scholarly journals Separating the direct effects of risk factors for atherosclerotic cardiovascular disease from those mediated by type 2 diabetes

2021 ◽  
Author(s):  
Venexia Walker ◽  
Marijana Vujkovic ◽  
Alice R Carter ◽  
Neil M Davies ◽  
Miriam Udler ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Atherosclerotic Cardiovascular Disease ◽  
Peripheral Artery ◽  
Artery Disease

Background: Type 2 diabetes and atherosclerotic cardiovascular disease share several risk factors. However, it is unclear whether the effect of these risk factors on liability to atherosclerotic cardiovascular disease is independent of their effect on liability to type 2 diabetes. Methods: We performed univariate Mendelian randomization to quantify the effects of continuous risk factors from the IEU OpenGWAS database on liability to three outcomes: type 2 diabetes, coronary artery disease, and peripheral artery disease, as well as the effects of liability to type 2 diabetes on the risk factors. We also performed two-step Mendelian randomization for mediation to estimate the mediating pathways between the risk factors, liability to type 2 diabetes, and liability to the atherosclerotic cardiovascular disease outcomes where possible. Results: We found evidence for 53 risk factors as causes of liability to coronary artery disease, including eight which were causes of liability to type 2 diabetes only and four which were consequences only. Except for fasting insulin and hip circumference, the direct and total effects from the two-step Mendelian randomization were similar. This suggests that the combination of these risk factors with liability to type 2 diabetes was unlikely to alter liability to coronary artery disease beyond their individual effects. We also found 13 risk factors that were causes of liability peripheral artery disease, including six which were causes of liability to type 2 diabetes only and four which were consequences only. Again, the direct and total effects were similar for these ten risk factors apart from fasting insulin. Conclusions: Most risk factors were likely to affect liability to atherosclerotic cardiovascular disease independently of their relationship with liability to type 2 diabetes. Control of modifiable risk factors therefore remains important for reducing atherosclerotic cardiovascular disease risk regardless of patient liability to type 2 diabetes.

scholarly journals Cardiometabolic Risk Factors for COVID-19 Susceptibility and Severity: A Mendelian Randomization Analysis

2020 ◽  
Author(s):  
Aaron Leong ◽  
Joanne Cole ◽  
Laura N. Brenner ◽  
James B. Meigs ◽  
Jose C. Florez ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Chronic Kidney Disease ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Cardiometabolic Diseases ◽  
Artery Disease ◽  
Population Controls

Importance: Early epidemiological studies report associations of diverse cardiometabolic conditions especially body mass index (BMI), with COVID-19 susceptibility and severity, but causality has not been established. Identifying causal risk factors is critical to inform preventive strategies aimed at modifying disease risk. Objective: We sought to evaluate the causal associations of cardiometabolic conditions with COVID-19 susceptibility and severity. Design: Two-sample Mendelian Randomization (MR) Study. Setting: Population-based cohorts that contributed to the genome-wide association study (GWAS) meta-analysis by the COVID-19 Host Genetics Initiative. Participants: Patients hospitalized with COVID-19 diagnosed by RNA PCR, serologic testing, or clinician diagnosis. Population controls defined as anyone who was not a case in the cohorts. Exposures: Selected genetic variants associated with 17 cardiometabolic diseases, including diabetes, coronary artery disease, stroke, chronic kidney disease, and BMI, at p<5 x 10-8 from published largescale GWAS. Main outcomes: We performed an inverse-variance weighted averages of variant-specific causal estimates for susceptibility, defined as people who tested positive for COVID-19 vs. population controls, and severity, defined as patients hospitalized with COVID-19 vs. population controls, and repeated the analysis for BMI using effect estimates from UKBB. To estimate direct and indirect causal effects of BMI through obesity-related cardiometabolic diseases, we performed pairwise multivariable MR. We used p<0.05/17 exposure/2 outcomes=0.0015 to declare statistical significance. Results: Genetically increased BMI was causally associated with testing positive for COVID-19 [6,696 cases / 1,073,072 controls; p=6.7 x 10-4, odds ratio and 95% confidence interval 1.08 (1.03, 1.13) per kg/m2] and a higher risk of COVID-19 hospitalization [3,199 cases/897,488 controls; p=8.7 x 10-4, 1.12 (1.04, 1.21) per kg/m2]. In the multivariable MR, the direct effect of BMI was abolished upon conditioning on the effect on type 2 diabetes but persisted when conditioning on the effects on coronary artery disease, stroke, chronic kidney disease, and c-reactive protein. No other cardiometabolic exposures tested were associated with a higher risk of poorer COVID-19 outcomes. Conclusions and Relevance: Genetic evidence supports BMI as a causal risk factor for COVID-19 susceptibility and severity. This relationship may be mediated via type 2 diabetes. Obesity may have amplified the disease burden of the COVID-19 pandemic either single-handedly or through its metabolic consequences.

