This essay has been written as a contribution to the discussion concerning the role played by plasma lipids in the aetiology of coronary heart disease. Evidence is now regarded as conclusive that there is a definite correlation between raised plasma lipid levels and the onset of ischaemic heart disease, and that appropriate therapeutic intervention lowers this risk *.
*The Lipid Research Clinics Coronary Primary Prevention Trial Results. Reduction in Incidence of Coronary Heart Disease. JAMA. 251:351-364. 1984.
The underlying theme of this essay is that the apoproteins may serve as better, even more useful, indicators of the existence of familial hyperlipidaemias (Avogaro et al, 1979). Especially because the determination of plasma apolipoproteins may enable earlier diagnosis to be made – hopefully amongst younger age groups than is at present possible. In this context special consideration will be paid to Type IV familial hypertriglyceridaemia which at present defies pre-adulthood detection by current methods.
Furthermore, consideration will be given to present knowledge of the inheritance of Type, IV hyperlipoproteinaemia and current research into the determination of associated apoproteins as genetic markers for the condition. Finally there will be a proposal for further avenues of research that are aimed at determining apoprotein levels that may enable the detection of familial hypertriglyceridaemia in younger age groups. The specific theory underpinning this essay is that, even though plasma lipid levels indicating Type IV are difficult to demonstrate amongst young persons, the apoproteins related to the condition may prove to be a more reliable diagnostic tool and possibly demonstrable in children and adolescents.
The apolipoproteins – a review
Many proteins require, for their biological activity, tightly bound and specific non-polypeptide units. Such units are termed prosthetic groups. Thus a “…protein without its characteristic prosthetic group is termed an apoprotein.” (Stryer, L. 1974). All lipoproteins contain proteins and the apolipoproteins represent the lipid free components of plasma lipoproteins. Chylomicrons (fat globules) were the first lipoproteins discovered. Apolipoproteins are obtained by treatment of intact lipoproteins with detergents, organic solvents, and chaotropic agents. It is known that the proteins consistently isolated with the chylomicrons are specific apoproteins. Furthermore, all lipoproteins that are isolated from liver and intestinal cells are seen to consistently contain one or more apoproteins. Lipoprotein densities “…are inversely related to their content of lipids relative to proteins, i.e,,thegreater the lipid content, the less dense their particles.” (Schonfeld, G. 1983, 91). There occurs in the circulation an extensive exchange and net transfer of apolipoproteins and this “…contributes considerably to the apolipoprotein content of serum VLDL.” (Herbert, F. N. et al, 1983, 592). It is also known that some apoproteins are confined to HDL, some are confined to LDL and VLDL, and that some are shared by all forms of lipoproteins. And moreover “…the apoprotein compositions of intestinal lymph and plasma chylomicrons are different.” (Schonfeld, G. 1983, 91).
With regard to the nomenclature of the apoproteins they were originally named by their individual discoverers. In recent years an ABC nomenclature was proposed (Alaupovic, P. 1971) and ,this classification has since been adopted by most researchers in the field. The nomenclature is based upon the hypothesis that plasma lipids are transported by different families of lipid-protein complexes (Alaupovic, P. 1972). The apoproteins that are of importance in lipid transport are those in the series apoA to apoB. For example, the lipoprotein family A consists of complexes of lipids and the apoproteins A. Lipoproteins isolated from plasma by ultra-centrifugation, are, according to this concept, either complexes of or single lipoprotein families. For example, virtually all of the lipoprotein B family are associated with LDL, and VLDL comprises a complex of B, C and E. The Roman letter and numeral designation was adopted by Alaupovic and then applied to all isolated single lipoprotein families. But, as has been noted above, the nomenclature is not universally accepted yet. For example, there is no apoA-I;II because other researchers named it apoD
The apolipoproteins have been studied according to their functions, origins, distribution, concentrations, molecular weights and polymorphisms. The primary structures of five of the apolipoproteins have been determined and these are A-II, C-I, C-II, and C-III, (Jackson, R. L. et al, 1977). Moreover, it has been shown that these proteins contain about the same proportion of non-polar and polar amino-acids as do other soluble proteins. This gave rise to the hypothesis that “…there are specific and specialised lipid-binding regions within these molecules.” (Herbert, P. N. et al, 1983, 593) because sequences of apolipoproteins do not contain long stretches of hydrophobic amino-acids, (Segrest, J. P. et al, 1974). These lipid-binding regions are described as amphipathic helices and have been shown to exist in the five apolipoproteins of which the primary structure is known (Sparrow, J. T. et al, 1975). These amphipathic helices are thought to enable apolipoproteins to form stable structures with polar phospholipids. It is thus probable that most apoproteins are bound to phospholipids and even other apoproteins “…on or near the surface…” (Schonfeld, G. 1983 93) thus approximating a monolayer on the plasma lipoproteins. Thus the “…outer layer or surface regions of lipoprotein particles are formed by hydrophilic molecules, the phospholipids and apoproteins, while the inner or core regions contain the hydrophobic, cholesterol esters, and triglycerides.” (Schonfeld, G. 1983, 93).
