Giuseppe Gallus

Pravastatin reduces carotid intima-media thickness progression in an asymptomatic hypercholesterolemic Mediterranean population: The Carotid Atherosclerosis Italian Ultrasound Study

PURPOSE The Carotid Atherosclerosis Italian Ultrasound Study (CAIUS) was performed to test the effects of lipid lowering on the progression of carotid intima-media thickness (IMT) in 305 asymptomatic patients from a Mediterranean country. PATIENTS AND METHODS Eligibility included hypercholesterolemia (baseline means: low-density lipoprotein [LDL] = 4.68 mmol/L, high-density lipoprotein [HDL] = 1.37 mmol/L), and at least one 1.3 < IMT < 3.5 mm in the carotid arteries. Patients (mean age 55 years, 53% male) were assigned to pravastatin (40 mg/day, n = 151) or placebo (n not equal to 154). Ultrasound imaging was used to quantify IMT at baseline, and semiannually thereafter for up to 3 years. The mean of the 12 maximum IMTs (MMaxIMT), was calculated for each patient visit, and used to determine each patients longitudinal progression slope. The intention-to-treat group difference in the MMaxIMT progression was chosen a priori as the primary end point. RESULTS Five serious cardiovascular events (1 fatal myocardial infarction), and 7 drop-outs for cancer were registered. In the pravastatin group, LDL decreased -0.22 after 3 months versus -0.01 in the placebo group, and remained substantially unchanged afterward (-0.23 versus +0.01 at 36 months, respectively). Progression of the MMaxIMT was 0.009 +/- 0.0027 versus -0.0043 +/- 0.0028 mm/year (mean +/- SE, P < 0.0007) in the placebo and pravastatin groups, respectively. IMT progression slopes diverged after 6 months of treatment. CONCLUSIONS Pravastatin stops the progression of carotid IMT in asymptomatic, moderately hypercholesterolemic men and women. This finding extends the beneficial effects of cholesterol lowering to the primary prevention of atherosclerosis in a population with relatively low cardiovascular event rates, and suggests that this benefit is mediated by specific morphological effects on early stages of plaque development.

Different effects of antihypertensive regimens based on fosinopril or hydrochlorothiazide with or without lipid lowering by pravastatin on progression of asymptomatic carotid atherosclerosis: Principal results of PHYLLIS - A randomized double-blind trial

Background and Purpose— The Plaque Hypertension Lipid-Lowering Italian Study (PHYLLIS) tested whether (1) the angiotensin-converting enzyme (ACE) inhibitor fosinopril (20 mg per day) was more effective on carotid atherosclerosis progression than the diuretic hydrochlorothiazide (25 mg per day), (2) pravastatin (40 mg per day) was more effective than placebo when added to either hydrochlorothiazide or fosinopril, and (3) there were additive effects of ACE inhibitor and lipid-lowering therapies. Methods— A total of 508 hypertensive, hypercholesterolemic patients with asymptomatic carotid atherosclerosis were randomized to: (A) hydrochlorothiazide; (B) fosinopril; (C) hydrochlorothiazide plus pravastatin; and (D) fosinopril plus pravastatin, and followed up blindly for 2.6 years. B-Mode carotid scans were performed yearly by certified sonographers in 13 hospitals and read centrally. Corrections for drift were calculated from readings repeated at study end. Primary outcome was change in mean maximum intima-media thickness of far and near walls of common carotids and bifurcations bilaterally (CBMmax). Results— CBMmax significantly progressed (0.010±0.004 mm per year; P=0.01) in group A (hydrochlorothiazide alone) but not in groups B, C, and D. CBMmax changes in groups B, C, and D were significantly different from changes in group A. Changes in group A were concentrated at the bifurcations. “Clinic” and “ambulatory” blood pressure reductions were not significantly different between groups, but total and low-density lipoprotein cholesterol decreased by ≈1 mmol/L in groups C and D. Conclusions— Progression of carotid atherosclerosis occurred with hydrochlorothiazide but not with fosinopril. Progression could also be avoided by associating pravastatin with hydrochlorothiazide.