Characterization of Glyoxal Modified LDL: Role in the Generation of Circulating Autoantibodies in Type 2 Diabetes Mellitus and Coronary Artery Disease

2021 ◽  
Vol 22 ◽  
Author(s):  
Md Masum Rizwee ◽  
Minhal Abidi ◽  
Safia Habib ◽  
Abdul Rouf Mir ◽  
Asif Ali ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Antigenic Determinants ◽  
Modified Ldl ◽  
Circulating Antibodies ◽  
Artery Disease

Aims: To investigate role of glyoxal modified LDL in immunopathology of diabetes and cardiovascular disease. Background: Glycoxidation of proteins is widely studied in relation to diabetes and cardiovascular disease. Objective: This study probed the glyoxal mediated modifications in LDL, analyzed the immunogenicity of the glycated LDL and ascertained the presence of circulating antibodies against modified LDL in patients with type 2 diabetes mellitus (T2DM), coronary artery disease (CAD) and patients with both (T2DM+CAD). Methods: Glyoxal mediated modifications in LDL were studied by multiple spectroscopic techniques, high performance liquid chromatography and electron microscopy. Immunization studies were carried in New Zealand rabbits. Presence of antibodies against glyoxal modified LDL in immunized rabbits and human subjects were analyzed by ELISA. Results: Glyoxal altered the structural integrity of LDL and lead to the formation of AGEs. It decreased the alpha helix content of LDL; increased β sheet formation; increased carbonyl content and decreased free lysine and arginine content. Modified LDL showed aggregation, generation of of Nε-(Carboxymethyl) lysine and the formation of amorphous type aggregates. It exhibited high antigenicity and generated specific immune response that shared common antigenic determinants with other glycated proteins. Direct binding data showed the presence of anti- glyoxal modified LDL antibodies in patients with T2DM, CAD and patients with both T2DM and CAD. Further analysis in competitive binding assay revealed specific binding characteristics of auto-antibodies. Sera from patients with T2DM+CAD exhibited highest binding with glyoxal modified LDL. Conclusion: Glyoxal modified LDL has neo-antigenic determinants that cause the generation of circulating antibodies in diabetes and coronary artery disease. The study might have potential relevance in biomarker development.

scholarly journals Type 2 diabetes and risk of major cardiovascular events in peripheral artery disease versus coronary artery disease patients

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
C H Saely ◽  
A Vonbank ◽  
B Larcher ◽  
A Mader ◽  
M Maechler ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Peripheral Artery Disease ◽  
Cardiovascular Events ◽  
Peripheral Artery ◽  
Major Cardiovascular Events ◽  
Multivariate Adjustment ◽  
Artery Disease

