Z. Sangiorgi

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.

Total Cholesterol, High‐Density Lipoprotein Cholesterol, and Triglycerides in Children Receiving Antiepileptic Drugs

Summary: The influence of antiepileptic drug (AED) therapy on total cholesterol (TC), high‐density lipoprotein (HDL) cholesterol, and triglycerides was studied in 208 epileptic children compared with 175 normal children. A significant increase in TC plasma levels was observed with carbamazepine (CBZ), phenobarbital (PB), and phenytoin (PHT). The patients receiving valproate (VPA) showed levels very similar to those of the control population. The results may be explainable by the different biotransformation pathway of these drugs. HDL cholesterol and triglycerides were not altered by any of the AEDs. We recommend monitoring TC level in patients receiving CBZ, PB, and PHT and prescription of diet treatment, at least during the time of AED treatment.

Solid monounsaturated diet lowers LDL unsaturation trait and oxidisability in hypercholesterolemic (Type IIb) patients

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.

Effects of a New Soy/β-Sitosterol Supplement on Plasma Lipids in Moderately Hypercholesterolemic Subjects

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%).

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).

Serum Lipopotein (a) Levels in a Large Sample of Subjects Affected by Familial Combined Hyperlipoproteinaemia and in General Population

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.

A suggestion for familial hypercholesterolemia (FH) heterozygosity clinical diagnosis based on epidemiological observations in a large Italian population.

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.

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.

Asymptomatic massive hypertriglyceridemia in an octogenarian.

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/m2, 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.

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.