Causal Effect of Lipoprotein-associated Phospholipase A2 Activity on Coronary Artery Disease and Myocardial Infarction: A Two-Sample Mendelian Randomization Study

2021 ◽  
Author(s):  
Lulu Sun ◽  
Zhengbao Zhu ◽  
Mengyao Shi ◽  
Yiming Jia ◽  
Pinni Yang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Phospholipase A2 ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Artery Disease ◽  
Phospholipase A2 Activity

scholarly journals Physical activity, sedentary behavior and risk of coronary artery disease, myocardial infarction and ischemic stroke: a two-sample Mendelian randomization study

2021 ◽  
Author(s):  
Martin Bahls ◽  
Michael F. Leitzmann ◽  
André Karch ◽  
Alexander Teumer ◽  
Marcus Dörr ◽  
...  
Keyword(s):  
Physical Activity ◽  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Ischemic Stroke ◽  
Coronary Artery ◽  
Sedentary Behavior ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Artery Disease

Abstract Aims Observational evidence suggests that physical activity (PA) is inversely and sedentarism positively related with cardiovascular disease risk. We performed a two-sample Mendelian randomization (MR) analysis to examine whether genetically predicted PA and sedentary behavior are related to coronary artery disease, myocardial infarction, and ischemic stroke. Methods and results We used single nucleotide polymorphisms (SNPs) associated with self-reported moderate to vigorous PA (n = 17), accelerometer based PA (n = 7) and accelerometer fraction of accelerations > 425 milli-gravities (n = 7) as well as sedentary behavior (n = 6) in the UK Biobank as instrumental variables in a two sample MR approach to assess whether these exposures are related to coronary artery disease and myocardial infarction in the CARDIoGRAMplusC4D genome-wide association study (GWAS) or ischemic stroke in the MEGASTROKE GWAS. The study population included 42,096 cases of coronary artery disease (99,121 controls), 27,509 cases of myocardial infarction (99,121 controls), and 34,217 cases of ischemic stroke (404,630 controls). We found no associations between genetically predicted self-reported moderate to vigorous PA, accelerometer-based PA or accelerometer fraction of accelerations > 425 milli-gravities as well as sedentary behavior with coronary artery disease, myocardial infarction, and ischemic stroke. Conclusions These results do not support a causal relationship between PA and sedentary behavior with risk of coronary artery disease, myocardial infarction, and ischemic stroke. Hence, previous observational studies may have been biased. Graphic abstract

Influence of phospholipase A2 and paraoxonase activity on endothelial function changes in various forms of coronary artery disease

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
VI Maslovskyi ◽  
IA Mezhiievska ◽  
YV Maslovskyi
Keyword(s):  
Coronary Artery Disease ◽  
Blood Flow ◽  
Coronary Artery ◽  
Endothelial Function ◽  
Phospholipase A2 ◽  
Brachial Artery ◽  
Vascular Disorders ◽  
Paraoxonase Activity ◽  
Artery Disease ◽  
Phospholipase A2 Activity

Abstract Funding Acknowledgements Type of funding sources: None. High phospholipase A2 activity is associated with atherosclerotic disorders of the arteries, while paraoxonase activity decreases with increasing atherogenic plasma activity. The purpose is to study the relationship between the combined effect of phospholipase A2 and paraoxonase activity on vascular endothelial dysfunction in various forms of coronary artery disease. We examined 152 men 52.5 ± 0.8 years, including 53 - STEMI, 32 - NSTEMI, 67 - chronic chronic coronary syndromes (CCS). Methods. All patients were examined for endothelial function of the brachial artery with a test for reactive hyperemia and vasodilation with exogenous NO, as well as determination of phospholipase A2 activity and plasma paraoxonase activity. All studiies conform to the principles of the Declaration of Helsinki of the World Medical Association. Results. Dynamics evaluation of endothelial function indicates a significant increase in blood flow in the brachial artery after compression in the NSTEMI group, but a decrease in the STEMI group after vasodilation of exogenous NO. Analysis of phospholipase A2 activity and paraoxonase showed an increasing the first in STEMI group compared to NSTEMI one and CCS while decreasing the second in the corresponding groups (Tab. 1). The results of the study confirm the association of increased activity of phospholipase A2 with vascular disorders severity, the correction of which should be considered a priority in prospective studies. The fact of reducing the activity of paraoxonase should be considered in the correction treatment of vascular disorders. Tab. 1 CCS NSTEMI STEMI LSD criteria D% 7,48 ± 0,39 6,65 ± 0,54 6,77 ± 0,62 {1-2} V% 54,71 ± 1,01 51,13 ± 1,92 42,16 ± 3,29 p1 < 0,0001 p2 = 0,010 {3} / {1, 2} D% (NO) 10,35 ± 0,47 8,24 ± 0,96 10,28 ± 0,98 {1, 2} V% (NO) 55,60 ± 1,12 37,71 ± 3,72 p1 < 0,0001 28,12 ± 3,94 p1 < 0,0001 {1} / {2, 3} sPA2 1,12 ± 0,03 1,25 ± 0,04 p1 < 0,0001 1,34 ± 0,04 p1 < 0,0001 {1} / {2, 3} PAO 0,54 ± 0,01 0,50 ± 0,01 0,44 ± 0,01 p1 < 0,0001 p2 < 0,0001 {1} / {2,3} D% - diameter of brachial artery after compression. V% - blood flow velocity after compression. sPA2 -phospholipase A2. PAO - paraoxanase. p - reliability on Sheffe"s criteria.

