A. Dormi

Association of serum C3 levels with the risk of myocardial infarction

PURPOSE Serum complement and IgA levels have been found to be retrospectively associated with the presence of diffuse atherosclerosis. This study was performed to assess whether serum immunoglobulins and complement components are predictive of future ischemic events. PATIENTS AND METHODS The baseline values of IgG, IgA, IgM, C3, and C4 were measured in the sera from a cohort of 860 inhabitants of the town of Brisighella, Italy. They were 444 men and 416 women, mean age 53.9 years (SD 12.4, range 23 to 84), who had not had any ischemic events (myocardial infarction [MI], angina pectoris, stroke, transient ischemic attack, or intermittent claudication) at the time of blood sampling in 1984. Their baseline values for the main recognized risk factors for atherosclerosis were known at baseline and for 4 years of follow-up. Multiple logistic regression analysis was performed for associations between ischemic events and immunologic variables (including serum IgG, IgA, IgM, C3, and C4) and risk factors for atherosclerosis (including age, sex, diastolic blood pressure, cigarette consumption, Quetelet index, total cholesterol, HDL cholesterol, triglycerides and blood glucose). RESULTS During follow-up, 57 subjects experienced ischemic events, including 28 cases of coronary heart disease (17 MI and 11 angina pectoris). Of the immunologic variables studied, only serum C3 was found to be independently associated with ischemic events (P < 0.005 for any ischemic events, coronary heart disease, and MI). The population was divided into thirds according to C3 values. The cumulative incidence of MI was 7.1/1,000 in the low third, 10.6/1,000 in the middle third and 40.8/1,000 in the high third (risk ratio for high versus middle plus low = 4.2 after adjustment for age and sex; 95% CI 1.5 to 11.7). A separate analysis for the sexes showed that serum C3 was a particularly powerful predictor of MI in men. Men whose C3 levels were in the top third had a 72.6/1,000 incidence of MI while the incidence in the rest of the male population was 6.2/1,000 (risk ratio 10.7 after adjustment for age; 95% CI 2.3 to 49.0). When similar analyses were performed for angina pectoris, stroke, and intermittent claudication, no significant increase in risk was found to be associated with serum C3. CONCLUSION C3 levels measured in sera from male subjects without previous ischemic events are independently associated with the risk of MI.

Ten year incidence of HCV infection in northern Italy and frequency of spontaneous viral clearance

Background: Little is known of the incidence of hepatitis C virus (HCV) infection, and the frequency of spontaneous viral clearance in the general population is unknown. We conducted an epidemiological study in two Apennine towns in northern Italy. Methods: Anti-HCV (ELISA and RIBA third generation) and HCV-RNA by polymerase chain reaction were tested in thawed sera from an adult general population of Loiano-Monghidoro in 1986 and 1996, obtained in the context of the MICOL (Multicenter Italian Study on Cholelithiasis). In 1999, anti-HCV positive subjects and sex and age matched controls were recalled in order to identify risk factors for acquiring HCV infection and to assess the family composition of anti-HCV+ subjects. Results: For 1646 subjects, sera were available from both 1986 and 1996 (mean age in 1986 43 (0.39) years). In 1986, 57 (3.46%) subjects were HCV antibody positive (HCV-Ab+). Eight new cases were recorded in 1996: adult incidence was 50.3 cases/100 000 inhabitants/year. Fifty three of 63 (84.1%) HCV-Ab+ sera were also HCV-RNA+. Genotype 2a/2c accounted for 44% and 1b for 47.0% of cases. HCV-Ab+ subjects had higher serum levels of alanine aminotransferase with respect to controls (p<0.005), as did subjects infected with genotype 1 with respect to those with genotype 2 (p<0.05). Eleven of 65 (16.9%) HCV-Ab+ subjects spontaneously cleared HCV-Ab; 7/11 also lost HCV-RNA− in both serum and leucocytes. Sixteen anti-HCV+ subjects belonged to families containing more than one infected member. Married couples accounted for 10 of these 16 subjects. In four of these five married couples, HCV genotype was identical in the two spouses. Conclusions: In rural northern Italy, the adult incidence of HCV is approximately 50 cases/100 000 inhabitants/year. Our findings suggest that as many as 17% of infected subjects may spontaneously clear HCV-Ab. Interfamilial transmission seems to have a role in the spread of infection.

Improved Tolerability of the Dihydropyridine Calcium-Channel Antagonist Lercanidipine: The Lercanidipine Challenge Trial

The objective of this 8-week open-label study was to compare the tolerability of lercanidipine, a dihydropyridine calcium-channel antagonist (CA), with that of other CAs in the treatment of hypertension. Subjects already taking amlodipine, felodipine, nifedipine gastrointestinal therapeutic system (GITS), or nitrendipine and experiencing CA-specific adverse effects (AEs) were switched to lercanidipine for 4 weeks and then rechallenged with their initial treatment for 4 weeks. Results showed that at comparable levels of BP, lercanidipine was associated with a significantly lower incidence of ankle edema, flushing, rash, headache and dizziness compared with other CAs (p < 0.001). After 4 weeks of lercanidipine, mean systolic blood pressure (SBP)/diastolic blood pressure (DBP) was 142.1/86.7 mmHg. After rechallenge with other CAs for 4 weeks, mean SBP/DBP was 141.1/86.7 mmHg. In this open-label study, lercanidipine compared with other CA seems to provide a significant improvement in tolerability with comparable antihypertensive effect.

