We now know more about cholesterol and its role in cardiovascular disease than ever before. Ample clinical trial data has established unequivocally that lowering low-density lipoprotein (LDL) ("bad cholesterol") with statins and other drugs in appropriately selected patients delivers meaningful cardiovascular risk reduction.1 Furthermore, the advent of PCSK9-inhibiting drugs in the mid-2010s paved the way for further LDL lowering and risk reduction in people whose cholesterol is not adequately controlled by statins, although cost remains a barrier.2,3
That said, keeping cholesterol levels in check is still only one piece of the cardiovascular health puzzle. As described in Life Extension's Atherosclerosis and Cardiovascular Disease protocol, many other risk factors should be appropriately addressed for optimal cardiovascular health. Nevertheless, keeping cholesterol levels in a healthy range remains a central pillar of cardiovascular risk reduction.
Cholesterol and related blood lipids are far more complex than the traditional cholesterol blood test would lead us to believe. Most people are familiar with their LDL, high-density lipoprotein (HDL), total cholesterol, and triglyceride levels. What few people outside the cardiovascular research community appreciate is that a more detailed look at the properties of their blood lipids can offer important insights into to their cardiovascular risk.
For example, an important component of LDL cholesterol is the protein apolipoprotein B (ApoB), and cholesterol experts consider it an even stronger predictor of risk than LDL alone.4,5 A 2018 expert panel on cholesterol management, representing numerous cardiology and physician societies, including the American College of Cardiology and the American Heart Association, recommended measurement of ApoB for cardiovascular risk assessment, especially in those with elevated triglycerides.5
Also, the size and density of cholesterol-transporting proteins, called lipoproteins, are important factors that influence cardiovascular risk. Large, buoyant LDL particles are less atherogenic than smaller, more dense LDL particles. Similarly, large, buoyant HDL particles offer greater vascular protection than smaller, denser HDL. The development of advanced lipid testing strategies that take the importance of lipoprotein particle size into consideration, such as the NMR LipoProfile, allows for a deeper assessment of cardiovascular risk than a conventional lipid profile.6
Furthermore, metabolic processes, such as oxidation and glycation, modify the functionality of lipoproteins, transforming them from cholesterol transport vehicles into highly reactive compounds capable of damaging the delicate endothelial cells that line our arterial walls. This endothelial damage both initiates and promotes atherogenesis. Some natural interventions and lifestyle changes can target the formation of these modified lipoproteins and help avert vascular damage and dysfunction.
A comprehensive strategy for decreasing vascular risk should incorporate dietary and lifestyle changes along with thorough cholesterol and lipoprotein testing and strategic nutrient and pharmaceutical interventions.