SVIBOR - Project code: 3-01-148

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Project code: 3-01-148


HYPERLIPOPROTEINEMIA AS A RISK FACTOR IN THE GENESIS OF ATHEROSCLEROSIS


Main researcher: SUČIĆ, MATE (45390)


Assistants
Type of research: applied
Duration from: 01/01/91. to 12/31/95.
Papers on project (total): 25
Papers on project quoted in Current Contents: 9
Institution name: Institut za dijabetes, endokrinologiju i bolesti metabolizma "Vuk Vrhovac", Zagreb (45)
Department/Institute: Metabolism Department
Address: Dugi dol 4a
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0) 41 232-222 / 266,203
Fax: 385 (0) 41 231-515
E-mail: BABI]¦INDIJA.IDB.HR
Summary: Hyperlipoproteinemia is close to smoking and elevated blood pressure, the most important risk factor in the genesis of atherosclerosis and its complications (coronary heart disease, stroke, peripheral vascular disease). Lipoprotein particles are not of the same aterogenecity. In distinction from aterogenic LDL (low-density-lipoprotein) particle, with its main component apoprotein B (apo B), HDL (high-density-lipoprotein) particle, with its main component apoprotein A1 (apo A1), is protective (antiaterogenic). Few years ago, lipoprotein particle Lp (a) has been discovered. The Lp (a) level strong correlate with coronary heart disease incidence. Lp (a) consists of apoprotein (a), apoprotein B and LDL particle. It is thought to be hereditary determined. Atherosclerosis is also, very frequent diabetes mellitus complication, and to that purpose besides hyperlipoproteinemia (primarily hypertriglyceridemia), hyperinsulinemia significantly contribute, too. Hyperinsulinemia is most often the consequence of present peripheral insulin resistance. Hyperinsulinemia could cause hypertriglyceridemia, and hyperlipoproteinemia peripheral insulin resistance with compensatory hyperinsulinemia, as well. That cycle is potentialy of importance in the atherosclerosis genesis, particularly in the sense of hypertriglyceridemia and hyperinsulinemia link with early blood vessel atherosclerotic alterations. Contemporary, due to pancreatic beta-cell exhaustion, glucose intolerance could also be developed. It was planned to investigate possible correlation of a certain apoprotein groups (apo A1, apo B, apo (a)), as well as Lp (a), with the development of blood vessel atherosclerotic alterations. The effect of hyperlipoproteinemia (primarily hypertriglyceridemia) on the development of insulin resistance and hyperinsulinemia, particularly related to possible glucose intolerance and diabetes mellitus occurence, was enquired. The consequence of dietary and/or hypolipemic drug treatment on lipoprotein levels, insulin resistance and peripheral insulinemia, was also studied. The effect of arterial hypertension, in the framework of Syndroma X, on the atherosclerosis development was additionaly investigated. The level of single lipoprotein particles can be affected by;nutrition, physical activity and medications. 1. Of 255 subjects with hyperlipoproteinemia 46 (18%)had hyperlipoproteinemia type 2a (acc.to Frederickson), 123 (48%) type 2b, 57 (22%) type 4 and 29 (12%) type 5. The increased apo (a) level had 32 (12,5%) subjects. Apo B correlates with LDL only in hyperlipoproteinemia 2a, somewhat less in type 2b. The decrease of apo A1 correlates with decrease of HDL only in type 4. Lp(a) level does not correlate with apo (a) level - of 32 subjects with increased apo (a) 6 of them had increased Lp(a). 2. Of 60 subjects with hyperlipoproteinemia (primary or linked to diabetes) tested with CIGMA (screening test), and 20 with CLAP technique, a connection of peripheral resistance to diabetes and hypertriglycerdemia and improvement of aterogenic lipides particles by application of medications and also without effect to insulin resistence, is found. 3. Of 62 fertile women (31 control group and 31 subjects) a seasonal application of single lipoprotein partices was established (control group), and positive effect of kinesiologic recreationon decrease of aterogenic and increase of protective lipoprotein particles. on decrease of aterogenic

Keywords: Atherosclerosis, Hyperlipoproteinemia, Apoproteins (A1, B, (a)), Lipoprotein Lp (a), Non-insulin-dependent diabetes mellitus (NIDDM), Hyperinsulinemia, Hypertension, Peripheral insulin resistance, fertile women, kinesiologic recreation

Research goals: The investigation was carried out as prospective program,consisting of two parts: 1) It is believed that apoprotein A1 and B, better than HDL andLDL particle, determination enable us the assessment of hyperlipoprotein aterogenicity. Therefore, the levels of apoprotein A1, B and (a) will be determined in subjects with proven hyperlipoproteinemia, in attempt to answer on followingquestions: - in which hyperlipoproteinemia types changes of particular apoproteins are most frequent; - is there any difference in particular apoprotein levels in relation to possible hyperlipoproteinemia etiology; - what is the frequency of apoprotein levels increase in our population (small sample); - what is the Lp (a) level in subjects with increased apo (a)? 2) In the subjects with primary hyperlipoproteinemia, as well as in the subjects with secondary hyperlipoproteinemia related to NIDDM, the impact of hyperlipoproteinemia, respectively particular lipoprotein fractions, on insulin resistance will be carried out. The aim of the study is to investigate: - the type and size of the peripheral insulin resistance in subjects with primary hyperlipoproteinemia (particularly hipertriglyceridemia), and posssible correlation with plasma insulin levels; - the type and size of the peripheral insulin resistance in hyperlipemic NIDDM patients (secondary hyperlipoproteinemia); - the dietary and/or drug treatment effect on lipoprotein levels and consequently on peripheral insulin resistance and plasma insulin levels; - the role of arterial hypertension as a risk factor for the atherosclerosis development (particularly coronary disease),in the context of complex metabolic disturbances syndroma (syndrom X). As many factors can change single lipoprotein particles levels (nutrition, physical activity, medications and sim.) in healthy persons, the effect of kinesiologic recreation in healthy persons. For that purpose fertile healthy women were tested as great number of works dealed with the influence of physical activity to lipoprotein level in men and women after menopause. In healthy fertile women the influence of kinesologic recreation to single lipoprotein particles level was tested.

COOPERATION - PROJECTS


  1. Name of project: Acipimox in the treatment of NIDDM patients with concomitant hyperlipoproteinemia (A multicenter trial)
    Name of institution: Central-Eastern Europe Metabolic Diseases Study Group & Farmitalia Carlo Erba, Regional Office Eastern Europe, Vienna
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