scholarly journals Gene polymorphisms associated with lipid metabolism disorders in young adults with risk of ­sudden cardiac death

2021 ◽  
Vol 102 (6) ◽  
pp. 805-814
Author(s):  
V A Kachnov ◽  
E V Kryukov ◽  
S N Kolyubaeva ◽  
G G Kutelev ◽  
V V Tyrenko
Keyword(s):  
At Risk ◽  
Lipid Metabolism ◽  
Sudden Cardiac Death ◽  
Young People ◽  
Mathematical Models ◽  
Cardiac Death ◽  
Gene Polymorphisms ◽  
Pon1 Gene ◽  
Lipid Metabolism Disorders ◽  
Increased Risk

Aim. To study the frequency of polymorphisms in genes associated with lipid metabolism disorders in young people with risk of sudden cardiac death, to identify the relationships between gene polymorphisms and risk factors of sudden cardiac death, and to develop mathematical models to identify the probability of carrying mutations in these genes. Methods. The study included 436 young people (mean age 19.81.6 years). A standard examination and survey by questionnaire specially developed by us were conducted to identify an increased risk of sudden cardiac death. 59 individuals with a risk of sudden cardiac death were selected. The control group was 65 people, which was comparable to the study group. A blood test was performed to determine lipid profile and polymorphisms: Leu28Pro (rs 429358) in gene APOE, C3238G (rs 5128) in gene APOC3, Gln192Arg (rs 662) in gene PON1, Ser447Ter (rs 328) in gene LPL, G250A (rs 1800588) in gene LIPC. Statistical analysis was performed using the statistical package SPSS 17.0 and Statistica 6.0. The parametric KruskalWallis test, the MannWhitney U-test, the Pearsons chi-squared test, the Spearman rank correlation coefficient, and logistic regression analysis were used. Results. We revealed a high frequency of Gln192Arg (rs 662) polymorphism in the PON1 gene in the group of individuals at risk of sudden cardiac death and its correlation with the deaths in relatives under age 50 years. Mathematical models for predicting the presence of polymorphisms in genes associated with lipid metabolism disorders have been developed. Among the developed mathematical models, the models for identifying carriers of the minor allele of Gln192Arg polymorphism in the PON1 gene, Ser447Ter in the LPL gene, and 250 GA in the LIPC gene had the highest sensitivity, specificity, and accuracy. Conclusion. In persons at risk for sudden cardiac death, it is advisable to conduct a screening for mutations in genes associated with lipid metabolism disorders, especially in Gln192Arg polymorphism in gene PON1.

Association of arterial hypertension gene polymorphisms with the risk of sudden cardiac death in young people

2020 ◽  
Vol 22 (3) ◽  
pp. 18-22
Author(s):  
V. A. Kachnov ◽  
V. V. Tyrenko ◽  
S. N. Kolubaeva ◽  
D. V. Cherkashin ◽  
G. G. Kutelev ◽  
...  
Keyword(s):  
At Risk ◽  
Sudden Cardiac Death ◽  
Young People ◽  
Arterial Hypertension ◽  
Mathematical Models ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Risk Variants ◽  
Close Relatives ◽  
The Relationship

Abstract. The frequency of occurrence of arterial hypertension genes in individuals at risk of sudden cardiac death was studied. The relationship between risk factors for sudden cardiac death and the presence of polymorphisms of arterial hypertension genes was revealed. There was a high incidence of homozygous risk variants AGTR2 AA and CYP11B2 TT-polymorphisms responsible for the development of left ventricular hypertrophy, including in young individuals. A correlation was found between deaths in close relatives under 50 years of age and the presence of polymorphisms in the CYP11B2 344 CT gene in young people at risk of sudden cardiac death. We have obtained data indicating the feasibility of conducting a study of the polymorphism of the CYP11B2 gene in the presence of a risk of sudden cardiac death. A direct correlation was found between the presence of fatal outcomes in relatives under 50 years of age by the mechanism of sudden cardiac death and the number of homozygous variants of arterial hypertension genes. Mathematical models for predicting the presence of polymorphisms in genes responsible for the possibility of arterial hypertension are constructed. Among the constructed mathematical models, the most informative were models for detecting carriers of mutations in the genes ADD1 1378 GT, CYP11B2 344 CT and NOS3 894 GT. The expediency of the analysis to search for mutations of arterial hypertension genes, especially in the CYP11B2 344 CT gene, for the possibility of earlier and more intensive preventive measures in young people is shown. The data obtained indicate that there are relationships between the risk of sudden cardiac death, some known predictors of its occurrence, and the genes for arterial hypertension.