scholarly journals Mendelian randomization analyses reveal mediating factors of the causal effect of height on coronary artery disease

2021 ◽  
Author(s):  
Daniel Hui ◽  
Christopher S. Thom ◽  
Kimberly Lorenz ◽  
Scott M. Damrauer ◽  
Themistocles L. Assimes ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Lung Function ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Multivariable Analysis ◽  
Inverse Correlation ◽  
Artery Disease ◽  
Cad Risk

An inverse correlation between stature and risk of coronary artery disease (CAD) has been observed in several epidemiologic studies, and recent Mendelian randomization (MR) experiments have suggested evidence that this association may be causal. However, the extent to which the effect estimated by MR can be explained by established cardiovascular risk factors is unclear, with a recent report suggesting that lung function traits could fully explain the height-CAD effect. To clarify this relationship, we utilized the largest set of genetic instruments for human stature to date, comprising >2,000 genetic variants for height and CAD. In univariable analysis, we confirmed that a one standard deviation decrease in height (~6.5 cm) was associated with a 12.0% increase in the risk of CAD, consistent with previous reports. In multivariable analysis accounting for effects from up to 12 established risk factors, we observed a >3-fold attenuation in the causal effect of height on CAD susceptibility (3.7%, p = 2.1x10-2). We observed minimal effects of lung function traits on CAD risk in our analyses, indicating that these traits are unlikely to explain the residual association between height and CAD risk. In sum, these results suggest that height does not add meaningful clinical impact on CAD risk prediction beyond established risk factors.

scholarly journals Lipoprotein-Associated Phospholipase A2 Activity Predicts Cardiovascular Events in High Risk Coronary Artery Disease Patients

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e48171 ◽  
Author(s):  
Giuseppe Maiolino ◽  
Luigi Pedon ◽  
Maurizio Cesari ◽  
Anna Chiara Frigo ◽  
Robert L. Wolfert ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
High Risk ◽  
Phospholipase A2 ◽  
Cardiovascular Events ◽  
Artery Disease ◽  
Phospholipase A2 Activity

Genetically rheumatoid arthrits and risk of comorbidities: a Mendelian randomization study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Fokina ◽  
J Fill ◽  
G Klappacher
Keyword(s):  
Rheumatoid Arthritis ◽  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Funding Source ◽  
Artery Disease ◽  
Genetically Determined ◽  
Genetic Instruments

Abstract Background Ample observational evidence indicates that patients with rheumatoid arthritis (RA) are at increased risk of developing comorbid conditions, in particular cardiovascular disease. The pathogenesis of these comorbidities is still largely unknown. For effective preventive measures, it would however be important to discriminate between those that are causally linked with rheumatoid arthritis and those that are the results of concomitant treatments or other confounding factors. Purpose Our objective was to explore whether genetically determined manifestation of RA was associated with any comorbidities, in particular cardiovascular disease, by conducting a 2-sample Mendelian randomization (MR) study on publicly available summary statistics from genome-wide association study (GWAS) consortia. Methods Genetic instruments for RA were obtained from a GWAS of 14,361 autoantibody-positive individuals with RA and 43,923 controls of European descent (Okada et al. 2014). The CARDIoGRAMplusC4D consortium comprising 60,801 cases with coronary artery disease and 123,504 controls was used to evaluate the associations with cardiovascular outcomes applying inverse variance–weighted meta-analysis, weighted-median analysis, Mendelian randomization–Egger regression, and multivariable Mendelian randomization. Genetic instruments for RA were further tested for association with other etiologically related traits by using publicly available GWAS data. Results Genetic predisposition to RA was not associated with higher risk of coronary artery disease (beta coefficient [b] ± standard error [se] = 0.02±0.03; P=0.4913), and myocardial infarction (b ± se = 0.03±0.03; P=0.3338). In contrast, IgA nephropathy (b ± se = 0.47±0.18; P=0.0225) and triglyceride levels were significantly related as outcomes to genetically determined RA as exposure. Other significantly related outcomes were the manifestation of squamous cell lung cancer (b ± se = 0.17±0.08; P=0.0496), serous ovarian cancer (b ± se = 0.13±0.05; P=0.0202), and prostate cancer (b ± se = 0.06±0.02; P=0.0041). Conclusions Despite the high prevalence of coronary artery disease and myocardial infarction among RA patients in observational studies, cardiovascular outcomes were not significantly associated with RA by Mendelian randomization. This paradox might partly be explained by the traits such as IgA nephropathy and elevated triglyceride levels that could act as mediators for the increased cardiovascular risk by their causal link with genetically determined RA. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Medical University of Vienna, Austria

scholarly journals Modifiable Factors for Coronary Artery Disease, Myocardial Infarction, and Stroke: A Mendelian Randomisation Analysis (P15-006-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Tao Huang
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Pulse Pressure ◽  
Causal Effect ◽  
Mendelian Randomisation ◽  
Carotid Artery Plaque ◽  
Modifiable Factors ◽  
Artery Disease

