Higher serum urate levels are associated with an increased risk for sudden cardiac death

2021 ◽  
pp. jrheum.210139
Author(s):  
Lisandro D. Colantonio ◽  
Richard J. Reynolds ◽  
Tony R. Merriman ◽  
Angelo Gaffo ◽  
Jasvinder A. Singh ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Racial Differences ◽  
Cardiac Death ◽  
Cohort Analysis ◽  
Serum Urate ◽  
Hazard Ratio ◽  
Baseline Serum ◽  
Serum Urate Level ◽  
Increased Risk ◽  
History Of

Objective Determine the association of serum urate levels with sudden cardiac death and incident coronary heart disease (CHD), separately, among adults without a history of CHD. Methods We conducted a case-cohort analysis of Black and White participants ≥45 years of age enrolled in the REason for Geographic And Racial Differences in Stroke (REGARDS) study without a history of CHD at baseline between 2003 and 2007. Participants were followed for sudden cardiac death or incident CHD (i.e., myocardial infarction or death from CHD excluding sudden cardiac death) through December 31, 2013. Baseline serum urate was measured in a random sample of participants (n=840) and among participants who experienced sudden cardiac death (n=235) or incident CHD (n=851) during follow-up. Results Participants with higher serum urate levels were older and more likely to be male or Black. The crude hazard ratio (95%CI) per 1 mg/dL higher serum urate level was 1.26 (1.14-1.40) for sudden cardiac death and 1.17 (1.09-1.26) for incident CHD. After adjustment for age, gender, race, and cardiovascular risk factors, the hazard ratio (95%CI) per 1 mg/dL higher serum urate level was 1.19 (1.03-1.37) for sudden cardiac death and 1.05 (0.96-1.15) for incident CHD. Hazard ratios for sudden cardiac death were numerically higher among participants 45-64 versus ≥65 years of age, without versus with diabetes, and among those of White versus Black race, although p-values for effect modification were all ≥0.05. Conclusion Higher serum urate levels were associated with an increased risk for sudden cardiac death but not with incident CHD.

Abstract P110: High Serum Urate Levels are Associated With an Increased Risk for Sudden Cardiac Death in the Reasons for Geographic and Racial Differences in Stroke (regards) Study

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Lisandro D Colantonio ◽  
Richard Reynolds ◽  
Tony Merriman ◽  
Angelo Gaffo ◽  
Jasvinder A Singh ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Racial Differences ◽  
Cardiac Death ◽  
Statistical Power ◽  
Cohort Analysis ◽  
Large Population ◽  
Serum Urate ◽  
Increased Risk ◽  
History Of ◽  
Regards Study

Background: Higher serum urate (SU) levels were shown to causally increase the risk for sudden cardiac death (SCD) in a Mendelian randomization analysis of white adults, most of whom had coronary heart disease (CHD). It is unclear if these results are generalizable to more racially diverse adults without CHD. Objective: To assess the risk for SCD and incident CHD associated with SU levels in adults without a history of CHD using data from a large, population-based cohort of US black and white men and women ≥45 years of age, the REason for Geographic And Racial Differences in Stroke (REGARDS) study. Methods: We conducted a case-cohort analysis of REGARDS study participants without a history of CHD at baseline between 2003 and 2007. Participants were followed for SCD or incident CHD (i.e., myocardial infarction or CHD death excluding SCD) from baseline through December 31, 2013. Baseline SU levels were measured in a random sample of participants (n=840) and among 235 participants with SCD and 851 participants with incident CHD. Results: Participants with higher SU levels were older and more likely to be black and male. The crude hazard ratio (95%CI) per 1 mg/dL higher SU level was 1.26 (1.14, 1.40) for SCD and 1.17 (1.09, 1.26) for incident CHD. Analyses modeling SU levels using splines supported that these associations were linear. After multivariable adjustment, higher SU levels remained associated with an increased risk for SCD, but not for incident CHD ( Table ). There was no effect modification in the association of SU levels with SCD or incident CHD by either age, gender, race or chronic kidney disease. However, the increased risk for SCD associated with higher SU levels was present in whites but not among blacks. Limitations: The study has limited statistical power for subgroup comparisons. Race differences in the association between SU levels and SCD require further investigation. Conclusions: In adults without a history of CHD, higher SU levels appear to be an independent risk factor for SCD, but no association was detected with incident CHD.