Morbidity, mortality, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation ☆

Objectives This study was designed to investigate the potential of circumferential pulmonary vein (PV) ablation for atrial fibrillation (AF) to maintain sinus rhythm (SR) over time, thus reducing mortality and morbidity while enhancing quality of life (QoL). Background Circumferential PV ablation is safe and effective, but the long-term outcomes and its impact on QoL have not been assessed or compared with those for medical therapy. Methods We examined the clinical course of 1,171 consecutive patients with symptomatic AF who were referred to us between January 1998 and March 2001. The 589 ablated patients were compared with the 582 who received antiarrhythmic medications for SR control. The QoL of 109 ablated and 102 medically treated patients was measured with the SF-36 survey. Results Median follow-up was 900 days (range 161 to 1,508 days). Kaplan-Meier analysis showed observed survival for ablated patients was longer than among patients treated medically (p < 0.001), and not different from that expected for healthy persons of the same gender and calendar year of birth (p = 0.55). Cox proportional-hazards model revealed in the ablation group hazard ratios of 0.46 (95% confidence interval [CI], 0.31 to 0.68; p < 0.001) for all-cause mortality, of 0.45 (95% CI, 0.31 to 0.64; p < 0.001) for morbidities mainly due to heart failure and ischemic cerebrovascular events, and of 0.30 (95% CI, 0.24 to 0.37; p < 0.001) for AF recurrence. Ablated patients’ QoL, different from patients treated medically, reached normative levels at six months and remained unchanged at one year. Conclusions Pulmonary vein ablation improves mortality, morbidity, and QoL as compared with medical therapy. Our findings pave the way for randomized trials to prospect a wider application of ablation therapy for AF.

Systolic and pulse blood pressures (but not diastolic blood pressure and serum cholesterol) are associated with alterations in carotid intima-media thickness in the moderately hypercholesterolaemic hypertensive patients of the Plaque Hypertension Lipid Lowering Italian Study

Objective The Plaque Hypertension Lipid Lowering Italian Study (PHYLLIS), is the first study in patients with hypertension (diastolic blood pressure (DBP) 95–115 mmHg; systolic blood pressure (SBP) 150–210 mmHg), moderate hypercholesterolaemia (LDL-cholesterol 4.14–5.17 mmol/l (160–200 mg/dl) and initial carotid artery alterations (maximum intima–media thickness (IMT) Tmax ⩾ 1.3 mm). The primary objective of PHYLLIS is investigating whether in these patients administration of an angiotensin converting enzyme inhibitor, fosinopril, and a statin, pravastatin, is more effective than administration of a diuretic and a lipid-lowering diet in retarding or regressing alterations in carotid IMT. While the study is in progress, baseline data are here reported to clarify the association of various risk factors with carotid IMT in these medium–high risk hypertensive patients. Methods Patients numbering 508 have been randomized to PHYLLIS by 13 peripheral units, in Italy. Age was (mean ± SD) 58.4 ± 6.7 years, males were 40.2%, current smokers 16.5%, means ± SD of serum total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol and triglycerides concentrations were 6.79 ± 0.67, 4.69 ± 0.51, 1.37 ± 0.38, 1.59 ± 0.64 mmol/l (262.4 ± 25.8, 181.3 ± 19.8, 53.0 ± 14.6, 141.0 ± 56.7 mg/dl). Means ± SD of clinic sitting SBP/DBP were 159.8 ± 9.0/98.3 ± 4.2 mmHg. 483 of the 508 patients also had 24 h ambulatory BP monitoring, edited and read at a centralized unit (mean ± SD 24 h SBP/DBP averages 136.3 ± 14.1/84.0 ± 10.0 mmHg). Quantitative B-mode ultrasound (Biosound 2000 II 5A, Biosound, Indianapolis, Indiana, USA) recordings of carotid arteries were taken by certified sonographers in the peripheral units and tracings were all read at a central unit. CBMmax (mean IMT of eight sites at common carotids and bifurcations) was 1.21 ± 0.17; Mmax (mean of 12 sites also including internal carotids) 1.16 ± 0.17, and Tmax (single maximum) 1.85 ± 0.48 mm. Results Ambulatory SBP and pulse pressure (PP) (24 h, daytime, night-time averages) and their variability indices (24 h SD) were always significantly correlated with CBMmax and Mmax (P 0.01–0.001), and the correlations remained significant after adjustment for age, gender and smoking. No measurement of DBP was ever associated with any IMT measurement. Likewise, no lipid variable was found associated with any IMT measurement. Conclusions Baseline data from PHYLLIS indicate that in this population of hypertensive patients with moderate hypercholesterolaemia, SBP and PP are with age among the most significant factors associated with carotid artery alterations. However, the narrow range of inclusion LDL-cholesterol and DBP values may have obscured an additional role of these variables.

