Hyperlipidemias: Gaddi A

Poli A, Marangoni F, Paoletti R, Mannarino E, Lupattelli G, Notarbartolo A, Aureli P, Bernini F, Cicero A, Gaddi A, Catapano A, Cricelli C, Gattone M, Marrocco W, Porrini M, Stella R, Vanotti A, Volpe M, Volpe R, Cannella C, Pinto A, Del Toma E, La Vecchia C, Tavani A, Manzato E, Riccardi G, Sirtori C, Zambon A, Anonymous00119. · Nutrition Foundation of Italy, Italy. · Nutr Metab Cardiovasc Dis. · Pubmed #18258418 No free full text.

Abstract: The importance of non-pharmacological control of plasma cholesterol levels in the population is increasing, along with the number of subjects whose plasma lipid levels are non-optimal, or frankly elevated, according to international guidelines. In this context, a panel of experts, organized and coordinated by the Nutrition Foundation of Italy, has evaluated the nutritional and lifestyle interventions to be adopted in the control of plasma cholesterol levels (and specifically of LDL cholesterol levels). This Consensus document summarizes the view of the panel on this topic, with the aim to provide an updated support to clinicians and other health professionals involved in cardiovascular prevention.

Gaddi A, Galetti C, Pauciullo P, Arca M. · Centro per lo Studio dell'Arteriosclerosi e delle Malattie Dismetaboliche Giancarlo Descovich, Servizio di Gerontologia, Policlinico S. Orsola-Malpighi, Bologna, Italy. · Nutr Metab Cardiovasc Dis. · Pubmed #10765523 No free full text.

Abstract: The Atherosclerosis and Dysmetabolic Disorders Study Group, headed by Prof. Rodolfo Paoletti, decided in 1994 to compose a committee of experts to formulate a clear description of familial combined hyperlipoproteinemia (FCH), a disorder illustrated in the literature, but still unknown to most physicians in spite of its severity and relative diffusion. The Committee consists of experts from the Lipid Clinics of the Universities of Ancona, Bari, Bologna, Ferrara, Genoa, Milan, Naples, Padua, Palermo, Perugia, Rome, Sassari, Turin, Verona and Venice. It has held several meetings coordinated by the national secretary at the "Giancarlo Descovich" Atherosclerosis Centre of the University of Bologna. This paper summarizes its conclusions.

Gaddi A, Cicero AF, Odoo FO, Poli AA, Paoletti R, Anonymous00278. · Center for Metabolic diseases and Atherosclerosis, University of Bologna, Italy. · Vasc Health Risk Manag. · Pubmed #18200807 links to  free full text

Abstract: Familial combined hyperlidemia (FCH) is a common metabolic disorder characterized by: (a) increase in cholesterolemia and/or triglyceridemia in at least two members of the same family, (b) intra-individual and intrafamilial variability of the lipid phenotype, and (c) increased risk of premature coronary heart disease (CHD). FCH is very frequent and is one of the most common genetic hyperlipidemias in the general population (prevalence estimated: 0.5%-2.0%), being the most frequent in patients affected by CHD (10%) and among acute myocardial infarction survivors aged less than 60 (11.3%). This percentage increases to 40% when all the myocardial infarction survivors are considered without age limits. However, because of the peculiar variability of laboratory parameters, and because of the frequent overlapping with the features of metabolic syndrome, this serious disease is often not recognized and treated. The aim of this review is to define the main characteristics of the disease in order to simplify its detection and early treatment by all physicians by mean of practical guidelines.

Cicero AF, Gaddi A. · Atherosclerosis and Dysmetabolic Disease Study Center 'G. Descovich', Clinical Medicine and Applied Biotechnology Dept. 'D. Campanacci', University of Bologna, Italy. · Phytother Res. · Pubmed #11406848 No free full text.

Abstract: Diet is the first (and sometimes the only) therapeutic approach to hyperlipoproteinaemias. Rice bran oil and its main components (unsaturated fatty acids, triterpene alcohols, phytosterols, tocotrienols, alpha-tocopherol) have demonstrated an ability to improve the plasma lipid pattern of rodents, rabbits, non-human primates and humans, reducing total plasma cholesterol and triglyceride concentration and increasing the high density lipoprotein cholesterol level. Other potential properties of rice bran oil and gamma-oryzanol, studied both in vitro and in animal models, include modulation of pituitary secretion, inhibition of gastric acid secretion, antioxidant action and inhibition of platelet aggregation. This paper reviews the available data on the pharmacology and toxicology of rice bran oil and its main components with particular attention to those studies relating to plasma lipid altering effects.

