Age- and sex-related utilisation of cardiac procedures and interventions: a multicentric study in Italy.

BACKGROUND: Cardiovascular diseases represent the leading cause of death in Italy and one of the most frequent cause of disability in the elderly. The aim of the study was to investigate the influence of age and sex of patient on the utilisation of cardiac procedure and interventions in Italy. METHODS: Retrospective analysis of 2805 patients' medical case notes in cardiology, internal medicine and elderly clinics in six Italian Regions during the period 1996-1997, considering coronary catheterisation (CC), percutaneous transluminal coronary angioplasty (PCTA), coronary artery bypass grafting (CABG), thrombolysis (THR) and permanent pacemaker (PPM) implantation. RESULTS: Older patients (more than 75 years old) were less likely to undergo CC (OR=0.062). Trends for age and sex did not achieve significance for CAGB (OR=0.815 for older patient). Age is a strong predictor of receiving PTCA, with the oldest group of patients being discriminated (OR=0.093 for people older than 75 years), and the same trend was observed for THR (OR=0.264 for patients older than 75 years). For PPM, older patient has a higher likelihood of receiving this type of intervention (OR=3.45 for 65-74 years, and OR=7.77 for patients older than 75 years). As far as gender of patients is concerned, statistically significant differences for all cardiac procedures or interventions considered were not found. CONCLUSIONS: Clinical management of older patients with cardiac disease in Italy may be different from that of younger patients. One possible explanation would be that these patients are being discriminated against mainly because of their age.

Exposure levels and cytochrome P450 1A2 activity, but not N-acetyltransferase, glutathione S-transferase (GST) M1 and T1, influence urinary mutagen excretion in smokers.

We investigated the polymorphic enzymes cytochrome P450 1A2 (CYP1A2), N-acetyltransferase (NAT2), glutathione S-transferase (GST) M1 (GSTM1), and T1 (GSTT1) in relation to cigarette smoking-associated urinary mutagenicity detected on YG1024 Salmonella typhimurium strain with S9 mix in 97 smokers. In each subject, cigarette smoke intake was checked by analysis of urinary nicotine plus its metabolites. NAT2 and CYP1A2 phenotypes were determined by the molar ratio of urinary caffeine metabolites detected by high-performance liquid chromatography, and GSTT1 and GSTM1 genotypes were determined by PCR. An increase in urinary mutagenicity was significantly related to levels of exposure to cigarette smoke and CYP1A2 N-hydroxylation activity (linear multiple regression analysis t = 4.51 and P < 0.001 and t = 3.09 and P = 0.003; F = 6.31, P < 0.001). Urinary mutagenicity was significantly higher in CYP1A2 extensive metabolizer smokers (n = 49) than in CYP1A2 poor metabolizer ones (n = 48; 2176 +/- 1525 versus 1384 +/- 1206 revertants/mmol creatinine, Mann-Whitney U-test, z = 2.65, P < 0.001). The highest mutagenic activity was seen in subjects CYP1A2 extensive metabolizer/NAT2 slow acetylators (n = 29) with respect to the other phenotype combinations (n = 68; 2392 +/- 1660 versus 1525 +/- 1238 revertants/mmol creatinine, Mann-Whitney U-test, z = 2.37, P = 0.017). NAT2 acetylation activity was slightly but inversely related to urinary mutagenicity, and the association was not significant. No effect of GSTM1 and GSTT1 genotypes in lowering (detoxifying) urinary mutagens was found. The significant enhancement of urinary mutagenicity associated with increased CYP1A2 activity, as already seen for diet-caused urinary mutagenicity, allows for many analogies between the process of mutagen formation derived from cooked meat and that from cigarette smoke condensate. In conclusion, the intensity of tobacco smoke exposure, modulated by CYP1A2 activity, is the major determinant of mutagenic urine among smokers, whereas GSTM1 and GSTT1 genotypes have no influence on this biomarker. This study suggests that CYP1A2 should definitely be determined in future studies involving urinary mutagenicity in cases in which smoking is a factor.

Tobacco-smoke exposure indicators and urinary mutagenicity.

In this study, the correlation of indicators of external (i.e. mean daily intake of condensate, nicotine, tobacco and tobacco proteins, and daily number of cigarettes smoked) and of internal tobacco-smoke exposure (i.e. urinary 1-pyrenol, nicotine and its metabolites and trans,trans-muconic acid) with urinary mutagenicity, detected on YG1024 Salmonella typhimurium strain with S9, were examined in 118 smokers. An increase in urinary mutagenicity was clearly significantly correlated with each external and internal indicators of exposure to tobacco smoke (correlation coefficient (r) ranging between 0.22 and 0.54, P<0.01), with a greater extent in the case of indicators of internal dose. In multiple regression analysis, among the indicators of external exposure, daily tobacco intake was the only variable significantly associated with urinary mutagenicity (t=2.47, P=0.015, with partial contribution to r(2)=5.15%). Instead, when all indicators of exposure (external and internal) were considered in the analysis, the influence of urinary 1-pyrenol on urinary mutagenicity was predominant, followed by those of urinary trans,trans-muconic acid and nicotine plus metabolites (t=4.63, 2.73 and 2.08, P<0.001, P=0.002 and 0.04, with partial contribution to r(2)=17.0, 6.66 and 3.96%, respectively), with no influence at all of external tobacco-smoke exposure indicators. In conclusion, our results show that indicators of internal dose are better correlated with formation of mutagens in urine of smokers. Among these, the best indicator was urinary 1-pyrenol and this result designates the combustion processes of tobacco as the determining step for the formation of urinary mutagens. However, as these biomarkers cannot be analysed the amount of daily tobacco intake represent the best valuable index of external (presumptive) exposure to tobacco-smoke genotoxins.