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 The impact of growth differentiation factor 15 on the risk of cardiovascular disease: evidence from Mendelian randomization study

2020 ◽  
Author(s):  
Zhuo Wang ◽  
Fangkun Yang ◽  
Menghuai Ma ◽  
Qinyi Bao ◽  
Jinlian Shen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Causal Relationship ◽  
Mendelian Randomization ◽  
Cardioembolic Stroke ◽  
Growth Differentiation Factor 15 ◽  
Artery Disease

Abstract Background: Growth differentiation factor 15(GDF-15) concentration is apparently associated with cardiovascular disease, but whether there is a causal relationship has not been testified. Methods: We utilized Mendelian randomization to assess the function of GDF-15 in incidence of cardiovascular disease. The single-nucleotide polymorphism- GDF-15 association evaluations came from meta-analysis of genome-wide association study (GWAS). Besides inverse-variance weighted, MR-Egger test and weighted median method were applied to examine sensitivity. Results: Based on the instruments, GDF-15 level linked to the increasing risk of cardioembolic stroke (OR 1.09 per SD increase, 95% CI 1.01, 1.19) , atrial fibrillation (OR 1.03 per SD increase, 95% CI 1.0, 1.06), coronary artery disease (OR 0.94 per SD increase, 95% CI 0.89, 0.99) and myocardial infarction (OR 0.94 per SD increase, 95% CI 0.90, 0.98). However, the significant causal relationship between GDF-15 and the other cardiovascular diseases was not found in our study. Conclusions: The result suggested that GDF-15 was causally associated with the risk of cardioembolic stroke,atrial fibrillation, coronary artery disease and myocardial infarction, providing us conceivable strategies to alleviate the burden of cardiovascular disease.

scholarly journals The impact of growth differentiation factor 15 on the risk of cardiovascular disease: evidence from Mendelian randomization study

2020 ◽  
Author(s):  
Zhuo Wang ◽  
Fangkun Yang ◽  
Menghuai Ma ◽  
Qinyi Bao ◽  
Jinlian Shen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Causal Relationship ◽  
Mendelian Randomization ◽  
Cardioembolic Stroke ◽  
Growth Differentiation Factor 15 ◽  
Artery Disease

Abstract Background: Growth differentiation factor 15(GDF-15) concentration is apparently associated with cardiovascular disease, but whether there is a causal relationship has not been testified. Methods: We utilized Mendelian randomization to assess the function of GDF-15 in incidence of cardiovascular disease. The single-nucleotide polymorphism- GDF-15 association evaluations came from meta-analysis of genome-wide association study (GWAS). Besides inverse-variance weighted, MR-Egger test and weighted median method were applied to examine sensitivity. Results: Based on the instruments, GDF-15 level linked to the increasing risk of cardioembolic stroke (1.06, OR 1.09 per SD increase, 95% CI 1.01, 1.19) , atrial fibrillation (OR 1.03 per SD increase, 95% CI 1.0, 1.06), coronary artery disease (OR 0.94 per SD increase, 95% CI 0.89, 0.99) and myocardial infarction (OR 0.94 per SD increase, 95% CI 0.90, 0.98). However, the significant causal relationship between GDF-15 and the other cardiovascular diseases was not found in our study. Conclusions: The result suggested that GDF-15 was causally associated with the risk of cardioembolic stroke,atrial fibrillation, coronary artery disease and myocardial infarction, providing us conceivable strategies to alleviate the burden of cardiovascular disease.

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

Associations of observational and genetically determined caffeine intake with coronary artery disease and diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Said ◽  
Y.J Van De Vegte ◽  
N Verweij ◽  
P Van Der Harst
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Cox Regression ◽  
Caffeine Intake ◽  
Uk Biobank ◽  
Genome Wide ◽  
Artery Disease ◽  
Genetically Determined

