Exploring Cholesterol & CVD

A series of papers published recently in Current Opinion in Endocrinology, Diabetes and Obesity highlights the growing divide between approaches to cardiovascular disease (CVD) that focus on LDL-cholesterol (LDL-C) and clinical observations that are leading researchers and practicing physicians to refocus attention on other factors that may play a bigger role in atherosclerosis and CVD.

One paper summarizes online tools intended to help clinicians make more informed decisions regarding prescribing statin drugs. These tools are designed to target primary prevention and employ algorithms that take into account several factors other than LDL-C.

Another paper in the series presents the rationale for why statin drugs may not be appropriate for individuals who experience a dramatic rise in total cholesterol and LDL-C when following a low-carbohydrate diet. A related paper reviews the evidence indicating that dietary carbohydrate restriction typically improves type 2 diabetes, insulin resistance, obesity, and hypertension—all of which are more powerful risk factors for CVD than is elevated LDL-C. Low-carb or ketogenic diets are also effective for improving the atherogenic risk triad (elevated triglycerides, low HDL-C and a preponderance of small, dense LDL particles), another indicator that is more suggestive of risk compared to LDL-C.

The series also includes a paper that explores the thrombogenic model of atherosclerotic cardiovascular disease (ASCVD)—an explanation for the pathogenesis and progression of ASCVD that better fits real-world observations and clinical reality while being free of some of the “paradoxes” that plague the LDL-C-centric model. (If LDL-C were the primary driver of ASCVD, then a much larger reduction in incidence or mortality would be expected among individuals taking drugs to lower LDL-C than is typically observed in clinical trials.)

An additional paper presents a case study with an intriguing finding: the subject consumed three ketogenic diets that varied in caloric content: eucaloric (intended to maintain weight), calorie-restricted, and hyper-caloric or “overfeeding.” Despite substantially increased consumption of saturated fat, LDL-C and apolipoprotein B decreased during the short-term overfeeding and increased during caloric restriction. (Similar results were seen among 24 other individuals who followed similar protocols.) These findings contradict the common perception that saturated fat is the primary driver of increases in LDL-C among some who follow ketogenic diets.