Cicero AF, Derosa G, Miconi A, Laghi L, Nascetti S, Gaddi A. · GC Descovich Atherosclerosis Research Centre, D. Campanacci Clinical Medicine and Applied Biotechonology Department, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. · Biomed Pharmacother. · Pubmed #15932792 No free full text.

Abstract: OBJECTIVE: To describe the effect of Coenzyme Q10 (CoQ10) (added to either a fibrate, or polyunsaturated fatty acids (PUFA) or association of both) in patients affected by massive hypertriglyceridemia (MHTG) resistant to fibrates and PUFA. DESIGN: Open, sequential, comparative intervention study. SETTING: Specialised centres for dyslipidemia management. SUBJECTS: Fifteen subjects (mean age: 45.1+/-12.5 years) affected by MHTG and hyporesponsive to either fibrates, or PUFA, or fibrates-PUFA association, and 15 age-matched subjects regularly responders to PUFA and fenofibrate treatment. INTERVENTIONS: Treatment for periods of 6 weeks each with the following consecutive treatments: CoQ10 150 mg/day, PUFA 3000 mg/day, fenofibrate 200 mg/day, PUFA 3000 mg/day+fenofibrate 200 mg/day, PUFA 3000 mg/day+CoQ10 150 mg/day, fenofibrate 200 mg/day+CoQ10 150 mg/day, and finally, fenofibrate 200 mg/day+PUFA 3000 mg/day + CoQ10 150 mg/day. RESULTS: CoQ10 supplementation did not improve any monitored parameter in the control group except for systolic and diastolic blood pressure, creatinine and Lp(a) plasma levels, both during fenofibrate and/or PUFA treatment. In MHTG group, CoQ10 supplementation significantly improved TG, TC, Lp(a), uric acid and blood pressure during fenofibrate treatment, but only Lp(a) and blood pressure during PUFA treatment. Fenofibrate appeared to have better effect on hsCRP and gamma-GT plasma levels than PUFA. No significant change was observed in any group and under any treatment in regards to homocysteinemia, PAI-1, or t-PA. CONCLUSION: Even though the mechanism of action through which the effects were obtained is yet to be elucidated, adding CoQ10 to fenofibrate could improve the drug's efficacy in MHTG patients not responding to fenofibrate alone.

Cicero AF, Minardi M, Mirembe S, Pedro E, Gaddi A. · Atherosclerosis and Metabolic Diseases Study Centre G. Descovich, Clinical Medicine and Applied Biotechnology, Dept. D. Campanacci, S. Orsola-Malpighi University Hospital, Via Massarenti, 9, 40138 Bologna, Italy. · Eur J Nutr. · Pubmed #15309453 No free full text.

Abstract: BACKGROUND: High doses of soy protein are able to decrease plasma cholesterolemia significantly, but they unbalance daily protein intake and strongly modify nutritional habits in patients. AIM OF THE STUDY: To evaluate the antihypercholesterolemic efficacy of a low dose soy protein product with added beta-sitosterol (rapport = 4:1) in 36 moderately hypercholesterolemic subjects. METHODS: The study was divided into 3 separate periods of 40 days each: a stabilization diet period, followed by a treatment period during which all subjects took 10 g of the test product once daily and, finally, a wash out period. The following parameters were monitored: weight, dietary habits, plasma lipid levels, glycemia, uric acid, fibrinogenemia and antibodies against oxidized LDL (ox-LDL Ab). RESULTS: From the end of the stabilization diet period to the end of the supplementation with the soy protein product with added beta-sitosterol we observed a 19.64 +/- 20.32 mg/dL, 8.47 +/- 54.61 mg/dL, 1.69 +/- 10.92 mg/dL, and 7.06 +/- 16.66 mg/dL mean +/- SD decrease respectively in LDL-C (p < 0.001), TG (p = 0.358), VLDLs (p = 0.358) and apoB (p = 0.016) levels, associated with a 1.31 +/- 8.08 mg/dL and 1.03 +/- 19.09 mg/dL mean increase respectively in HDLC (p = 0.251) and apoAI (p = 0.749) plasma concentrations. The dietary supplementation did not influence Lp(a) (p = 0.984) and ox-LDL Ab (p = 0.953) plasma levels. A statistically significant correlation was observed for LDL-C plasma levels, between the end of the stabilization diet period and the end of the period of supplementation with soy proteins with added beta-sitosterols (p < 0.001). CONCLUSION: Although further long-term clinical studies are necessary before claims can be made regarding the therapeutic effects of the tested formulation, the preliminary findings regarding its efficacy and safety as an antihypercholesterolemic agent are encouraging.

