Aspirin-Resistant Thromboxane Biosynthesis and the Risk of Myocardial Infarction, Stroke, or Cardiovascular Death in Patients at High Risk for Cardiovascular Events

Aim. As part of a pilot study, to investigate the potential significance of cardiac troponin I (cTnI) in assessing the risk of cardiovascular diseases (CVD) in general population aged 35-64 years of one of the regions from the ESSE-RF study.Material and methods. The study is based on the ESSE-RF observational prospective study using a sample from one Russian region. The analysis included socio-demographic variables, risk factors, history of CVD. The cTnI level was measured from November to December 2021 in serum samples stored at -70° C using high sensitivity chemiluminescent microparticle immunoassay using Architect Stat High Sensitivity Troponin I (Abbott) reagents on an Architect i2000SR immunoassay analyzer (Abbott, Abbot Park IL USA). The endpoints were hard (cardiovascular death and myocardial infarction) and composite endpoints (cardiovascular death, new cases of myocardial infarction, stroke, coronary artery disease and revascularization). The median follow-up was 5,5 years. In total, the analysis included 1120 people aged 35-64 years.Results. Analysis of the associations between Systematic Coronary Risk Evaluation (SCORE) and cTnI showed a significant difference in risk stratification for these two parameters. In women from cTnI-related high-risk category for cardiovascular events (CVE), there were no endpoints at all. In men of moderate and high risk, the proportion of endpoints increases with increasing cTnI-related risk. The survival curves corresponding to first 3 quintiles of cTnI risk distribution did not diverge, and, therefore, the number of CVEs in these groups did not differ. At the same time, the curves corresponding to 4th and 5th quintiles significantly differed from the first 3 quintiles, which indicates a higher CVE risk in subjects from these groups (p<0,001). Considering that there were only 3 endpoints in cTnI-related high-risk group, a survival analysis was performed for low-risk versus moderate-high risk. The curves obtained diverge significantly (p=0.006). Cox proportional hazards models were analyzed to assess the relationship between the cTnI level and endpoints. It was shown that cTnI itself or its logarithm is significantly associated with hard and composite endpoints. The cTnI cut-off point of 12/10 pg/ml (males/females) was associated with hard endpoint, and 6/4 pg/ml — with composite one. It should be noted that the recommended cut-off point of 6/4 pg/ml is close to the upper quartile of cTnI distribution in the European population. For the Russian population, the upper quartile corresponds to cTnI level of 3,5/2,1 pg/ml, which indicates the need to reduce the critical cTnI values in Russia. To assess risk reclassification, Cox models were analyzed using the Net Reclassification Index (NRI), as well as NRIsurvival for survival analysis. For categorical variables, the NRIcategorial was used. Both methods of including cTnI in the model significantly improve the risk classification of severe endpoints in men.Conclusion. The results obtained confirm the need to lower the threshold values for predicting combined endpoints, in particular, in Russian men. cTnl has an independent effect on CVE risk and its addition to SCORE improves the prediction of CVEs among men. However, the data obtained are preliminary and require clarification sing larger sample. At the same time, it is obvious that the determination of cТnI level can play a significant role in cardiovascular risk assessment and be an unfavorable prognosis marker among Russian population.

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Abstract P019: A Single Model For Predicting Major Adverse Cardiovascular Events In Individuals With And Without History Of Atherosclerotic Cardiovascular Disease: The Atherosclerosis Risk In Communities (aric) Study

Circulation ◽

10.1161/circ.143.suppl_1.p019 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Yejin Mok ◽

Lena Mathews ◽

Ron C Hoogeveen ◽

Michael J Blaha ◽

Christie M Ballantyne ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiovascular Disease ◽