The apoproteins display a4number of important metabolic functions. These functions are related to the specific domains found on the three-dimensional structures of individual proteins. All apoproteins bind to lipids. This is because they share the structural feature known as the amphipathic helix domain in common. The hydrophobic face of this helix is thought to interact with the hydrophobic and fatty acid portion of the phospholipids – whereas the helix’s hydrophilic face interacts with the phospholipids polar region. Researches have shown that the association of lipids and apoproteins is regulated by the law of mass action. This is because apoproteins may dissociate themselves from one lipoprotein and move to another, (Brewer, H. B. jr, 1981). Alterations in lipid-protein interactions appear to be routine during lipoprotein metabolism. Virtually all apoproteins (excepting apoB) are able to alter their plasma lipoprotein associations. In the case of apoB – this appears to remain associated with the same lipoprotein–particles throuighout– its– metabolic life. We can outline the essential structure and functions of the major apoproteins.
Apolipoprotein A-I is a major protein component of primate HDL. The amino-acid sequences of the apoA’s are known and none of which are chemically related. Each possesses a different function (which may suggest a four gene complex) and apoA-I and apoA-IV are single proteins. ApoA-I consists of a single chain of between 243 and 245 ammino-acid residues (excluding cystine, cysteine, leucine and carbohydrate). Mutant forms of apoA-I have been recognised as have several isoforms (A-I, A-I2 ). ApoA-I is a potent activator of Lecithin Cholesterol Acyl Transferase (LCAT) which is “…a plasma enzyme catalyzing the conversion of cholesterol and phosphatidylcholine to chclesteryl esters and lysophosphatidylcholine.” (Herbert, P. N. et al, 1983, 594). It is the specific lipid-binding domains of apoA-I that activates LCAT – this activity is associated with the property of lipid-binding.
ApoA-I is synthesised in the intestines and liver and has a molecular weight of 28,300. It has a plasma concentration of 90 to 130 mg/dl and more than 90% of plasma apoA-I is associated with HDL. Less than 1% is associated with VLDL and LDL. ApoA-I constitutes no more than 10% of the lipoprotein free fraction of plasma (Cheung, M. C. et al, 1977), and comprises a major (5% or more) component of chylomicrons and HDL, a minor portion of VLDL and a trace of LDL.
Apolipoprotein A-II is a major constituent of human HDL constituting about one third of the total protein and 15% of the HDL mass. ApoA-II has a molecular weight of 17,000 with a plasma concentration of 30 to 50 mg/dl. It is synthesised in the liver and intestines but its function is unknown. ApoA-II has a similar component distribution to ApoA-I in HDL and VLDL etc. This apoprotein exists as a dimer of two identical chains that comprise 77 amino-acid residues each but, however, the primary structure is unknown (Brewer, H. B. jr et al, 1972). Both forms of apoA-II (monomeric and dimeric) are capable of reassembling with phospholipid and specific lipid-binding segments have been identified (Mao, S. J. T. et al, 1970). In so far as lipid transport is concerned the specific role of apoA-II has not been determined, but it is established that the bulk of apoA-II is found in HDL but less than 55, in other lipoprotein classes
Apolipoprotein A-IV is found predominantly in the lipoprotein free fraction of plasma and lymph. It is synthesised in the liver and intestine and has a molecular weight of 46,000 (Beisieg, U. et al, 1979). ApoA-IV is a major chylomicron constituent (5% or more), appears as a trace in VLDL, as a minor component of HDL but is absent from LDL.