Borghi C, Dormi A, Veronesi M, Sangiorgi Z, Gaddi A, Anonymous00301. · Department of Internal Medicine, University of Bologna, Bologna, Italy. · Am Heart J. · Pubmed #15308998 No free full text.

Abstract: BACKGROUND: Small studies have suggested that lipid-lowering strategies, and particularly statins, could influence blood pressure (BP) control. The aim of the present study was to evaluate the effect of different lipid-lowering strategies on BP control of subjects with hypercholesterolemia who were enrolled in the prospective, population-based, longitudinal Brisighella Heart Study. METHODS: A total of 1356 subjects with total cholesterol levels >or=239 mg/dL were randomly treated for 5 years (1988-1993) with 1 of these lipid-lowering regimens: low-fat diet, cholestyramine, gemfibrozil, or simvastatin. Participants were divided at baseline into 4 quartiles according to systolic BP level and examined for the percent change in systolic and diastolic BP during the 5 years of treatment. RESULTS: A significant decrease in BP was observed in the 2 upper quartiles of systolic BP (>or=140 mm Hg) and was greater in subjects treated with cholesterol-lowering drugs who also had a greater reduction in plasma levels of low-density lipoprotein cholesterol. The BP decrease was greater in patients treated with statin drugs and, among those treated with antihypertensive drugs, in subjects in the fourth quartile. CONCLUSION: The use of lipid-lowering measures could significantly improve BP control in subjects with both hypercholesterolemia and hypertension. The reduction in BP seems to be enhanced in subjects treated with statins.

Derosa G, Cicero AF, Gaddi A, Mugellini A, Ciccarelli L, Fogari R. · Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy. · Clin Ther. · Pubmed #12867219 No free full text.

Abstract: BACKGROUND: A previous study has demonstrated that L-carnitine reduces plasma lipoprotein(a) (Lp[a]) levels in patients with hypercholesterolemia. OBJECTIVE: To test a tolerable Lp(a)-reducing agent in diabetic patients, we assessed the effect of a dietary supplementation of L-carnitine on plasma lipid levels, particularly Lp(a), of patients with type 2 diabetes mellitus (DM) and hypercholesterolemia. METHODS: In this 6-month, randomized, double-masked, placebo-controlled clinical trial, patients were enrolled, assessed, and followed up at the Diabetic and Metabolic Diseases Center of the Department of Internal Medicine and Therapeutics at the University of Pavia, Pavia, Italy. All study patients had newly diagnosed type 2 DM that was managed through dietary restriction alone throughout the study, as well as hypercholesterolemia. Patients were randomized to 1 of 2 groups. One group received L-carnitine, one 1-g tablet BID. The other group received a corresponding placebo. We assessed body mass index, fasting plasma glucose, postprandial plasma glucose, glycosylated hemoglobin, fasting plasma insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein (apo) A-I, apo B, and Lp(a) at baseline and at 1, 3, and 6 months of treatment. RESULTS: This study included 94 patients. The treatment group included 24 men and 22 women (mean [SD] age, 52 [6] years). The placebo group included 23 men and 25 women (mean [SD] age, 50 [7] years). The baseline characteristics of the groups did not differ significantly. The mean (SD) body weight, height, and body mass index were 78.2 (5.8) kg, 1.70 (0.04) m, and 27.3 (2.5) kg/m(2), respectively, in the L-carnitine group and 77.6 (6.4) kg, 1.71 (0.05) m, and 26.8 (2.2) kg/m(2), respectively, in the placebo group. In the treatment group, Lp(a) was significantly reduced at 3 and 6 months compared with baseline (P < 0.05) and P < 0.01, respectively). We observed a significant improvement after 6 months (P < 0.05) in the Lp(a) value in patients taking L-carnitine compared with those taking placebo. Between-group differences in other variables did not reach a level of significance at months 3 and 6. No drug-related adverse events were reported or observed. CONCLUSION: In this preliminary study, after 3 and 6 months, L-carnitine significantly lowered the plasma Lp(a) level compared with placebo in selected hypercholesterolemic patients with newly diagnosed type 2 DM.