Abstract Objectives We aimed to examine the causal associations of potentially risk factors, including lifestyle/dietary, cardiometabolic, and inflammatory factors, with risks of coronary artery disease (CAD), myocardial infarction (MI), and stroke. Methods We used single nucleotide polymorphisms (SNPs) associated with risk factors as instrumental variables to test the causal effect of risk factors on cardiovascular diseases using summary-level data from consortia. Results A total of 53 potentially risk factors were included. A Bonferroni corrected threshold of P = 0.00094 was considered to be significant. Genetically predicted higher BMI (odds ratio: 1.43, confidence interval: 1.26 to1.63 per 1 kg/m2, P = 7.64 × 10−8), smoking initiation (1.62, 1.42 to1.85 per year, P = 2.72 × 10−12), vitamin E (3.22, 1.81 to 4.63, P = 1.33 × 10−6). sIL-6R (1.63, 1.22 to 2.05, P = 0.0002), LDL (1.60, 1.46 to 1.75, P = 8.78 × 10−23), TC (1.48, 1.34 to 1.64, P = 1.14 × 10−13), TG (1.27, 1.13 to 1.43, P = 7.32 × 10−5), SBP (1.03, 1.02 to 1.05, P = 6.8 × 10−5), asthma (1.07, 1.05 to 1.09, P = 3.94 × 10−12), T2DM (1.12, 1.08 to 1.17, P = 4.37 × 10−8) were associated with higher risk of CAD; whilst, genetically predicted education (0.64, 0.55 to 0.75 per year, P = 2.68 × 10−8), and HDL (0.84, 0.76 to 0.92, P = 0.0003) were associated with lower risk of CAD. Similar results were observed for MI. In addition, atrial firillation (1.24, 1.18 to 1.30 P = 2.75 × 10−17), carotid artery plaque (1.24, 1.10 to 1.41, P = 0.0006), asthma (1.04 to 1.02, 1.06, P = 6.81 × 10−5), and T2DM (1.09, 1.04 to 1.14, P = 0.0002) were associated with higher risk of stroke per unit increase in log odds. We further observed suggestive associations of morning person, iron, fasting glucose, insulin, HbA1c, uric acid, and pulse pressure with CAD and suggestive associations of education, intelligence, Hcy, HDL, and pulse pressure with stroke. Conclusions Our results identified several modifiable factors as treatment targets for prevention of CAD, MI, or stroke. Funding Sources None. Supporting Tables, Images and/or Graphs

scholarly journals Causal associations of insulin resistance with coronary artery disease and ischemic stroke: a Mendelian randomization analysis

2020 ◽  
Vol 8 (1) ◽  
pp. e001217 ◽  
Author(s):  
Weiqi Chen ◽  
Shukun Wang ◽  
Wei Lv ◽  
Yuesong Pan
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Ischemic Stroke ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Artery Occlusion ◽  
Small Artery ◽  
Small Artery Occlusion ◽  
Weighted Median ◽  
Artery Disease

IntroductionThe relationship between insulin resistance (IR) and cardiovascular diseases is unclear. We aimed to examine the causal associations of IR with cardiovascular diseases, including coronary artery disease, myocardial infarction, ischemic stroke and its subtypes, using Mendelian randomization.Research design and methodsDue to low sample size for gold standard measures and in order to well reflect the underlying phenotype of IR, we used 53 single nucleotide polymorphisms associated with IR phenotypes (ie, fasting insulin, high-density lipoprotein cholesterol and triglycerides) from recent genome-wide association studies (GWASs) as instrumental variables. Summary-level data from four GWASs of European individuals were used. Data on IR phenotypes were obtained from meta-analysis of GWASs of up to 188 577 individuals and data on the outcomes from GWASs of up to 446 696 individuals. Mendelian randomization (MR) estimates were calculated with inverse-variance weighted, simple and weighted-median approaches and MR-Egger regression was used to explore pleiotropy.ResultsGenetically predicted 1-SD increase in IR phenotypes were associated with a substantial increase in risk of coronary artery disease (OR=1.79, 95% CI: 1.57 to 2.04, p<0.001), myocardial infarction (OR=1.78, 95% CI: 1.54 to 2.06, p<0.001), ischemic stroke (OR=1.21, 95% CI: 1.05 to 1.40, p=0.007) and the small-artery occlusion subtype of stroke (OR=1.80, 95% CI: 1.30 to 2.49, p<0.001), but not associated with the large-artery atherosclerosis and cardioembolism subtypes of stroke. There was no evidence of pleiotropy. Results were broadly consistent in sensitivity analyses using simple and weighted-median approaches accounting for potential genetic pleiotropy.ConclusionsThis study provides evidence to support that IR was causally associated with risk of coronary artery disease, myocardial infarction, ischemic stroke and the small-artery occlusion subtype of stroke.

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