Apolipoprotein B is a constituent of chylomicrons (major), of LDL (major), and VLDL (major) and only a minor component of HDL. ApoB comprises more than 90% of protein LDL but little is known about its structure. There is evidence for heterogeneity for human apoB. It has been shown that apoB exists as a series of proteins in plasma LDL with the following types: apoB 100 (molecular weight 549,000); apoB-74 (molecular weight 407,000); and apoB-26 (molecular weight 126,000), (Kane, J. P. et al, 1980). ApoB-100 is the predominant species from which both apoB-74 and apoB-76 are derived, and this is indicated by size and amino-acid composition. It also appearsthat a second distinct type of apoB comprises a major constituent of the chylomicrons and which is not found in LDL and has an m/wt of 265,000, so “Immunological differences between the large and small varieties of apoB probably…exist…together with evidence for structural and chemical differences; suggest that they are products of different genes” (Herbert, P. N. et al, 1983).
The amino-acid sequence of apoB is unknown but it is thought that it may consist of four proteins (Kane, J. P. et al, 1980). Further to this apoB plays a role in the synthesis of both chylomicrons and VLDL – appearing to be critical to the receptor-mediated uptake of LDL. In addition there is also evidence for a role of apoB in LDL clearance as well as formation (Shepherd, J. et al, 1979., and Shepherd, J.et al, 1980). More than 907 of plasma apoB in normal subjects and in hypercholesterolaemic patients is found in LDL. ApoB in VLDL and chylomicrons constitutes between 20 and 507 of the total in moderate to severe hypertriglyceridaemia (Schonfeld, G. et al, 1974; Albers, J. J. et al, 1975).
Apolipoproteins C-I, C-II, and C-III are “…distinctive proteins with distinctive functions.” (Herbert, P. N. et al, 1983) of which the amino-acid sequences are known. ApoC-I is a single protein with a molecular weight of 6,500 to 7,000 (Shulman, R. S. et al, 1975). ApoC-I constitutes 107 of the protein in VLDL and 2% in HDL. Synthesised in the liver it can activate LCAT and bind phospholipid. It is a single chain protein of 57 amino-acid residues (Shulman, R. S. et al, 1975: Jackson, R. L. et al, 1974). ApoC-I is a major component of chylomicrons and VLDL, a minor constituent of HDL and occurs as a trace in LDL.
Apolipoprotein C-II (apoC-II) is synthesised in the liver and functions as an activator of lipoprotein lipase. It constitutes 10% of VLDL protein, between 1 and 2% of HDL-2 and less than 1% of HDL-3 (Kashyap, M. L. et al, 1977). ApoC-II is a single chain protein of 78 Or 79 amino-acid residues whose sequence is now known (Shulman, R. S. et al, 1975: Jackson, R. L. et al, 1974; Jackson, R. L. et al, 1974). As mentioned above apoC-II is a potent activator of lipoprotein lipase “…the enzyme catalyzing the hydrolysis of triglyceride in chylomicrons and VLDL.” (Herbert, P. N. et al, 1983, 595). The importance physiologically of lipase activation has been documented and where it was shown to-be (in one case of severe familial hypertriglyceridaemia) secondary to an absolute deficiency of apoC-II (Beckenridge, W. K. et al, 1978). This has to be considered against the normal situation where “…the quantity of apoC-II in plasma considerably exceeds that required for lipoprotein lipase activation.” (Herbert, P. N. et al, 1983, 596). ApoC-II has also been shown to occur in two forms – apoC-II-1 and apoC-II-2 (Havel, R. J. et al, 1979). It has a molecular weight of 8,800 to 9,000 (Jackson, R. L. et al, 1977a).
Apoprotein C-III. (ApoC-IIl) has a molecular weight of about 9,000 (Brewer, H. B. jr et al, 1974). It is the most abundant of the C proteins and constitutes about 50% of VLDL protein (Catapano, A. L. 1980) but also 2g of HDL. It is a single chain of 79 amino-acid residues of a known sequence (Brewer, H. B. jr. et al, 1974; Shulman, R. S. et al, 1974). ApoC-III occurs in three polymorphic or isoelectric forms – apoC-III-2, apoC-III-1, and apoC-III-0. They are classified according to the number of sialic acid residues at the end of the carbohydrate chain. ApoC-III-0 has no sialic acid content, apoC-III-1 has one molecule of sialic acid and apoC-III-2 has two molecules. (Vaith, P. et al, 1978). About 25% of apoC-III in normal plasma is associated with VLDL whereas 60% is in the HDL. However, more than 50% of the total apoC-III may be in the VLDL in hypertriglyceridaemic serum (Curry, M. D. et al, 1980).
