Genetically Predicted Cardiac Troponin I Concentrations and Risk of Stroke and Atrial Fibrillation

Abstract Background: Observational studies have shown that elevated circulating cardiac troponin I (cTnI) concentrations were associated with higher risk of stroke and atrial fibrillation, but the causality remains unclear. Therefore, we conducted a two-sample mendelian randomization study to evaluate the causal effects of cTnI concentrations on the risk of stroke subtypes and atrial fibrillation.Methods: The instrumental variables for circulating cTnI concentrations were selected from a genome-wide association study meta-analysis of 48,115 European individuals. Applying a 2-sample mendelian randomization approach, we examined the associations of circulating cTnI concentrations with stroke (40,585 cases and 406,111 controls), ischemic stroke (34,217 cases and 406,111 controls), ischemic stroke subtypes (cardioembolic, large artery, small vessel stroke), intracerebral hemorrhage (1,545 cases and 1,481 controls) and atrial fibrillation (60,620 cases and 970,216 controls). Results: Genetically predicted elevated circulating cTnI concentrations were associated with increased risk of cardioembolic stroke (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.20-2.68; P = 0.004). However, no significant association was observed for cTnI concentrations with large artery stroke, small vessel stroke, total stroke, ischemic stroke and intracerebral hemorrhage. Additionally, we also found that elevated cTnI concentrations were associated with higher risk of atrial fibrillation (OR, 1.30; 95% CI, 1.10-1.53; P = 0.003).Conclusions: This study provides evidence that genetically predicted circulating cTnI concentrations are causally associated with increased risk of cardioembolic stroke and atrial fibrillation.

Download Full-text

Relation of Cardiac Troponin I Levels With In-Hospital Mortality in Patients With Ischemic Stroke, Intracerebral Hemorrhage, and Subarachnoid Hemorrhage

The American Journal of Cardiology ◽

10.1016/j.amjcard.2008.04.036 ◽

2008 ◽

Vol 102 (5) ◽

pp. 632-634 ◽

Cited By ~ 62

Author(s):

Rasham Sandhu ◽

Wilbert S. Aronow ◽

Archana Rajdev ◽

Rishi Sukhija ◽

Harshad Amin ◽

...

Keyword(s):

Ischemic Stroke ◽

Subarachnoid Hemorrhage ◽

Intracerebral Hemorrhage ◽

Hospital Mortality ◽

Cardiac Troponin ◽

Troponin I ◽

Cardiac Troponin I

Download Full-text

High Cardiac Troponin I Is Associated With Transesophageal Echocardiographic Risk of Thromboembolism and Ischemic Stroke Events in Non-Valvular Atrial Fibrillation Patients

Circulation Journal ◽

10.1253/circj.cj-17-1238 ◽

2018 ◽

Vol 82 (6) ◽

pp. 1699-1704 ◽

Cited By ~ 1

Author(s):

Shuhei Tanaka ◽

Tadakazu Hirai ◽

Kyoko Inao ◽

Nobuyuki Fukuda ◽

Keiko Nakagawa ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Cardiac Troponin ◽

Troponin I ◽

Cardiac Troponin I

Download Full-text

Circulating Vitamin K1 Levels in Relation to Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study

Nutrients ◽

10.3390/nu10111575 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1575 ◽

Cited By ~ 3

Author(s):

Susanna Larsson ◽

Matthew Traylor ◽

Hugh Markus

Keyword(s):