Cicero AF, Fiorito A, Panourgia MP, Sangiorgi Z, Gaddi A. · Atherosclerosis and Dysmetabolic Disease Study Center G. Descovich, Clinical Medicine and Applied Biotechnologies D. Campanacci, University of Bologna, Italy. · J Am Diet Assoc. · Pubmed #12487546 No free full text.

Abstract: Our aim was to test the hypocholesterolemic effect of a low-dose formulation of soy proteins supplemented with isolated b-sitosterol in a ratio of 4:1 in 20 moderately hypercholesterolemic subjects. The study has been divided in three different periods of forty days each: a stabilization diet period, then a treatment period during which all subjects assumed 10 g one time a day of the tested product and, finally, a wash out period. From the end of the stabilization diet period to the end of the soy protein added in b-sitosterol supplementation we observed a 0.45 +/- 0.30 mmol/L, 0.09 +/- 0.31 mmol/L and 0.17 +/- 0.22 mmol/L mean +/- SE decrease in respectively LDL-C, TG and apoB levels, associated with a 0.12 +/- 0.25 and 0.03 +/- 0.51 mg/dL mean increase respectively in HDL-C and apoA plasma concentrations. According to this recommends, low doses of soy protein added in b-sitosterol seems to be a practical and safe alternative for patients seeking modest reductions in LDL-C (< 15%).

Svegliati Baroni S, Amelio M, Fiorito A, Gaddi A, Littarru G, Battino M. · Institute of Biochemistry, University of Ancona, Italy. · Biofactors. · Pubmed #10416048 No free full text.

Abstract: The purpose of the present study was to evaluate the effects of MUFA vs PUFA enriched diets on the plasma and LDL lipid profile and antioxidant contents in mild hypercholesterolemic and triglyceridemic subjects. The study was divided in two consecutive diet periods. Two groups of 11 dyslipidemic patients each (type IIb and type IV) were recruited and during the first period (lasting four weeks) received a linoleic rich diet while during the following four weeks took an oleate rich diet. Both groups showed no significant changes in cholesterol and TG concentration either in plasma or in LDL. Coenzyme Q10 and vitamin E were also unaffected by the dietary treatments. LDL proneness to be oxidatively modified increased after dietary PUFA administration and markedly decreased following the virgin olive oil enriched diet. In fact, LDL from hypertrigliceridemic subjects on a oleate-enriched diet displayed a 26% (p < 0.05) longer lag-phase in conjugated dienes generation than during linoleate-enriched diet and at recruitment. In hypercholesterolemic subjects similar results were obtained: the lag-phase was 28% longer after MUFA diet that after PUFA diet. No differences were found in the maximum propagation rate and maximum concentration of conjugated dienes among dietary periods and at recruitment. Since we found that the vit. E and CoQ10 levels in plasma and in LDL particles remained unchanged during the course of the study, we may conclude that LDL proneness to undergo oxidative modifications is mainly the result of compositional change due to the enrichment from the different diets of the relative fats.

Baroni SS, Amelio M, Sangiorgi Z, Gaddi A, Battino M. · Institute of Biochemistry, Faculty of Medicine, University of Ancona, Italy. · Free Radic Res. · Pubmed #10230806 No free full text.

Abstract: Lowering high cholesterol concentration decreases the probability of atherosclerotic-related pathology onset. MUFA and PUFA decrease total plasma and LDL cholesterol but PUFA may increase the susceptibility of LDL to undergo oxidative modifications thus becoming more atherogenetic. Olive oil, the predominant fat source in Mediterranean diet, may combine the advantages of both lowering cholesterol level and decreasing LDL susceptibility to oxidation. We studied the effects of feeding MUFA vs PUFA enriched diet on LDL composition and feature in hypercholesterolemic (IIb) patients. Antioxidant values remained constant during the study while LDL fatty acids composition reflected the dietary intake: MUFA concentration increased 11% whereas PUFA decreased 10% after olive oil diet (p < 0.05). PUFA/MUFA ratio and the unsaturation index were lower at the end of MUFA-enriched diet. The challenge, in vitro, of oleate-enriched LDL with Cu2- yielded to lower lag-phase (p < 0.05) in diene conjugated production; the same LDL gave lower lipid hydroperoxide contents after exposition to AAPH. We conclude that oleate-enriched LDL and with lower PUFA content were more resistant to oxidative modifications, as measured by different peroxidation indexes. This feature acquired with the diet may be an useful tool for lowering LDL oxidation and indirectly their atherogenicity.

