Genetic Polymorphisms, LDL-C and sdLDL-C Help Optimize Coronary Heart Disease (CHD) Therapy

Abstract

Background: Low-density lipoprotein cholesterol (LDL-C) and small, dense LDL-C (sdLDL-C) are important risk indicator of coronary heart disease (CHD), but their application in therapy monitoring of CHD is still far from being elucidated. Following the concept of precision medicine, we investigated whether the scientific medication based on medication-sensitive genes can reverse the LDL-C and sdLDL-C status in human bloodstream, so as to reveal the possibility of them as a monitoring indicator of CHD efficacy.Methods: A prospective study of CHD cohort containing 208 Chinese CHD patients (158 males and 50 females) and 20 healthy people (14 males and 6 females) was recruited. LDL-C and its subfractions were detected before and after treatment. Polymorphism of medication-sensitive genes, including SLCO1B1 (rs4149056, 521T>C), CYP2C19*2 (rs4244285, c.681G>A), and CYP2C19*3 (rs4986893, c.636G>A) were detected for medication guidance.Results: Nearly half of Chinese CHD patients (47.60%, 99/208) had genetic polymorphisms with homozygous or heterozygous mutations within these three genes. LDL-1 and LDL-2, subfractions of LDL-C, had a 100% positive rate in CHD patients and healthy people. However, sdLDL-C components of LDL-5 to LDL-7 were only enrichment in CHD patients. Moreover, the mean amount of sdLDL-C subfractions in CHD patients was significantly higher than that in healthy people. Among 180 patients with treatment remission, 81.67% (n=147) of CHD patients had decreased LDL-C, while 61.67% (n=111) of patients had decreased sdLDL-C.Conclusion: sdLDL-C has better accuracy on CHD screening than LDL-C, while LDL-C was more suitable for CHD therapy monitoring. Combined medication-sensitive genes polymorphism, LDL-C and sdLDL-C detection would optimize the treatment strategy for CHD patients.

Modeling cholesterol metabolism and atherosclerosis

“…Males with mild CHD, had concentrations of 28.9 mg/dL when compared to 39.9 mg/dL for individuals with acute CHD. Recently several genotypes have been associated with the different LDL-C subfractions (Dai et al, 2021).The relationship between sdLDL and ASCVD could have several underlying mechanisms. For example, sdLDL have an increased residence time compared to larger LDL-C (Thongtang et al, 2017).…”