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

2021 ◽  
Author(s):  
Ruozhu Dai ◽  
Huilin Zhuo ◽  
Wei Wang ◽  
Xinjun Wang ◽  
Xiaoyu Zhao
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Genetic Polymorphisms ◽  
Therapy Monitoring ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Healthy People ◽  
Risk Indicator ◽  
Before And After ◽  
A Prospective Study

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.

Drug related metabolites and genetic polymorphisms predict low low-density lipoprotein cholesterol response to atorvastatin treatment in patients with coronary heart disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Munkhaugen ◽  
E Sverre ◽  
O Kristiansen ◽  
M.W Fagerland ◽  
K Peersen ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Genetic Polymorphisms ◽  
Individual Variation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Funding Source ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Atorvastatin Treatment

Abstract Background There is considerable individual variation in the low-density lipoprotein cholesterol (LDL-C) reduction at all classes and doses of statins. Knowledge of the determinants of individual variation LDL-C response upon statin treatment may pave the way for personalized and optimized statin treatment. Purpose We aimed to determine clinical and drug related predictors of variability of LDL-C response to atorvastatin 40 mg in patients with coronary heart disease. Methods This is an explorative study among 70 patients enrolled in the MUscle Side-Effects of atorvastatin in coronary patients (MUSE) randomized double blinded cross-over trial. Absolute and relative changes in LDL-C after 7 weeks treatment with atorvastatin 40 mg/day and 7 weeks treatment with placebo, were calculated for each patient. Linear regression analyses were applied to investigate the association between clinical (10 variables) and drug related (atorvastatin and/or metabolites, 18 variables) predictors and changes in LDL-C. Results Adherence to allocated treatment was high as confirmed by atorvastatin levels in blood and a mean proportion of days covered of 99% (range 91–100%). Mean reduction in LDL-C on atorvastatin treatment (LDL-C atorvastatin – LDL-C placebo) was 2.1 (SD 0.7, range 0.3 to 3.4) mmol/L. Mean percentage reduction in LDL-C was 51.1 (SD 11.2, range 29 to 60)%, and 37 patients (52.9%) had <50% LDL-C reduction. Genetic polymorphisms in SLCO1B1 or CYP3A (B 0.06, 95% CI 0.01 to 0.12, p=0.026), increasing number of coronary events (B 0.06, 95% CI 0.002 to 0.10, p=0.005), increasing trough concentration of 4-OH atorvastatin lactone (B 0.05, 95% CI 0.01 to 0.08, p=0.005) and increasing trough concentration of 4-OH atorvastatin acid (B 0.05, 95% CI 0.01 to 0.08, p=0.006) were the significant determinants of lower relative change (%) in LDL-C, in adjusted analyses. Age, gender, somatic comorbidity, cardiovascular risk factors, statin dependent muscle side-effects and other clinical and drug related determinants were not associated with changes in LDL-C. Conclusions There is considerable inter-individual variation in the LDL-C response upon treatment with atorvastatin despite confirmed high statin adherence. This is the first study reporting that genetic polymorphisms involved in the metabolism of statins and atorvastatin metabolites predict lower LDL-C response. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National Association of Health, Grant/Award

Abstract P249: Effects of Lifestyle Changes on Metabolism and Early Vascular Lesion in Healthy People

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Xu Fengcheng ◽  
Yu Chaoping ◽  
Liu Tianhu
Keyword(s):  
Healthy Lifestyle ◽  
Low Density Lipoprotein ◽  
Fasting Blood Glucose ◽  
Ankle Brachial Index ◽  
Density Lipoprotein ◽  
Vascular Lesion ◽  
Lifestyle Changes ◽  
Healthy People ◽  
Vascular Lesions ◽  
Before And After