Abstract 572: Hyperglycemia and Poor Outcomes in Patients without Diabetes Mellitus in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS): A Propensity Matched Analysis

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Prakash C Deedwania ◽  
Bertram Pitt ◽  
Enrique V Carbajal ◽  
Ali Ahmed
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Propensity Scores ◽  
Cox Regression ◽  
Baseline Serum ◽  
Increased Risk

Background: The effect of hyperglycemia on outcomes in patients with acute MI (AMI) and low LVEF without diabetes mellitus is not well known. Methods: In the EPHESUS trial, of the 4411 non-DM patients, 554 had baseline hyperglycemia (≥140 mg/dL). Propensity scores for hyperglycemia were calculated for each of the 4411 patients based on 63 baseline covariates, and a greedy 1:8 matching protocol was used to match 400 and 2542 patients respectively with and without hyperglycemia. Matched Cox regression models were used to estimate associations between hyperglycemia and outcomes during 16 months of follow up. Results: Patients with hyperglycemia were more likely to be older, have higher heart rate, lower LVEF, and receive nitrates, statins, digoxin, loop diuretics, and PTCA during index admission. Unadjusted hazard ratios {HR} and 95% confidence intervals {CI} for hyperglycemia were: all-cause death (1.51; 1.22–1.87; P<0.001), cardiovascular (CV) death (1.52; 1.21–1.90; P<0.001), heart failure (HF) death (2.19, 1.46–3.29; P<0.001), all-cause hospitalization (1.23; 1.08–1.40; P=0.002), CV hospitalization (1.51, 1.24–1.84; P<0.001) and HF hospitalization (1.75; 1.37–2.25; P<0.001). In the matched cohort, hyperglycemia was significantly associated with CV death (HR=1.25, 95%CI=1.01–1.54; P=0.039), sudden cardiac death (HR=1.33; 95%CI=1.02–1.73, P=0.035) and fatal/nonfatal AMI (HR=1.53, 95%CI=1.07–2.19; P=0.04; Figure ). Conclusions: In non-diabetic post-AMI HF patients, hyperglycemia is a poor prognosticator and is associated with increased risk of fatal and non-fatal AMI, CV death, HF deaths, sudden cardiac death, and CV hospitalization. Figure Fatal or non fatal acute myocardial infarction (AMI) by baseline serum glucose in post-AMI patients with no known history of diabetes mellitus

Sudden Cardiac Death in Athletes: What Sport-Rehabilitation Specialists Need to Know

2003 ◽  
Vol 12 (3) ◽  
pp. 259-271 ◽  
Author(s):  
Christian C. Evans ◽  
Sandra L. Cassady
Keyword(s):  
Sudden Cardiac Death ◽  
Los Angeles ◽  
Health Care Professionals ◽  
Cardiac Death ◽  
Signs And Symptoms ◽  
Data Sources ◽  
Los Angeles Times ◽  
Increased Risk ◽  
History Of ◽  
Artery Disease

Objective:To describe the underlying conditions that predispose athletes to sudden cardiac death (SCD) and review signs and symptoms that indicate an athlete is at risk.Data Sources:MEDLINE, theLos Angeles TimesandTriathlon Timesarchives, and other sources identified in the references of articles initially located therein. A total of 43 references were included.Conclusions:Most cases of SCD in younger athletes (≤35 years) are attributable to multiple hereditary conditions, with familial hyper-trophic cardiomyopathy being the primary cause, whereas the major cause of SCD in older athletes (>35 years) is coronary artery disease. Health-care professionals evaluating athletes should pay particular attention to past medical and family history. Items in an athlete’s screening that suggest increased risk include a history of chest pain, syncope, excessive shortness of breath, irregular heart rate or murmur, or a history of SCD in an immediate family member.

scholarly journals MYBPC3Δ25bp intronic deletion in hypertrophic cardiomyopathy patients and healthy Iranian population

2021 ◽  
Vol 43 (1) ◽  
pp. 22-28
Author(s):  
Leila Emrahi ◽  
Shirin Shahbazi ◽  
Mehrnoush Toufan Tabrizi ◽  
Mohammad Mahdi Mortazavipour ◽  
Mir Ali Seyyedi
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Positive Family History ◽  
Healthy Population ◽  
Increased Risk ◽  
Study Results ◽  
Pcr Products ◽  
History Of ◽  
Sporadic Cases

