FATS Familial Atherosclerosis

Carlson and Rosenhamer 1988) Cholesterol Lowering Atherosclerosis Study (CLAS) (Blankenhom et al. 1987) Familial Atherosclerosis Treatment Study (FATS) (Brown et al. 1990)... 

The Familial Atherosclerosis Treatment Study (FATS) randomized 146 men with elevated apolipoprotein B and family history of coronary artery disease to one of three strategies for 2.5 years niacin and colestipol, lovastatin and colestipol, or conventional therapy. Mean stenosis increased by 2.1% in the control group. In contrast, it decreased by 0.9% with niacin and colestipol and 0.7% with lovastatin and colestipol (F<0.003). Although clinical outcomes were not the primary endpoint, there was a 73% reduction in the combined intensive groups versus the conventionally treated group (Brown et al. 1990). 

Familial lipoprotein lipase deficiency is characterized by a massive accumulation of chylomicrons and a corresponding increase in plasma triglycerides or a type I lipoprotein pattern. Presenting manifestations include repeated attacks of pancreatitis and abdominal pain, eruptive cutaneous xanthomatosis, and hepatosplenomegaly beginning in childhood. Symptom severity is proportional to dietary fat intake, and consequently to the elevation of chylomicrons. Accelerated atherosclerosis is not associated with this disease. 

Primary increases of VLDL probably reflect a number of genetic determinants and are worsened by factors that increase the rate of VLDL secretion from liver, ie, obesity, alcohol, diabetes, and estrogens. A major indication for treatment is the presence of atherosclerosis in the patient or the patient s family. Treatment includes weight reduction, restriction of all types of dietary fat, and avoidance of alcohol. Fibrates or niacin usually produce further reduction in triglyceride levels if dietary measures are not sufficient. Marine omega fatty acids may also be of value. 

Probucol is a lipid-lowering agent, but the results are not consistent with respect to LDL cholesterol. It lowers HDL cholesterol hence it is not the first drug of choice in therapy. The ability of probucol to correct atherosclerosis has been attributed to its antioxidant properties.77 The usual oral dose is 500 mg twice daily and is administered after food. Many experts use it as adjuvant therapy in familial hypercholesterolemia. The drug is well tolerated but causes GI side effects such as nausea and flatulence, headache, and dizziness. Patients taking probucol must be on a low-fat diet. Probucol should not be used in patients with recent myocardial infarction, and it should not be given to children or pregnant women. 

In hypobetalipoproteinenia the plasma LDL level is decreased (10-20% of normal), but that of HDL is normal, and that of VLDL is mildly lowered. Of 23 affected individuals from the four known affected families, one had central nervous system dysfunction and fat malabsorption. The others had mild or no pathological changes. The disease is inherited as an autosomal dominant trait. The benign nature of this condition is in sharp contrast with the seriousness of hyperbetalipoproteinemia. In the latter, LDL cholesterol concentrations are two to six times normal, and patients are predisposed to premature atherosclerosis. In another form of hypobetalipoproteinemia, the patient synthesized apo B-48 and secreted chylomicrons but did not produce apo B-lOO or secrete VLDL. 

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