Abstract 15714: Prediction of Sudden Cardiac Death With Automated High-Throughput Analysis of T-Wave Heterogeneity in Standard 12-Lead Electrocardiogram

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tuomas Kenttä ◽  
Bruce D Nearing ◽  
Kimmo Porthan ◽  
Jani T Tikkanen ◽  
Matti Viitasalo ◽  
...  
Keyword(s):  
At Risk ◽  
Relative Risk ◽  
Sudden Cardiac Death ◽  
General Population ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Adjusted Relative Risk ◽  
T Wave ◽  
Increased Risk ◽  
Patients At Risk

Introduction: Noninvasive identification of patients at risk for sudden cardiac death (SCD) remains a major clinical challenge. Abnormal ventricular repolarization is associated with increased risk of lethal ventricular arrhythmias and SCD. Hypothesis: We investigated the hypothesis that spatial repolarization heterogeneity can identify patients at risk for SCD in general population. Methods: Spatial R-, J- and T-wave heterogeneities (RWH, JWH and TWH, respectively) were automatically analyzed with second central moment technique from standard digital 12-lead ECGs in 5618 adults (46% men; age 50.9±12.5 yrs.) who took part in Health 2000 Study, an epidemiological survey representative of the entire Finnish adult population. During average follow-up of 7.7±1.4 years, a total of 72 SCDs occurred. Thresholds of RWH, JWH and TWH were based on optimal cutoff points from ROC curves. Results: Increased RWH, JWH and TWH (Fig.1) in left precordial leads (V4-V6) were univariately associated with SCD (P<0.001, each). When adjusted with clinical risk markers (age, gender, BMI, systolic blood pressure, cholesterol, heart rate, left ventricular hypertrophy, QRS duration, arterial hypertension, diabetes, coronary heart disease and previous myocardial infarction) JWH and TWH remained as independent predictors of SCD. Increased TWH (≥102μV) was associated with a 1.9-fold adjusted relative risk (95% confidence interval [CI]: 1.2 - 3.1; P=0.011) and increased JWH (≥123μV) with a 2.0-fold adjusted relative risk for SCD (95% CI: 1.2 - 3.3; P=0.004). When both TWH and JWH were above threshold, the adjusted relative risk for SCD was 3.2-fold (95% CI: 1.7 - 6.2; P<0.001). When all heterogeneity measures (RWH, JWH and TWH) were above threshold, the risk for SCD was 3.7-fold (95% CI: 1.6 - 8.6; P=0.003). Conclusions: Automated measurement of spatial J- and T-wave heterogeneity enables analysis of high patient volumes and is able to stratify SCD risk in general population.

scholarly journals Left Posterior Fascicular Block and Increased Risk of Sudden Cardiac Death in Young People

2021 ◽  
Vol 77 (8) ◽  
pp. 1143-1145
Author(s):  
Leonardo Calò ◽  
Roberta Della Bona ◽  
Annamaria Martino ◽  
Cinzia Crescenzi ◽  
Germana Panattoni ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Young People ◽  
Cardiac Death ◽  
Increased Risk ◽  
Left Posterior

scholarly journals Comparison of variant detection rate in genes between two cohorts of Czech living patients versus victims of sudden cardiac death with clinical / post mortem diagnosis of non-ischemic cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Borisincova ◽  
P Votypka ◽  
K Rucklova ◽  
A Pilin ◽  
M Kulvajtova ◽  
...  
Keyword(s):  
At Risk ◽  
Czech Republic ◽  
Primary Prevention ◽  
Sudden Cardiac Death ◽  
Genetic Counselling ◽  
Cardiac Death ◽  
Detection Rate ◽  
Funding Source ◽  
Post Mortem ◽  
Custom Made

Abstract Introduction Hereditary cardiomyopathy is associated with an increased risk of ventricular arrhythmia and sudden cardiac death (SCD). Genetic stratification substantiates risk assessment and enables the primary prevention of SCD in relatives at risk. We have analyzed the genetic aetiology of SCD in a representative Czech cohort with post mortem diagnosis of various forms of cardiomyopathy and compared it to living cases with these cardiac disorders. Patients and methods Between 2018 and 2019, altogether 47 victims of SCD with post mortem diagnosis of hypertrophic- (HCM; 18/47), arrhythmogenic- (ACM; 19/47) and dilated cardiomyopathy (DCM; 10/47) were identified. Concurrently, genetic testing was performed in 114 living patients (HCM 54/114, ACM 22/114, DCM 38/114). Genetic counselling and cardiologic examination had been carried out in first-degree relatives in all patients/SCD victims. Massively parallel sequencing (MiSeq platform; Illumina.com) was utilized for a custom-made panel comprising 100 candidate genes (Sophia Genetics, Switzerland). The presence of pathogenic variants was validated by Sanger DNA sequencing and through family segregation analyses. Results The causative detection rate (according to ACMG.net classes 4 or 5) in SCD victims with DCM was 60% (6/10) and in living patients with DCM 47.4% (18/38). Variants in TTN, RBM20, DES and FLNC (mainly truncating variants) prevailed in both groups. The detection rate in ACM was 5% (1/19 in SCN5A gene) in SCD victims and 31.8% (7/22) in living patients. Interestingly, the most prevalent mutated gene PKP2 in living patients was not detected in SCD victims. The detection rate in SCD victims with post mortem diagnosis of HCM was 16% (3/18) and in living patients 35% (19/54). The most prevalent gene was MYBPC3 in both groups, while PRKAG2 was detected in one SCD victim and in one living case who survived cardiac arrest. Conclusion Post-mortem genetic analysis in DCM yields a high detection rate and allows potentially effective primary prevention of SCD in relatives at risk. In contrast, the molecular autopsy of HCM and ACM renders a much lower yield which is below the mutation detection rate in living phenotype positive individuals. The results help to improve the genetic counselling in affected families in Czech Republic. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of the Czech Republic