Background: Hypertrophic cardiomyopathy is a common genetic cardiovascular disease with autosomal dominant inheritance and MYBPC3 gene has been frequently linked to its pathogenesis. Since, carriers of the 25 nucleotides deletion located on intron 32 of the MYBPC3 are at increased risk of heart disease we aimed to investigate this variant in hypertrophic cardiomyopathy patients and healthy population. Methods: DNA was extracted from 350 Blood samples including 42 hypertrophic cardiomyopathies and 308 healthy subjects and the region containing the deletion was amplified by PCR method. PCR products were analyzed on agarose gel and genotyping results were recorded. Results: Genetic counseling results revealed that 26.2% of patients were sporadic cases vs 59.5% with positive family history and there was a history of sudden cardiac death in the first degree relatives of 42.3% of the patients. Genotyping results showed that all samples had a single band of 198 bp, indicating no MYBPC3Δ25bp variant in HCM patients as well as 308 controls. Bioinformatics assessments revealed that MYBPC3Δ25bp had a frequency of 0.00438 on Iranome database with the highest incidence reported in the Baloch population. Conclusion: Since hypertrophic cardiomyopathy is related to sudden cardiac death, population studies in terms of predisposing factors are of particular importance. Our study results showed that MYBPC3Δ25bpshould not be considered as risk factor in the patients of northwest of Iran. However, according to the bioinformatics findings and reports of neighboring countries, it is suggested that MYBPC3Δ25bp to be studied in the eastern and southern Iranian hypertrophic cardiomyopathy patients.

scholarly journals Does the Age of Sudden Cardiac Death in Family Members Matter in Brugada Syndrome?

2021 ◽  
Author(s):  
Pattara Rattanawong ◽  
Jakrin Kewcharoen ◽  
Chanavuth Kanitsoraphan ◽  
Timothy Barry ◽  
Anusha Shanbhag ◽  
...  
Keyword(s):  
Family History ◽  
Sudden Cardiac Death ◽  
Brugada Syndrome ◽  
Cardiac Death ◽  
Meta Analysis ◽  
Positive Family History ◽  
Family Members ◽  
Increased Risk ◽  
History Of ◽  
Risk Predictor

Background Brugada syndrome is an inherited cardiac channelopathy associated with major arrhythmic events (MAEs). The presence of a positive family history of sudden cardiac death (SCD) as a risk predictor of MAE remains controversial. We aimed to examine the association between family history of SCD and MAEs stratified by age of SCD with a systematic review and meta‐analysis. Methods and Results We searched the databases of MEDLINE and EMBASE from January 1992 to January 2020. Data from each study were combined using the random‐effects model. Fitted metaregression was performed to evaluate the association between the age of SCD in families and the risk of MAE. Twenty‐two studies from 2004 to 2019 were included in this meta‐analysis involving 3386 patients with Brugada syndrome. The overall family history of SCD was not associated with increased risk of MAE in Brugada syndrome (pooled odds ratio [OR], 1.11; 95% CI, 0.82–1.51; P =0.489, I 2 =45.0%). However, a history of SCD in family members of age younger than 40 years of age did increase the risk of MAE by ≈2‐fold (pooled OR, 2.03; 95% CI, 1.11–3.73; P =0.022, I 2 =0.0%). When stratified by the age of cut point at 50, 45, 40, and 35 years old, a history of SCD in younger family member was significantly associated with a higher risk of MAE (pooled OR, 0.49, 1.30, 1.51, and 2.97, respectively; P =0.046). Conclusions A history of SCD among family members of age younger than 40 years was associated with a higher risk of MAE.

scholarly journals Diagnosis of Brugada Syndrome, a Rare Inherited Arrhythmogenic Disorder

2020 ◽  
Vol 3 (2) ◽  
pp. 70-73
Author(s):  
Juwairiya Syed Iqbaluddin ◽  
Fathima Murthuza ◽  
Sumaiya Iqbal
Keyword(s):  
Family History ◽  
Sudden Cardiac Death ◽  
Brugada Syndrome ◽  
Cardiac Death ◽  
Genetic Disorder ◽  
Positive Family History ◽  
Provocation Test ◽  
Increased Risk ◽  
History Of ◽  
Electrocardiogram Ecg

Brugada syndrome (BrS) is a rare, autosomal dominant genetic disorder with mutation in the SCN5A gene. It is associated with an increased risk of arrhythmias and sudden cardiac death. BrS can be diagnosed by characteristic electrocardiogram (ECG) findings and significant events, such as syncope, palpitations, nocturnal respiratory agonia, and family history of sudden cardiac death below the age of 45 years. Special investigations, such as electrophysiology study, ajmaline provocation test, and genetic testing, play an important role in its diagnosis. This case report describes a patient who presented with chest pain and dizziness along with a positive family history of sudden cardiac deaths below the age of 45 years. He was discovered to have type 2 Brugada pattern on ECG, and by ajmaline provocation test, the type 1 pattern was unmasked, which established a definitive diagnosis of BrS. The patient was then advised for an implantable cardioverter-defibrillator. This case highlights the need for physicians to be competent in identifying patients with BrS in order to provide the necessary management and prevent fatal outcomes.

