Table 1.

Genetic and environmental factors associated with atherosclerosis and coronary heart disease (CHD)

Factors with a strong genetic component
Elevated levels of LDL/VLDL	Associations demonstrated in epidemiological studies and supported by studies of genetic disorders and animal models. Clinical trials have shown benefits of cholesterol reduction54.
Reduced levels of HDL	Associations demonstrated by numerous epidemiological studies and supported by studies of genetic diseases and animal models58.
Elevated levels of lipoprotein(a)	Associations observed in many, but not all, epidemiological studies. Animal studies have been contradictory59.
Elevated blood pressure	Associations observed in epidemiological studies. Clinical trials have demonstrated benefits of blood pressure reduction, with particularly strong effects on stroke54,60.
Elevated levels of homocysteine	Associations have been observed in epidemiological studies, and homocystinuria results in severe occlusive vascular disease36.
Family history	When all known risk factors are controlled for, family history remains a very significant independent factor6.
Diabetes and obesity	Associations observed in epidemiological studies and in studies with animal models54.
Elevated levels of haemostatic factors	Significant independent associations have been observed with elevated levels of fibrinogen, plasminogen activator inhibitor type 1 and platelet reactivity54.
Depression and other behavioural traits	Associations observed in several population studies61.
Gender (male)	Below age 60, men develop CHD at more than twice the rate of women38.
Systemic inflammation	Elevated levels of inflammatory molecules such as C-reactive protein are associated with CHD, as are inflammatory diseases such as rheumatoid arthritis62.
Metabolic syndrome	This cluster of metabolic disturbances, with insulin resistance as a central feature, is strongly associated with CHD5.

Environmental factors
High-fat diet	Population migration and epidemiological studies indicate strong associations with lifestyle, and diet appears to be the most significant factor. High-fat, high-cholesterol diets are usually required for development of atherosclerosis in experimental animals54.
Smoking	Strong associations observed in numerous epidemiological studies. Clinical trials have demonstrated the benefit of stopping smoking54.
Low antioxidant levels	Results of clinical trials with antioxidants have not been conclusive. Fat-soluble antioxidants protect against atherosclerosis in experimental animals, however63.
Lack of exercise	Significant independent associations with CHD54.
Infectious agents	Epidemiological studies provide suggestive evidence for associations with various infectious agents, such as Chlamydia pneumoniae. Preliminary animal studies support the relationship64.