Apolipoprotein D (apoD or apoAIII) is a protein of a molecular weight of approximately 32,000 and constitutes less than 5g of HDL apoprotein (Kostner, G. M. 1974). ApoA-III is Kostner’s designation but apoD derives from another group of researchers (McConathy, W. J. et al, 1973). ApoD is a minor apoprotein of HDL but its componency of chylomicrons is unknown. In VLDL it is a minor constituent if present at all and occurs as a trace in LDL.
Apolipoprotein E (apoE) comprises 10 to 20% of VLDL protein and has been detected immunochemically in all lipoprotein classes. It usually occurs as a single chain with a molecular weight of 35,000 to 39,000 (Rall, S. C. jr et al, 1982). Extensive heterogeneity has been reported. Three major forms, or isoforms, of apoE (E-2, E-3, and E-4) are thought to be products of three alleles at a single locus (Zannis, V. I. et al, 1981). ApoE heterogeneity has three sources. One source is genetic due to substitutions in its primary amino-acid sequence and the other is due to varying degrees of sialylation (Zannis, V. I. et al, 1981). It is thought that the recognition of apoE-3 and apoE-4 by hepatocyte receptors may provide a link in the normal conversion of VLDL remnants to LDL (Havel RJ et al, 1980). Furthermore, serum levels of apoE appear to correlate highly with triglyceride concentrations (Blum, C. B. et al, 1980). ApoE is synthesised in the liver and may be a receptor-mediated lipoprotein remnant of catabolism. The apoE receptor on hepatocytes is known to bind chylomicron remnants and serves as a recognition marker for the uptake of lipoproteins by several cell types.
In addition to the apoproteins there are certain enzymes and cellular receptors that play a role in lipoprotein metabolism. For example, beta VLDL and chemically altered lipoproteins are found on macrophages (Mahley, R. W. et al, 1980; Goldstein, J. L. et al, 1979). All receptors mediate the internalization of the lipoproteins they bind.
Dietary triglycerides and phospholipids undergo partial hydrolysation in the lumen of the gut and are absorbed together with cholesterol by the enterocytes. It is within the enterocytes that these lipids are re-esterified. These re-esterified lipids are assembled with specific apoproteins (apoB, apoA-I and apoA-IV) to form chylomicron particles. Intestinal lymph, which contains chylomicrons; is collected and enters the venous system via the thoracic lymphatic duct (Schonfeld, G. 1983). The chylomicron component of the lymph passes to the venous plasma where it undergoes a series of changes. Chylomicrons in the plasma acquire apoC proteins and apoE proteins by transfer from the circulating plasma HDL (Havel, R. J. et al, 1973). The triglycerides and phospholipids are also hydrolyzed by LPL (lipoprotein lipase) which is located on the endothelial cell surfaces of the arteries and capillary beds (Blanchette Mackie, E. J. et al, 1973; Higgins, J. M. et al, 1975). From this it can be deduced that an excess of circulating lipids will lead to excessive binding to the arterial and capillary walls.
Lipoprotein lipase interacts with apoC-II on the surfaces of the chylomicrons. This catalytic activity results in lipolytic products that include free fatty acids, lysophospholipids, and glycerol. These products are taken up by the tissues and thus form sources of energy and for membrane synthesis. Thus the “…net result of the intravascular catalysis and the movement of lipids and apoproteins is the conversion of chylomicrons to chylomicron remnants.” (Schonfeld, G. 1983). Smaller than the chylomicrons, these remnants are enriched with cholesterol and apoproteins. Important apoproteins in this respect are particularly apo’s B and E.
Inheritance, hypertriglyceridaemia and the apoproteins.
Hypertriglyceridaemia in its familial form demonstrates a “….wide variety of as yet unidentified biochemical defects, each of which produces a similar phenotype.” (Fredrickson, D. S. et al, 1978). It has not so far been possible to determine what proportions of familial (type IV) hypertriglyceridaemia are polygenic or monogenic, although the trait appears to act as a Mendelian dominant in some families (Murphy, E. A. et al, 1977). It does seem probable that the inheritance of type IV is polygenic. A developing trend of research is progressing along the lines of searching for genetic markers, especially those associated with the apoproteins.
