scholarly journals The Role of Genetic Polymorphism and Other Factors on Clopidogrel Resistance (CR) in an Asian Population with Coronary Heart Disease (CHD)

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1987
Author(s):  
Mohammed Ahmed Akkaif ◽  
Nur Aizati Athirah Daud ◽  
Abubakar Sha’aban ◽  
Mei Li Ng ◽  
Muhamad Ali Sk Abdul Kader ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Genetic Polymorphism ◽  
Racial Differences ◽  
Personalised Medicine ◽  
Asian Population ◽  
Antiplatelet Drug ◽  
Valuable Insight ◽  
Platelet Activity ◽  
Clopidogrel Resistance

Clopidogrel is a widely-used antiplatelet drug. It is important for the treatment and prevention of coronary heart disease. Clopidogrel can effectively reduce platelet activity and therefore reduce stent thrombosis. However, some patients still have ischemic events despite taking the clopidogrel due to the alteration in clopidogrel metabolism attributable to various genetic and non-genetic factors. This review aims to summarise the mechanisms and causes of clopidogrel resistance (CR) and potential strategies to overcome it. This review summarised the possible effects of genetic polymorphism on CR among the Asian population, especially CYP2C19 *2 / *3 / *17, where the prevalence rate among Asians was 23.00%, 4.61%, 15.18%, respectively. The review also studied the effects of other factors and appropriate strategies used to overcome CR. Generally, CR among the Asian population was estimated at 17.2–81.6%. Therefore, our overview provides valuable insight into the causes of RC. In conclusion, understanding the prevalence of drug metabolism-related genetic polymorphism, especially CYP2C19 alleles, will enhance clinical understanding of racial differences in drug reactions, contributing to the development of personalised medicine in Asia.

scholarly journals Analysis of the Reactivity of Aspirin and Clopidogrel and Its Influencing Factors in Patients with Coronary Heart Disease at High Altitude

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Rong Chang ◽  
Jinchun Wu ◽  
Xiaofei Zhang ◽  
Yi Ye ◽  
Wenqin Zhou ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Drug Resistance ◽  
Heart Disease ◽  
High Altitude ◽  
Venous Blood ◽  
Univariate Analysis ◽  
Composite Index ◽  
Antiplatelet Drug ◽  
Clopidogrel Resistance ◽  
Significant Difference

Objective. To evaluate the efficacy of dual-antiplatelet treatment (DAPT) in patients with coronary heart disease (CHD) at high altitude by using thrombelastogram (TEG) and to analyze the related biochemical factors affecting drug reactivity. Methods. Totally 118 CHD patients who admitted to the Qinghai People’s Hospital from September 2019 to September 2020 were enrolled in the group. Those people have lived in Qinghai for a long time. Seven days after DAPT, venous blood was collected on an empty stomach in the early morning of the next day; blood routine, coagulation function, and biochemical items were tested. Thrombelastogram (TEG) was used to draw curves to calculate platelet, coagulation and fibrinolysis functions, and drug inhibition rate. Patients were divided into the aspirin resistance (AR) group, clopidogrel resistance (CR) group, dual-antiplatelet drug resistance (DAR) group, and drug-sensitive group according to different inhibition rates. The drug efficacy was analyzed, and the clinical data, biochemical indexes, and TEG parameters of each group were compared to identify the risk factors of drug resistance. Results. Those 118 CHD patients at high altitude were incorporated into the study, ranging from 38 to 84 years of age, including 81 males (68.64%) and 37 females (31.36%). The platelet function and coagulation-fibrinolysis function were detected by TEG, and MATHROMBI, MAADP, and MAAA were higher than the reference range. There were 82 cases (69.49%) of drug resistance, 36 cases (32.53%) of drug sensitivity, 17 cases (14.41%) of AR alone, and 16 cases (12.71%) of CR alone. There was no significant difference in age, gender, BMI, oxygen saturation, TG, GFR, and history of diabetes and hypertension between ACS and CCS groups ( P > 0.05 ). PLT and FIB in the ACS group were higher than those in the CCS group, and the difference was statistically significant ( P < 0.05 ). In addition, MATHROMBIN, MAFIBRIN, E, A, A30, and coagulation composite index were also higher than those in the CCS group, with a statistically significant difference ( P < 0.05 ). Univariate analysis and logistic regression analysis suggested that age, HbA1c, FBG, and diabetes were the main factors of drug resistance. Conclusion. Antiplatelet drugs aspirin and clopidogrel resistance are associated with increased age, elevated HbA1c and FBG, and diabetes. Therefore, it is necessary to take reasonable treatment measures based on the actual situation of patients.

