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February 1987, Volume 37, Issue 2

Original Article

APOLIPOPROTE1N A-I AND APOLIPOPROTEIN B iN SURVIVORS OF MYOCARDIAL

Khem Karira  ( Biochemistry Department, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi. )
Abdul Baseer  ( Biochemistry Department, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi. )

Abstract

Sixty eight survivors of myocardial infarction were compared with similar age ot 34 normal controls, aged 31 - 70 years. A decreased apolipoprotein A-I and HDL cholesterol and an increased apolipoprotein B were observed in age range from 31-70 years. Total cholesterol and triglyceride were significantly high upto the age of 50 years, whereas no change was found above this age. LD L cholesterol showed significant  rise upto the age of 60 years. Ratio ofapo A-I and apo B remains significantly low in all the survivors of myocardial infarction (JPMA 37: 44, 1987).

INTRODUCTION

Coronary heart disease has been the most important cause of death in most North European, North American and other industrialized Caucasian societies1. In Pakistan too, as in other developing countries, the incidence of coronary heart disease appears to be on the rise. A biochemical metabolic abnormality in lipid metabolism is probably the principal factor in the pathogenesis of coronary artery disease. Clinical and experimental studies suggest that the apolipo­protein composition and concentration of particular lipoprotein classes could be important for atherogenicity2-4.
Initially human plasma lipids and lipopro­teins attracted attention because of their role in intravascular lipid transport. However recent research points to a multiplicity of their functions, ranging from lipid metabolism to the regulation of cell surface receptors. The protein component (apolipoprotein) maintains lipoprotein structure and in part directs metabolic activity. In addition Onitiri and Jover5  specified that the apolipopro­teins have been implicated as the specific abnor­malities in many disorders of lipid metabolism. Recently the study of Sveger and Fex6 suggests that the analysis of apolipoprotein especially apolipoprotein B. are of value to trace adolescents at risk for future coronary heart disease. Similarly it has been proposed7  that a change in the levels of plasma lipid and lipoprotein does not remain as a sensitive index for the prevision of risk factor for atherogenicity over an entire age range, while the levels of apolipoproteins A-I and B has been regarded as a better discriminator for the above aspect.
This study was also proposed to observe the changes in the level and the composition of lipKl and lipoprotein in the patients of myocardial infarction. Particular attention has been given to the quantification of apolipoprotein A-I and apolipoprotein B which are considered at present as more accurate parameters than lipid analysis for the prevision of cardiovascular disease related to atherosclerosis.

MATERIAL AND METHODS

Sixty eight survivors of myocardial infarction who had recovered from earlier attack of acute myocardial infarction were studied. The patients selected were outdoor patients attending for follow up at the National Institute of Cardiovascular Diseases and Cardiovascular Depart­ment of Jinnah Postgraduate Medical Centre, Karachi.
Apparently 34 healthy normal subjects of similar age and socio-economic status as that of patients were selected from staff and postgraduate students of Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, and various areas of Karachi. The information about their blood pressure, smoking habbit, body weight and any family history of cardiovascular disease were also recorded.
The survivors of myocardial infarction having diabetes were excluded from the study.
They were classified on the basis of age into 4 groups ranging from 3140, 41-50, 51.60 and 61-70 years. Their lipids, lipoproteins and apolipo­proteins were compared with similar age groups of normal subjects.
Blood was drawn in the morning after 12 hours fast and allowed to clot for 1 hour at 37°C. The serum was recovered by centrifugation.
The samples were analysed for total cholesterol (Boehringer Kit), triglycerides (Cromatest Kit), High density lipoprotein cholesterol (HDL-C)8 and Low density lipoprotein cholesterol (LDL-C) were calculated by the method of Friedewald et al~. Apolipoprotein A-I (Apo A-I) and apolipoprotein (Apo B) were measured by immunochemical assay (Orion Diagnostica Kit).

