Abstract 2365: Pharmacogenomic Application Of The Haptoglobin Genotype To Identify Individuals With Diabetes Mellitus Who Benefit From Vitamin E Supplementation: A Prospective Randomized, Double-blind, Placebo Controlled Trial

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Uzi Milman ◽  
Shany Blum ◽  
Chen Shapira ◽  
Doron Aronson ◽  
Rachel Miller-Lotan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Vitamin E ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
Composite Outcome ◽  
Anti Oxidant ◽  
Primary Composite Outcome ◽  
Fatal Myocardial Infarction ◽  
Vitamin E Supplementation

Background. Large clinical trials of antioxidant therapy with vitamin E have failed to demonstrate a decrease in cardiovascular events. However, these studies did not address possible benefit to subgroups with increased oxidative stress. Haptoglobin (Hp), a major anti-oxidant protein, is a determinant of cardiovascular events in patients with diabetes mellitus (DM). The Hp gene is polymorphic with two common alleles, 1 and 2. The Hp 2 allelic protein product provides inferior anti-oxidant protection as compared to the Hp 1 allelic product. In a retrospective analysis of HOPE participants with DM and the Hp 2–2 genotype, vitamin E significantly reduced the incidence of myocardial infarction and cardiovascular death. We sought to validate this observation in a prospective trial. Methods and Results. 984 DM individuals with the Hp 2–2 genotype were randomized and treated with either natural source vitamin E (400IU/day) or placebo. The primary composite outcome was non-fatal myocardial infarction, stroke and cardiovascular death. The study was intended to last 4 years with initial evaluation of endpoints scheduled 12 months after enrollment of the first patient. At the initial evaluation, the primary composite outcome was significantly reduced in patients receiving vitamin E compared to placebo (1.0% vs. 3.8%, p=0.004). This was predominately due to a significant decrease in the incidence of non-fatal myocardial infarction (0.2% vs. 2.1%, p=0.004) and led to early termination of the study. Conclusions . Vitamin E supplementation appears to reduce cardiovascular events in individuals with DM and the Hp 2–2 genotype. (ClinicalTrials.gov number NCT00220831 ).

scholarly journals Prognostic Impact of Serum Albumin for Developing Heart Failure Remotely after Acute Myocardial Infarction

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2637
Author(s):  
Goro Yoshioka ◽  
Atsushi Tanaka ◽  
Kensaku Nishihira ◽  
Yoshisato Shibata ◽  
Koichi Node
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Serum Albumin ◽  
Primary Outcome ◽  
Independent Predictor ◽  
Cardiovascular Death ◽  
Prognostic Impact ◽  
Composite Outcome ◽  
The Relationship ◽  
Primary Composite Outcome

Low serum albumin (LSA) on admission for acute myocardial infarction (AMI) is related to adverse in-hospital outcomes. However, the relationship between LSA and long-term post-AMI cardiovascular outcomes is unknown. A single-center, non-randomized, retrospective study was performed to investigate the prognostic impact of LSA at admission for AMI on cardiovascular death or newly developed HF in the remote phase after AMI. Admission serum albumin tertiles (<3.8, 3.8–4.2, ≥4.2 g/dL) were used to divide 2253 consecutive AMI from February 2008 to January 2016 patients into three groups. Primary outcome was a composite of hospitalization for HF and cardiovascular death remotely after AMI. Cox proportional hazard models were used to explore the relationship between admission LSA and primary outcome. During follow-up (median: 3.2 years), primary composite outcome occurred in 305 patients (13.5%). Primary composite outcome occurred individually for hospitalization for HF in 146 patients (6.5%) and cardiovascular death in 192 patients (8.5%). The cumulative incidence of primary composite outcome was higher in the LSA group than the other groups (log-rank test, p < 0.001). Even after adjustments for relevant clinical variables, LSA (<3.8 mg/dL) was an independent predictor of remote-phase primary composite outcome, irrespective of the clinical severity and subtype of AMI. Thus, LSA on admission for AMI was an independent predictor of newly developed HF or cardiovascular death and has a useful prognostic impact even remotely after AMI.

Variability in body weight and the risk of cardiovascular complications in type 2 diabetes: results from the Swedish National Diabetes Register

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Antonio Ceriello ◽  
Giuseppe Lucisano ◽  
Francesco Prattichizzo ◽  
Björn Eliasson ◽  
Stefan Franzén ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Body Weight ◽  
Cardiovascular Complications ◽  
Composite Outcome ◽  
All Cause Mortality ◽  
Diabetes Register ◽  
Primary Composite Outcome ◽  
Fatal Myocardial Infarction

