Astonishingly, the risk in men appeared to increase steeply with rising TGs well below 100 mg/dL, at which point it began to level off. In women, the CV-risk rose more gradually with TG levels than in men, yet continued to increase over a much broader TG range, up to 200 mg/dL (Figure 3). Interestingly, the relationship between TG and CVD risk varied significantly between men and women, with a stronger association for women vs. Unfortunately, apoB is often not included in standard lipid panels, and thus, TGs (and, if available, non-HDL-C) may provide valuable – albeit imperfect – information on CVD risk in the absence of apoB measurements. Over time, the guideline-recommended TG threshold for considering treatment has dropped from 250 to 150 mg/dL, and currently, TG levels 500 mg/dL) levels, which would signal high risk of pancreatitis. Indeed, there has long been a debate on whether serum TG constitutes an independent risk factor for CVD – and if so, at what levels. TGs affect the structure, size, composition, catabolism, plasma residence time, clearance, functionality, and concentration of all lipoproteins, including both the potentially atherogenic apolipoprotein B (apoB) family and the apoA-I (HDL family), yet historically, unlike all cholesterol metrics, TGs have not been included as part of CV-risk algorithms apart from their contribution to the definition the metabolic syndrome (though it’s always noted that at fairly extreme levels, typically >500-800 mg/dL, TGs increase the risk of acute pancreatitis). Serum TG is a component of a standard lipid panel, which, in addition to TG, typically reports several cholesterol metrics – total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and non-HDL cholesterol. Triglycerides – also known as triacylglycerols – are composed of three fatty acid molecules bound to a glycerol backbone. (Two centuries ago, a normal life expectancy was around 30-40 years, but I doubt anyone would call that normal or optimal today.) This semantic problem was highlighted in a 2020 study investigating the relationship between serum triglycerides (TG) and cardiovascular disease (CVD) risk: is “normal” really “optimal?” What are triglycerides (TG)?
In medicine, “normal” is often erroneously used interchangeably with “optimal.” Not only are these two words not necessarily synonyms, their individual definitions – and how closely one approximates the other – are subject to change with changing populations and advancements in scientific knowledge.
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