Lipoproteins and Cardiovascular Disease: An Update on the Clinical Significance of Atherogenic Small, Dense LDL and New Therapeutical Options

Abstract

Dyslipidemia is a potent risk factor for the genesis and progression of cardiovascular disease (CVD), and both the concentration and type of low-density lipoproteins (LDL) augment this association. The small, dense LDL (sdLDL) subfraction is the subtype which is most strongly predictive of atherosclerosis and cardiovascular events. In addition to the traditionally available lipid-lowering treatment options, certain novel therapies have been shown to favorably impact sdLDL, among them the antidiabetic class of agents known as glucagon-like peptide 1 receptor agonists (GLP1-RAs). These drugs seem to alter the pathophysiologic mechanisms responsible for the formation and accumulation of atherogenic lipoprotein particles, thus potentially reducing cardiovascular outcomes. They represent a uniquely targeted therapeutic approach to reduce cardiometabolic risk and warrant further study for their beneficial nonglycemic actions.

Protective Roles of Adansonia digitata (African Baobab), Cucumeropsis mannii (Melon), and Abelmoschus esculentus (Okro) Supplemented Diets against Cadmium-Induced Lipotoxicity, Bone Demineralization, and Cytotoxicity in Rabbits

“…Hypercholesterolemia, hypertriglyceridemia, elevated LDL-C levels, and diminished LDL-C are known cardiovascular disease (CVD) risk factors among the human population. Similarly, compelling experimental data from animal studies have implicated high serum total cholesterol (TC) concentration, high LDL-C, and low HDL-C as major risk factors in the onset of CVD (Noh et al, 2022;Rizvi, et al, 2021). Additionally, studies have shown a strong positive association between elevated TC to HDL-C ratio (TC/HDL-C) and pathogenesis of left ventricular hypertrophy, ischemic stroke, and coronary heart disease (CHD) (Zhang, et al, 2019).…”

Effect of Oral Semaglutide on Cardiovascular Parameters and Their Mechanisms in Patients with Type 2 Diabetes: Rationale and Design of the Semaglutide Anti-Atherosclerotic Mechanisms of Action Study (SAMAS)

“…This beneficial action is expected to be supported with additional beneficial effects on improvements in lipid profiles, mainly through reduction of the atherogenic small dense LDL subclasses, which have a specific physico-chemical composition and metabolic properties, including a reduced affinity for the LDL receptor, lower antioxidant capabilities and higher susceptibility to oxidation [32]. Small dense LDLs have greater arterial entry and retention abilities, and their oxidation in the intima is considered to represent the very first step of the atherosclerotic cascade [33]. Additionally, HbA1c improvement as well as reduction in hsCRP will be studied.…”

Qualitative and Quantitative Effects of Fatty Acids Involved in Heart Diseases

“…Furthermore, n-3 PUFAs suppress the generation of small dense LDL by reducing the expression of cholesterol ester transfer protein (CETP) which shuttles cholesteryl ester from HDL to apo-B protein [ 117 ]. Thus, n-3 PUFAs have various improving effects on lipid profile, and as a result, exert a strong anti-arteriosclerotic effect in combination [ 118 , 119 ].…”