scholarly journals 2042 CYP2C19*2 and PON1 Q192R polymorphisms are associated with platelet reactivity to clopidogrel in Puerto Rican Hispanics with cardiovascular disease

2018 ◽  
Vol 2 (S1) ◽  
pp. 8-8
Author(s):  
Dagmar F. H. Suarez ◽  
Mariana R. Botton ◽  
Stuart A. Scott ◽  
Matthew I. Tomey ◽  
Kyle Melin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cardiovascular Disease ◽  
Puerto Rican ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Antiplatelet Agents ◽  
Group I ◽  
Increased Risk ◽  
History Of ◽  
Artery Disease

OBJECTIVES/SPECIFIC AIMS: High on-treatment platelet reactivity (HTPR) with clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Although more potent antiplatelet agents are available, clopidogrel remains the most commonly used P2Y12 inhibitor in Puerto Rico. Platelet reactivity varies with ethnicity and is influenced by both clinical and genetic variables; however, no clopidogrel pharmacogenetic studies with Puerto Rican patients have been reported. Therefore, we sought to identify clinical and genetic determinants of on-treatment platelet reactivity in a cohort of Puerto Rican patients with cardiovascular disease. METHODS/STUDY POPULATION: We performed a retrospective study of 111 Puerto Rican patients on 75 mg/day maintenance dose of clopidogrel. Patients were allocated into 2 groups: Group I, without HTPR; and Group II, with HTPR. Clinical data was obtained from the medical record. Platelet function was measured ex vivo using the VerifyNow® P2Y12 assay and HTPR was defined as P2Y12 reaction units (PRU)≥230. Genotyping of CYP2C19, ABCB1, PON1, PY2R12, B4GALT2, CES1, and PEAR1 was performed using Taqman® Genotyping Assays. RESULTS/ANTICIPATED RESULTS: The mean PRU across the cohort was 203±61 PRU (range, 8–324), and 42 (38%) patients had HTPR. One in four individuals carried at least 1 copy of the CYP2C19*2 variant allele. Hematocrit and PON1 p.Q192R variant were inversely correlated with platelet reactivity (p<0.05). Multiple logistic regression showed that 27% of the total variation in PRU was explained by a history of diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R. Body mass index (OR=1.15; CI: 1.03–1.27), diabetes mellitus (OR=3.46; CI: 1.05–11.43), hematocrit (OR=0.75; CI: 0.65–0.87), and CYP2C19*2 (OR=4.44; CI: 1.21–16.20) were the only independent predictors of HTPR. DISCUSSION/SIGNIFICANCE OF IMPACT: In a representative sample of Puerto Rican patients with cardiovascular disease, diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R were associated with on-treatment platelet reactivity. These factors may identify a subset of patients at higher risk for adverse events on clopidogrel in the Hispanic population.

scholarly journals Effect of cilostazol on platelet reactivity among patients with peripheral artery disease on clopidogrel therapy

2018 ◽  
Vol 33 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Dagmar F. Hernandez-Suarez ◽  
Hector Núñez-Medina ◽  
Stuart A. Scott ◽  
Angel Lopez-Candales ◽  
Jose M. Wiley ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Puerto Rican ◽  
Peripheral Artery Disease ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Quantitative Polymerase Chain Reaction ◽  
Peripheral Artery ◽  
History Of ◽  
Clopidogrel Therapy ◽  
Artery Disease

AbstractBackground:Antiplatelet therapy with clopidogrel is recommended to reduce cardiovascular events in patients with peripheral artery disease (PAD); however, clopidogrel efficacy has not been adequately studied in this patient population. Therefore, we aimed to determine the effects of cilostazol therapy on platelet reactivity among PAD patients on clopidogrel.Methods:We performed a cross-sectional pilot study of 46 Puerto Rican patients diagnosed with PAD. The cohort was divided based on use of clopidogrel and cilostazol (n=24) or clopidogrel alone (n=22). Platelet function was measuredex vivousing the VerifyNow P2Y12 assay. Genomic DNA was extracted from peripheral blood samples using the QIAamp DNA Blood Midi Kit, which was subjected to candidate variant genotyping (CYP2C19,ABCB1,PON1andP2RY12) using TaqMan quantitative polymerase chain reaction assays. All analyses were performed using SAS version 9.4 (SAS Institute).Results:Among all enrolled patients, 18 (39%) had high on-treatment platelet reactivity (HTPR). The mean platelet reactivity was 207±53 (range, 78–325) with higher P2Y12 reaction units in the non-cilostazol group, 224±45 vs. 191±55 on the cilostazol group (p=0.03). No significant differences were observed in the clinical or genetic variables between the two groups. A multiple regression analysis determined that history of diabetes mellitus (p=0.03), use of cilostazol (p=0.03) and hematocrit (p=0.02) were independent predictors of platelet reactivity.Conclusions:In Puerto Rican PAD patients on clopidogrel therapy, history of diabetes mellitus, use of cilostazol and hematocrit are independent predictors of platelet reactivity. Adjunctive cilostazol therapy may enhance clopidogrel efficacy among PAD patients with HTPR.

