Faktore wat lipoproteïen(a)-vlakke van hiperlipidemiese pasiënte beïnvloed

Abstract

Lipoprotein ( a ) (Lp ( a )) is auniue glycoprotein which was first described by Berg in 1963. This lipoprotein displays structural similarities with both low density lipoprotein (LDL) and plasminogen and it is suspected that these similarities may provide a link between atherogenesis and thrombosis. Lp(a) differs from LDL only in that it is a l so linked to a glycoprotein, apo(a). Lp(a) and plasminogen display structural similarities, since Lp(a) has approximately 37 copies of a kringle similar to kringle 4 of plasminogen, as well as one copy of a kringle similar to kringle 5 of plasminogen. However, Lp (a) and plasminogen differs in that Lp(a) does not display the same fibrinolytic activities as plasminogen. The true function of Lp (a) is unknown. Also, the metabolism of Lp(a) has not been determined fully, mainly because of controversy surrounding the role of the LDL-receptor. Since apo B-100 is a structural component of both LDL and Lp(a), as well as the factor which triggers recognition for LOL by the LOL receptor, the possibility exists that the metabolism of Lp(a) is mediated by the LDL receptor. This leads to the possibility that Lp(a) could be elevated in familial hypercholesterolaemic (FH) patients. Lp(a) is a risk factor for stroke, coronary heart disease (CHO) as well as myocardial infarcti9n (MI). CHO is the largest cause of death in whites and Asians in South Africa, while the incidence of FH is very high in white Afrikaners. Little information on Lp(a) levels in Afrikaners is available. The aim of this study was to describe the Lp(a) concentrations in white concentrations in control hyperlipidaemic, confirmed were compared. Afrikaner FH patients. ( normolipidaemic), diet and suspected FH and Another Lp(a) induced diabetic subjects whether compare spontaneous variations in the associations between aim was to determine Lp(a) exist, and to Lp(a) and other risk factors for CHD in Afrikaners, such as some haemostatic variables. Three hundred and forty patients who attended the Lipid Clinic, PU for CHE, in the period from January 1992 to May 1993, were classified into five groups according to defined criteria. Standard methods were applied to determine each subjects' low density lipoprotein cholesterol (LDL-c ), high density lipoprotein cholesterol (HDL-c ), triglycerides (TG ), apolipoprotein B (apo B) and apolipoprotein A-1 (apo A-1 ) at baseline. Serum Lp(& ) concentrations were determined with a radio- immunological (RIA) method of Pharmacia, fibrinolytic parameters measured were fibrinogen, tissue plasminogen activator antigen (tPA-Ag) as well as plasminogen activator inhibitor activity (PAI-act). The apo Egenotype and LDL-receptor mutation were determined for selected patients. Variations in Lp(a ) levels were determined for subjects who attended the clinic twice or more. Statistical calculations were done by the Statistical Consultation Services of the PU for CHE with the SAS-package. Tukey's Test and an ANOVA were used to determine significant differences between groups. Pearson correlation coefficients were determined between baseline Lp(a) and other parameters. The results of this study showed that there were no significant differences in baseline Lp( a) between the different experimental groups or sexes. displayed Lp(a) In each group there were both women and men who values less than 16 U/L and more than 840 U/L (which were the ranges between which the method was able to measure accurately). The typical non-Gaussian distribution of Lp(a) (skewed to the left), frequently reported by other researchers in regard to other populations, was also observed in this population. A high percentage of individuals (± 32 %) displayed elevated levels of Lp(a). This indicates that elevated Lp(a) may be a contributing factor towards the higher CHD risk in Afrikaners. The results further show that the significant correlations which were noted between Lp(a) and LDL-c in the control and OM-patients, were not present in the hypercholesterolaemic individuals. This indicates that an elevated LDL-c does not necessarily imply an elevated Lp(a). The investigation into the affected and non-affected members of families, with a parent who suffers from heterozygous FH, showed that Lp(a) is not necessarily elevated in PH-patients. The results therefore question the role of the LDL receptor in Lp(a) metabolism. We were unable to identify other factors which correlated with the observed variations in Lp(a) (14 % of the subjects median and 5 % high). The possibility that a specific substance may exist in the serum of these subjects, which may cross-react with the antibodies used to determine Lp(a ), deserves further investigation. An important finding was that Lp ( a ) displayed a positive correlation with plasma fibrinogen in hyperlipidaemic Afrikaners. There may therefore exist a commen factor, possibly genetic, which raises the levels of both these risk factors. The most salient conclusion, is that a substantial percentage of hyperlipidaemic Afrikaners who attend the Lipid Clinic of the PU for CHE, display elevated Lp( a) as well as elevated fibrinogen. Their risk for CHD are the ref ore compounded by these additional risk factors. This implies that factors which can be treated, for example, TC, LDL and TG, combined with a low HDL, should receive vigorous attention with medication, diet and exercise. Further studies should be done to establish the role of the apo(a)polymorphism in Afrikaner FH patients, as well as the role of the apo E-polymorphism in the distribution of Lp (a). Research to establish the importance of treatment for elevated Lp(a) and fibrinogen, should also receive high priority.