High Risk ◽

Risk Stratification ◽

Cardiovascular Events ◽

Major Adverse Cardiovascular Events ◽

Atherosclerotic Cardiovascular Disease ◽

Single Model ◽

History Of ◽

Very High

Background: In the 2018 AHA/ACC Cholesterol guideline, risk stratification is an essential element. The use of a Pooled Cohort Equation (PCE) is recommended for individuals without atherosclerotic cardiovascular disease (ASCVD), and the new dichotomous classification of very high-risk vs. high-risk has been introduced for patients with ASCVD. These distinct risk stratification systems mainly rely on traditional risk factors, raising the possibility that a single model can predict major adverse cardiovascular events (MACEs) in persons with and without ASCVD. Methods: We studied 11,335 ARIC participants with (n=885) and without (n=10,450) a history of ASCVD (myocardial infarction, ischemic stroke, and symptomatic peripheral artery disease) at baseline (1996-98). We modeled factors in the PCE and the new classification for ASCVD patients (Figure legend) in a single CVD prediction model. We examined their associations with MACEs (myocardial infarction, stroke, and heart failure) using Cox models and evaluated the discrimination and calibration for a single model including those factors. Results: During a median follow-up of 18.4 years, there were 3,658 MACEs (3,105 in participants without ASCVD). In general, the factors in the PCE and the risk classification system for ASCVD patients were associated similarly with MACEs regardless of baseline ASCVD status, although age and systolic blood pressure showed significant interactions. A single model with these predictors and the relevant interaction terms showed good calibration and discrimination for those with and without ASCVD (c-statistic=0.729 and 0.704, respectively) (Figure). Conclusion: A single CVD prediction model performed well in persons with and without ASCVD. This approach will provide a specific predicted risk to ASCVD patients (instead of dichotomy of very high vs. high risk) and eliminate a practice gap between primary vs. secondary prevention due to different risk prediction tools.

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Cardiovascular family history increases the risk of disease recurrence after a first myocardial infarction

European Heart Journal ◽

10.1093/ehjci/ehaa946.2979 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Wahrenberg ◽

P Magnusson ◽

R Kuja-Halkola ◽

H Habel ◽

K Hambraeus ◽

...

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Family History ◽

Cardiovascular Events ◽

Cardiovascular Death ◽

Funding Source ◽

History Of ◽

First Time ◽

Early Family

Abstract Background Despite recent advances in secondary prevention, recurrent cardiovascular events are common after a myocardial infarction (MI). It has been reported that genetic risk scores may predict the risk of recurrent cardiovascular events. Although patient-derived family history is a composite of both genetic and environmental heritability of atherosclerotic cardiovascular disease (ASCVD), it is an easily accessible information compared to genetically based risk models but the association with recurrent events is unknown. Purpose To evaluate whether a register-verified family history of ASCVD is associated with recurrent cardiovascular events (rASCVD) in patients after a first-time MI. Methods We included patients with a first-time MI during 2005 – 2014, registered in the SWEDEHEART SEPHIA registry and without prior ASCVD. Follow-up was available until Dec 31st, 2018. Data on relatives, diagnoses and prescriptions were extracted from national registers. A family history of ASCVD was defined as a register-verified hospitalisation due to MI, angina with coronary revascularization procedures, stroke or cardiovascular death in any parent. Early history was defined as such an event before the age of 55 years in fathers and 65 years in mothers. The association between family history and a composite outcome including recurrent MI, angina requiring acute revascularization, ischaemic stroke and cardiovascular death during follow-up was studied with Cox proportional hazard regression with time from SEPHIA registry completion as underlying time-scale, adjusted for age with splines, gender and year of SEPHIA registry. Regression models were then further adjusted for hypertension, diabetes, smoking and for a subset of patients, LDL-cholesterol (LDL_C) at time of first event. Results Of 25,615 patients, 2.5% and 32.1% had an early and ever-occurring family history of ASCVD, respectively. Patients with early family history were significantly younger than other patients and were more likely to be current smokers and have a higher LDL-C (Median (IQR) 3.5 (1.1) vs 3.3 (1.1) mmol/L). In total, 3,971 (15.5%) patients experienced the outcome. Early family history of ASCVD was significantly associated with rASCVD (Hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.23–1.87), and the effect was sustained when adjusted for cardiovascular risk factors (HR 1.48, 95% CI 1.20–1.83) and LDL-C (HR 1.35, 95% CI 1.04–1.74). Ever-occurring family history was weakly associated with ASCVD (HR 1.09, 95% CI 1.02 – 1.17) and the association remained unchanged with adjustments for risk factors. Conclusions Early family history of cardiovascular disease is a potent risk factor for recurrent cardiovascular events in a secondary prevention setting, independent of traditional risk factors including LDL-C. This is a novel finding and these patients may potentially benefit from intensified secondary preventive measures after a first-time MI. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): This work was funded by grants from The Swedish Heart and Lung Association

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The Impact of Cytochrome P450 2C19 Polymorphism on Cardiovascular Events in Indonesian Patients with Coronary Artery Disease

Clinical Cardiology and Cardiovascular Medicine ◽

10.33805/2639.6807.104 ◽

2017 ◽

pp. 18-24

Author(s):