When considering the apoproteins and type IV it is seen that there are many shared metabolic and physical properties between VLDL and chylomiccons. They serve thus as a transport mechanism for triglyceride. It is not known with any certainty, however, whether intestinal VLDL are more closely related to chylomicrons or to the hepatic VLDL. It has been said that “…the apoprotein composition suggests that chylomicrons and intestinal VLDL represent a class of lipoproteins that should be distinguished from hepatic VLDL.” (Simons, L. A. et al, 1980). With regard to type IV and the search for genetic markers we can state that VLDL contains the major apoproteins apoB, apoC-I, apoC-II, apoC-III and apoE. VLDL only contains traces or minor constituents of apo’s A-I and it is known that plasma VLDL contains approximately 8 to 10% protein, ithe principal ones being apo’s B, C and E (Kane, J. P. et al, 1975).
It is the hypothesis of this essay that the techniques applied to the determination of genetic factors – especially using the apoproteins as genetic markers – could be applied more widely to hypertriglyceridaemia. A recent trial and study (Sveger, T. et al, 1983) suggested that the analyses of apolipoproteins, especially apoB, are of value to trace adolescents at risk for future coronary heart disease. In this study the subjects were tested for apoA-I, apoB and HDL. The conclusion was that it is “…well established that elevated total-C and/or elevated apoB as well as low HDL-C and/or apoA-I are risk factors for CHD (Sveger, T. et al, 1983 ), see also (Avogaro, P. et al, 1978: Whayne, T. F. et al, 1981). Another study (Strobl, W. et al, 1983) determined the levels of apolipoproteins A-I, AII, B and E, as well as total cholesterol and triglycerides in cord serum and capillary serum from infants in the first week of life. The study set out to determine the cord serum lipoproteins. It was found that the serum apolipoproteins A-II, and B were lower at birth than in adulthood. Interestingly it was also seen that apoE showed no difference between neonates and adult levels. Furthermore, during the first five days of life the apoB levels more than doubled whilst apoA-I increased moderately. ApoE also showed a moderate rise whereas apoA-II showed no significant change. The study’s conclusion was that the “…changes of the apolipoprotein pattern during the first week of life reflect the evolution of the lipid transport system.” (Strobl, W. et al. 1983). Of interest here is that the Strobl study shows that apoproteins can be detected early – a useful tool to detect early type IV?
A proposal for further research.
It has been shown that in rare instances hypertriglyceridaemia can be caused by a structural gene mutation affecting lipoprotein lipase or apolipoprotein C-II (Galton, D. J. et al, 1982). In the majority of type IV cases no mutation is detectable. This raises the possibility again that a polygenic mechanism is involved. It is thus worthwhile to thus “…consider the apoprotein genes as one of the genetic factors determining the common forms of hypertriglyceridaemia.” (Rees, A. et al, 1983). The Rees study was to detect a DNA polymorphism adjacent to the human apoprotein gene isolated earlier (Shoulders, C. C. et al, 1982) and its relation to type IV familial hypertriglyceridaemia.
A research requires subjects and this in the case of hypertriglyceridaemia implies a register of patients. The main aim would be to determine the levels of apoproteinin young or pre-adult age groupsloosely related to VLDL. As we have seen, VLDL contains the major apoproteins B, C-I, C-II, C-III and E (Kane, J. P. et al, 1975). Tests would have to be directed firstly to the offspring and siblings (and their offspring) of known patients with type IV hyperlipoproteinaemia. The tested siblings for associated VLDL apoproteins, as well as tested offspring, would depend on the age of the proband. The central theme is that where standard lipid level tests are inconclusive in adolescent (and younger) offspring of type IV patients, it may be possible to determine apoprotein levels indicative of type IV in the pre-clinical phase.
Methods employed must go beyond, as already stated, the standard lipid plasma level tests. Techniques could include the use of labelled apoproteins with radioactive iodine complexed to lipoproteins and injected into the subjects to be tested. Such a method was used (Fisher, A. et al, 1982) to study familiaI type III “…associated–with, a particular isoform of apolipoproteim E .(apoE) called–E-2.” As is known apoE is an important constituent of chylomicrons and VLDL remnants. It was seen that the amino-acid sequences of E-2, E-1 and E-4 were identical except at two sites (A and B) and it was further shown that “Arginine residues seem to be essential for proper lipoprotein-receptor binding in general…” (Fisher, A. et al, 1982). The techniques of isoelectric focusing and 2-D electrophoresis were used, and the results from each method compared, to determine a variant of apoA-I (Schamaun, 0. et al, 1983). The variant isolated was termed apoA-I 2-1 and established as a co-dominant autosomal Mendelian inheritance. Despite its not being associated with any disease process the conclusion was that the apoprotein “…may be regarded as a valuable marker for genetic mapping purposes”. Isoelectric focusing of lipoprotein VLDL was employed to apoE phenotype type V hyperlipidaemic patients (Stuyt, F. M. J. et al, 1982). All the patients involved had severe hypertriglyceridaemia with 10 mmo1/1 or more. It was found that none of the “…twenty type V patients had the homozygous E-4 phenotype and eight had the heterozygous E-4 phenotype…apoE allele frequency was similar in the control group and in the type V patients.