scholarly journals Risk of Acute Coronary Heart Disease After Sepsis Hospitalization in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort

2017 ◽  
Vol 65 (1) ◽  
pp. 29-36 ◽  
Author(s):  
Henry E Wang ◽  
Justin X Moore ◽  
John P Donnelly ◽  
Emily B Levitan ◽  
Monika M Safford
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Racial Differences

Abstract P316: Prehypertension and Incident Acute Coronary Heart Disease in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Stephen P Glasser ◽  
Yulia Khodneva ◽  
Daniel Lackland ◽  
Ronald Prineas ◽  
Monika Safford
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Racial Differences ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Community Dwelling ◽  
Cox Proportional Hazards Models ◽  
Chd Risk ◽  
Regards Study ◽  
Chd Risk Factors

Objective: The independent prognostic value of prehypertension (preHTN) for incident coronary heart disease (CHD) remains unsettled. Using the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study, we examined associations between preHTN and incident acute CHD and CVD death. Methods: REGARDS includes 30,239 black and white community-dwelling adults age 45 and older at baseline. Recruitment occurred from 2003-7, with baseline interviews and in-home data collection for physiologic measures. Follow-up is conducted by telephone every 6 months to detect events and deaths, which are adjudicated by experts. Systolic BP was categorized into <120 mmHg (n=4385), 120-129 mmHg (n=4000), 130-139 (n=2066), and hypertension was categorized into controlled (<140/90 mmHg on treatment) (n=8378), and uncontrolled (>140/90 mmHg) (n=5364). Incident acute CHD was defined as definite or probable myocardial infarction (MI) or acute CHD death. CVD death was defined as acute CHD, stroke, heart failure or other cardiovascular disease related. Cox proportional hazards models estimated the hazard ratios (HR) for incident CHD by BP categories, adjusting for sociodemographics and CHD risk factors. Results: The 23,393 participants free of CHD at baseline were followed for a median of 4.4 years. Mean age was 64.1, 58% were women and 42% were black. There was a significant interaction between sex and BP categories, therefore analyses were stratified by sex. There were 252 non-fatal and fatal acute CHD events among women and 407 among men. Among women, compared with SBP<120 mmHg, BP categories above SBP 120 mmHg were associated with incident CHD (adjusted HR for SBP120-129 mmHg=1.94 {95% CI 1.04-3.62]; SBP 130-139 mmHg=1.92 {0.95-3.87}; controlled HTN=2.16 {1.25-3.75}; uncontrolled HTN=3.25 {1.87-5.65}) in fully adjusted models. Among men, only uncontrolled HTN was associated with incident CHD (HR=1.55 {1.11-2.17}). Conclusion: In this sample, preHTN may be associated with incident CHD among women but not men.

Abstract P276: Differential Association of D-dimer with Stroke and Coronary Heart Disease: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Neil A Zakai ◽  
George Howard ◽  
Leslie A McClure ◽  
Suzanne E Judd ◽  
Brett M Kissela ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Vascular Disease ◽  
Racial Differences ◽  
Statistical Significance ◽  
Female Gender ◽  
Cox Models ◽  
The Difference ◽  
Chd Risk Factors ◽  
D Dimer