Excimer laser photorefractive keratectomy for myopia: results in 1165 eyes

BACKGROUND We report the results of a prospective study conducted in Italy to evaluate the efficacy, safety, predictability, and complications of excimer laser photorefractive keratectomy for the correction of myopia. METHODS. Photorefractive keratectomy was performed on 1236 myopic sighted eyes in 16 centers, using the Summit Excimed 193 nm excimer laser. The attempted correction ranged from -0.80 to -25.00 diopters (mean, -7.83 +/- 3.88 D). The population was divided into three groups of attempted correction: between -0.80 and -6.00 D, between -6.10 and -9.90 D, and between -10.00 and -25.00 D. We report the data of 1165 eyes at 1 month, 970 eyes at 3 months, 752 at 6 months, and 330 at 12 months. At each visit, we evaluated (1) the refractive changes over time; (2) the difference between attempted and achieved correction; (3) uncorrected and best spectacle corrected visual acuity; and (4) haze. RESULTS Twelve months after surgery, the spherical equivalent refractive error in 146 eyes with attempted correction of -0.80 to -6.00 D was -0.52 +/- 1.04 D; 104 eyes (71.2%) were within +/- 1.00 D of attempted correction. In 145 eyes with attempted correction of -6.10 to -9.90 D, the spherical equivalent refractive error was -1.66 +/- 1.88 D; 50 eyes (34.5%) were within +/- 1.00 D of attempted correction. The spherical equivalent refractive error in 39 eyes with attempted correction of -10.00 to -25.00 D was -1.86 +/- 3.47 D; 11 eyes (28.2%) were within +/- 1.00 D of attempted correction. Eight eyes (2.4%) lost two or more Snellen lines of best spectacle corrected visual acuity. None of the treatments caused severe postoperative complications, or scarring. CONCLUSIONS Photorefractive keratectomy proved safe and effective, but highly predictable only in the correction of myopia up to -6.00 D.

Nutritional markers as prognostic indicators of postoperative sepsis in cancer patients.

A study was undertaken to identify the nutritional parameters associated with a high risk of postoperative sepsis. The nutritional status of 162 cancer patients subjected to clean or clean-contaminated elective surgery was preoperatively evaluated according to the following parameters: percentage weight loss, arm circumference, triceps skinfold, arm muscle circumference, creatinine-height index, total serum protein, serum albumin, total iron-binding capacity, cholinesterase, peripheral lymphocytes, complement C3-C4 components, and skin tests. Patients were followed postoperatively according to a precise protocol to classify them as infected or noninfected. Postoperative sepsis was present in 40 patients who had significantly different mean values for four nutritional parameters from those of 114 patients with no complications, ie, total serum protein, 6.60 vs 6.99 g/dl, p = 0.008; serum albumin, 3.39 vs 3.66 g/dl, p = 0.001; total iron-binding capacity 301.32 vs 337.17 mmg/dl, p = 0.006; and cholinesterase, 2389.77 vs 2770.10 mU/ml, p = 0.005. Moreover, the relative risk and the attributable risk for these variables were evaluated and the significance was tested by the chi 2 test. By using multiple logistic analysis it appeared that only total serum protein and total iron-binding capacity gave an independent contribution to the risk of postoperative sepsis, while serum albumin disappeared and cholinesterase became non significant when the contribution of the first two variables was accounted for. It was also possible to identify, in a small number of patients, combinations of two variables that were associated with a very high risk of postoperative sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic Role of Preoperative Nutritional and Immunological Assessment in the Surgical Patient

