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The size of LDL particles distinguishes phenotype pattern A from pattern B. Pattern A is defined by large buoyant LDL particles. It is associated with a reduced risk of developing cardiovascular disease. Pattern B is characterized by small dense lipoprotein particles and is associated with an increased risk of developing cardiovascular disease.
Pattern A is associated with larger, more buoyant LDL particles and a reduced risk of developing cardiovascular disease (Nikolic 2013), especially with elevated apoB (Superko 2009).
Pattern B is associated with small, dense LDL, increased risk of atherogenic cardiovascular disease, insulin resistance, and genetic factors (Nikolic 2013). However, some research indicates that pattern B presenting after myocardial infarction may be associated with decreased all-cause mortality (Pokharel 2017).
Overview
The size and density of low-density lipoprotein (LDL) particles can range from small to large and dense to buoyant, respectively, depending on surface lipid content and apoB-100 orientation. These variables determine the metabolic characteristics of LDL particles, as well as their association with cardiometabolic risk. The predominance of small dense LDLs (sdLDLs) distinguishes the proatherogenic phenotype pattern B from the protective phenotype pattern A. The presence of sdLDLs, accompanied by elevated triglycerides and low HDL cholesterol, characterizes the “atherogenic lipid triad,” or atherogenic dyslipidemia associated with cardiovascular disease, insulin resistance, and obesity. To categorize phenotypic patterns, very small LDLs have a diameter of 220-242 Angstrom (A); small LDLs range from 242-256 A; medium LDLs range from 256-271 A; and large LDLs range from 272-285 A (Nikolic 2013).
When measured by nuclear magnetic resonance (NMR), small dense LDLs have a diameter of 20.5 nanometers (nm) or below, while large buoyant particles are 25 nm or above. Peak LDL size can be increased with nutrition interventions, including inositol-enriched beverages, psyllium fiber, plant sterols, fish oil, strawberry powder, avocadoes, oolong tea, and a Mediterranean diet supplemented with nuts (Talebi 2020). Research also indicates that reducing weight and adiposity to a healthy level can promote the favorable conversion of pattern B to pattern A (Nikolic 2013).
The presence of small dense LDLs and a pattern B phenotype identifies individuals with a 3-fold greater risk of developing coronary heart disease and a 2-fold increased rate of arteriographic progression of atherosclerosis. The relevance of sdLDL to cardiovascular risk is further magnified when apoB is elevated. Reducing sdLDL predominance provides arteriographic benefits independent of blood pressure, smoking, weight, and age factors and beyond the benefits observed with changes in apoB or LDL-cholesterol (Superko 2009).
Although most contemporary research identifies LDL pattern B as a risk factor for the development of cardiovascular disease, follow-up during one prospective cohort study of 1,286 myocardial infarction patients revealed that post-MI patients with pattern B had a 32% reduced relative risk of all-cause and non-cardiac mortality in unadjusted models with a trend toward a lower incidence of cardiovascular mortality. Although unable to explain the apparent paradox, researchers note that LDL may be an acute phase respondent, and its characteristics may change following myocardial infarction (Pokharel 2017).
References
Ivanova, Ekaterina A et al. “Small Dense Low-Density Lipoprotein as Biomarker for Atherosclerotic Diseases.” Oxidative medicine and cellular longevity vol. 2017 (2017): 1273042. doi:10.1155/2017/1273042
Nikolic, Dragana et al. “Lipoprotein subfractions in metabolic syndrome and obesity: clinical significance and therapeutic approaches.” Nutrients vol. 5,3 928-48. 18 Mar. 2013, doi:10.3390/nu5030928
Pokharel, Yashashwi et al. “Association of low-density lipoprotein pattern with mortality after myocardial infarction: Insights from the TRIUMPH study.” Journal of clinical lipidology vol. 11,6 (2017): 1458-1470.e4. doi:10.1016/j.jacl.2017.09.002
Superko HR. Advanced lipoprotein testing and subfractionation are clinically useful. Circulation. 2009;119:2383-2395.
Talebi, Sepide et al. “The beneficial effects of nutraceuticals and natural products on small dense LDL levels, LDL particle number and LDL particle size: a clinical review.” Lipids in health and disease vol. 19,1 66. 11 Apr. 2020, doi:10.1186/s12944-020-01250-6
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