Abstract Background There is a high incidence of cardiovascular disease in diabetes. Weight variability has been reported as independent risk factor for cardiovascular disease in the general population and preliminarily also in people with type 2 diabetes. Methods Using data from the Swedish National Diabetes Register the possible link between visit-to-visit body weight variability and the risk of cardiovascular complications among people with type 2 diabetes and without prevalent cardiovascular diseases at baseline has been evaluated. Overall, 100,576 people with type 2 diabetes, with at least five measurements of body weight taken over three consecutive years, were included. Variability was expressed as quartiles of the standard deviation of the measures during the three years. The primary composite outcome included non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality and was assessed during five years following the first 3 years of exposure to weight variability. Results After adjusting for known cardiovascular risk factors, the risk of the primary composite outcome significantly increased with increasing body weight variability [upper quartile HR = 1.45; 95% confidence interval 1.39–1.52]. Furthermore, elevated body weight variability was associated with almost all the other cardiovascular complications considered (non-fatal myocardial infarction, non-fatal stroke, all-cause mortality, peripheral arterial disease, peripheral vascular angioplasty, hospitalization for heart failure, foot ulcer, and all-cause mortality). Conclusions High body weight variability predicts the development of cardiovascular complications in type 2 diabetes. These data suggest that any strategy to reduce the body weight in these subjects should be aimed at maintaining the reduction in the long-term, avoiding oscillations.

scholarly journals Glucagon-like peptide-1 (GLP-1) receptor agonists and cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis of double-blind, randomized, placebo-controlled clinical trials

2019 ◽  
Author(s):  
Jing Qin ◽  
Li Song
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Double Blind ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Fatal Myocardial Infarction

Abstract Background The cardiovascular effects of glucagon-like peptide-1 (GLP-1) receptor agonists are still controversial in the treatment of type 2 diabetes mellitus (T2DM) patients. The purpose of this study was to evaluate the risk of cardiovascular events of GLP-1 (albiglutide, exenatide, liraglutide and semaglutide) receptor agonists in T2DM patients.Methods PubMed and Embase were searched to find relevant randomized controlled trials (RCTs) from inception to June 2019 that evaluated the effect of GLP-1 receptor agonists on cardiovascular events in patients with T2DM. The T2DM patients of all the eligible trials received either GLP-1 therapy or placebo, and the cardiovascular outcomes included death from cardiovascular causes, fatal or non-fatal myocardial infarction and fatal or non-fatal stroke.Results We included 4 multinational double-blind randomized placebo-control trials that included a total of 36852 T2DM patients. The results indicated that GLP-1 receptor agonists reduced the risk of death from cardiovascular causes (RR: 0.86; 95% CI: 0.78–0.96; P = 0.005), fatal or non-fatal myocardial infarction (RR: 0.85; 95% CI: 0.74–0.98; P = 0.03) and fatal or non-fatal stroke (RR: 0.84; 95% CI: 0.75–0.95; P = 0.007) compared with the placebo controls.Conclusion We concluded that GLP-1 receptor agonist therapy had a protective cardiovascular effect compared with the placebo in the treatment of T2DM patients in trials with cardiovascular outcomes.

scholarly journals Glucagon-like peptide-1 (GLP-1) receptor agonists and cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis of double-blind, randomized, placebo-controlled clinical trials

2020 ◽  
Author(s):  
Jing Qin ◽  
Li Song
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
Double Blind ◽  
Receptor Agonists ◽  
Risk Of Death ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Fatal Myocardial Infarction

Abstract Background: The cardiovascular effects of glucagon-like peptide-1 (GLP-1) receptor agonists are still controversial in the treatment of type 2 diabetes mellitus (T2DM) patients. The purpose of this study was to evaluate the risk of cardiovascular events of GLP-1 (albiglutide, exenatide, liraglutide, semaglutide, lixisenatide and dulaglutide) receptor agonists in T2DM patients.Methods: PubMed and Embase were searched to find relevant randomized controlled trials (RCTs) from inception to June 2019 that evaluated the effect of GLP-1 receptor agonists on cardiovascular events in patients with T2DM. The T2DM patients of all the eligible trials received either GLP-1 therapy or placebo, and the cardiovascular outcomes included death from cardiovascular causes, fatal or non-fatal myocardial infarction and fatal or non-fatal stroke.Results: We included 6 multinational double-blind randomized placebo-control trials that included a total of 52821 T2DM patients. The results indicated that GLP-1 receptor agonists reduced the risk of death from cardiovascular causes (RR: 0.90; 95% CI: 0.83–0.97; P = 0.004) and fatal or non-fatal stroke (RR: 0.85; 95% CI: 0.77–0.94; P = 0.001) compared with the placebo controls. But GLP-1 receptor agonists did not significantly alter the fatal or non-fatal myocardial infarction compared with the placebo (RR: 0.91; 95% CI: 0.82 – 1.01; P = 0.06).Conclusion: We concluded that GLP-1 receptor agonist therapy could reduce the risk of death from cardiovascular causes and fatal or non-fatal stroke compared with the placebo in the treatment of T2DM patients in trials with cardiovascular outcomes.

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

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

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

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.

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

2019 ◽  
Vol 105 (5) ◽  
pp. 1670-1681 ◽  
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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