Introduction: D-dimer, a marker of coagulation activation, has higher levels in blacks than whites and has been variably associated with stroke and coronary heart disease (CHD). Methods: REGARDS recruited 30,239 participants in their homes across the continental US between 2003-07; by design 55% were female, 41% black, and 56% lived in the southeast. In a case-cohort study, D-dimer was measured in 646 participants with incident stroke, 515 with incident CHD, and 1104 in a cohort random sample. D-dimer was log transformed and modeled per 1-unit increase. Cox models were used to determine the HR for vascular disease for D-dimer and the difference in HR (95% CI) by race and vascular disease calculated by bootstrapping with 1000 replicate samples and using the 2.5 and 97.5 percentiles of the distribution (see Table for model variables). Results: Median D-dimer was higher in blacks (0.45 mcg/mL; IQR 0.26, 0.85) than whites (0.38 mcg/mL; IQR 0.23, 0.69); p <0.001. D-dimer was higher with increasing age, female gender, diabetes, hypertension and prebaseline cardiovascular disease (all p <0.05). The table shows the HR of stroke and CHD by baseline D-dimer. In minimally-adjusted models, D-dimer was associated with both stroke and CHD. Accounting for Framingham stroke and CHD risk factors, D-dimer remained associated with CHD (HR 1.45; 95% CI 1.18, 1.79), but was marginally associated with stroke (HR 1.20; 95% CI 0.99, 1.45). The difference in the HR of D-dimer between CHD and stroke was 0.22 in the basic model and 0.25 in the Framingham model, but this difference was of marginal statistical significance (Table). There was no difference in the HRs for stroke or CHD for D-dimer in blacks compared to whites (Table). Discussion: The association of D-dimer with stroke appeared smaller than for CHD with similar associations by race. Findings suggest that hemostasis activation may play a greater role in pathogenesis of CHD than stroke. Further study is needed to confirm these findings and evaluate the association of D-dimer with different stroke subtypes.

Abstract P323: Pulse Pressure and Incident Acute Coronary Heart Disease Events in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Stephen P Glasser ◽  
Daniel L Halberg ◽  
Charles Sands ◽  
Paul Muntner ◽  
Monika Safford
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Racial Differences ◽  
Pulse Pressure ◽  
Proportional Hazards ◽  
Linear Trend ◽  
Cox Proportional Hazards ◽  
Cvd Risk

Background: Increased attention has been given to pulse pressure (PP) as a potential independent risk factor of cardiovascular disease. We examined the relationship between PP and incident acute coronary heart disease (CHD). Methods: We used data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) national cohort study of 30,239 black and white participants aged 45 years or older and enrolled between 2003 and 2007. Baseline data included a 45-minute interview and in-home visit during which blood pressure was assessed and recorded as the average of two measurements obtained after a 5 minute seated rest. PP (SBP-DBP) was classified into 4 groups (<45, 45-54, 54.1-64, >64.1 mmHg). Telephone follow-up occurred every six months for self or proxy-reported suspected events, triggering medical record retrieval and adjudication by experts. Cox-proportional hazards models examined the association of incident CHD with PP groups, adjusting for socio-demographic and clinical risk factors. Results: This analysis included 22,909 participants free of CHD at baseline, with mean age 64.7±9.4 years; 40.4%were black, 44.6% were male and they experienced a total of 515 incident CHD events over a mean 3.4 yrs of follow-up (maximum 6 years). In unadjusted analyses, compared with PP<45 mmHg, each higher PP group had incrementally higher hazard ratios (HR) for incident CHD (HR 1.28 {95% CI 1.02-1.60}, 2.05 {1.63-2.56}, 3.82 {3.08-4.74}, p<0.001 for linear trend). This relationship persisted after fully adjusting including SBP for the highest PP group (HR 0.96 {0.75-1.21}, 1.12 {0.86-1.46}, 1.51 {1.09-2.10}, p trend <0.0001). Conclusions: High PP was associated with incident CHD, even when accounting for SBP and numerous other CVD risk factors.

Abstract P266: Change in the Association Between Serum Lipids and Coronary Heart Disease among Middle-Aged Adults: Observational Data from the Pre- and Post-Statin Era.