Abstract Background Caffeine is the most widely consumed psychostimulant and is associated with lower risk of coronary artery disease (CAD) and type 2 diabetes (T2D). However, whether these associations are causal remains unknown. Objectives This study aimed to identify genetic variants associated with caffeine intake, and to investigate possible causal links between genetically determined caffeine intake and CAD or T2D. Additionally, we aimed to replicate previous observational findings between caffeine intake and CAD or T2D. Methods Genome wide associated studies (GWAS) were performed on caffeine intake from coffee, tea or both in 407,072 UK Biobank participants. Identified variants were used in a two-sample Mendelian randomization (MR) approach to investigate evidence for causal links between caffeine intake and CAD in CARDIoGRAMplusC4D (60,801 cases; 123,504 controls) or T2D in DIAGRAM (26,676 cases; 132,532 controls). Observational associations were tested within UK Biobank using Cox regression analyses. Results Moderate observational caffeine intakes from coffee or tea were associated with lower risks of CAD or T2D compared to no or high intake, with the lowest risks at intakes of 120–180 mg/day from coffee for CAD (HR=0.77 [95% CI: 0.73–0.82; P<1e-16]), and 300–360 mg/day for T2D (HR=0.76 [95% CI: 0.67–0.86]; P=1.57e-5). GWAS identified 51 novel genetic loci associated with caffeine intake, enriched for central nervous system genes. In contrast to observational analyses, MR analyses in CARDIoGRAMplusC4D and DIAGRAM yielded no evidence for causal links between caffeine intake and the development of CAD or T2D. Conclusions MR analyses indicate caffeine intake might not protect against CAD or T2D, despite protective associations in observational analyses. Manhattan_plot_CaffeineIntake Funding Acknowledgement Type of funding source: None

scholarly journals Genetically Predicted Type 2 Diabetes Mellitus Liability, Glycated Hemoglobin and Cardiovascular Diseases: A Wide-Angled Mendelian Randomization Study

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1644
Author(s):  
Bowen Liu ◽  
Amy M. Mason ◽  
Luanluan Sun ◽  
Emanuele Di Angelantonio ◽  
Dipender Gill ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Diseases ◽  
General Population ◽  
Mendelian Randomization ◽  
Causal Effects ◽  
Disease Outcomes ◽  
Artery Disease ◽  
Diagnosed Diabetes

(1) Aim: To investigate the causal effects of T2DM liability and glycated haemoglobin (HbA1c) levels on various cardiovascular disease outcomes, both in the general population and in non-diabetic individuals specifically. (2) Methods: We selected 243 variants as genetic instruments for T2DM liability and 536 variants for HbA1c. Linear Mendelian randomization analyses were performed to estimate the associations of genetically-predicted T2DM liability and HbA1c with 12 cardiovascular disease outcomes in 367,703 unrelated UK Biobank participants of European ancestries. We performed secondary analyses in participants without diabetes (HbA1c < 6.5% with no diagnosed diabetes), and in participants without diabetes or pre-diabetes (HbA1c < 5.7% with no diagnosed diabetes). (3) Results: Genetically-predicted T2DM liability was positively associated (p < 0.004, 0.05/12) with peripheral vascular disease, aortic valve stenosis, coronary artery disease, heart failure, ischaemic stroke, and any stroke. Genetically-predicted HbA1c was positively associated with coronary artery disease and any stroke. Mendelian randomization estimates generally shifted towards the null when excluding diabetic and pre-diabetic participants from analyses. (4) Conclusions: This genetic evidence supports causal effects of T2DM liability and HbA1c on a range of cardiovascular diseases, suggesting that improving glycaemic control could reduce cardiovascular risk in a general population, with greatest benefit in individuals with diabetes.

scholarly journals Good long-term survival of Icelandic women following acute myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H.R Gardarsdottir ◽  
M.I Sigurdsson ◽  
K.K Andersen ◽  
I.J Gudmundsdottir
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Significant Risk ◽  
Female Gender ◽  
Funding Source ◽  
Term Survival ◽  
Artery Disease ◽  
Long Term Mortality

