ArticleFrontiers in cardiovascular medicine2022
Roles of Cardiometabolic Factors in Mediating the Causal Effect of Type 2 Diabetes on Cardiovascular Diseases: A Two-Step, Two-Sample Multivariable Mendelian Randomization Study.
Article in Frontiers in cardiovascular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 2 of them syntheses that pooled it.
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8 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.
- Mendelian randomization studies of lifestyle-related risk factors for stroke: a systematic review and meta-analysis.Frontiers in endocrinology · 2024Pooled it
- Appraising the Causal Role of Risk Factors in Coronary Artery Disease and Stroke: A Systematic Review of Mendelian Randomization Studies.Journal of the American Heart Association · 2023Pooled it
- Exploring Stroke Risk through Mendelian Randomization: A Comprehensive Study Integrating Genetics and Metabolic Traits in the Korean Population.Biomedicines · 2024Article
- Coffee and the risk of osteoarthritis: a two-sample, two-step multivariable Mendelian randomization study.Frontiers in genetics · 2024Article
- The causal relationship between COVID-19 and seventeen common digestive diseases: a two-sample, multivariable Mendelian randomization study.Human genomics · 2023Article
- Severe mental illness and the risk of breast cancer: A two-sample, two-step multivariable Mendelian randomization study.PloS one · 2023Article
- Sex differences in the non-linear association between BMI and LDL cholesterol in type 2 diabetes.Frontiers in endocrinology · 2023Article
- Assessment of the causal association between celiac disease and cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Article
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Authors and funding
8 authors at 5 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Objective: The objective of this study is to investigate the roles of cardiometabolic factors (including blood pressure, blood lipids, thyroid function, body mass, and insulin sensitivity) in mediating the causal effect of type 2 diabetes (T2DM) on cardiovascular disease (CVD) outcomes. Design: Two-step, two-sample multivariable Mendelian randomization (MVMR) study. Setting: International genome-wide association study (GWAS) consortia data. Exposure: Type 2 diabetes, blood pressure: systolic blood pressure (SBP), diastolic blood pressure (DBP); blood lipids: low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglycerides (TG); thyroid function: hyperthyroidism, hypothyroidism; body mass index (BMI), waist-hip-ratio (WHR), and insulin sensitivity. Main Outcomes: Cardiovascular disease includes coronary heart disease (CHD), myocardial infarction (MI), and stroke. Methods: Summary-level data for exposures and main outcomes were extracted from GWAS consortia. We used two-sample MR to illustrate the causal effect of T2DM on CVD subtypes and regression-based MVMR to quantify the possible mediation effects of cardiometabolic factors on CVD. Results: Each additional unit of log odds of T2DM increased 16% risk of CHD [odds ratio (OR): 1.16, 95% CI: 1.12-1.21], 15% risk of myocardial infarction (MI) (OR: 1.15, 95% CI: 1.10-1.20), and 10% risk of stroke (OR: 1.10, 95% CI: 1.06-1.13). In mediation analysis, SBP, DBP, and TG were found as main mediators, while the mediation effects of other cardiometabolic factors were not significant. The proportion of total effect of T2DM on CHD mediated by SBP, DBP, and TG was 16% (95% CI: 8-24%), 7% (95% CI: 1-13%) and 10% (95% CI: 2-18%), respectively. Mediation effect of SBP and DBP on MI and stroke, TG on MI was also prominent, while mediation effect of TG on stroke was not significant. The combined mediation effect of all the three mediators accounted for 29%, 26%, and 13% of the total effect of T2DM on CHD, MI, and stroke, respectively. Conclusion: Systolic blood pressure, DBP, and TG mediate a substantial proportion of the causal effect of T2DM on CVD and thus interventions on these factors might reduce the considerable excess risk of CVD among patients with T2DM.
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