The Genetics of the Familial Hyperlipidaemias

 1.  Introduction

2.  Classification of the Hyperlipidaemias

3.  Familial hypercholesterolaemia

4.  Familial Type 3 hyperlipoproteinaemia

5.  Familial hypertriglyceridaemia

6.  Familial Type 5 hyperlipoproteinaemia

7.  Familial combined hyperlipidaemia

8.  Paediatric studies

9.  Conclusion

10. References

1.  Introduction

Degenerative cardiovascular disease has been shown to possess great antiquity, having been identified retrospectively in ancient Egyptian and Peruvian mummies. This indicates that cardiovascular disease is not entirely an affliction of modern industrial civilisation. However, apart from the studies of mummified tissues, the evidence for the palaeopathology of cardiovascular disease is almost non-existent.

Until the 20th century ischaemic heart disease (IHD), the major complication of atherosclerosis, ranked low among causes of death in all countries. Within decades IHD has reached epidemic proportions in the USA and Europe, and together with other complications of atherosclerosis accounts for one half of the total deaths in the USA (Dayton, 1975). Myocardial infarction is thus the most common cause of death in men aged 35 to 55, and furthermore the proportion of female deaths in proportion to males is also on the increase (Dickerson, 1981). In 1967 some 39% of male deaths (25 to 64 years) were due to cardiovascular disease. IHD accounted for three quarters of these deaths, but more alarmingly IHD mortality is increasing to a greater extent among younger than older subjects (WHO Chronicle, 1974).

Mortality from coronary heart disease exhibits a wide variation in different countries. he rates for males are still greater than those for females in the young and early middle age groups. The difference narrows however in the elderly (Tunstall Pedoe, 1982). Ischaemic heart disease is therefore the most important cause of premature death and disability occurring among men at a time when their contribution in productive terms to society is most valuable. Mortality from CHD between the ages of 35 and 74 shows a wide international variation. The following figures for 1977 represent deaths per 100,000 (Tunstall Pedoe, 1982). A female:male ratio of 231:744 existed in Finland, whereas Northern Ireland and Scotland were 320:760 and 311:712 respectively. England and Wales had a ratio of 266:588 and the USA 251:587. However, France was 61:172, and Japan lowest with only 44:88.

Male rates in most western countries rose between 1950 and 1960, but then in the USA the rate declined steadily until they reached a similar position to England and Wales. The reasons for this decline are not quite clear, but there may be perhaps an association between risk factors and a dietary awareness (Tunstall Pedoe, 1982). In Belgium and Australia the rates have declined also, whereas Britain remained static. Conversely the rate in Sweden and some East European countries is on the increase.

Epidemiological studies have revealed populations (national and regional) with high and low incidence rates for CHD in relation to predisposing factors (WHO, 1974 a). In less developed countries the populations are relatively free from CHD (if not from other forms of disease), but their patterns of incidence change as they as they too achieve technological progress (WHO, 1974 b). Some studies have related increased morbidity in patients to their psychological make-up, in addition to their life-style and certain other environmental risk factors (Friedman, et al. 1958; Lappiccirella, 1964; Ostfeld, et al. 1961; Rosenman, et al. 1964; Russek, 1964; Wolf, 1971). Several surveys have also attempted to demonstrate the highly multifactorial pathogenesis of cardiovascular pathology – encompassing genetic as well as environmental factors – that include diet, smoking, sedentary life-style, and response to psychosocial stimuli of a harmful nature (Levi, 1972; Theorell, 1970). Pyschosocial stimuli have been described as those “…suspected of being able to cause disease, which originate in social relationships or arrangements (i.e., the environment) and affect the organism through the medium of higher nervous activity.” (Kagan & Levi, 1974).

There are primary risk factors of prognostic importance with regard to individuals free of symptoms and signs of coronary heart disease. These include : age; sex; cigarette smoking; blood pressure; and serum cholesterol. Factors of secondary consideration include: high density lipoprotein cholesterol; other lipids; obesity; glucose intolerance and levels of insulin; physical activity; familial factors; clotting factors and fibrinolysis; and psychosocial factors (Tunstall Pedoe, 1982).

Winning contribution to the Simon Broome Heart Research Trust Essay Competition, 1983.


Amidi, M.  (1972).  Type 4 hyperlipoproteinaemia in a consanguinous family.  Circulation. 45 (988).

Beaumont, J. L. et al.  (1971).  Classification of hyperlipidaemias and hyperlipoproteinaemias.  Bulletin.  WHO.  43 (891).

Berenson, G. S. et al.  (1980).  Prognostic significance of lipid profiles in children.  In: Laver, & Shekelle (eds).  Childhood Prevention of Atherosclerosis and Hypertension.  New York.

Dayton, S.  (1975).  Nutrition and Atheroclerosis.  Prog.Food.Nut.Sci.

Dickerson, J. W.  ((1981). Risk fact0rs in myocardial infarction.  Nursing, 32.

Tunstall Pedoe, H.  (1982).  Epidemiology and primary prevention of coronary heart disease. Med. Int. 20.

To be continued.


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