RESULTS



Table shows the serum levels of lipids, lipoproteins and apolipoproteins in different age groups of the participant. Serum levels of total cholesterol and triglycerides remain significantly higher in patients as compared with normal subjects in age groups of 3140 and 41-50 years. Above this range no significant increase in lipids been observed in age groups of 51-60 and 61-70 years.
The serum HDL-C level was significantly lower within an age range of 3 1-70 years, whereas LDL-C showed a significant increase within an age range of 31-60 years. Apolipoprotein A-I and apolipoprotein B showed a significant change in all age groups.
A significant decrease in the level of serum apolipoprotein A-I and an increase in the level of apolipoprotein B has been observed in all the age groups (3 1-70 years) of survivors of myocardial infarction.
The ratio of apolipoprotein A-I and apolipoprotein B was also significantly low in survivors in all age groups (31-70 years).

DISCUSSION

The debate on the value of plasma lipids as a predictive risk factor for atherogenesis has centered for many years on cholesterol, triglycerides and low density lipoprotein cholesterol. Lately interest has focussed on the role of high density lipoprotein cholesterol as an anti risk factor. Nevertheless a large proportion of patients who suffer a major clinical event from atherosclerosis may present with a completely normal lipid and lipoprotein pattern. A partial explanation of these heterodox cases has been offered by the recognition of the fact that chemical composition of lipoproteins is more relevant than the simple plasma level of the total cholesterol. Recently some workers have stressed on the reduced level of serum apolipopro. tein A-I and increased level of apolipoprotein B in atherosclerotic patients as diagnostic feature. This changed level of apolipoproteins were also observed even in normolipidemic patients7.
Alterations in I-IDL composition may well have relevance to atherogenesis since the ability of HDL to remove cholesterol from cell culture can be modified by the apolipoprotein level, indicating that apolipoprotein A-I is a functional unit of HDL10. Miller and Miller11 pointed out the inverse relation between HDL and coronary artery disease and suggested that HDL might promote the clearance of cholesterol from arterial wall. Schonfeld et al12. found an altered HDL structure and molecular association of apolipo­protein A-I in hyperlipidemia. Recently Noma et al12 reported a significantly low level of apolipoprotein A-I in survivors of myocardial infarction. Similarly14 low level of apolipoprotein A-l have been reported in patients angiographically assessed coronary artery disease and concluded that apolipoprotein A-I by itself is more useful index than high density lipoprotein for identifying patients with coronary artery disease. It has been observed in the present study that serum levels of apolipoprotein A-I is significantly lower in survivors of myocardial infarction in all age groups ranging from 31-70 years as compared to control subjects.
On the contrary, elevated levels of plasma apolipoprotein B were found regardless of whether they were normo cholesterolemic or hypercho les­terolemic in the individuals with coronary artery disease15 5 In a comparative study Avogaro et al8. observed significantly low level of apolipoprotein A-I and high level of apolipoprotein B in survivors and concluded that the protein moeity of lipoprotein is a better discriminator than lipids between atherosclerotic subjects and controls. Value of Serum levels of apolipoprotein A-I and apolipo. protein B rather than on the levels of serum lipids has been emphasized for evaluation of the athero. sclerosis. Our data (Table) is in agreement with the study of above workers in all age groups whether they may be hyperlipidemic (31.50 years) or normolipidemic (51.70 years).
The serum level of LDL cholesterol in survivors were found significantly higher within an age range of 3 1-60 years. In a prospective study of the Framingharn and Liverpool populations it was demonstrated that LDL.C is a powerful risk factor for coronary artery disease in men younger than 50.55 years of age. However above this age the predictive power of LDL.C deteriorates with increasing age177
Ratio of apolipoprotein A-I and apolipopro­tein B was also determined in the present stud7 and found significantly low in all age groups (31—70 years). The observation is in constant with the findings of many workers7-13
The serum levels of total cholesterol and triglycerides remains significantly high in survivors of myocardial infarction within the age range of 31-50 years. Above this age range no significant increase in the serum lipid have been observed. Similar findings have been observed by Avogaro et al7. and Trilokinath et al18
It has been concluded that apolipoproteins may be better predictive factors than cholesterol and triglyceride in discriminating between atherosclerotic patients and controls. When matched, the mean values of apolipoproteins A-I and B and their ratio seem as good as total cholesterol, triglyceride, LDL & HDI cholesterol in younger age. When patients and controls of old age with similar levels of total cholesterol and triglyceride were compared, survivors still showed significant differences in their values of apolipo­protein A-I and apolipoprotein B and their ratio.

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