scholarly journals Incidence and risk factors for recurrent cardiovascular disease in middle-eastern adults: a retrospective study

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Romona D. Govender ◽  
Saif Al-Shamsi ◽  
Elpidoforos S. Soteriades ◽  
Dybesh Regmi
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Incidence Rate ◽  
United Arab Emirates ◽  
Cox Proportional Hazards ◽  
Cvd Risk ◽  
Female Sex ◽  
Increased Risk ◽  
History Of

Abstract Background Individuals with established cardiovascular disease (CVD) and risk factors such as age, smoking, hypertension, and diabetes mellitus are at an increased risk of recurrent cardiovascular events and death. The incidence rate of recurrent CVD events varies between countries and populations. The United Arab Emirates (UAE) has one of the highest age-standardized death rates for CVD worldwide. The aim of our study was to estimate the incidence rates and determine the predictors of recurrent CVD events among UAE nationals. Methods We investigated an outpatient-based cohort of patients with a history of CVD visiting Tawam Hospital between April 1, 2008 and December 31, 2008. They were followed-up until July 31, 2018. Univariable and multivariable Cox proportional hazards regression models were used to determine the association between major CVD risk factors and the risk of CVD recurrence. Results A total of 216 patients (167 males, 49 females) with a history of CVD were included. They were followed for a median (interquartile range) of 8.1 (5.5–9.3) years, with a total of 1184 patient-years of follow-up. The overall incidence rate of recurrent CVD events was 92.1 per 1000 patient-years. The 8-year cumulative incidence was 73.7%. Age, female sex, and diabetes mellitus were significant predictors of recurrent CVD events, where females had a 1.96 times higher risk of recurrent CVD events than males. Conclusion Significant predictors of recurrent CVD events are older age, female sex, and diabetes mellitus. The incidence rate of recurrent CVD events was 92.1 per 1000 patient-years. Preventive measures, based on international guidelines for CVD management, may improve CVD morbidity and mortality in the UAE population.

Abstract 3477: Platelet Hyper-responsiveness in Aspirin-Treated Patients with Clinical Cardiovascular Disease Compared to Matched High Risk Controls

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nauder Faraday ◽  
Lisa R Yanek ◽  
Taryn F Moy ◽  
Dhananjay Vaidya ◽  
J. E Herrera-Galeano ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
High Risk ◽  
Platelet Function ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Increased Risk

Background: Platelet hyper-responsiveness to activating stimuli during aspirin (ASA) therapy may discriminate between high risk subjects who have developed acute thrombotic cardiovascular disease (CVD) events (coronary disease and stroke) and those who are at increased risk but are disease free. We hypothesized that subjects with documented CVD would have greater platelet reactivity on ASA therapy compared to matched high risk non-CVD subjects. Methods: Subjects (N=228; 61 +/− 8 yrs, 69% male, 60% white) were selected from families with known CVD; 114 had prevalent CVD and were matched on age, sex, and race to 114 apparently healthy controls with risk factors but without clinical CVD. CVD risk factors were measured and therapy adherence was determined by questionnaires. Platelet reactivity on 81 mg ASA/day was determined by whole blood (WB) aggregometry, platelet function analyzer (PFA) closure time, thromboxane B2 (TxB2) release ex vivo , and urinary excretion of 11-dehyrothromboxane B2 (Tx-M) in vivo . Results. CVD cases had greater platelet reactivity by all measures, both unadjusted, and adjusted for age, sex, race and adherence (Table ). Multivariable adjustment for cardiac risk factors and statin therapy eliminated case-control differences for Tx-M, but not for the ex vivo measures of platelet activation. ASA therapy duration in CVD subjects (8.8 +/− 6.2 yrs) was not related to platelet function. Conclusions: Greater residual platelet reactivity exists during ASA therapy in CVD subjects compared to matched high risk controls, even controlling for CVD risk factors and adherence to therapy. The data suggest that platelet hyper-responsiveness during ASA chemoprophylaxis may differentiate patients with CVD from those who are at risk for CVD, but have not developed it. Platelet hyper-responsiveness may be an intrinsic property of CVD, related to as yet unidentified environmental or genetic factors.