It seems unlikely that apoE-4 is a major determining factor in the expression of the disorder.” This may be contrasted with phenotypes determined by gel isoelectro-focusing used elsewhere (Ghiselli, G. et al, 1982). It was pqinted out that apolipoprotein E (apoE) may be inherited at a single locus with three common alleles (E-3, E-2, and E-4). The products of these alleles are termed apoE-2, apoE-3, and apoE-4. Results showed that patients with types I, IIa, IIb, and IV hyperlipoproteinaemias had a similar apoE- phenotype distribution similar to normal with 40 to 60„, homozygous for E-3. The conclusion drawn was that apoE-2 and apoE-4 are associated with two distinctly different dyslipoproteinaemias and that apoE has also two different physiological functions. More sophisticated techniques were employed for genetic analysis (Rees, A. et al, 1983) using appropriate recombinant DNA plasmid probes. The purpose was to detect variations “…of the genotype…by comparison of characteristic genomic patterns of recombinat DNA.” Rees A et al stated that they used techniques of digestion with restriction endonucleases and the Southern blot hybridisation method for their nuclear whole blood pellets (Baralle, F. E. et al, 1980; Southern, E. M. 1975).
There exist techniques for the determination of the apoproteins that are associated with VLDL and especially with type IV hypertriglyceridaemia. It is therefore suggested that if these techniques were applied to the offspring, siblings, and immediate relatives of known type IV patients, that it may be possible to detect those children and adolescents liable to develop clinical hypertriglyceridaemia later in life – especially before standard plasma lipid level determinations become an effective diagnostic tool during adult life.
Summary and conclusions.
Analyses of serum lipid cholesterol and triglycerides have been carried out. One such programme determined these levels on an autoanalyzer (Cresanta, J. L. et al, 1983) using a random sample of the population. The difference is that the register based research avenue suggested in this essay would not be random because subjects would be selected on the basis of their relationship to a known hypertriglyceridaemic proband. However, Cresanta et al found that the “Mean beta-LPC declined during early adolescence…as did the adolescent decline in mean total cholesterol, while mean pre-beta-LPC increased during the same period as did the early adolescent increase in mean triglycerides.” (my italics).
In conclusion it is worthwhile saying that research into the earlier detection of hypertriglyceridaemia (as well as the other types of hyperlipoproteinaemia) is a contribution to the development of preventive cardiology. By concentrating on the younger age groups it is intended to try and raise the diagnostic capabilities for type IV to the level at present available for hypercholesterolaemia in younger age groups.- One important study,: “…examined the hypothesis that familial aggregation of lipids and lipoproteins facilitates within-family identification and hyperlipoproteinamia.” Using this model and applying it to a lipid register it may be possible to extend apoprotein techniques of determination into known family groups. As the above study pointed out “As the categorizalion of probands hypercholesterolaemia or hypertriglyceridaemia increased from sporadic, to persistent, to severe, the percentage of hypercholesterolaemic or hypertriglyceridaemic offspring and siblings increased.” Furthermore, and to a certain extent relevant to family entries on lipid registers)it can be shown that “Close sibling and parent-offspring lipid and lipoprotein risk factor associations in hypercholesterolaemic and hypertriglyceridaemic family units during and after the period of shared common-household environment facilitate within-family identification of dyslipoproteinaemia and suggest potential sharing of coronary heart disease risk.” (Morrison, J. A. et al, 1983).
Such a conclusion posits not only the value of further lipid gene and apoprotein detection within at risk families for CHD,it also hints at family orientated dietary changes – especially when that family contains one or more diagnosed hyperlipoproteinaemic patients. However, thisimportant preventive avenue is beyond the scope of this present essay which has to concentrate on its set taskand that is to add to preventive cardiology by elucidating as soon as possible all individuals who later in life may be at risk from coronary heart disease.
Eric .W. Edwards March 16th, 1984.
Essay contribution to the Simon Broome Heart Disease Research Trust.
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