Abstract 12925: Combination of Cardiac I-123 Metaiodobenzylguanidine Imaging Findings and Early Repolarization Pattern Improve the Predictive Power of Sudden Cardiac Death in Patients With Chronic Heart Failure

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Atsushi Kikuchi ◽  
Takahisa Yamada ◽  
Takashi Morita ◽  
Yoshio Furukawa ◽  
Shunsuke Tamaki ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Chronic Heart Failure ◽  
Cardiac Death ◽  
Hazard Ratio ◽  
Mibg Imaging ◽  
Imaging Findings ◽  
Prognostic Information ◽  
Early Repolarization ◽  
Increased Risk

Background: Identification of patients with chronic heart failure (CHF) at risk for sudden cardiac death (SCD) is an important objective. Cardiac I-123 metaiodobenzylguanidine (MIBG) imaging findings provide prognostic information in patients with CHF. On the other hand, early repolarization pattern (ERP) is associated with life-threatening arrhythmia events. Moreover, it has been shown that ERP would be associated with an increased risk of SCD in CHF patients. However, there is no information available on the long-term prognostic value of combining cardiac MIBG imaging findings and ERP for the prediction of SCD in CHF patients. Methods: We studied 92 CHF outpatients (NYHA class: 2.1±0.6) with LVEF < 40% [30±7%) in our prospective cohort study. We performed MIBG scintigraphy, and measured the heart-to-mediastinum ratio on the delayed image (HMRd), of which the abnormal value was defined as < 1.7. Furthermore, we obtained the standard 12-lead electrocardiogram at enrollment. ERP was defined as J-point elevation ≤ 0.1 mV in at least 2 inferior or lateral leads. Results: At enrollment, 41 patients had abnormal HMRd and 19 patients had ERP. During a follow-up period of 7.7±4.3 yrs, 22 patients died suddenly. A multivariate Cox analysis revealed that HMRd (p=0.001) and ERP (p=0.017) were significantly and independently associated with SCD. Kaplan-Meier analysis showed that SCD was significantly more frequently observed in patients with both abnormal HMRd and ERP and those with either abnormal HMRd or ERP than those with neither abnormal HMRd nor ERP (55% vs 33% vs 7%, respectively, p<0.0001). The hazard ratio for SCD prediction in patients with both abnormal HMRd and ERP was 14.7 (95%CI 3.6 to 60.1), which was twofold of the hazard ratio in patients with either abnormal HMRd or ERP (HR 6.5 [95%CI 1.8 to 7.8]) Conclusion: The combination of cardiac MIBG imaging and ERP would provide the incremental prognostic information for the prediction of SCD in CHF patients.

scholarly journals Genotype-Phenotype Correlation of SCN5A Genotype in Patients With Brugada Syndrome and Arrhythmic Events: Insights From the SABRUS in 392 Probands

2021 ◽  
Author(s):  
Anat Milman ◽  
Elijah R. Behr ◽  
Belinda Gray ◽  
David C. Johnson ◽  
Antoine Andorin ◽  
...  
Keyword(s):  
Family History ◽  
Sudden Cardiac Death ◽  
Brugada Syndrome ◽  
Odds Ratio ◽  
Cardiac Death ◽  
Variants Of Unknown Significance ◽  
Increased Risk ◽  
Cardiac Sodium Channel ◽  
Arrhythmic Event ◽  
History Of