Oral antiplatelet agents in cardiovascular disease

VASA ◽  
2019 ◽  
Vol 48 (4) ◽  
pp. 291-302 ◽  
Author(s):  
Joseph Pultar ◽  
Patricia P. Wadowski ◽  
Simon Panzer ◽  
Thomas Gremmel
Keyword(s):  
Cardiovascular Disease ◽  
Antiplatelet Agent ◽  
Antiplatelet Agents ◽  
Adenosine Diphosphate ◽  
Current Evidence ◽  
Mortality And Morbidity ◽  
Beneficial Effects ◽  
History Of ◽  
Coronary Syndromes ◽  
Artery Disease

Abstract. Antiplatelet agents significantly reduce mortality and morbidity in ischemic heart disease, cerebrovascular disease and peripheral artery disease (PAD), and are therefore part of guideline-driven daily medical treatment in these patients. Due to its beneficial effects in the secondary prevention of atherothrombotic events, aspirin remains the most frequently prescribed antiplatelet agent in cardiovascular disease. In patients with acute coronary syndromes (ACS) and in those undergoing angioplasty with stent implantation dual antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) receptor antagonist is indicated. The development of the newer ADP P2Y12inhibitors prasugrel and ticagrelor has further improved prognosis in ACS patients compared to clopidogrel. Moreover, vorapaxar allows the inhibition of platelet activation by thrombin via protease-activated receptor-1 and has been approved for the use in patients with PAD and in those with a history of myocardial infarction. This review article summarizes the current evidence on oral antiplatelet agents in cardiovascular disease.Keywords: Aspirin, clopidogrel, prasugrel, ticagrelor, vorapaxar, cardiovascular disease

Abstract 15609: Plasma Fibrin Clot Properties Measured Ex-vivo Are Associated With Intracoronary Thrombus Ultrastructure

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jaroslaw Zalewski ◽  
Jan Bogaert ◽  
Marcin Sadowski ◽  
Olga Woznicka ◽  
Constantinos Doulaptsis ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Platelet Reactivity ◽  
Positive Family History ◽  
Adenosine Diphosphate ◽  
Fibrin Clot ◽  
Reactivity Index ◽  
Clot Lysis ◽  
Infarct Related Artery ◽  
History Of ◽  
Artery Disease

Introduction: Fibrin is a major component of intracoronary thrombus obtained during ST-elevation myocardial infarction (STEMI). Apart of the time of ischemia determinants of intracoronary thrombus composition are largely unknown. Hypothesis: We sought to investigate whether ex-vivo measured plasma fibrin clot properties are associated with intracoronary thrombus ultrastructure. Methods: In the intracoronary thrombus aspirated from 80 of the 156 consecutive STEMI patients within 12 hours since symptom onset, we assessed the content of fibrin, erythrocytes and platelets and thrombus heterogeneity by scanning electron microscopy. On admission plasma fibrin clot permeability (Ks), which indicates pore size, clot lysis time (t50%), platelet reactivity index (PRI) and aggregation induced by 5 μM of adenosine diphosphate (ADP) were correlated with intracoronary thrombus composition. Results: All patients received 300 mg of aspirin and 45 (56.3%) 600 mg of clopidogrel, 70 (41-120) min prior to aspiration. PRI inversely correlated (r=-0.24, P=0.035) with the time elapsed since clopidogrel pretreatment. The median content of fibrin, erythrocytes and platelets in intracoronary thrombus was 49.1 (25.0-72.6)%, 29.0 (4.8-57.7)% and 6.8 (1.0-15.1)%, respectively. Fibrin content was correlated with baseline Ks (r=-0.45, P<0.0001), t50% (r=0.32, P<0.0001), fibrinogen (r=0.32, P<0.0001), the time to opening of infarct-related artery (r=0.24, P<0.001), reference lumen diameter of infarct-related artery (r=0.15, P<0.001), but not with PRI and ADP-induced platelet aggregation. Fibrin content was higher in patients without pre-hospital loading with clopidogrel (58 vs. 43%, P<0.0001), treated with aspirin prior to STEMI (62 vs. 47%, P<0.0001) or with positive family history of coronary artery disease (62 vs. 46%, P=0.0004). Multiple regression analysis adjusted for age and fibrinogen showed that Ks, time of ischemia and clopidogrel pretreatment independently predicted fibrin content in intracoronary thrombus (R2=0.44, P<0.0001). Conclusion: Formation of denser fibrin clots displaying resistance to lysis, and clopidogrel pretreatment contributed to fibrin content within the intracoronary thrombus during an acute phase of STEMI.

