to 6.60; P<0.02) in the entire cohort. This risk was found to be even higher in the subgroups of obese subjects (odds ratio [OR] 6.97, 95% CI 2.24 to 21.4; P<0.001) and subjects with clinical features of insulin resistance syndrome (OR 27.3, 95% CI 7.19 to 104.0; P<0.001). The IRS-1 gene variant was associated with a higher frequency of diabetes mellitus (14.9% among carriers versus 6.5% among noncarriers; P<0.01) and with a 60% increase of plasma total triglycerides (P<0.001). Also, plasma concentrations of total cholesterol and the ratio of total cholesterol to HDL cholesterol were significantly (P<0.001) higher among carriers than noncarriers, although to lesser a extent. These effects were independent of CAD status. The G972R mutation in the IRS-1 gene was found to be a significant independent predictor of CAD. Moreover, this mutation greatly increased the risk of CAD in obese subjects and in patients with the cluster of abnormalities of insulin resistance syndrome. Besides the increased frequency of diabetes, carriers showed a more atherogenic lipid profile, suggesting a potential role of the IRS-1 gene in the pathogenesis of lipid abnormalities associated with CAD.

Prediction of cardiac events after uncomplicated acute myocardial infarction by clinical variables and dobutamine stress test.

OBJECTIVES: We sought to determine the relative prognostic power of several clinical and dobutamine stress test variables in patients after a first uncomplicated acute myocardial infarction (AMI). BACKGROUND: The value of dobutamine echocardiography (DE) for determining prognosis after AMI is not yet defined. In particular, the influence of dobutamine stress test response on the outcome of these patients is unknown. METHODS: A graded predischarge DE (from 5 to 40 microg/kg/min, plus atropine if needed) was performed in 245 patients (mean age 60 +/- 10 years) with a first uncomplicated AMI. RESULTS: At follow-up (17 +/- 13 months), an adverse outcome occurred in 40 patients: cardiac death in 7, nonfatal myocardial infarction in 9 (hard events = 16) and unstable angina requiring hospital readmission in 24. Significant predictors of adverse outcome by univariate analysis were positive DE, ischemic wall motion score index (WMSI), angina during DE and diabetes for all events, and positive DE, ischemic WMSI and age for hard events. At multivariate analysis, the only independent predictors of adverse outcome were positive DE, diabetes and angina during DE for all events, and positive DE and age for hard events. The presence of both age >60 years and a history of diabetes identified patients at high risk of cardiac events (event rate 37%), compared with patients <60 years and no diabetes (event rate 11%). In patients with intermediate risk (only one clinical risk factor, event rate 18%), DE added prognostic information (event rate 10% in the negatives, 25% in the positives and 35% in the positives with angina). CONCLUSIONS: After uncomplicated AMI, dobutamine stress test variables offer additional prognostic information to clinical data.

Effects of early treatment with captopril and metoprolol singly or together on six-month mortality and morbidity after acute myocardial infarction. Results of the RIMA (Rimodellamento Infarto Miocardico Acuto) study. The RIMA researchers.