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

N-terminal pro-brain natriuretic peptide and sudden cardiac death in hypertrophic cardiomyopathy

Heart ◽  
2020 ◽  
pp. heartjnl-2020-317701
Author(s):  
Guixin Wu ◽  
Jie Liu ◽  
Shuiyun Wang ◽  
Shiqin Yu ◽  
Ce Zhang ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Sudden Cardiac Death ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Cardiac Death ◽  
Cardiac Fibrosis ◽  
Discrimination Performance ◽  
Net Reclassification Improvement ◽  
C Statistic ◽  
Increased Risk

ObjectiveElevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with heart failure-related death in hypertrophic cardiomyopathy (HCM), but the relationship between NT-proBNP level and sudden cardiac death (SCD) in HCM remains undefined.MethodsThe study prospectively enrolled 977 unrelated patients with HCM with available NT-proBNP results who were prospectively enrolled and followed for 3.0±2.1 years. The Harrell’s C-statistic under the receiver operating characteristic curve was calculated to evaluate discrimination performance. A combination model was constructed by adding NT-proBNP tertiles to the HCM Risk-SCD model. The correlation between log NT-proBNP level and cardiac fibrosis as measured by late gadolinium enhancement (LGE) or Masson’s staining was analysed.ResultsDuring follow-up, 29 patients had SCD. Increased log NT-proBNP levels were associated with an increased risk of SCD events (adjusted HR 22.27, 95% CI 10.93 to 65.63, p<0.001). The C-statistic of NT-proBNP in predicting SCD events was 0.80 (p<0.001). The combined model significantly improved the predictive efficiency of the HCM Risk-SCD model from 0.72 to 0.81 (p<0.05), with a relative integrated discrimination improvement of 0.002 (p<0.001) and net reclassification improvement of 0.67 (p<0.001). Furthermore, log NT-proBNP levels were significantly correlated with cardiac fibrosis as detected either by LGE (r=0.257, p<0.001) or by Masson’s trichrome staining in the myocardium (r=0.198, p<0.05).ConclusionNT-proBNP is an independent predictor of SCD in patients with HCM and may help with risk stratification of this disease.

scholarly journals Vital exhaustion and sudden cardiac death in the Atherosclerosis Risk in Communities Study

Heart ◽  
2017 ◽  
Vol 104 (5) ◽  
pp. 423-429 ◽  
Author(s):  
Brittany M Bogle ◽  
Nona Sotoodehnia ◽  
Anna M Kucharska-Newton ◽  
Wayne D Rosamond
Keyword(s):  
Risk Factors ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Disease Risk ◽  
Ventricular Tachyarrhythmia ◽  
Atherosclerosis Risk In Communities ◽  
Vital Exhaustion ◽  
Increased Risk ◽  
Atherosclerosis Risk ◽  
Aric Study

ObjectiveVital exhaustion (VE), a construct defined as lack of energy, increased fatigue and irritability, and feelings of demoralisation, has been associated with cardiovascular events. We sought to examine the relation between VE and sudden cardiac death (SCD) in the Atherosclerosis Risk in Communities (ARIC) Study.MethodsThe ARIC Study is a predominately biracial cohort of men and women, aged 45–64 at baseline, initiated in 1987 through random sampling in four US communities. VE was measured using the Maastricht questionnaire between 1990 and 1992 among 13 923 individuals. Cox proportional hazards models were used to examine the hazard of out-of-hospital SCD across tertiles of VE scores.ResultsThrough 2012, 457 SCD cases, defined as a sudden pulseless condition presumed due to a ventricular tachyarrhythmia in a previously stable individual, were identified in ARIC by physician record review. Adjusting for age, sex and race/centre, participants in the highest VE tertile had an increased risk of SCD (HR 1.48, 95% CI 1.17 to 1.87), but these findings did not remain significant after adjustment for established cardiovascular disease risk factors (HR 0.94, 95% CI 0.73 to 1.20).ConclusionsAmong participants of the ARIC study, VE was not associated with an increased risk for SCD after adjustment for cardiovascular risk factors.

Sign in / Sign up

Export Citation Format

Share Document