Background: Brugada syndrome (BrS) is associated with mutations in the cardiac sodium channel gene, SCN5A. However, genetic studies of patients with BrS with arrhythmic events have been limited. We sought to compare various clinical, ECG, and electrophysiological parameters according to SCN5A genotype in a large cohort of BrS probands with first arrhythmic event. Methods: Survey on Arrhythmic Events in Brugada Syndrome is a survey of 10 Western and 4 Asian countries, gathering 678 patients with BrS with first arrhythmic event. Only probands were included, and SCN5A genotype adjudicated. Patients without appropriate genetic data were excluded. Associations of genotype with clinical features were analyzed. Results: The study group comprised 392 probands: 92 (23.5%) SCN5A+ (44 pathogenic/likely pathogenic [P/LP] and 48 variants of unknown significance) and 300 (76.5%) SCN5A−. SCN5A missense variants and the patients hosting them were similar regardless of adjudication. A higher proportion of patients with P/LP were pediatric (<16 years) compared with SCN5A− (11.4% versus 3%, P =0.023). The proportion of females was higher among patients with P/LP compared with SCN5A − (18.2% versus 6.3%, P =0.013). P/LP probands were more likely to have a family history of sudden cardiac death compared with SCN5A − (41.9% versus 16.8%, P <0.001). A higher proportion of patients with P/LP were White compared with SCN5A− (87.5% versus 47%, P <0.001). Ethnicity (odds ratio, 5.41 [2.8–11.19], P <0.001) and family history of sudden cardiac death (odds ratio, 2.73 [1.28–5.82], P =0.009) were independent variables associated with P/LP genotype following logistic regression. Conclusions: The genetic basis of BrS has a complex relationship with gender, ethnicity, and age. Probands hosting a P/LP variant tended to experience their first arrhythmic event at a younger age and to have events triggered by fever compared with patients with SCN5A− . In addition, they were more likely to be White and to have family history of sudden cardiac death. Among females, a P/LP variant suggests an increased risk of being symptomatic. This association should be further studied on an ethnically specific basis in large prospectively collected international cohorts.

scholarly journals Arrhythmia Burden in Patients with Indolent Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Mujtaba Soniwala ◽  
Saadia Sherazi ◽  
Susan Schleede ◽  
Scott McNitt ◽  
Tina Faugh ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Arrhythmias ◽  
Cardiac Death ◽  
Research Funding ◽  
Cumulative Probability ◽  
Prior History ◽  
Indolent Lymphoma ◽  
Genetics Research ◽  
Increased Risk ◽  
History Of

Introduction Indolent Non-Hodgkin lymphomas (NHL) comprise a heterogeneous group of diseases including marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), and follicular lymphoma (FL). These compose a heterogenous group of disorders that frequently measures survival in years due to the long natural history of these diseases. Frequency and morbidity of cardiac arrhythmias in patients with indolent lymphoma is unknown, but recent observations note that arrhythmias are an increasing problem. Due to advances in treatment for indolent NHL with emergence of novel therapeutics, combined with an aging population and a long natural history, understanding of arrhythmia burden in indolent lymphoma is an area of research with important implications for patients undergoing active treatment as well as for long term lymphoma survivors. Methods Adult patients 18 years or older with indolent NHL treated at the University of Rochester Wilmot Cancer Institute between 2013-2019 were included in the Cardio-Oncology Lymphoid Malignancies Database and analyzed. The primary objective of this study was to define the rate of arrhythmic events and sudden cardiac death in patients with indolent lymphoma during treatment. Cardiac arrhythmias including ventricular arrhythmias (VT/VF), atrial arrhythmias (atrial fibrillation (afib), flutter, SVT and atrial tachycardia), and bradyarrhythmias were identified using ICD-10 codes. Kaplan-Meier survival analysis was used to assess cumulative probability of arrhythmia. Results There were nine hundred and eighteen patients who were diagnosed with indolent lymphoma. Diagnoses included: CLL, N=414; FL, N=284; MZL, N=144; LPL, N=76. Median age was 64, and 43% were female. There were 383 (42%) patients who received treatment. Treatments were classified as chemotherapy, targeted therapy, monoclonal antibodies/immunotherapy, and combination therapy. There were no significant differences in baseline characteristics between treated and never treated patients. At the time of diagnosis, 277 patients (30%) had hypertension, 101 (11%) had prior history of arrhythmia. During median follow up of 24 months, 168 patients (18%) developed a new or recurrent arrhythmia based on ICD-10 codes documented in the electronic medical record. Sixty-three out of one hundred sixty-eight patients had both prior history of and recurrence of arrhythmia, while one hundred five had a new diagnosis of arrhythmia. Afib was the most common arrhythmia, noted in 81 patients (9%). At 6 months from diagnosis, cumulative probability of developing any arrhythmia was 8% (Figure 1). Of all arrhythmias, 89/168 (53%) occurred in SLL/CLL, 35/168 (21%) in FL, 17/168 (10%) in LPL, 27/168 (16%) in MZL. Arrhythmias on treatment occurred in 4/95 patients receiving chemotherapy alone (4.2%), 12/95 patients receiving monoclonal antibodies/immunotherapy (12.6%), and 28/95 patients receiving targeted therapy (29.4%). Most arrhythmias (51/95; 53.6%) occurred in patients receiving combination therapy (chemoimmunotherapy or targeted/immunotherapy). Overall, there were 80 (9%) deaths. Ten deaths were related to cardiovascular diseases; of which 8/10 (80%) were from sudden cardiac death. Conclusions This real-world cohort demonstrates that patients with indolent lymphoma could have an increased risk of cardiac arrhythmias that is increased by treatment. Afib was the most common arrhythmia identified in this study and appears increased compared to the incidence in the general age matched population (1-1.8 per 100 person-years). Surprisingly, of 80 deaths, 8 (10%) were attributed to sudden cardiac death. This data set contributes important information that can help identify patients at increased risk of cardiovascular morbidity and mortality that can impact treatment. Prospective monitoring in these patients may better define the incidence and associated risks of arrhythmias. Future directions will focus on risk factors for arrhythmias and developing an approach to prevent and treat arrhythmias in this patient population. Updated results will be presented at the meeting. Disclosures Zent: Acerta / Astra Zeneca: Research Funding; TG Therapeutics, Inc: Research Funding; Mentrik Biotech: Research Funding. Barr:Janssen: Consultancy; Abbvie/Pharmacyclics: Consultancy, Research Funding; Verastem: Consultancy; Celgene: Consultancy; Seattle Genetics: Consultancy; TG therapeutics: Consultancy, Research Funding; Morphosys: Consultancy; Gilead: Consultancy; AstraZeneca: Consultancy, Research Funding; Merck: Consultancy; Genentech: Consultancy. Reagan:Kite, a Gilead Company: Consultancy; Seattle Genetics: Research Funding; Curis: Consultancy. Friedberg:Seattle Genetics: Research Funding; Roche: Other: Travel expenses; Bayer: Consultancy; Astellas: Consultancy; Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Kite Pharmaceuticals: Research Funding; Portola Pharmaceuticals: Consultancy.