UNLABELLED: The RIMA (Rimodellamento Infarto Miocardico Acuto) study was designed to assess the relative effects of angiotensin-converting enzyme (ACE) inhibition by captopril, beta-blocker therapy by metoprolol, and their combination in patients with a first acute myocardial infarction on: 1. echocardiographically detected left ventricular remodeling; 2. prognosis. The second goal will be the argument of the present paper. Two-hundred fifty < or = 75 years consecutive patients (mean age: 58 yrs, males = 203) with acute myocardial infarction were randomly allocated to receive for > or = 3 months captopril (up to 75 mg/day, Group 1), metoprolol (up to 200 mg/day, Group 2) or captopril + metoprolol (Group 3) starting in the first 24 hours after the onset of symptoms. Intravenous beta-blockers in the acute phase of myocardial infarction and all other cardioactive drugs were allowed. The effect of the randomized therapy at six months from admission to the coronary care unit was considered in relation to: 1. recurrence of spontaneous cardiac events and of elective revascularization procedures; 2. adverse reactions (hypotension, atrioventricular block, cough, allergy, need of beta-blockers in Group 1, need for ACE inhibition in Group 2) requiring treatment modification based on physician's decision. RESULTS: Definite follow-up data were available in 226 patients and 195/226 patients (86%) had a complete treatment period. In these patients (per protocol analysis), 37 spontaneous cardiac events occurred: cardiac death = 6, non-fatal reinfarction = 9, unstable angina requiring hospitalization = 16, congestive heart failure = 6. Moreover, seven patients received a coronary revascularization procedure. Events occurred in 11/67 patients from Group 1, 16/63 patients from Group 2, 10/65 patients from Group 3 (16% vs 25% vs 15%, p = 0.28). The multiple logistic regression analysis demonstrated an increased odds ratio (OR) for spontaneous cardiac events in patients from Group 2 (OR = 2.82, 95% Cl: 1.16-6.87: p < 0.05). Elective revascularization procedures were statistically less frequent in patients treated with metoprolol (Group 1 = 9%, Group 2 = 1.6%, Group 3 = 0%; Group 1 vs Groups 2 and 3; p = 0.03). The intention-to-treat analysis on the overall population (226 patients) confirmed the presence of a trend towards a higher risk in patients from Group 2 (OR = 2.1, 95% Cl: 0.96-4.59; p = 0.06). Adverse reactions were observed in 16 patients from Group 1, 6 patients from Group 2 and 15 patients from Group 3 (22% vs 10% vs 23%; Group 2 vs Groups 1 and 3; p = 0.08). At the multivariate regression analysis, a trend towards less adverse reactions in patients assigned to the beta-blocker therapy alone was confirmed (OR = 0.41, 95% Cl: 0.15-1.13; p = 0.07). CONCLUSIONS: In a randomized early post-infarction treatment strategy, ACE inhibition with captopril alone or in combination with metoprolol demonstrated an increased protection against spontaneous cardiac events at six months in comparison with metoprolol alone. On the other hand, the beta-blocker treatment was associated with a lower number of elective revascularization procedures and appeared better tolerated than ACE inhibition.

Can the intraprostatic concentration of epidermal growth factor influence the variance of serum prostate specific antigen levels in patients with benign prostatic hyperplasia?

PURPOSE: Except for prostate volume, little is known about the factors influencing serum prostate specific antigen (PSA) levels. Considering that dihydrotestosterone and epidermal growth factor are regulators of the proliferation and differentiation in the epithelial component of human prostate tissue and that PSA is produced only by the epithelial cells of the gland, studies were performed on patients with a histological diagnosis of benign prostatic hyperplasia (BPH) to establish whether a significant association exists between the intraprostatic concentration of dihydrotestosterone or epidermal growth factor and serum PSA levels. MATERIALS AND METHODS: A total of 20 patients with BPH who had not been previously treated were part of a larger study on the correlation among PSA, prostate volume and age, and were evaluated according to the algorithm in the guidelines of the international consultation on BPH. All men underwent open suprapubic prostatectomy to enucleate the entire adenoma and in each case sections were made in the periurethral, subcapsular and intermediate zones of the BPH tissue. Dihydrotestosterone and epidermal growth factor concentrations were evaluated by radioimmunoassay in the periurethral zone and in total BPH tissue. RESULTS: In these 20 patients with BPH serum PSA levels were significantly associated with epidermal growth factor but not with dihydrotestosterone concentrations in total BPH tissue (r = 0.7762, p = 0.00002836 and r = 0.3923, p = 0.0956307, respectively). A stronger association was found between PSA levels and the periurethral concentration of epidermal growth factor and dihydrotestosterone (r = 0.8117, p = 0.000005 and r = 0.5656, p = 0.0098326, respectively). On the contrary, epidermal growth factor and dihydrotestosterone were not significantly associated with prostate volume (p = 0.957415 and p = 0.531439, respectively). CONCLUSIONS: To our knowledge this study is the first report in the literature to demonstrate an association between serum PSA, and dihydrotestosterone and epidermal growth factor levels, particularly in the periurethral zone of human BPH tissue. These data suggest the importance of epidermal growth factor and dihydrotestosterone in influencing serum PSA levels.

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.

Angiotensin-converting enzyme gene polymorphism is not associated with coronary atherosclerosis and myocardial infarction in a sample of Italian patients.

