scholarly journals Effect of glutamate and aspartate on ischemic heart disease, blood pressure, and diabetes: a Mendelian randomization study

2019 ◽  
Vol 109 (4) ◽  
pp. 1197-1206 ◽  
Author(s):  
Jie V Zhao ◽  
M K Kwok ◽  
C Mary Schooling

ABSTRACT Background Evolutionary biology suggests reproduction trades off against longevity. Genetic selection in favor of fertility and ischemic heart disease (IHD) exists in humans. Observationally, soy protects against IHD. Soy amino acids, glutamate and aspartate, may lower androgens. No large randomized controlled trials testing their health effects exist. Objective Using Mendelian randomization, we assessed how genetically predicted glutamate and aspartate affected IHD, blood pressure, and diabetes. Methods A separate sample instrumental variable analysis with genetic instruments was used to obtain unconfounded estimates using genetic variants strongly (P < 5 × 10−8) and solely associated with glutamate or aspartate applied to an IHD case (n ≤76,014)–control (n ≤ 264,785) study (based on a meta-analysis of CARDIoGRAMplusC4D 1000 Genomes, UK Biobank CAD SOFT GWAS and Myocardial Infarction Genetics and CARDIoGRAM Exome), blood pressure from the UK Biobank (n ≤ 361,194), and the DIAbetes Genetics Replication And Meta-analysis diabetes case (n = 26,676)–control (n = 132,532) study. A weighted median and MR-Egger were used for a sensitivity analysis. Results Glutamate was not associated with IHD, blood pressure, or diabetes after correction for multiple comparisons. Aspartate was inversely associated with IHD (odds ratio (OR) 0.92 per log-transformed standard deviation (SD); 95% confidence interval (CI) 0.88, 0.96) and diastolic blood pressure (−0.03; 95% CI −0.04, −0.02) using inverse variance weighting, but not diabetes (OR 1.00; 95% CI 0.91, 1.09). Associations were robust to the sensitivity analysis. Conclusions Our findings suggest aspartate may play a role in IHD and blood pressure, potentially underlying cardiovascular benefits of soy. Clarifying the mechanisms would be valuable for IHD prevention and for defining a healthy diet.

2018 ◽  
Vol 108 (2) ◽  
pp. 237-242 ◽  
Author(s):  
Hanish P Kodali ◽  
Brian T Pavilonis ◽  
C Mary Schooling

ABSTRACTBackgroundDespite great progress in prevention and control, ischemic heart disease (IHD) remains a leading cause of global morbidity and mortality. Diet plays a key role in IHD, but a comprehensive delineation of the role of dietary factors in IHD is not yet quite complete.ObjectiveThe aim of this study was to test the long-standing hypothesis that copper is protective and zinc harmful in IHD.DesignWe used separate-sample instrumental variable analysis with genetic instruments (Mendelian randomization). We obtained single nucleotide polymorphisms (SNPs) from a genome wide association study, strongly (P value < 5 × 10−8) and independently associated with erythrocyte copper and zinc. We applied these genetic predictors of copper and zinc to the largest, most extensively genotyped IHD case (n ≤ 76014)-control (n ≤ 264785) study, based largely on CARDIoGRAMplusC4D 1000 Genomes and the UK Biobank SOFT CAD, to obtain SNP-specific Wald estimates for the effects of copper and zinc on IHD, which were combined through the use of inverse variance weighting. Sensitivity analysis included use of the MR-Egger method, and reanalysis including SNPs independently associated with erythrocyte copper and zinc at P value < 5 × 10−6.ResultsGenetically instrumented copper was negatively associated with IHD (OR: 0.94; 95% CI: 0.90, 0.98). Genetically instrumented zinc was positively associated with IHD (OR: 1.06; 95% CI: 1.02, 1.11). Sensitivity analysis via MR-Egger gave no indication of unknown pleiotropy; less strongly associated SNPs gave similar results for copper.ConclusionGenetic validation of a long-standing hypothesis suggests that further investigation of the effects, particularly of copper, on IHD may provide a practical means of reducing the leading cause of mortality and morbidity.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mengyu Li ◽  
Jie V. Zhao ◽  
Man Ki Kwok ◽  
C. Mary Schooling

AbstractAPOE genotypes are associated with ischemic heart disease (IHD), several other cardiovascular diseases and dementia. Previous studies have not comprehensively considered all genotypes, especially ε2ε2, nor associations by age and sex, although IHD incidence differs by sex. In the UK Biobank, including 391,992 white British participants, we compared effects of APOE genotypes on IHD and its risk factors. Compared to the ε3ε3 genotype, ε2ε2 was not clearly associated with IHD but was associated with lower plasma apolipoprotein B (apoB). The ε2ε3 genotype conferred lower IHD risk, systolic blood pressure (SBP), pulse pressure and plasma apoB than ε3ε3. ε3ε4 and ε4ε4 conferred higher IHD risk, higher pulse pressure and plasma apoB, but lower glycated haemoglobin (HbA1c) than ε3ε3. The associations by age and sex were fairly similar, except ε2ε2 compared to ε3ε3 was marginally positively associated with IHD in the younger age group and nominally inversely associated with SBP in men. ε3ε4 compared to ε3ε3 was nominally positively associated with SBP in women. APOE genotypes affect IHD risk increasingly from ε2ε3, ε3ε3, ε3ε4 to ε4ε4, with similar patterns for pulse pressure and plasma apoB, but not for diabetes. Associations with blood pressure differed by sex. Greater understanding of products of APOE and their effects might generate targets of intervention.