Cicero AF, Derosa G, Miconi A, Laghi L, Nascetti S, Gaddi A. · GC Descovich Atherosclerosis Research Centre, D. Campanacci Clinical Medicine and Applied Biotechonology Department, S. Orsola-Malpighi Hospital, University of Bologna, Italy. · Biofactors. · Pubmed #15817994 No free full text.

Abstract: OBJECTIVE: To describe the effect of CoQ10 (added to either a fibrate, or PUFA or association of both) in patients affected by massive hypertriglyceridemia (MHTG) resistant to fibrates and PUFA. DESIGN: Open, sequential, comparative intervention study. SETTING: Specialised centres for dyslipidemia management. SUBJECTS: 15 subjects (mean age: 45.1 +/- 12.5 years) affected by MHTG and hyporesponsive to either fibrates, or PUFA, or fibrates-PUFA association, and 15 age-matched subjects regularly responders to PUFA and fenofibrate treatment. INTERVENTIONS: Treatment for periods of 6 weeks each with the following consecutive treatments: CoQ10 150 mg/day, PUFA 3000 mg/day, fenofibrate 200 mg/day, PUFA 3000 mg/day + fenofibrate 200 mg/day, PUFA 3000 mg/day + CoQ10 150 mg/day, fenofibrate 200 mg/day + CoQ10 150 mg/day, and finally, fenofibrate 200 mg/day + PUFA 3000 mg/day + CoQ10 150 mg/day. RESULTS: CoQ10 supplementation improved, in the control group, systolic and diastolic blood pressure, creatinine and Lp(a) plasma levels, both during fenofibrate and/or PUFA treatment. In MHTG group, CoQ10 supplementation significantly improved TG, TC, Lp(a), uric acid and blood pressure during fenofibrate treatment, but only Lp(a) and blood pressure during PUFA treatment. Fenofibrate appeared to have better effect on hsCRP and gamma-GT plasma levels than PUFA. No significant change was observed in any group and under any treatment in regards to homocysteinemia, PAI-1, or t-PA. CONCLUSION: Even though the mechanism of action through which the effects were obtained is yet to be elucidated, adding CoQ10 to fenofibrate could improve the drug's efficacy in MHTG patients not responding to fenofibrate alone.

Cicero AF, Panourgia MP, Linarello S, D'Addato S, Sangiorgi Z, Gaddi A. · Atherosclerosis Study Center G Descovich, Clinical Medicine and Applied Biotechnologies, Dept. D Campanacci, University of Bologna, Italy. · J Cardiovasc Risk. · Pubmed #12668913 No free full text.

Abstract: BACKGROUND: Serum lipoprotein (a) [Lp(a)] is a lipidic parameter, strictly under genetic control. Lp(a) levels vary in different dyslipidaemias according to the underlying disease. DESIGN: The aim of this study was to evaluate and compare serum Lp(a) mean levels distribution in a large familial combined hyperlipoproteinaemia (FCH) patients sample with a normolipidaemic group. METHODS: FCH group included 138 subjects (74 males and 65 females) aged from 16 to 88 years; the control group included 438 normolipidaemic subjects (238 males and 200 females) aged from 16 to 91 years. In both groups we have measured Lp(a) concentrations and other lipidic parameters. RESULTS: Serum lipid levels as well as Lp(a) log-transformed concentrations were on average higher in FCH patients than in control subjects. Lp(a) concentrations were not significantly different between sexes and among 20-year age classes in both groups. CONCLUSIONS: The relationship between FCH and Lp(a) remains controversial. However, since both are considered independent risk factors for premature CHD development, even if their pathogenic interaction is still unclear, we suggest that Lp(a) values should be carefully monitored in dyslipidaemic subjects and particularly in FCH ones. In FCH subjects with elevated Lp(a) levels, aggressive intervention could be required.

Cicero AF, Panourgia MP, Nascetti S, Sangiorgi Z, Gaddi A. · Atherosclerosis and Metabolism Diseases Study Centre GC Descovich, Clinical Medicine and Applied Biotechnology Department D Campanacci, University of Bologna, Italy. · Med Princ Pract. · Pubmed #12566970 No free full text.