Long-Term Metabolic Consequences in Patients with a History of Gestational Diabetes

2020 ◽  
Vol 26 (43) ◽  
pp. 5564-5572
Author(s):  
Eleni Kousta ◽  
Adamantia Kontogeorgi ◽  
Stephen Robinson ◽  
Desmond G. Johnston
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Increased Risk ◽  
Metabolic Complication ◽  
History Of

Gestational diabetes mellitus is a common metabolic complication of pregnancy. Universal guidelines on gestational diabetes have been impeded by the long-term controversies on its definition and screening strategies. The prevalence of gestational diabetes is rising all over the world, is significantly influenced by ethnicity and its rise is mainly attributed to increasing maternal obesity and age. Gestational diabetes mellitus has important long-term implications, including gestational diabetes recurrence, increased risk for developing type 2 diabetes, metabolic syndrome and cardiovascular disease for the mother. Gestational diabetes mellitus may be viewed as a chronic metabolic disorder that is identified in women during gestation and may provide a unique opportunity for the early identification and primary prevention of type 2 diabetes mellitus and cardiovascular disease in these women. In this mini-review, the evolution of screening tests for gestational diabetes and guidelines are briefly described and metabolic and cardiovascular long-term consequences of women with a history of gestational diabetes are summarized. A summary of our own St. Mary’s Hospital-UK Research series on long-term metabolic consequences of 368 women with a history of gestational diabetes of 3 different ethnic groups and 482 control women is also included. We found that approximately 2 years following delivery, 37% of women with a history of gestational diabetes had abnormal glucose concentrations, but, most importantly, even those who were normoglycaemic, postpartum displayed metabolic abnormalities on detailed testing. Future research needs to focus on the prevention of gestational diabetes long-term complications, but also in identification of pre-pregnancy predictors and risk reduction before conception.

Incidence and mortality of myocardial infarction among Catalonian older adults with and without underlying risk conditions: The CAPAMIS study

2018 ◽  
Vol 25 (17) ◽  
pp. 1822-1830 ◽  
Author(s):  
M José Forcadell ◽  
Angel Vila-Córcoles ◽  
Cinta de Diego ◽  
Olga Ochoa-Gondar ◽  
Eva Satué
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Acute Myocardial Infarction ◽  
Population Based ◽  
Chronic Heart Disease ◽  
Increased Risk ◽  
Incidence And Mortality ◽  
History Of ◽  
Artery Disease

Background Population-based data about the epidemiology of acute myocardial infarction is limited. This study investigated incidence and mortality of acute myocardial infarction in older adults with specific underlying chronic conditions and evaluated the influence of these conditions in developing acute myocardial infarction. Design and methods This was a population-based cohort study involving 27,204 individuals ≥ 60 years of age in Tarragona (Catalonia, Spain). Data on all cases of hospitalised acute myocardial infarction were collected from 1 December 2008–30 November 2011. Incidence rates and 30-day mortality were estimated according to age, sex, chronic illnesses and underlying conditions. Multivariable Cox regression analysis was used to calculate hazard ratios and to estimate the association between baseline conditions and risk of developing acute myocardial infarction. Results The incidence of acute myocardial infarction was 475 per 100,000 person-years. Maximum rates appeared among individuals with history of coronary artery disease (2839 per 100,000), chronic severe nephropathy (1407 per 100,000), atrial fibrillation (1226 per 100,000), chronic heart disease (1149 per 100,000), history of stroke (1147 per 100,000) and diabetes mellitus (914 per 100,000). Thirty-day mortality was 15.3% overall, reaching 31.6% among patients over 80 years. In the multivariable analysis, history of coronary artery disease, age > 70 years, sex male, chronic heart disease, history of stroke, atrial fibrillation, diabetes mellitus and hypertension emerged as significantly associated with an increased risk of acute myocardial infarction. Conclusions The incidence and mortality of acute myocardial infarction remain considerable in our setting. Considering classical major risk factors, diabetes mellitus and hypertension were the underlying conditions most strongly associated with an increased risk in our study population.