Abstract   The prevalence of type 2 diabetes (T2DM) is higher in peripheral artery disease (PAD) than in coronary artery disease (CAD) patients, and PAD overall confers higher cardiovascular risk than CAD. The purpose of this study was to investigate how the incidence of major cardiovascular events compares between PAD and CAD patients when analyses are stratified by the presence of type 2 diabetes (T2DM). We prospectively recorded major cardiovascular events and death over 10.0±4.7 years in 923 patients with stable CAD, of whom 26.7% had T2DM and in 292 patients with PAD, of whom 42.1% had T2DM. Four groups were analyzed: CAD patients without diabetes (CAD/T2DM-; n=677), CAD patients with T2DM (CAD/T2DM+; n=246), PAD patients without diabetes (PAD/T2DM-; n=169) and PAD patients with T2DM (PAD/T2DM+; n=123). When compared to the incidence of MACE in CAD+/T2DM- patients (25.1%), it was significantly higher in CAD+/T2DM+ patients (35.4%; p&lt;0.001), in PAD+/T2DM- patients (30.2%; p=0.022) and in PAD+/T2DM+ patients (47.2%; p&lt;0.001). Patients with both PAD and T2DM in turn were at a higher risk than CAD+/T2DM+ or PAD+/T2DM- patients (p=0.001 and p&lt;0.001, respectively). The incidence of MACE did not differ significantly between PAD+/T2DM- and CAD+/T2DM+ patients (p=0.413). Compared to patients with CAD, Cox regression analyses after multivariate adjustment showed an adjusted hazard ratio of 1.46 [1.14–1.87], p=0.002 for the presence of PAD. Conversely, T2DM increased the risk of MACE after multivariate adjustment in CAD and PAD patients (adjusted HR 1.58 [1.27–1.98], p&lt;0.001). In conclusion, our data show that T2DM and the presence of PAD are mutually independent predictors of MACE. Patients with both PAD and T2DM are at an exceedingly high risk of MACE. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals A study of prevalence of silent coronary artery disease in asymptomatic type II diabetes mellitus

2021 ◽  
Vol 9 (1) ◽  
pp. 1-4
Author(s):  
Moogaambiga S ◽  
Kirubhakaran K ◽  
Devi PL ◽  
Santhosh P
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Diabetic Patients ◽  
Treadmill Test ◽  
Silent Coronary Artery Disease ◽  
Artery Disease

Background: Cardiovascular disease is a major cause of morbidity and mortality in diabetics. However diabetic patients do not present with typical anginal symptoms or may be even asymptomatic and silent coronary artery disease (CAD) is prevalent in diabetics. Moreover silent CAD is not different from symptomatic CAD with respect to prognosis and adverse effects. Aim: The study was done to demonstrate the prevalence of silent myocardial ischemic changes in asymptomatic type 2 diabetes mellitus patients with normal resting ECG by doing a stress exercise test. Methodology: This descriptive study was done in 100 patients with type 2 diabetes more than 2 years who did not have any history of cardiovascular disease or symptoms. Detailed history was taken and investigations such as HbA1c, fasting and postprandial blood sugar, serum creatinine, urine examination were done. Resting ECG, Echocardiogram was found to be normal and they were subjected to a treadmill test. Results: Among the 100 participants 18 persons (18%) had positive ECG findings in treadmill test. A positive association was found between the duration of diabetes and prevalence of positive treadmill test. Conclusion: There is significant prevalence of silent CAD in diabetic patients and they tend to present with advanced disease at presentation and have poorer prognosis compared to non diabetic population. Hence it is necessary to screen early for silent CAD in diabetics to improve disease outcomes.

scholarly journals Silent coronary artery disease in type 2 diabetes: a narrative review on epidemiology, risk factors, and clinical studies

2021 ◽  
Author(s):  
Saula Vigili de Kreutzenberg
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Point Of View ◽  
Narrative Review ◽  
Silent Coronary Artery Disease ◽  
Artery Disease ◽  
Associated Risk Factors

Silent coronary artery disease (CAD) is one of the manifestations of heart disease that particularly affects subjects with type 2 diabetes mellitus (T2DM). From a clinical point of view, silent CAD represents a constant challenge for the diabetologist, who has to decide whether a patient could or could not be screened for this disease. In the present narrative review, several aspects of silent CAD are considered: the epidemiology of the disease, the associated risk factors, and main studies conducted, in the last 20 years, especially aimed to demonstrate the usefulness of the screening of silent CAD, to improve cardiovascular outcomes in type 2 diabetes.

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