Assessment of the causal association between celiac disease and cardiovascular diseases

Abstract

BackgroundEpidemiological studies have reported inconsistent results of the association between celiac disease (CD) and cardiovascular diseases. Moreover, the causality remains largely unknown. Therefore, we aimed to investigate whether CD is causally associated cardiovascular diseases, including ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke, coronary heart disease, myocardial infarction, angina, heart failure, atrial fibrillation, and venous thromboembolism using an mendelian randomization (MR) approach.MethodsSummary-level data for CD were derived from a large-sample genome-wide association study (GWAS) including 12,041 CD cases and 12,228 controls of European ancestry. The corresponding data for ischemic stroke (34,217 cases and 406,111 controls), large artery stroke (4,373 cases and 406,111 controls), cardioembolic stroke (7,193 cases and 406,111 controls), small vessel stroke (5,386 cases and 192,662 controls), coronary heart disease (22,233 cases and 64,762 controls), myocardial infarction (11,622 cases and 187,840 controls), angina (18,168 cases and 187,840 controls), heart failure (47,309 cases and 930,014 controls), atrial fibrillation (60,620 cases and 970,216 controls), and venous thromboembolism (9,176 cases and 209,616 controls) were obtained from the IEU GWAS database. We calculated the causal effect using the inverse variance weighted method. Sensitivity analyses and leave-one-out analyses were performed to ensure the consistency and robustness of causal estimates.ResultsThe MR inverse variance weighted estimates indicated no causal effect of genetically predicted CD on ischemic stroke (OR = 1.001, 95% CI: 0.984-1.018), large artery stroke (OR = 1.003, 95% CI: 0.961-1.048), cardioembolic stroke (OR = 1.009, 95% CI: 0.977-1.042), small vessel stroke (OR = 1.023, 95% CI: 0.981-1.066), coronary heart disease (OR = 0.995, 95% CI: 0.977-1.013), myocardial infarction (OR = 0.994, 95% CI: 0.959-1.030), angina (OR = 1.006, 95% CI: 0.981-1.032), heart failure (OR = 0.999, 95% CI: 0.982-1.016), atrial fibrillation (OR = 1.000, 95% CI: 0.990-1.011), and venous thromboembolism (OR = 1.001, 95% CI: 0.971-1.032). Sensitivity analyses using the MR-Egger, weighted median, and simple mode methods yielded similar results. No evidence of horizontal pleiotropy was identified (MR Pleiotropy Residual Sum and Outlier global test and MR-Egger intercept with P > 0.05).ConclusionOur findings do not support a causal contribution of CD itself to ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke, coronary heart disease, myocardial infarction, angina, heart failure, atrial fibrillation, and venous thromboembolism risk.

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“…. (18) The main limitation of the study is the small number of the patients and controls in the study. Additionally, although all the patients left ventricular systolic function were normal in the study, we did not evaluated the left ventricular diastolic function.…”

The association between celiac disease and digestive system cancers: A Mendelian randomization study.

“…Primarily, it focuses on a European population, and caution should be exercised in generalizing these ndings to other ethnic groups. Furthermore, as CD is a multifactorial autoimmune disorder, genetic factors account for only a fraction of its pathogenesis [32],and the role of dietary habits and living conditions in the causal relationship between CD and digestive system cancers warrants further investigation. Future studies are needed to explore the mechanisms by which malignancy develops in CD patients.…”

Celiac Disease and Cardiovascular Risk: A Retrospective Case-Control Study

“…While the mainstream scientific literature reports an increased CVD risk among celiac patients, on the contrary, studies supporting a null or reduced risk are not very numerous [ 16 , 23 , 24 , 27 , 46 , 52 , 53 ]. In an early prospective multicenter study recruiting 1072 Italian adult celiac patients, Corrao et al reported a nonsignificant reduced cardiovascular risk despite a two-fold increase in overall mortality [ 46 ].…”

“…More recently, an open cohort study detected a slightly lower cumulative incidence of cardiovascular deaths (35 vs. 51 per 10,000 person years) among 10,825 celiac patients from the UK [ 52 ]. Finally, a Mendelian randomization study aiming to investigate the causal effect of CD on CVD failed to provide evidence supporting a causal association of CD with a number of atherosclerosis-based disorders, including ischemic stroke and peripheral artery disease [ 27 ]. In support, the lack of association between CD and CVD was also described in the meta-analyses of Emilsson et al [ 23 ] and Heikkilä et al [ 24 ].…”

“…Following the first study by West et al in 2004 [ 16 ], which aimed to quantify the risk of malignancy and mortality in CD patients, a number of case-control studies [ 17 , 18 , 19 ] prospective studies [ 20 , 21 , 22 ] and meta-analyses [ 23 , 24 , 25 ] have been conducted to ascertain if CD patients are at risk of developing CVD. However, despite the steady growth of the literature on this topic, opinions regarding the occurrence of CVD in patients with childhood or adult-onset CD are still conflicting, and, currently, there is no consensus among gastroenterologists and cardiologists about the risk extent [ 26 , 27 , 28 ]. An additional difficulty lies in the fact that the cohorts of CD patients include both newly diagnosed cases and those on the gluten-free diet (GFD), whose duration may be variable from a few months to many years.…”