scholarly journals Impact of established cardiovascular disease on 10-year death after coronary revascularization for complex coronary artery disease

2021 ◽  
Author(s):  
Rutao Wang ◽  
Scot Garg ◽  
Chao Gao ◽  
Hideyuki Kawashima ◽  
Masafumi Ono ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Revascularization ◽  
Long Term Outcomes ◽  
Vital Status ◽  
Increased Risk ◽  
Artery Disease ◽  
The Impact

Abstract Aims To investigate the impact of established cardiovascular disease (CVD) on 10-year all-cause death following coronary revascularization in patients with complex coronary artery disease (CAD). Methods The SYNTAXES study assessed vital status out to 10 years of patients with complex CAD enrolled in the SYNTAX trial. The relative efficacy of PCI versus CABG in terms of 10-year all-cause death was assessed according to co-existing CVD. Results Established CVD status was recorded in 1771 (98.3%) patients, of whom 827 (46.7%) had established CVD. Compared to those without CVD, patients with CVD had a significantly higher risk of 10-year all-cause death (31.4% vs. 21.7%; adjusted HR: 1.40; 95% CI 1.08–1.80, p = 0.010). In patients with CVD, PCI had a non-significant numerically higher risk of 10-year all-cause death compared with CABG (35.9% vs. 27.2%; adjusted HR: 1.14; 95% CI 0.83–1.58, p = 0.412). The relative treatment effects of PCI versus CABG on 10-year all-cause death in patients with complex CAD were similar irrespective of the presence of CVD (p-interaction = 0.986). Only those patients with CVD in ≥ 2 territories had a higher risk of 10-year all-cause death (adjusted HR: 2.99, 95% CI 2.11–4.23, p < 0.001) compared to those without CVD. Conclusions The presence of CVD involving more than one territory was associated with a significantly increased risk of 10-year all-cause death, which was non-significantly higher in complex CAD patients treated with PCI compared with CABG. Acceptable long-term outcomes were observed, suggesting that patients with established CVD should not be precluded from undergoing invasive angiography or revascularization. Trial registration SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050. Graphic abstract

scholarly journals All-cause mortality and location of death in patients with established cardiovascular disease before, during, and after the COVID-19 lockdown: a Danish Nationwide Cohort Study

2021 ◽  
Author(s):  
Jawad H Butt ◽  
Emil L Fosbøl ◽  
Thomas A Gerds ◽  
Charlotte Andersson ◽  
Kristian Kragholm ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Mortality Rate ◽  
Hospital Mortality ◽  
Location Of Death ◽  
All Cause Mortality ◽  
History Of ◽  
Adjusted Incidence Rate ◽  
Artery Disease ◽  
Adjusted Incidence ◽  
Overall Mortality

Abstract Background On 13 March 2020, the Danish authorities imposed extensive nationwide lockdown measures to prevent the spread of the coronavirus disease 2019 (COVID-19) and reallocated limited healthcare resources. We investigated mortality rates, overall and according to location, in patients with established cardiovascular disease before, during, and after these lockdown measures. Methods and results Using Danish nationwide registries, we identified a dynamic cohort comprising all Danish citizens with cardiovascular disease (i.e. a history of ischaemic heart disease, ischaemic stroke, heart failure, atrial fibrillation, or peripheral artery disease) alive on 2 January 2019 and 2020. The cohort was followed from 2 January 2019/2020 until death or 16/15 October 2019/2020. The cohort comprised 340 392 and 347 136 patients with cardiovascular disease in 2019 and 2020, respectively. The overall, in-hospital, and out-of-hospital mortality rate in 2020 before lockdown was significantly lower compared with the same period in 2019 [adjusted incidence rate ratio (IRR) 0.91, 95% confidence interval (CI) CI 0.87–0.95; IRR 0.95, 95% CI 0.89–1.02; and IRR 0.87, 95% CI 0.83–0.93, respectively]. The overall mortality rate during and after lockdown was not significantly different compared with the same period in 2019 (IRR 0.99, 95% CI 0.97–1.02). However, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during and after lockdown compared with the same period in 2019 (in-hospital, IRR 0.92, 95% CI 0.88–0.96; out-of-hospital, IRR 1.04, 95% CI1.01–1.08). These trends were consistent irrespective of sex and age. Conclusions Among patients with established cardiovascular disease, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during lockdown compared with the same period in the preceding year, irrespective of age and sex.

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