Abstract Background Mortality from coronary artery disease has decreased considerably in recent decades in Western societies, but less in women compared with men. Possible explanations for this difference include delayed medical attention, atypical presenting symptoms and also a higher incidence of myocardial infarction with non-obstructive coronary arteries in women. In addition, recent studies suggest that women with acute myocardial infarction (AMI) are less likely to receive treatment according to guidelines, which results in worse prognosis for women. Iceland is listed as one of the most gender-equal countries in the world and we hypothesised that this may reduce the gender gap in treatment and survival following AMI. Purpose The aim of this nationwide study was to compare clinical characteristics and treatment of men and women with AMI, identify independent risk factors for long-term mortality and estimate the impact of gender on relative survival. Methods This was a retrospective cohort study on all patients in Iceland with STEMI (2008–2018) and NSTEMI (2013–2018) who had obstructive coronary artery disease on coronary angiography. Information about patients and angiography results and treatment were obtained from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and electronic health records. Data for all-cause mortality was extracted through linkage with Statistics Iceland and survival was estimated with Kaplan-Meier method and Cox regression analysis used to identify significant risk factors for long-term mortality. Excess mortality from the AMI episode was estimated by comparing the survival with age- and gender-matched population in Iceland in 30-day intervals. Results A total of 1345 STEMI patients (24% women) and 1249 NSTEMI patients (24% women) were evaluated. Women with both STEMI (mean age: 71±11. vs. 67±12) and NSTEMI (mean age: 69±13 vs. 62±12) were older and less likely to have a cardiovascular history. There was no gender difference in the extent of coronary artery disease or treatment. Whilst long-term survival for women following STEMI (A) was lower, female gender was not found to be an independent risk factor for mortality after adjusting for age and comorbidities (HR 0.98, 95%-CI: 0.75–1.29). The survival after NSTEMI was similar between genders (B) and female gender was a protective prognostic factor (HR 0.67, 95% CI: 0.46–0.97). There was an excess 30-day mortality following STEMI (C) and NSTEMI (D) for both women and men compared to the matched Icelandic population, but thereafter the mortality rate was similar. Conclusion Our findings indicates that women and men in Iceland receive comparable treatment for AMI, including invasive treatment. Prognosis following NSTEMI is better in women. Higher early mortality after STEMI may be caused by delays in presentation and diagnosis as well as older age of women because female gender was not a significant risk factor for mortality. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): University hospital of Iceland, 4 weeks research leave

scholarly journals Caronary Artery Disease in Women

2014 ◽  
Vol 15 (2) ◽  
pp. 135-140
Author(s):  
NS Neki
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Acute Coronary Syndrome ◽  
Coronary Artery ◽  
Coronary Disease ◽  
Coronary Syndrome ◽  
Artery Disease ◽  
Prevalent Form

Coronary artery disease (CAD) - which includes coronary atherosclerotic disease, myocardial infarction (MI), acute coronary syndrome and angina - is the most prevalent form of cardiovascular disease and is the largest subset of this mortality. Coronary artery disease (CAD) is a leading cause of death of women and men  worldwide. CAD’s impact on women traditionally has been underappreciated due to higher rates at younger ages in men. Microvascular coronary disease disproportionately affects women. Women have unique risk factors for CAD, including those related to pregnancy and autoimmune disease.DOI: http://dx.doi.org/10.3329/jom.v15i2.20687 J MEDICINE 2014; 15 : 135-140

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.

Diabetes is not a risk factor for myocardial infarction in patients without coronary artery disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Gyldenkerne ◽  
K.K.W Olesen ◽  
P.G Thrane ◽  
M Madsen ◽  
T Thim ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Risk Factor ◽  
Coronary Artery ◽  
Coronary Angiography ◽  
Cardiac Death ◽  
Coronary Revascularization ◽  
Hazard Ratio ◽  
Funding Source ◽  
Artery Disease

Abstract Background Diabetes is considered a risk factor for myocardial infarction (MI). However, we have previously found that diabetes was not a short-term risk factor for MI in the absence of obstructive coronary artery disease (CAD). Purpose As long-term data are not available, we aimed to assess adverse cardiac events in patients with and without diabetes stratified by CAD up to 11 years after coronary angiography. Methods We conducted a cohort study of patients undergoing coronary angiography from 2003 to 2012 and followed them by cross-linking Danish health registries. Patients were stratified according to the presence/absence of CAD and diabetes. Outcomes included MI, cardiac death, all-cause death, and coronary revascularization. Results A total of 86,202 patients were included (diabetes: n=12,652). Median follow-up was 8.8 years. Using patients with neither CAD nor diabetes as reference (cumulative MI incidence 2.6%), the risk of MI was similar for patients with diabetes alone (3.2%; hazard ratio 1.202, 95% CI: 0.996–1.451), was increased for patients with CAD alone (9.3%; hazard ratio 2.75, 95% CI: 2.52–3.01), and was highest for patients with both CAD and diabetes (12.3%; hazard ratio 3.79, 95% CI: 3.43–4.20), see Figure. Similar associations were observed for cardiac death and coronary revascularization. Conclusions Diabetes patients without CAD by coronary angiography have a similar risk of MI compared to patients with neither CAD nor diabetes. In the presence of CAD, however, diabetes increases the risk of MI. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): The Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.

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