Muzakkir Amir ◽

Mirnawati Mappiare ◽

Paskalis Indra

Keyword(s):

Myocardial Infarction ◽

Coronary Artery Disease ◽

Platelet Aggregation ◽

Cardiovascular Events ◽

Cardiovascular Death ◽

Cyp2c19 Genotype ◽

Cyp2c19 Polymorphism ◽

Cytochrome P450 2C19 ◽

Artery Disease ◽

The Impact

Background: The polymorphism of cytochrome P450 2C19 (CYP2C19) has been documented as the determinant variability in the antiplatelet effect of clopidogrel. The relation between CYP2C19 polymorphism and the antiplatelet efficacy of clopidogrel in Indonesian patients with coronary artery disease (CAD) is unknown. To address this issue, we examined the distribution of CYP2C19 genotypes and platelet aggregation, and assessed the impact of CYP2C19 polymorphism on response to clopidogrel and cardiovascular events. Methods: This observational analytic study with prospective cohort approach was conducted in Wahidin Sudirohusodo and Hasanuddin University Hospital, Makassar. We measured the CYP2C19 genotype by polymerase chain reaction-restriction fragment linked polymorphism (PCR-RFLP) method and platelet aggregation by optical platelet aggregometry with 10 μmol of adenosine diphosphate (ADP) in 69 patients with stable CAD who were treated with clopidogrel. Platelet hyperaggregation was defined as maximal platelet aggregation > 94.3%. The patients were followed up every month at the outpatient department for 6 months or at end point. The end point was acute myocardial infarction, ischemic stroke, or cardiovascular death. Results: Distribution of CYP2C19 alleles were 89.8%, 40.6%, and 11.6%, in CYP2C19*1, CYP2C19*2, and CYP2C19*3, respectively. Distribution of CYP2C19 genotype were 50.7%, 29.0%, 8.7%, 8.7%, and 2.9% in CYP2C19*1/*1, *1/*2, *1/*3, *2/*2, and *2/*3, respectively. Platelet hyper aggregation was more in patients with polymorphism than wild type (p 0.034; OR 3.707) and was associated with cardiovascular events (p 0.030; OR 13.250). There was acute myocardial infarction in 2 patients, ischemic stroke in 1 patient, and cardiovascular death in 1 patient. All of these patients were carrying at least one variant allele of CYP2C19; details of genotype were in two patients with CYP2C19*1/*2, one patient with *2/*2, and one with *2/*3 alleles. Conclusion: CYP2C19*2 and *3 were associated with cardiovascular events due to platelet hyper aggregation.

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P3609Temporal trends of the management and outcomes of patients after myocardial infarction according to the risk for recurrent cardiovascular events

European Heart Journal ◽

10.1093/eurheartj/ehz745.0468 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

T Grinberg ◽

T Bental ◽

Y Hammer ◽

A R Assali ◽

H Vaknin-Assa ◽

...

Keyword(s):

Myocardial Infarction ◽

High Risk ◽

Cardiovascular Events ◽

Risk Group ◽

Temporal Trends ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

High Risk Patients ◽

Risk Patients

Abstract Background Following Myocardial Infarction (MI), patients are at increased risk for recurrent cardiovascular events, particularly during the immediate period. Yet some patients are at higher risk than others, owing to their clinical characteristics and comorbidities, these high-risk patients are less often treated with guideline-recommended therapies. Aim To examine temporal trends in treatment and outcomes of patients with MI according to the TIMI risk score for secondary prevention (TRS2°P), a recently validated risk stratification tool. Methods A retrospective cohort study of patients with an acute MI, who underwent percutaneous coronary intervention and were discharged alive between 2004–2016. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time-periods. Patients were stratified by the TRS2°P to a low (≤1), intermediate (2) or high-risk group (≥3). Clinical outcomes included 30-day MACE (death, MI, target vessel revascularization, coronary artery bypass grafting, unstable angina or stroke) and 1-year mortality. Results Among 4921 patients, 31% were low-risk, 27% intermediate-risk and 42% high-risk. Compared to low and intermediate-risk patients, high-risk patients were older, more commonly female, and had more comorbidities such as hypertension, diabetes, peripheral vascular disease, and chronic kidney disease. They presented more often with non ST elevation MI and 3-vessel disease. High-risk patients were less likely to receive drug eluting stents and potent anti-platelet drugs, among other guideline-recommended therapies. Evidently, they experienced higher 30-day MACE (8.1% vs. 3.9% and 2.1% in intermediate and low-risk, respectively, P<0.001) and 1-year mortality (10.4% vs. 3.9% and 1.1% in intermediate and low-risk, respectively, P<0.001). During time, comparing the early to the late-period, the use of potent antiplatelets and statins increased among the entire cohort (P<0.001). However, only the high-risk group demonstrated a significantly lower 30-day MACE (P=0.001). During time, there were no differences in 1-year mortality rate among all risk categories. Temporal trends in 30-day MACE by TRS2°P Conclusion Despite a better application of guideline-recommended therapies, high-risk patients after MI are still relatively undertreated. Nevertheless, they demonstrated the most notable improvement in outcomes over time.

