The association of arterial stiffness index with cerebrovascular and cardiometabolic disease: A Mendelian randomization study

Background: Arterial stiffness index (ASI) is a potential risk factor for cerebrovascular and cardiometabolic diseases, but the causal links between them are inconclusive. The aim is to evaluate the causal effects of ASI on cerebrovascular and cardiometabolic diseases by Mendelian randomization (MR). Methods: Two-sample MR analysis was performed to infer causal links. Genetic variants significantly associated with ASI were extracted. The inverse variance weighted method was used for estimating the effects. Sensitivity analysis was performed to test heterogeneity or pleiotropy. Results: MR analysis indicated an effect of genetically predicted ASI on the risk of ischemic stroke (IS) of all causes (OR = 1.894, 95% CI 1.210–2.965, p = 0.005). No links were identified between genetically predicted ASI and other cerebrovascular or cardiometabolic diseases (all p > 0.05). Subgroup analysis of IS etiologies found a suggestive association between genetically predicted ASI and large artery atherosclerosis stroke (LAS) (OR = 3.726, 95% CI 1.230–11.286, p = 0.020). There were no effects of ASI on IS due to cardioembolism or small vessel occlusion. Conclusion: The current MR analysis suggested that genetically predicted ASI was associated with higher risk of IS of all causes. The results and the underlying pathways or mechanisms between ASI and IS needs further investigation.

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Is ambulatory arterial stiffness index a marker of large-artery stiffness? Evidence from intervention studies

Hypertension Research ◽

10.1038/hr.2015.101 ◽

2015 ◽

Vol 38 (12) ◽

pp. 799-801 ◽

Cited By ~ 2

Author(s):

Giuseppe Schillaci ◽

Giacomo Pucci

Keyword(s):

Arterial Stiffness ◽

Intervention Studies ◽

Stiffness Index ◽

Large Artery ◽

Artery Stiffness ◽

Arterial Stiffness Index

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A Mendelian randomization analysis of the relationship between cardioembolic risk factors and ischemic stroke

Scientific Reports ◽

10.1038/s41598-021-93979-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Danyang Tian ◽

Linjing Zhang ◽

Zhenhuang Zhuang ◽

Tao Huang ◽

Dongsheng Fan

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Mendelian Randomization ◽

P Wave ◽

Cardioembolic Stroke ◽

Large Artery ◽

Weighted Analysis ◽

Inverse Variance ◽

Weighted Median ◽

Genetically Determined

AbstractObservational studies have shown that several risk factors are associated with cardioembolic stroke. However, whether such associations reflect causality remains unknown. We aimed to determine whether established and provisional cardioembolic risk factors are causally associated with cardioembolic stroke. Genetic instruments for atrial fibrillation (AF), myocardial infarction (MI), electrocardiogram (ECG) indices and N-terminal pro-brain natriuretic peptide (NT-pro BNP) were obtained from large genetic consortiums. Summarized data of ischemic stroke and its subtypes were extracted from the MEGASTROKE consortium. Causal estimates were calculated by applying inverse-variance weighted analysis, weighted median analysis, simple median analysis and Mendelian randomization (MR)-Egger regression. Genetically predicted AF was significantly associated with higher odds of ischemic stroke (odds ratio (OR): 1.20, 95% confidence intervals (CI): 1.16–1.24, P = 6.53 × 10–30) and cardioembolic stroke (OR: 1.95, 95% CI: 1.85–2.06, P = 8.81 × 10–125). Suggestive associations were found between genetically determined resting heart rate and higher odds of ischemic stroke (OR: 1.01, 95% CI: 1.00–1.02, P = 0.005), large-artery atherosclerotic stroke (OR: 1.02, 95% CI: 1.00–1.04, P = 0.026) and cardioembolic stroke (OR: 1.02, 95% CI: 1.00–1.04, P = 0.028). There was no causal association of P‐wave terminal force in the precordial lead V1 (PTFVI), P-wave duration (PWD), NT-pro BNP or PR interval with ischemic stroke or any subtype.

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