2002 ◽  
Vol 110 (3) ◽  
pp. 307-317 ◽  
Author(s):  
Elise E M M van Kempen ◽  
Hanneke Kruize ◽  
Hendriek C Boshuizen ◽  
Caroline B Ameling ◽  
Brigit A M Staatsen ◽  
...  

2013 ◽  
Vol 141 (1-2) ◽  
pp. 104-106 ◽  
Author(s):  
Edita Stokic

Lipid and lipoprotein disorders are well known risk factors for atherosclerosis and its complications. The level of atherogenic LDL-cholesterol (LDL-C) is directly related to an increased risk of occurrence and progression of ischemic heart disease. Epidemiological and clinical studies have shown that the use of statin therapy to decrease LDL-C can significantly reduce the incidence of mortality, major coronary events and the need for revascularization procedures in the different groups of patients. The findings of a large meta-analysis conducted by the Cholesterol Treatment Trialists? (CTT) collaborators showed that every 1.0 mmol/l reduction of atherogenic LDL-C is associated with a 22% reduction in cardiovascular diseases mortality and morbidity. However, despite the impressive results of the benefits of statin therapy, the EUROASPIRE study showed that about 50% of patients with ischemic heart disease did not achieve target LDL-C levels. According to the new ESC/EAS Guidelines for the Management of Dyslipidaemias in patients with a very high cardiovascular risk, treatment goal should be to decrease LDL-C below 1.8 mmol/l or ?50% of initial values. In the majority of patients that can be achieved by statin therapy. For this reason an adequate choice of statins is of crucial importance, whereby the needed reduction in atherogenic LDL-C, after the identification of its target level based on the assessment of total cardiovascular risk, can be achieved.


10.2196/16695 ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. e16695 ◽  
Author(s):  
Praveen Indraratna ◽  
Daniel Tardo ◽  
Jennifer Yu ◽  
Kim Delbaere ◽  
Matthew Brodie ◽  
...  

Background Cardiovascular disease (CVD) remains the leading cause of death worldwide. Mobile phones have become ubiquitous in most developed societies. Smartphone apps, telemonitoring, and clinician-driven SMS allow for novel opportunities and methods in managing chronic CVD, such as ischemic heart disease, heart failure, and hypertension, and in the conduct and support of cardiac rehabilitation. Objective A systematic review was conducted using seven electronic databases, identifying all relevant randomized control trials (RCTs) featuring a mobile phone intervention (MPI) used in the management of chronic CVD. Outcomes assessed included mortality, hospitalizations, blood pressure (BP), and BMI. Methods Electronic data searches were performed using seven databases from January 2000 to June 2019. Relevant articles were reviewed and analyzed. Meta-analysis was performed using standard techniques. The odds ratio (OR) was used as a summary statistic for dichotomous variables. A random effect model was used. Results A total of 26 RCTs including 6713 patients were identified and are described in this review, and 12 RCTs were included in the meta-analysis. In patients with heart failure, MPIs were associated with a significantly lower rate of hospitalizations (244/792, 30.8% vs 287/803, 35.7%; n=1595; OR 0.77, 95% CI 0.62 to 0.97; P=.03; I2=0%). In patients with hypertension, patients exposed to MPIs had a significantly lower systolic BP (mean difference 4.3 mm Hg; 95% CI −7.8 to −0.78 mm Hg; n=2023; P=.02). Conclusions The available data suggest that MPIs may have a role as a valuable adjunct in the management of chronic CVD.


2015 ◽  
Vol 53 (2) ◽  
pp. 146-152
Author(s):  
Alexandra Dǎdârlat ◽  
D. Zdrenghea ◽  
Dana Pop

Abstract Ischemic heart disease is underdiagnosed in women due to atypical symptomatology as well as to the lower specificity of several paraclinical tests, such as exercise stress testing. The aim of the study was to ascertain whether the Duke treadmill score (DTS) could be an efficient parameter in the diagnosis of ischemic heart disease in women. Material and method. 105 patients were enrolled in the study, 45.71% women with average age ranged between 20 and 70 years, investigated in the Rehabilitation Hospital, Cardiology-Departament, Cluj-Napoca, Romania. All the patients were clinically assessed as concerns the presence of cardiovascular risk factors, and they underwent electrocardiographic, echocardiographic and treadmill stress tests. DST was calculated according to the formula: exercise time – 5 x (ST deviation expressed in mm–4 x Angina Index). Results. DTS was lower in women as compared to men: 2.54±5.36 vs. 6±4.69, p=0.0006. 54.28% of the patients were ranged with a low DTS risk category, whereas 45.71% belonged to a moderate and high risk category. DTS was significantly lower in women than in men with high blood pressure (2.03±4.8 vs. 5.8±4.28), hypercholesterolemia (1.14±4.51 vs. 6.24±4.13), diabetes mellitus (1.83 ± 3.73 vs. 6.13±4.8), and obesity (2.42±5.35 vs. 5.81±4.64). By analyzing the presence of cardiovascular risk factors only in women, we noticed that only those with high blood pressure (2.03±4.89 vs. 8.13 ±7.85) and hypercholesterolemia (2.31±4.76 vs. 3.89±5.95) had a statistically significant low DTS (p<0.05). In conclusion, our research, which showed differences in DTS between women and men, raises concerns about the early diagnosis of ischemic heart disease in women.


Sign in / Sign up

Export Citation Format

Share Document