The utilization of delayed hypersensitivity response (DHR) for the identification of high-risk patients with regard to postoperative septic complications is still discussed. The aim of this study was to clarify how much DHR may improve the prognostic capacity of nutritional assessment (NA). Nutritional and immunological evaluations were performed at admission on 405 patients undergoing elective general surgical procedures. Subjects with serum albumin less than or equal to 3.0 g/dl or total iron-binding capacity less than or equal to 220 micrograms/dl or weight loss greater than or equal to 10% with respect to usual body weight were classified as malnourished. DHR was assessed by performing skin tests with four recall antigens: PPD, candida, trichophyton, sk-sd. The incidence of postoperative complications resulted higher among the 187 malnourished patients (31.0%) than in the 218 well-nourished ones (14.2%) (p less than 0.001), and among the 213 anergic patients (29.6%) than in the 192 normal responders (13.5%) (p less than 0.001). To determine how much skin tests may improve the prognostic ability of NA, the relationship between DHR and postoperative complications was also studied in the malnourished and in the well-nourished patients, separately. In the malnourished group, the patients with an impairment of DHR had a higher incidence of postoperative infections than normal responders (p less than 0.05). In the well-nourished group, no significant differences were found between anergic patients and normal responders. In our study, DHR slightly improved the prognostic capacity of NA. Therefore, the first approach to identify the high-risk patients seems to be the unexpensive, quick and available determination of nutritional status.

Incidence and prevalence rates of diabetes mellitus in Italy from routine data: a methodological assessment.

This study was undertaken to identify and validate possible existing sources of information to estimate the prevalence of known diabetes and the incidence of Type I (insulin-dependent) diabetes in Italy.The prevalence of known diabetes was estimated on the basis of data on drug sale, using specific defined daily doses as index of drug consumption. The estimation of the average daily dose used for calculations was carried out on a consecutive series of 911 diabetic subjects from two outpatient clinics.The incidence of Type 1 (insulin-dependent) diabetes was obtained by processing data routinely collected by the Regional Health Services, related to hospital discharge diagnosis records mentioning diabetes mellitus. The validation was carried out in 12 hospitals of the same Region. The estimated prevalence rate of known diabetes was 1.7%, including patients on dietary treatment.In the Lombardia Region in 1982–83 the estimated annual average incidence of Type I (insulin-dependent) diabetes, under the age of 35 was 4.6/100,000. This rate appears much lower then that observed in Northern Europe and the United States while it is similar to the French rate. This is in agreement with the findings of studies showing changes with latitude of the incidence rates of Type 1 (insulin-dependent) diabetes.

Invasive cervical cancer in young women.

Summary. Between 1970 and 1979, 103 women below 35 years of age with invasive cervical cancer were treated at the First Obstetrics and Gynaecology Clinic of the University of Milan. Nine patients were pregnant or less than 3 months postpartum. Estimated 10–year disease–free survival, determined by the life–table method, was 100% in stage IA (37 patients), 79% in stage IB (45 patients), 67% in stage 11 (15 patients), 0% in stages III (5 patients) and IV (1 patient). Prognosis was also strongly associated with lymph–node involvement, 10–year actuarial survival decreasing from 93% in lymph–node–negative to 44% in lymph–node– positive patients (P

Prognostic features of endometrial cancer in estrogen users and obese women.

In a case-control study to evaluate risk factors for endometrial cancer in Italy, use of noncontraceptive estrogens was associated with a moderately increased risk, whereas obesity appeared to be the most important single risk factor related to cancer of the endometrium. This report considers the estrogen and obesity-related relative risks with regard to various prognostic features of tumors (clinical stage, histologic grade, extent of myometrial invasion, lymph node involvement). In both estrogen users and obese women, the increase in relative risk was greater for earlier than for more advanced tumors. These findings, therefore, provide further support for a specific role of both exogenous and endogenous estrogens in endometrial cancer.