Episode 124. Lipids and Atherosclerotic Cardiovascular Disease with Dr Brett Forge (Part 3/3)

Lipids are essential for cell function and healthy metabolism however clinical analysis of a patient’s lipid profile also addresses one of the fundamental drivers of atherosclerotic cardiovascular disease responsible for 25 % of all deaths in Australia. Modification of abnormal serum lipid levels by lifestyle and pharmacologic intervention aims to achieve a healthy coronary circulation reducing new atheroma formation and stabilizing preexisting atheromatous plaques.

Atheroma develops when cholesterol esters and triglycerides enter the vascular intima inducing local inflammation. Macrophages recruited to the inflammation engulf the cholesterol esters by phagocytosis. Stuffed with cholesterol these cells are referred to as foam cells. The inflammatory cascade is accentuated and recruits more inflammatory cells some of whom perish over time and calcium deposition and fibrosis develops within a forming plaque. Plaque enlargement may distort vascular anatomy expanding into the vessel lumen impeding blood flow and inducing ischaemia however not all plaques impact in this way and even large developing plaques may form in a way that does not disrupt blood flow. Instability in a growing plaque however may lead to rupture and the initiation of an acute thrombotic event. Whilst hyperlipidemia underscores atheroma pathogenesis this complex and life-threatening process is also adversely influenced by cigarette smoking, hypertension, genetics, and poor glycaemic control.

Having a clear understanding of lipid physiology allows us to appreciate both atheroma formation and how cardiovascular risk may be modified. One of the key points is that as lipids are water insoluble and they must be transported in specialized vesicles. These are called lipoproteins when produced by the liver for entry into the circulation and micelles for entry into the biliary system and subsequently the gastrointestinal tract. Chylomicrons are the specialized vesicles produced by gut enterocytes to transport lipids from the digestive tract via lymphatics ultimately into the circulation.

Current Australian guidelines for lipid management recommend:

Total Cholesterol < 4 mmol/l if high risk, < 5 .5 mmol/l for general population

LDL < 1.8 mmol/l for high risk, < 2.0mmol/l general population

Triglycerides < 2 mmol/l

HDL > 1.0 mmol/l

Lowering LDL cholesterol by 1mmol/l reduces the incidence of major vascular events (non-fatal myocardial infarction, coronary death, coronary revascularization, or stroke) by about one fifth. With 11 fewer vascular events per 1000 treated over 5 years. Similarly, triglyceride reduction per 1 mmol/l is associated with about half this cardiovascular risk reduction.

Interventions that are utilized to modify the cardiac risk associated with lipids include:

Dietary manipulation

Pharmacologic modification of lipid synthesis or absorption

Multiple epidemiological studies have demonstrated a greater incidence of coronary artery disease linked to non-HDL cholesterol and elevated serum triglycerides as well as a protective benefit from high HDL levels which includes when triglycerides and LDL levels are high and a lowering of CVD risk even when optimal triglyceride and non HDL cholesterol levels are achieved.

Given the critical importance of cardiovascular risk modification it was a pleasure to invite cardiologist Dr Brett Forge to the following two episodes of this podcast to expand on this fascinating subject.

References:

Basic and Clinical Pharmacology 14th ed -Bertram G. Katzung, LANGE Books, Ch 35.

Principles of Medical Biochemistry, Eisenberg & Simmons,3Rd Ed, Elsevier Saunders, Ch 23

Ganong’s Review of Medical Physiology, Barrett et al,25 th Ed, LANGE Books, Ch 26

Dietary Fat and Risk of Cardiovascular Disease: Recent Controversies and Advances, Annual Review of Nutrition, Vol. 37:423-446, Wang & Hu

Dietary Cholesterol and the Lack of Evidence in Cardiovascular Disease, Nutrients 2018Jun;10(6):780 Ghada A. Soliman

To be a guest on the show or provide some feedback, I’d love to hear from you: manager@gihealth.com.au. Dr Luke Crantock MBBS, FRACP, is a gastroenterologist in practice for over 25 years. He is the founder of The Centre for GI Health, based in Melbourne, Australia, and is passionate about educating General Practitioners and patients on disease prevention and how to manage and improve their digestive health.