Ischemic Stroke ◽

Mendelian Randomization ◽

Cardioembolic Stroke ◽

Small Vessel ◽

Large Artery ◽

Vitamin K1 ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Level Data ◽

Increased Risk

Vitamin K plays a crucial role in blood coagulation, and hypercoagulability has been linked to atherosclerosis-related vascular disease. We used the Mendelian randomization study design to examine whether circulating vitamin K1 (phylloquinone) levels are associated with ischemic stroke. Four single-nucleotide polymorphisms associated with vitamin K1 levels were used as instrumental variables. Summary-level data for large artery atherosclerotic stroke (n = 4373 cases), small vessel stroke (n = 5386 cases), cardioembolic stroke (n = 7193 cases), and any ischemic stroke (n = 34,217 cases and 404,630 non-cases) were available from the MEGASTROKE consortium. Genetically-predicted circulating vitamin K1 levels were associated with large artery atherosclerotic stroke but not with any other subtypes or ischemic stroke as a whole. The odds ratios per genetically predicted one nmol/L increase in natural log-transformed vitamin K1 levels were 1.31 (95% confidence interval (CI) 1.12–1.53; p = 7.0 × 10−4) for large artery atherosclerotic stroke, 0.98 (95% CI 0.85–1.12; p = 0.73) for small vessel stroke, 1.01 (95% CI 0.90–1.14; p = 0.84) for cardioembolic stroke, and 1.05 (95% CI 0.99–1.11; p = 0.11) for any ischemic stroke. These findings indicate that genetic predisposition to higher circulating vitamin K1 levels is associated with an increased risk of large artery atherosclerotic stroke.

Download Full-text

EXPRESS: Effect of genetic liability to visceral adiposity on stroke and its subtypes: a Mendelian randomization study

International Journal of Stroke ◽

10.1177/17474930211006285 ◽

2021 ◽

pp. 174749302110062

Author(s):

Bin Yan ◽

Jian Yang ◽

Li Qian ◽

Fengjie Gao ◽

Ling Bai ◽

...

Keyword(s):

Sensitivity Analysis ◽

Ischemic Stroke ◽

Genome Wide Association Study ◽

Mendelian Randomization ◽

Visceral Adiposity ◽

Large Artery ◽

Nucleotide Polymorphisms ◽

Genetic Liability ◽

A Genome ◽

Increased Risk

Background: Observational studies have found an association between visceral adiposity and stroke. Aims: The purpose of this study was to investigate the role and genetic effect of visceral adipose tissue (VAT) accumulation on stroke and its subtypes. Methods: In this two-sample Mendelian randomization (MR) study, genetic variants (221 single nucleotide polymorphisms; P<5Ã10-8) using as instrumental variables for MR analysis was obtained from a genome-wide association study (GWAS) of VAT. The outcome datasets for stroke and its subtypes were obtained from the MEGASTROKE consortium (up to 67,162 cases and 453,702 controls). MR standard analysis (inverse variance weighted method) was conducted to investigate the effect of genetic liability to visceral adiposity on stroke and its subtypes. Sensitivity analysis (MR-Egger, weighted median, MR-PRESSO) were also utilized to assess horizontal pleiotropy and remove outliers. Multi-variable MR analysis was employed to adjust potential confounders. Results: In the standard MR analysis, genetically determined visceral adiposity (per 1 SD) was significantly associated with a higher risk of stroke (odds ratio [OR] 1.30; 95% confidence interval [CI] 1.21-1.41, P=1.48Ã10-11), ischemic stroke (OR 1.30; 95% CI 1.20-1.41, P=4.01Ã10-10), and large artery stroke (OR 1.49; 95% CI 1.22-1.83, P=1.16Ã10-4). The significant association was also found in sensitivity analysis and multi-variable MR analysis. Conclusions: Genetic liability to visceral adiposity was significantly associated with an increased risk of stroke, ischemic stroke, and large artery stroke. The effect of genetic susceptibility to visceral adiposity on the stroke warrants further investigation.

Download Full-text

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.

Download Full-text

Atrial fibrillation-induced cardiac troponin I release

International Journal of Cardiology ◽

10.1016/j.ijcard.2013.03.087 ◽

2013 ◽

Vol 168 (3) ◽

pp. 2734-2737 ◽

Cited By ~ 42

Author(s):

Abdul Shokor Parwani ◽

Leif-Hendrik Boldt ◽

Martin Huemer ◽

Alexander Wutzler ◽

Daniela Blaschke ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cardiac Troponin ◽

Troponin I ◽

Cardiac Troponin I

Download Full-text

CLINICAL OUTCOMES OF ACUTE ISCHEMIC STROKE PATIENTS STRATIFIED BY CARDIAC TROPONIN-I: A RETROSPECTIVE ANALYSIS

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(17)33529-5 ◽

2017 ◽

Vol 69 (11) ◽

pp. 140

Author(s):

Dylan Stanger ◽

Siu Him Chan ◽

Samuel Yip ◽

Belinda Rodis ◽

Andrew Starovoytov ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Retrospective Analysis ◽

Clinical Outcomes ◽

Cardiac Troponin ◽

Troponin I ◽

Cardiac Troponin I ◽

Stroke Patients

Download Full-text

Prognostic Performance of a High-Sensitivity Cardiac Troponin I Assay in Patients with Non–ST-Elevation Acute Coronary Syndrome

Clinical Chemistry ◽

10.1373/clinchem.2013.206441 ◽

2014 ◽

Vol 60 (1) ◽

pp. 158-164 ◽

Cited By ~ 58

Author(s):

Erin A Bohula May ◽

Marc P Bonaca ◽

Petr Jarolim ◽

Elliott M Antman ◽

Eugene Braunwald ◽

...