BACKGROUND: The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene has been proposed as a genetic marker of the risk of ischaemic heart disease. However, the relationships between ACE genotypes, the development of coronary atherosclerosis and the occurrence of major coronary events are still controversial. METHODS: To investigate whether the ACE I/D (insertion/deletion) polymorphism predicts the risk of coronary stenosis and myocardial infarction (MI), ACE genotypes were determined in 394 consecutive patients who underwent coronary angiography. The presence determined in 394 consecutive patients who underwent coronary angiography. The presence of coronary artery disease (CAD) (defined by > 50% stenosis) was detected in 236 patients (CAD+); 85 of these individuals had a history of MI. Patients with coronary stenosis < 10% (n = 158) served as controls (CAD-). ACE genotypes were determined by agarose gel sizing after polymerase chain reaction (PCR) amplification. RESULTS: The distribution of ACE genotypes in CAD+ patients was not significantly different from that in CAD-patients (chi 2 = 2.63, P < 0.27). After controlling for other coronary risk factors, no significant increase in risk of CAD or MI was found to be associated with the D allele, regardless of whether the D allele was assumed to have a dominant, a codominant or a recessive effect. Similar results were observed in CAD+ patients at lower risk because of low body mass index and apolipoprotein B concentrations. Smoking, apolipoprotein B and history of hypertension were found to be independent predictors of CAD and MI. CONCLUSION: Our study did not provide evidence of a significant association between ACE genotypes and the development of coronary atherosclerosis. It also failed to support a role of ACE I/D polymorphism in favouring the conversion of coronary stenosis to MI.

Relationship among age, prostate-specific antigen, and prostate volume in men with lower urinary tract symptoms (LUTS) and in different groups of men with and without benign and malignant prostate diseases.

BACKGROUND: In order to enhance prostate-specific antigen (PSA) as a predictor of prostate cancer, it is necessary to understand the characteristics of this tumor marker in a population of men without evidence of prostate cancer but who are at risk for developing the condition. METHODS: In an age-stratified population of 328 men with lower urinary tract symptoms (LUTS), we analyzed the distribution of PSA levels as a function of age and prostate volume, and we analyzed the percentage of age-related variance in PSA that can be explained by the age-related variance in prostate volume. RESULTS: Classifying the 328 cases with LUTS according to four age groups, a correlation was found between PSA and prostate volume, becoming stronger from the younger (correlation coefficient, -0.1265) to the older group (correlation coefficient, 0.6044). Serum PSA variance per milliliter of prostate volume also increased from the younger (not significant, P > 0.1) to the older age decades (7.3% in men age 70 years or over). Moreover, the results of the regression analysis suggest that 10% of the variance in PSA with age can be accounted for by prostate volume in men under age 50 years, reaching 37% in men age 70 years or more. CONCLUSIONS: These data confirm that the serum PSA concentration increases with advancing age in the absence of clinically evident prostatic malignancy. In younger patients with LUTS, serum PSA variance with age seems to be less dependent upon the age-related variance in prostate volume.

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.

Relationship among symptom score, prostate volume, and urinary flow rates in 543 patients with and without benign prostatic hyperplasia.

BACKGROUND: Studies on the relationship among symptom score, urinary flow rate, and prostate volume in men with lower urinary tract symptoms (LUTS) continue to be of great interest. METHODS: A total of 2,418 men, aged 30-86 years, agreed to participate in an interview and to complete a questionnaire regarding voiding patterns. All subjects answering positively to one or more of the questions were submitted to a diagnostic assessment, based on the algorithm outlined by the guidelines of the International Consultation on Benign Prostatic Hyperplasia (BPH). Five hundred forty-three out of the 2,418 participants (22.45%) were evaluated. At the end of the diagnostic evaluation, 400 men with LUTS but without concomitant conditions (except BPH) known to interfere with normal voiding were selected. Descriptive statistics were used to characterize age, symptom score (International Prostate Symptom Score), prostate volume, and urinary flow rate distribution in these patients. Correlations among the aforementioned parameters were evaluated by means of a multivariate, multiple linear regression and logistic regression model. RESULTS: As reported in other studies, only weak or modest correlations were found. Moreover, the 400 cases were classified according to four age decades. The decrease in peak and mean flow rate per decade of age was similar (0.5 and 0.4 ml/sec); the increase in prostate volume and in total symptom score per decade was 3.3 cc and 0.6, respectively. In patients less than 50 years old, most of the correlations were stronger than those observed in the entire population of 400 men (age and prostate volume, c.c. 0.2864; age and peak flow rate, c.c. -0.2689; age and mean flow rate, c.c. -0.3034). However, symptom score continued to be weakly correlated with age and prostate volume (c.c. 0.0498 and 0.1966, respectively). In the last part of the study, men were assigned to different treatment strategies. Patients who were assigned to surgical treatment had higher prostate volume and IPSS and lower urinary flow rate than those assigned to nonsurgical treatment. CONCLUSIONS: We believe that the reason for the weak statistical association frequently reported in the literature is mainly the urology clinic-based population from which the patient samples were drawn. Data emerging from this analysis support the hypothesis that age is one of the principal factors influencing the relationship among symptom score, urinary flow rate, and prostate volume.