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Lisandro D Colantonio ◽  
Vera Bittner ◽  
Emily B Levitan ◽  
Shia Kent ◽  
Monika M Safford ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Racial Differences ◽  
Serum Lipids ◽  
Current Analysis ◽  
Middle Aged ◽  
Chd Risk Factors ◽  
Middle Aged Adults ◽  
Study Participants ◽  
Statin Use

Dyslipidemia is a major risk factor for coronary heart disease (CHD) and is usually treated with statins. Few observational studies have examined associations between lipids and CHD in the era of widespread statin use. The objective of the current analysis was to contrast the association between serum lipids and incident coronary heart disease (CHD) among middle-aged adults before and after statin use became widespread. Methods: We analyzed data from 14,590 Atherosclerosis Risk In Communities (ARIC) study participants who were recruited in 1987-1989 (pre-statins), and 13,196 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants (9,578 not taking statins) who were recruited in 2003-2007 (post-statins). Our analysis was restricted to participants 45 to 64 years of age without a history of CHD at baseline. Total and HDL cholesterol (HDL-C) and fasting triglycerides (TG) were measured at baseline and used to calculate LDL-C, non-HDL-C, total-to-HDL-C ratio and total-to-TG ratio. Each lipid parameter was categorized into four levels based on REGARDS quartile cut-points. Results: In ARIC, participants with higher LDL-C were more likely to have diabetes and use antihypertensive medication, whereas these CHD risk factors were progressively less common at higher LDL-C in REGARDS participants not taking statins. Over a maximum 7 years of follow up, 513 and 278 incident CHD events occurred among ARIC and REGARDS participants, respectively. After multivariable adjustment, higher categories of each lipid marker (lower categories of HDL-C) were associated with a higher hazard ratio (HR) for CHD among ARIC participants, but not among REGARDS participants not taking statins (figure). No association between lipid markers and CHD was observed among REGARDS participants taking statins. DISCUSION: The current analysis suggests that the widespread preferential use of statins among high risk individuals may have obscured the association between lipids and incident CHD.

Abstract P150: Association of Cholesterol Measures With Coronary Heart Disease Risk in Blacks and Whites in the Reasons for Geographic and Racial Differences in Stroke Study (regards)

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Neil Zakai ◽  
Jessica Minnier ◽  
Monika M Safford ◽  
Lisandro Colantonio ◽  
Marguerite M Irvin ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Total Cholesterol ◽  
Racial Differences ◽  
Cox Regression ◽  
Disease Risk ◽  
Point Estimate ◽  
Chd Risk ◽  
Increased Risk ◽  
Blacks And Whites

Introduction: Abnormal plasma lipid levels associate with coronary heart disease (CHD) risk. Race interaction for these associations are not established. Hypothesis: We hypothesized that the association of HDL, LDL, and triglyceride with CHD is stronger in whites versus blacks. Methods: The REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort recruited 30,283 black and white individuals aged 45+ from the contiguous U.S. from 2003-7. Participants were followed until December 31, 2016 for CHD events (i.e., myocardial infarction or CHD death), participants with history of CHD at baseline were excluded. Cox regression models were used to assess the association between baseline lipids and incident CHD events adjusting for traditional cardiovascular risk factors. Results: With 23,894 participants (57.8% white and 58.4% female, mean age 64.11± 9.32), over a median 9.9 years of follow-up, 1,487 CHD events occurred (615 among blacks). Overall, higher total Cholesterol, LDL cholesterol, and triglycerides were associated with increased risk of CHD in both blacks and whites with no evidence of a race interaction (Table 1). For HDL, the point estimate was more protective in whites (HR 0.90) than in blacks (HR 0.98), but the interaction was non-significant (p=0.15). However, when HDL was stratified into clinical categories (<40, 40-59, and ≥60), the reduction in point estimates was maintained among whites (HR 1.00, 0.88, and 0.74) but not among blacks (HR 1.00, 1.31, and 1.19) for HDL <40, 40-59, and ≥60 respectively, p-interaction 0.01. Conclusion: Total cholesterol, LDL, and triglycerides predict CHD risk equally in blacks and whites in the REGARDS study, however there is heterogeneity in the protective effect by race, especially when traditional clinical categories are used. In whites, higher HDL is associated with reduced risk, whereas in blacks the association is not maintained. These findings suggest that HDL levels are a more viable metric for white than blacks to predict CHD risk.

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