Type 4 hyperlipoproteinemia: one theory of atherogenesis

Although the authors specifically state that this is an 'opinionated' and not a 'scientific' article, it is provocative and informative, referable to a disease of epidemic proportion in which 600,000 deaths occur each year. There is a need for a multifactorial approach for a coronary prevention program. A better understanding of the interrelationship of coronary risk factors is needed. If one accepts the filtration theory of atherogenesis (either with or without prior arterial damage), it is easy to see how hypertension and hypercholesterolemia can induce subintimal lipid accumulation. The precise pathogenetic role of hypertriglyceridemia, obesity, smoking, stress, glucose intolerance and muscular inanition is much less easy to define. Endogenous hypertriglyceridemia has been recognized for over two decades as a factor in atherogenesis; its importance has been difficult to assess. This disorder, now called type 4 hyperlipoproteinemia, is characterized by an abundance of circulating triglyceride rich pre β lipoproteins (synonymous with very low density lipoprotein or VLDL). This type 4 disease has been found to be the most common metabolic factor in patients with premature coronary artery disease. It is not a disease of known etiology but may have diverse etiologies. Many type 4 subjects seem to fit a common metabolic mold. They are obese and commonly have glucose intolerance. The authors prepose that the basic metabolic process involves the triglyceride molecule coated by cholesterol and cholesterol ester, with a protein phospholipid shell. The details of this metabolic process are given. It interconnects the metabolic abnormalities of endogenous hypertriglyceridemia, obesity and glucose intolerance. Therapy for the prevention of coronary disease is discussed. If the patient has type 4 disease or diabetes, weight reduction, cholesterol restriction and increasing the polyunsaturated to saturated fat ratio are mandatory. Education of the population regarding health hazards is necessary. Starting with the children is vital, since the dietary patterns of adults are formed in childhood.