Relationship of some risk factors with typical and atypical manifestations of coronary heart disease.

BACKGROUND: This analysis explores whether 'typical' clinical manifestations of coronary heart disease (CHD) such as myocardial infarction and sudden death, relate to major cardiovascular risk factors in the same way as the 'atypical' manifestations, e.g. heart failure and chronic arrhythmias. PATIENTS AND METHODS: Sixteen cohorts of men aged 40-59 in seven countries were examined, risk factors measured (age, systolic blood pressure, serum cholesterol and smoking habits) and 25-year mortality data collected in a systematic way. Cohorts were located in the US (n = 1), Finland (n = 2), the Netherlands (n = 1), Italy (n = 3), former Yugoslavia (n = 5), Greece (n = 2) and Japan (n = 2), with a total of 12,763 individuals. Ecological analysis based on regression equations and correlation among cohorts, and individual analyses based on proportional hazard models in pools of cohorts were conducted with typical and atypical CHD deaths as dependent variables. RESULTS: The ecological analysis suggests a significant relationship of populational mean levels of serum cholesterol and of systolic blood pressure to age-adjusted death rates from typical CHD manifestations. The relationships for atypical CHD deaths were not statistically significant. In the ecological approach with multivariate analysis, none of the risk factors showed relevant associations with event rates, except serum cholesterol and typical CHD deaths. The ecological relationship of serum cholesterol to atypical CHD death rates was negative but not significant. On average, mean age at death was statistically higher among atypical CHD than typical CHD patients (70.2 vs. 65.8 years). In the individual multivariate analysis conducted on pools of countries, the relationship of risk factors with typical CHD deaths was direct and significant for age, systolic blood pressure, and smoking habits in Northern Europe and America and Southern Europe, but only for systolic blood pressure and smoking habits in Japan, whereas for atypical CHD, the predictive factors were age, systolic blood pressure and cigarette smoking in Northern Europe and America and Southern Europe, but only age in Japan. CONCLUSIONS: The usual relationship of blood pressure and smoking habits and the differential relationship of serum cholesterol with atypical CHD (negative or absent) versus typical CHD (direct and significant) could be explained by 'two different diseases' or by a mix of poorly classified conditions among the atypical cases.

Comparative total mortality in 25 years in Italian and Greek middle aged rural men.

STUDY OBJECTIVE: Mortality over 25 years has been low in the Italian and very low in the Greek cohorts of the Seven Countries Study; factors responsible for this particularity were studied in detail. PARTICIPANTS AND SETTINGS: 1712 Italian and 1215 Greek men, aged 40-59 years, cohorts of the Seven Countries Study, representing over 95% of the populations in designated rural areas. DESIGN: Entry (1960-61) data included age, systolic blood pressure (SBP), smoking habits, total serum cholesterol, body mass index (BMI), arm circumference, vital capacity (VC), and forced expiratory volume in 3/4 seconds (FEV); the same data were obtained 10 years later. Multivariate Cox analysis was performed with all causes death in 25 years as end point. MAIN RESULTS: Italian men had higher entry levels of SBP, arm circumference, BMI, and VC; Greek men had higher cholesterol levels, smoking habits, and FEV. Mortality of Italian men was higher throughout; at 25 years cumulative mortality was 48.3% and 35.3% respectively. Coronary heart disease and stroke mortality increased fivefold in Italy and 10-fold in Greece between years 10 and 25. The only risk factor with a significantly higher contribution to mortality in Italian men was cholesterol. However, differences in entry SBP (higher in Italy) and FEV (higher in Greece) accounted for, according to the Lee method, 75% of the differential mortality between the two populations. At 10 years increases in SBP, cholesterol, BMI, and decreases in smoking habits, VC, FEV, and arm circumference had occurred (deltas). SBP increased more and FEV and VC decreased more in Italy than in Greece. Deltas, fed stepwise in the original model for the prediction of 10 to 25 years mortality, were significant for SBP, smoking, arm circumference, and VC in Greece, and for SBP and VC in Italy. CONCLUSION: Higher mortality in Italian men is related to stronger positive effects of entry SBP and weaker negative (protective) effects of FEV; in addition 10 year increases in SBP are higher and 10 year decreases in FEV are larger in Italy. Unaccounted factors, however, related to, for example, differences in the diet, may also have contributed to the differential mortality of these two Mediterranean populations.

