Genetic and environmental aspects —
The aetiology of many human diseases includes the consequence of environmental factors. Until recently, infection was the major cause of premature mortality in the developing countries, but this is changing. When the gross national product per capita in a country becomes greater than $1200 per annum then the proportion of deaths from cardiovascular disease increases sharply. Equally, the proportion of deaths from cancer increases progressively as the gross national product per capita increases. The proportion of animal fat in the diet also increases progressively with increasing gross national product.
Diet, smoking and industrial pollution are important factors. Populations living in the Western world constantly seek the various elements in the environment which can be changed in order to prevent premature death. Hence an interest in diet in relation to coronary artery disease, and cancers such as breast and colon. In addition, human immunodeficiency virus (HIV) is causing significant numbers of deaths, particularly in Africa.
The interplay between diet, environment and genetic predisposition is important in most diseases. Two problems, cancer and coronary heart disease, are discussed in this section. Diet is a recognized aetiological factor. The individual’s genetic predisposition determines an individual response, which is dependent upon the isoenzyme constitution.
Key points —
1. Coronary heart disease (CHD) is associated with populations who eat a high saturated fat intake and in whom the serum lipids are increased. The CHD in such populations is, to a large extent, concentrated within genetically vulnerable families.
2. Dietary constituents which increase protection from CHD include n-3- and n-6- containing fatty acids and oils, fruit and vegetables, and possibly red wine.
3. The atheromatous plaque formation which is the basis of CHD progresses through stages of a fatty streak, a fibrous plaque and a complicated arterial wall lesion. These are associated with the deposition of cholesterol in the form of lipoproteins, e.g. LDL lipoprotein.
4. Familial hypercholesterolaemia is an autosomal dominant trait with varying frequency in the population. The LDL-receptor gene mutations are well described and the mutation dictates the metabolic response. Hyperhomocysteinaemia is a risk factor correctable with folic acid or betaine supplementation.
5. Other gene mutations, e.g. apoE2 allele have considerable effects on blood cholesterol concentrations.
6. There are well developed risk evaluation tables which take into consideration systolic hypertension, smoking, diabetes, total : HDL cholesterol ratio, age and gender.
7. Many of the risk factors are correctable.
Thinking points —
The short overweight middle aged man who smokes, enjoys drinking with his friends and takes little exercise is a problem . What approaches should be made to him?
Need to understand —
The risk factors of systolic hypertension, smoking, diabetes, total : HDL cholesterol ratio, age and gender for coronary events. How they may operate and how to treat the risk. Male gender, age and height are significant contibutors to these scores which cannot be changed. This means that some risk factors have modest effect on prognosiss.
Further Reading —
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