Association between digoxin use and sudden cardiac death in individuals with the rs10494366 variant of the NOS1AP gene

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Soroush ◽  
A Aarnoudse ◽  
F Shokri ◽  
M Van Den Berg ◽  
F Ahmadizar ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Smoking Status ◽  
Adaptor Protein ◽  
Therapeutic Window ◽  
P Value ◽  
Qtc Interval ◽  
Total Study Population ◽  
Increased Risk

Abstract Background Digoxin is one of the oldest cardiovascular medications still used to treat heart failure and atrial fibrillation. Due to its narrow therapeutic window, it is associated with life threatening intoxication and arrhythmias, and with QTc-shortening. Common genetic variation in the nitric oxide synthase-1 adaptor protein (NOS1AP) has been associated with QTc interval prolongation. Purpose We investigated whether the rs10494366 variant of the NOS1AP gene modified the risk of SCD in patients using digoxin. Methods In a prospective population-based cohort study, we included data of the three cohorts, started as of January 1st, 1991 until January 1st 2014. Digoxin current use on the date of cardiac death in cases and the same day of follow-up in the remainder of the cohort was a time-dependent exposure. The main outcome was SCD defined as sudden and unexpected death as a result of cardiac causes, according to international criteria. Identification and adjudication of SCD was performed independently, before the start of this study. We used Cox proportional hazard regression analysis to investigate the associations between NOS1AP rs10494366 variant and incident SCD among digoxin users compared to non-users. Associations were adjusted for age, sex (model 1) in addition to BMI, prevalent diabetes, myocardial infarction, baseline hypertension and smoking status (past, current, never) (model 2). Results We included 14,594 individuals, with a mean age of 65.3 (SD 10.3) years. Almost 59% were female. The cumulative incidence of SCD was 9.5% (609 cases) by the end of follow up. Among them, 98 (16%) individuals were exposed to digoxin at the time of death. In model 1, NOS1AP rs10494366 variant was not associated with SCD in the total study population. However, an interaction term of the gene with the daily dose of digoxin was significantly associated with increased risk of SCD (p-value 0.0001). In model 2, the risk of SCD in current users of digoxin was 4.2 [95% CI 1.3–13.8] for the GG genotype; 2.1 [95% CI 1.1–4.2] for the GT genotype, and 1.5 [95% CI 0.7–3.2] for the TT genotype. Conclusion NOS1AP rs10494366 variant modified the risk of sudden cardiac death in users of digoxin. Our study suggests that individuals with the homozygous minor GG allele have a fourfold increased risk of sudden cardiac death. Funding Acknowledgement Type of funding source: None

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