The relationship of cardiovascular risk factors measured at different ages to prediction of all-cause mortality and longevity.

The objective was to study the relationship of cardiovascular risk factors measured at different ages to all-cause mortality in a population-based sample of middle-aged Italian men over a 30-year period. Two rural populations of men aged 40-59 were examined in 1960 (n=1712, participation rate 98.8%). Cardiovascular disease risk factors measured at year 0, 10 and 20 were used for the multivariate prediction of all-cause mortality during 30, 20 and 10 years, respectively. In men aged 40-59 with follow-up of 30 years, age, systolic blood pressure, serum cholesterol, cigarette smoking, body mass index, arm circumference (inverse), vital status of father and mother, forced expiratory volume (inverse), arcus senilis and xanthelasma were strong, significant predictors of mortality. In men aged 50-69 followed for 20 years, age, systolic blood pressure, cigarette smoking, vital capacity (inverse), body mass index and arcus senilis were strong, significant predictors of mortality. In men aged 60-79 followed 10 years only age, arm circumference (inverse) and arcus senilis were significant predictors of mortality (respiratory measurements were not available). On two occasions body mass index and serum cholesterol showed curvilinear relationships with mortality (U-shaped). It is concluded that cardiovascular disease risk factors are strong predictors of all-cause mortality. Their predictive power (relative risk) declines with age. Some factors, such as body mass index and serum cholesterol level, show curvilinear relationship to mortality with greater age.

[Prognostic stratification after acute uncomplicated myocardial infarction: exercise test, echo-dobutamine test or both?]. / Stratificazione prognostica dopo infarto miocardico acuto non complicato: test da sforzo, test eco-dobutamina, o entrambi?

OBJECTIVES: The aims of this study were: 1) to assess the relative prognostic value of predischarge dobutamine echocardiography (DE) and exercise electrocardiography (EE) in patients after a first uncomplicated acute myocardial infarction (AMI), and 2) to evaluate the optimal prognostic strategy by using the two tests in different combinations. METHODS: DE (dobutamine infusion 5 to 40 micrograms/kg/min plus atropine 0.25 to 1 mg, if needed) and symptom-limited bicycle EE were performed in 208 patients (mean age 58 +/- 9 years, 90% males), on different days and in random order, 12 +/- 4 days after a first uncomplicated AMI and after pharmacological washout. A stress-induced dyssynergy and ST segment depression > 1 mm were considered criteria of positivity for DE and EE, respectively. Only spontaneous cardiac events were considered: cardiac death, reinfarction (= hard events), and unstable angina requiring hospitalization (= soft events). RESULTS: Thirty-eight events occurred during follow-up (16 +/- 13 months; range: 1-44 months); 5 cardiac deaths, 6 reinfarctions and 27 unstable angina. Patients with a positive DE had a twofold increase in all event rates (26 vs 12%, p < 0.01) and a fourfold increase in the rate of hard events (9 vs 2%, p < 0.05). In contrast, no statistically significant difference was observed in the distribution of the same events between patients with positive and negative EE. Both tests showed similar negative (DE 88%, EE 85%) and positive (DE 26%, EE 24%) predictive values. Among six different strategies (performing either DE or EE only in all patients; EE in all patients; EE in all patients and DE only in those with a positive EE; and DE only in those with a negative EE; EE in all patients and DE only in those with anterior AMI), EE only in patients with inferior or non-Q AMI and DE only in those with anterior AMI), performing DE only in patients with a positive EE gave the highest predictive accuracy-74% (95% confidence intervals 68 to 80) for all events and 77% (95% confidence intervals 71 to 83) for hard events. CONCLUSIONS: In patients with a first uncomplicated AMI, DE is useful in identifying patients at high and low risk of future spontaneous cardiac events. The optimal strategy for prognostication of these patients is to perform EE in all and DE only in the ones with a positive EE.