Abstract: OBJECTIVE: To report the case of an 85-year-old man with asymptomatic massive hypertriglyceridemia (MHTG). CLINICAL PRESENTATION AND INTERVENTION: Our case was a non-smoker, healthy 85-year-old Caucasian male, with no excessive alcohol intake and no evidence of an excessive sedentary lifestyle, body mass index = 23.2 kg/m(2), BP = 125/85 mm Hg and plasma triglyceride (TG) >1,000 mg/dl. The MHTG was an incidental finding at the age of 70. He had no cardiovascular disease, xanthomas, xanthelasmas or keratic precipitate. During the last 15 years, his average TG plasma levels showed a significant variability independent of specific diet treatment and fibrate therapy. Liver ultrasound examination excluded hepatomegaly and fatty degeneration. Carotid artery ultrasound showed only intimal thickening in both carotid bifurcations. CONCLUSION: In this patient, MHTG had been silent for many years, with no evidence of coronary heart disease and liver fatty degeneration, both typical complications present in MHTG subjects with low high-density lipoprotein. Hence, this case must be considered as a rarity.

Gaddi A, Cicero AF, Poli A, Nascetti S, Inzitari D, Anonymous00258. · Atherosclerosis and Dysmetabolic Disease Study Centre G. Descovich, University of Bologna, Italy. · J Cardiovasc Risk. · Pubmed #12202836 No free full text.

Abstract: In Italy and Europe, strokes are the third most common cause of death and resulting invalidity. In the ever-increasing 80-years-old-and-over people, strokes become more serious due to the clinical presentation during the acute phase and the ten-times higher mortality, but also in relation to the twice as high resulting disability as for younger subjects. However, stroke prevention is possible both through correct behavioural habits and pharmacological means. Besides the well-known preventive effects of an adequate anti-hypertensive, anti-diabetic and/or anti-aggregant/anti-coagulant therapy, there are increasing evidences of the effectiveness of the anti-hypercholesterolemic therapy in stroke prevention. Moreover, a great part of the risk factors for the cerebrovascular disease coincides with those for cardiovascular disease, for which the correction of the former automatically involves a reduction in incidence of both pathologies. In this context, a statin's rational use can therefore represent an important tool for the combined prevention of the two pathologies. Finally, different hypotheses link the origin of Alzheimer's disease to that of progressive cerebrovascular dementia caused by cerebral microcirculation damage. It is plausible that the application of a suitable early prevention of the cerebrovascular pathology could bring to a more late slatentisation and less serious demonstrations of Alzheimer's disease, when this is destined to develop.

Cicero AFG, Braiato A, D'Addato S, Sangiorgi Z, Gaddi A. · Atherosclerosis and Dvsmetabolic Disease Study Centre G.C. Descovich, Clinical Medicine and Applied Technologies Department, University of Bologna,Italy. · Int J Cardiol. · Pubmed #10854674 No free full text.

Abstract: We selected 247 subjects from 29 large familial hypercholesterolemia (FH) kindreds from 550 probable FH subjects in Emilia Romagna (Italy) on the basis of LDL-cholesterol plasmatic levels and family trees, in order to define the best diagnostic criteria for heterozygous patients. Familial hypercholesterolemia is a monogenic disease of cholesterol metabolism inherited as an autosomal dominant trait and characterised by early cardiovascular disease. A low xanthomas and xanthelasmas prevalence was found (8.6%); coronary heart disease (CHD) death occurs very frequently in heterozygous males (72% of all deaths; mean age at death 52 years), while in females the primary cause of death was thrombotic stroke (55%; mean age 69 years). Total cholesterol (TC) mean values were 389.8 (m) and 373.3 mg/dl (f) for FH trait carriers, and 223.3 (m) and 228.8 (f) for healthy relatives. No age-related change in TC was found in heterozygotes, while unaffected relatives of FH families showed mean TC and LDL-C values, and a TC frequency distribution and a TC age-related increasing trend similar to the expected values for the Italian population. The TC frequency distribution curve appeared bimodal, with a mid-point between heterozygous and homozygous FH modal values of 280 mg/dl. To identify the FH patients, the final FH heterozygosity risk was evaluated in an unselected free-living population (from 0.07 to 0.8%, respectively, for TC between 265-274 and 295-304 mg/dl) and in hypercholesterolemic families (31 to 83%, and the same TC classes). Our conclusion is that the clinical picture is rarely pathognomonic, while the FH heterozygosity final risk evaluation and the 280 mg/dl cut-off point can be used to guide the practical clinical diagnosis and to select the patients destined for B-E receptor activity evaluation.