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Pioglitazone for the Primary and Secondary Prevention of Cardiovascular and Renal Outcomes in Patients with or at High Risk of Type 2 Diabetes Mellitus: A Meta-Analysis

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz252 ◽

2019 ◽

Vol 105 (5) ◽

pp. 1670-1681 ◽

Cited By ~ 4

Author(s):

Yue Zhou ◽

Yajing Huang ◽

Xiaoyun Ji ◽

Xiang Wang ◽

Liyan Shen ◽

...

Keyword(s):

Diabetes Mellitus ◽

Myocardial Infarction ◽

Heart Failure ◽

High Risk ◽

Meta Analysis ◽

Cardiovascular Death ◽

Primary And Secondary Prevention ◽

All Cause Mortality ◽

History Of

Abstract Context The goal of the meta-analysis was to evaluate the effect of pioglitazone on the primary and secondary prevention of cardiovascular diseases (CVDs) and renal adverse events in patients with or at high risk of type 2 diabetes mellitus (T2DM). Design Randomized controlled trials (RCTs) comparing pioglitazone with any control were identified through PubMed, Embase, and the Cochrane Library. Cardiovascular outcomes included major adverse cardiovascular events (MACEs, defined as the composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death), hospitalization for heart failure, and all-cause mortality. Renal outcomes included change in urinary albumin to creatinine ratio and 24-hour urinary protein excretion. Weighted mean difference (WMD) and risk ratio (RR) with 95% confidence intervals (CIs) were pooled. Results A total of 26 studies with 19 645 participants were enrolled. Pioglitazone reduced the risk of MACE (RR, 0.8 [95% CI, 0.7–0.9]), with benefit only seen in patients with a history of established CVDs (0.8 [0.7–0.9]) and not in those without (1.0 [0.7–1.3]). Regarding the individual components, pioglitazone reduced the risk of nonfatal myocardial infarction (0.8 [0.6–1.0]) and nonfatal stroke (0.8 [0.7–0.9]), which was confined to patients with a history of established CVDs, whereas no treatment effect was found on cardiovascular death (1.0 [0.7–1.2]) regardless of the presence of established CVDs. Pioglitazone increased the risk of hospitalization for heart failure (1.3 [1.1–1.6]) and had no treatment effect on all-cause mortality (1.0 [0.8–1.1]). Pioglitazone reduced albuminuria by 18.5% (WMD 18.5% [95% CI, 21.1-16.0]), with a similar benefit in patients with different renal function categories. Conclusions Pioglitazone should be considered in patients with or at high risk of T2DM for the prevention of cardiovascular endpoints, especially in those with a history of established CVD who might benefit the most. Robust reductions in progression of renal disease are seen regardless of baseline renal function degree.

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Comparative risk evaluation for cardiovascular events associated with dapagliflozin vs. empagliflozin in real-world type 2 diabetes patients: a multi-institutional cohort study

Cardiovascular Diabetology ◽

10.1186/s12933-019-0919-9 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 13

Author(s):

Shih-Chieh Shao ◽

Kai-Cheng Chang ◽

Ming-Jui Hung ◽

Ning-I Yang ◽

Yuk-Ying Chan ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Type 2 Diabetes ◽

