Chylomicrons in disease-future challenges Invited keynote address.
It has taken many years to unravel the pathological implications of postprandial dyslipidaemia. Life-style and pharmacological interventions to reduce risk of atherosclerosis have developed empirically, without clear understanding of the underlying mechanisms. Acceptance of the premise that chylomicrons play a key role in atherogenesis brings new understanding to the mechanisms underlying empirical risk-reduction strategies. Raised LDL cholesterol while definitely associated with increased risk, is not present in many patients with established atherosclerosis. A large body of research points to a clear association of atherosclerosis with postprandial dyslipidaemia, not only for coronary disease but also for carotid lesions. Bayesian considerations imply that the majority of the community atherosclerosis burden is attributable to disordered chylomicron metabolism. Risk reduction by life-style interventions such as consumption of low fat meals, Mediterranean diets, low cholesterol intake, weight reduction and exercise can all be explained rationally in terms of the impact of these interventions on chylomicron metabolism. Diabetes is strongly associated with postprandial dyslipidaemia. Needed are long-term controlled trials of life-style interventions and management of dyslipidaemia, with endpoints of progression or regression of atherosclerosis. The paradigm that postprandial dyslipidaemia underlies much of the atherosclerosis burden should become a focus of drug development. Agents that reduce absorption of triglycerides and cholesterol will generally be beneficial. Probucol markedly affects chylomicron metabolism. The mechanism for optimization by Probucol is unclear but appears to be unrelated to effects on oxidation. Adrenergic agonists and thyromimetics are also likely to be beneficial. Statins and fish oils appear beneficial but data are limited. Long-term intervention studies are needed with appropriate attention to improvement in postprandial dyslipidaemia.
Redgrave
Trevor G
TG
Physiology, School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Nedlands, Western Australia 6009, Australia. redgrave@cyllene.uwa.edu.au
D050197:Atherosclerosis / Q000097:blood / Q000209:etiology* / Q000517:prevention & control; D002914:Chylomicrons / Q000097:blood*; D050171:Dyslipidemias / Q000097:blood* / Q000150:complications / Q000517:prevention & control; D015444:Exercise / Q000502:physiology; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008019:Life Style; D019518:Postprandial Period / Q000502:physiology; D012307:Risk Factors
D002914:Chylomicrons; D000960:Hypolipidemic Agents