Ten-year incidence of HCV infection in northern Italy and frequency of spontaneous viral clearance

BACKGROUND Little is known of the incidence of hepatitis C virus (HCV) infection, and the frequency of spontaneous viral clearance in the general population is unknown. We conducted an epidemiological study in two Apennine towns in northern Italy. METHODS Anti-HCV (ELISA and RIBA third generation) and HCV-RNA by polymerase chain reaction were tested in thawed sera from an adult general population of Loiano-Monghidoro in 1986 and 1996, obtained in the context of the MICOL (Multicenter Italian Study on Cholelithiasis). In 1999, anti-HCV positive subjects and sex and age matched controls were recalled in order to identify risk factors for acquiring HCV infection and to assess the family composition of anti-HCV+ subjects. RESULTS For 1646 subjects, sera were available from both 1986 and 1996 (mean age in 1986 43 (0.39) years). In 1986, 57 (3.46%) subjects were HCV antibody positive (HCV-Ab+). Eight new cases were recorded in 1996: adult incidence was 50.3 cases/100 000 inhabitants/year. Fifty three of 63 (84.1%) HCV-Ab+ sera were also HCV-RNA+. Genotype 2a/2c accounted for 44% and 1b for 47.0% of cases. HCV-Ab+ subjects had higher serum levels of alanine aminotransferase with respect to controls (p<0.005), as did subjects infected with genotype 1 with respect to those with genotype 2 (p<0.05). Eleven of 65 (16.9%) HCV-Ab+ subjects spontaneously cleared HCV-Ab; 7/11 also lost HCV-RNA- in both serum and leucocytes. Sixteen anti-HCV+ subjects belonged to families containing more than one infected member. Married couples accounted for 10 of these 16 subjects. In four of these five married couples, HCV genotype was identical in the two spouses. CONCLUSIONS In rural northern Italy, the adult incidence of HCV is approximately 50 cases/100 000 inhabitants/year. Our findings suggest that as many as 17% of infected subjects may spontaneously clear HCV-Ab. Interfamilial transmission seems to have a role in the spread of infection.

From observational to intervention programmes. The Brisighella study

The past target of epidemiology concerned the study of chronic degenerative/proliferative diseases, with the aim of detecting and evaluating some suspected etiological and/or risk factors (RF).

Early Invasive Strategy for Unstable Angina: a New Meta-Analysis of Old Clinical Trials.

Randomized controlled trials (RCTs) were conflicting to support whether unstable angina versus non-ST-elevation myocardial infarction (UA/NSTEMI) patients best undergo early invasive or a conservative revascularization strategy. RCTs with cardiac biomarkers, in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from 1975–2013 were reviewed considering all cause mortality, recurrent non-fatal myocardial infarction (MI) and their combination. Follow-up lasted from 6–24 months and the use of routine invasive strategy up to its end was associated with a significantly lower composite of all-cause mortality and recurrent non-fatal MI (Relative Risk [RR] 0.79; 95% confidence interval [CI], 0.70–0.90) in UA/NSTEMI. In NSTEMI, by the invasive strategy, there was no benefit (RR 1.19; 95% CI, 1.03–1.38). In the shorter time period, from randomization to discharge, a routine invasive strategy was associated with significantly higher odds of the combined end-point among UA/NSTEMI (RR 1.29; 95% CI, 1.05–1.58) and NSTEMI (RR 1.82; 95% CI, 1.34–2.48) patients. Therefore, in trials recruiting a large number of UA patients, by routine invasive strategy the largest benefit was seen, whereas in NSTEMI patients death and non-fatal MI were not lowered. Routine invasive treatment in UA patients is accordingly supported by the present study.

The Brisighella heart study report from 1984 to 1989

Epidemiological research in the cardiovascular field, with particular reference to coronary heart disease (CHD) and other pathologies linked to atherosclerosis, has in recent years revealed the need for an exact assessment of the individual risk factors (RF) together with an evaluation of the preventive results which can be obtained with their correction.

Mathematical model: interpolation and simulation

The application of most advanced mathematical models to epidemiology may prove useful and make it possible to test some methods of modern medicine.

Nutrition habits in free living community: the Brisighella Study

The aim of this paper is to evaluate the importance of the combination of the major components of lipid intake and the possible interrelationship between vitamin intake and cardiovascular deaths in an observational longitudinal survey: the Brisighella Study. A population sample with diet P/S ratio (polyunsaturated/saturated fatty acids) over the third quintile and saturated fatty acids/1000 calories (C), lipids/1000 C, diet cholesterol under the third quintile was isolated to define an arbitrarily “correct diet” opposite to the “rich diet”. The arbitrarily correct diet and the rich diet samples showed clearly different coronary mortality and morbidity rates (no pathology in the correct diet group). These characteristics emphasize the “per se” independent role of diet in the development of coronary heart disease.

FH gene phenotypic expression: insight for therapeutic strategy

For the last few years an Official Health Research Project of the Emilia Romagna Region has been underway to define the best diagnostic and therapeutic strategy for familial hypercholesterolemia. The data collected to date, referring to a survey of more than 500 subjects, indicate the severity and early type of coronary and carotid atheromatous lesions in Italian heterozygotes but also report, unlike surveys in other countries, the low prevalence of xanthomata and of xanthelasmas. The aim of this paper is to discuss the current diagnostic possibilities in relation to the clinical-laboratory picture and to the therapeutic needs and cardiovascular instrumental diagnosis of the FH patient.