Objective: Through propaganda and education on lifestyle change, we study the effects on metabolism and vascular lesions in healthy people. Methods: the healthy subjects that conform to the requirements, through propaganda and education on vascular health, through moderate exercise, proper control of starchy foods, low salt, low fat diet, reduce smoking and other lifestyle changes, compare changes in weight, renal function, fasting blood glucose, blood lipids and ankle brachial index (ABI), cardio ankle vascular index(CAVI) before and after lifestyle changes. Results: After lifestyle changed, the subjects’ body mass index [(23.13±3.18)kg/m 2 vs (22.67±3.36)kg/m 2 ], ABI[1.11±0.08 vs 1.09±0.09], CAVI[(7.14±1.13 ) vs (7. 01±1.18) ], serum creatinine[(84.31±22.41)umol/L vs (79.92±23.64)umol/L], blood uric acid[(337.79±102.17 )umol/L vs (328.12±88.33)umol/L], low density lipoprotein cholesterol[(2.49±0.65) mmol/L vs (2.37±0.69) mmol/L],all have good changes. Conclusion: Healthy lifestyle is good for metabolism and early vascular lesions, can improve metabolic disorder and slow the occurrence of arteriosclerosis.

scholarly journals Knockdown of lncRNA ENST00000609755.1 Confers Protection Against Early oxLDL-Induced Coronary Heart Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Yi Sun ◽  
Shuna Huang ◽  
Chunyu Wan ◽  
Qishuang Ruan ◽  
Xiaoxu Xie ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Peripheral Blood ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Peripheral Blood Leukocyte ◽  
Loss Of Function ◽  
Human Coronary Artery ◽  
Injury Model

Background: This study investigated the association between long non-coding RNAs (lncRNAs) and coronary heart disease (CHD) and further elucidated the potential biological roles of lncRNAs in CHD pathogenesis.Methods: A case-control study (590 patients and 590 controls) was conducted from February 2017 and March 2019 in Fuzhou, China. Environmental factors were investigated using questionnaires and physical examinations. Five representative lncRNAs were screened using lncRNA microarray (peripheral blood in 5 cases and 5 controls) and further verified by quantitative real-time polymerase chain reaction (peripheral blood leukocyte in 100 cases and 100 controls). Oxidized low-density lipoprotein (oxLDL) was used to induce a human coronary artery endothelial cell (HCAECs) injury model, and loss of function was used to elucidate the role of lncRNA ENST00000609755.1 (lnc-MICALL2-2) in oxLDL-induced HCAECs injury.Results: A total of 320 lncRNAs were found dysregulated in CHD patients (fold change> 2, p < 0.05). The results of a discovery microarray, population verification and HCAEC experiments suggested the lnc-MICALL2-2 is upregulated in CHD subjects and in an oxLDL-induced HCAECs injury model. Conversely, lnc-MICALL2-2 inhibition in vitro attenuated the effects of oxLDL on HCAECs morphology, proliferation, and apoptosis.Conclusion: Elevated expression of lnc-MICALL2-2 is an independent risk factor for CHD, and knockdown subsequently confers protection against early pathological processes of oxLDL-induced CHD.

Isolation of plasma small-dense low-density lipoprotein using a simple air-driven ultracentrifuge and quantification using immunassay of apolipoprotein B

2004 ◽  
Vol 42 (1) ◽  
Author(s):  
Valentine C. Menys ◽  
Yifen Liu ◽  
Michael I. Mackness ◽  
See Kwok ◽  
Muriel J. Caslake ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Coronary Heart Disease Risk ◽  
Apolipoprotein B ◽  
Disease Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Heart Disease Risk

AbstractSmall-dense low-density lipoprotein (SD-LDL) is associated with coronary heart disease risk. Current methods for its quantification are expensive, complex and time-consuming. Plasma was adjusted to a density (D) of 1.044 g/ml in a volume of 0.18 ml and centrifuged in a Beckman Airfuge at 160 000×

Familial hypercholesterolaemia

2020 ◽  
pp. 343-348
Author(s):  
Perry Elliott ◽  
Pier D. Lambiase ◽  
Dhavendra Kumar
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Inborn Error ◽  
Familial Hypercholesterolaemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Clinical Criteria ◽  
Premature Coronary Heart Disease ◽  
Coronary Artery Atherosclerosis

Familial hypercholesterolaemia (FH) is an inborn error of metabolism that leads to accumulation of low-density lipoprotein cholesterol (LDL-C) particles in the blood and premature coronary artery atherosclerosis. This chapter covers the clinical criteria for the diagnosis of FH, the genetics that underpins the condition, cascade testing, premature coronary heart disease, and treatment methods.

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