Keyword(s):

Cardiac Troponin ◽

Troponin I ◽

High Sensitivity ◽

Cardiovascular Death ◽

Cardiac Troponin I ◽

Fourth Generation ◽

Prognostic Performance ◽

Coronary Syndrome ◽

Low Concentrations ◽

Increased Risk

Abstract BACKGROUND High-sensitivity assays for cardiac troponin enable more precise measurement of very low concentrations and improved diagnostic accuracy. However, the prognostic value of these measurements, particularly at low concentrations, is less well defined. METHODS We evaluated the prognostic performance of a new high-sensitivity cardiac troponin I (hs-cTnI) assay (Abbott ARCHITECT) compared with the commercial fourth generation cTnT assay in 4695 patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) from the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in NSTE-ACS) and SEPIA-ACS1-TIMI 42 (Otamixaban for the Treatment of Patients with NSTE-ACS) trials. The primary endpoint was cardiovascular death or new myocardial infarction (MI) at 30 days. Baseline cardiac troponin was categorized at the 99th percentile reference limit (26 ng/L for hs-cTnI; 10 ng/L for cTnT) and at sex-specific 99th percentiles for hs-cTnI. RESULTS All patients at baseline had detectable hs-cTnI compared with 94.5% with detectable cTnT. With adjustment for all other elements of the TIMI risk score, patients with hs-cTnI ≥99th percentile had a 3.7-fold higher adjusted risk of cardiovascular death or MI at 30 days relative to patients with hs-cTnI <99th percentile (9.7% vs 3.0%; odds ratio, 3.7; 95% CI, 2.3–5.7; P < 0.001). Similarly, when stratified by categories of hs-cTnI, very low concentrations demonstrated a graded association with cardiovascular death or MI (P-trend < 0.001). Use of sex-specific cutpoints did not improve prognostic performance. Patients with negative fourth generation cTnT (<10 ng/L) but hs-cTnI ≥26 ng/L were at increased risk of cardiovascular death/MI compared to those with hs-cTnI <26 ng/L (9.2% vs 2.9%, P = 0.002). CONCLUSIONS Application of this hs-cTnI assay identified a clinically relevant higher risk of recurrent events among patients with NSTE-ACS, even at very low troponin concentrations.

Download Full-text

Evaluation of Myocardial Damage After Electroconvulsive Therapy: Analyses of High-Sensitive Cardiac Troponin I and N-Terminal pro-B-type Natriuretic Peptide

Pharmacopsychiatry ◽

10.1055/a-0646-4278 ◽

2018 ◽

Vol 52 (02) ◽

pp. 92-93

Author(s):

Laura Kranaster ◽

Johanna Badstübner ◽

Suna Aksay ◽

Jan Bumb ◽

Rayan Suliman ◽

...

Keyword(s):

Natriuretic Peptide ◽

Electroconvulsive Therapy ◽

Cardiac Troponin ◽

Cardiovascular Events ◽

Troponin I ◽

Myocardial Damage ◽

Cardiac Troponin I ◽

Safe Procedure ◽

Increased Risk ◽

Before And After

AbstractElectroconvulsive therapy (ECT) is a remarkably safe procedure. However, there might exist a subgroup of patients with an increased risk for cardiovascular events. The cardiac-specific enzymes high-sensitive cardiac troponin I (hscTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured before and after ECT in 23 patients. No relevant increase of hscTnI after ECT was found. Mean NT-proBNP levels were higher after ECT and in three patients a new NT-proBNP elevation after ECT was identified. In conclusion, our small study did not find any evidence for myocardial damage due to ECT by measuring hsTnI, but an increase of NT-proBNP, whose clinical relevance could only be speculated, yet.

Download Full-text