Cohort Study ◽

Ischemic Stroke ◽

Cardiovascular Events ◽

Cardiovascular Death ◽

Sglt2 Inhibitors ◽

Diabetes Patients

Abstract Background To compare the cardiovascular event risk in type 2 diabetes patients newly receiving dapagliflozin vs. empagliflozin. Methods We conducted a retrospective cohort study by analyzing a multi-institutional electronic medical records database (Chang Gung Research Database) in Taiwan and included adult type 2 diabetes patients who were newly receiving sodium–glucose co-transporter 2 (SGLT2) inhibitors from 2016 to 2017. The primary outcome was a composite of cardiovascular death, myocardial infarction, ischemic stroke and heart failure. We followed up patients from initiation of SGLT2 inhibitors until the occurrence of cardiovascular events before December 31, 2018. We performed multivariable Cox proportional hazard modeling, adjusting for patients’ age, sex, laboratory data, co-morbidities, and concomitant medications. Results We identified 12,681 new SGLT2 inhibitor users with a mean age of 58.9 (SD 11.8) years, of whom 43.9% were female and 45.8% were new dapagliflozin users. A total of 10,442 person-years of dapagliflozin use and 12,096 person-years of empagliflozin use were included. Compared to empagliflozin users, new users of dapagliflozin were found to have similar risks for primary composite outcome (adjusted HR: 0.91; 95% CI 0.73–1.14), cardiovascular death (adjusted HR: 0.54; 95% CI 0.14–2.12), myocardial infarction (adjusted HR: 0.77, 95% CI 0.49–1.19) and ischemic stroke (adjusted HR: 1.15; 95% CI 0.80–1.65), but a lower risk of heart failure (adjusted HR: 0.68; 95% CI 0.49–0.95). Conclusion The risk of cardiovascular events was similar between dapagliflozin and empagliflozin new users, but dapagliflozin may have a better outcome in the reduction of heart failure in type 2 diabetes patients. Future prospective studies are required to confirm the findings.

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Sodium glucose cotransporter 2 inhibitors and risk of major adverse cardiovascular events: multi-database retrospective cohort study

BMJ ◽

10.1136/bmj.m3342 ◽

2020 ◽

pp. m3342 ◽

Cited By ~ 2

Author(s):

Kristian B Filion ◽

Lisa M Lix ◽

Oriana HY Yu ◽

Sophie Dell’Aniello ◽

Antonios Douros ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiovascular Events ◽

Retrospective Cohort ◽

Meta Analysis ◽

Cardiovascular Death ◽

Sglt2 Inhibitors ◽

Major Adverse Cardiovascular Events ◽

Site Specific ◽

Sodium Glucose Cotransporter ◽

All Cause Mortality

Abstract Objective To compare the risk of cardiovascular events between sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors among people with type 2 diabetes in a real world context of clinical practice. Design Multi-database retrospective cohort study using a prevalent new user design with subsequent meta-analysis. Setting Canadian Network for Observational Drug Effect Studies (CNODES), with administrative healthcare databases from seven Canadian provinces and the United Kingdom, 2013-18. Population 209 867 new users of a SGLT2 inhibitor matched to 209 867 users of a DPP-4 inhibitor on time conditional propensity score and followed for a mean of 0.9 years. Main outcome measures The primary outcome was major adverse cardiovascular events (MACE, a composite of myocardial infarction, ischaemic stroke, or cardiovascular death). Secondary outcomes were the individual components of MACE, heart failure, and all cause mortality. Cox proportional hazards models were used to estimate site specific adjusted hazards ratios and 95% confidence intervals, comparing use of SGLT2 inhibitors with use of DPP-4 inhibitors in an as treated approach. Site specific results were pooled using random effects meta-analysis. Results Compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with decreased risks of MACE (incidence rate per 1000 person years: 11.4 v 16.5; hazard ratio 0.76, 95% confidence interval 0.69 to 0.84), myocardial infarction (5.1 v 6.4; 0.82, 0.70 to 0.96), cardiovascular death (3.9 v 7.7; 0.60, 0.54 to 0.67), heart failure (3.1 v 7.7; 0.43, 0.37 to 0.51), and all cause mortality (8.7 v 17.3; 0.60, 0.54 to 0.67). SGLT2 inhibitors had more modest benefits for ischaemic stroke (2.6 v 3.5; 0.85, 0.72 to 1.01). Similar benefits for MACE were observed with canagliflozin (0.79, 0.66 to 0.94), dapagliflozin (0.73, 0.63 to 0.85), and empagliflozin (0.77, 0.68 to 0.87). Conclusions In this large observational study conducted in a real world clinical practice context, the short term use of SGLT2 inhibitors was associated with a decreased risk of cardiovascular events compared with the use of DPP-4 inhibitors. Trial registration ClinicalTrials.gov NCT03939624 .

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