Summary
Highlights
Reducing atherogenic burden remains a significant challenge. While LDL cholesterol reduction is proven to decrease cardiovascular disease, many events occur without elevated LDL. Newer research indicates atherogenic potential in other lipoprotein particles, particularly in hypertriglyceridemic patients with low HDL, often associated with metabolic syndrome and diabetes. The focus is also shifting to cholesterol within the artery wall's macrophages and the newly discovered receptors and transporters involved in cholesterol movement.
Dyslipidemia treatment is advancing from measuring lipid cargo (cholesterol and triglycerides) to understanding the functionality of lipid transport pathways. Lipoproteins package insoluble lipids like triglycerides (energy source) and cholesterol (essential for cell membranes, bile acids, steroid hormones) for transport. Cholesterol can be esterified or unesterified (free) and is enveloped by a phospholipid monolayer with apolipoproteins woven through it.
Apolipoproteins are increasingly recognized as influential in lipoprotein metabolism. They facilitate lipoprotein assembly, provide structural integrity, co-activate enzymes, and act as receptor ligands for cellular uptake. The unique collection of apolipoproteins on each lipoprotein's surface indicates its origin, function, destination, and fate. Examples include Apo B48 in chylomicrons, Apo E for hepatic uptake, and Apo B100 in VLDL and LDL. HDL, involved in reverse cholesterol transport, primarily features Apo A1 and carries other exchangeable apolipoproteins like Apo A2, C2, and C3.
Our understanding of apolipoproteins is advancing knowledge of lipoprotein dynamics and lipid distribution. Guidelines for evaluating fasting plasma lipids have evolved from total cholesterol and triglycerides to focusing on LDL ('bad cholesterol') and HDL ('good cholesterol'). While LDL is the main atherogenic particle, elevated levels of other triglyceride-rich lipoproteins (IDL, VLDL, chylomicron remnants) also contribute to arterial wall cholesterol accumulation. These are collectively termed 'non-HDL cholesterol'.
In patients with a predominance of non-HDL lipoproteins and elevated triglycerides, current guidelines recommend calculating non-HDL cholesterol (total cholesterol minus HDL cholesterol) to reflect all atherogenic plasma cholesterol. Non-HDL and HDL can be differentiated by apolipoprotein content; for instance, Apo B100 and Apo B48 are unique to non-HDL, while Apo A1 is unique to HDL. Routine measurement of plasma apolipoprotein concentrations may provide more sophisticated decisions for dyslipidemia diagnosis and management in the future.