scholarly journals Does Sex Modify an Association of Electrophysiological Substrate with Sudden Cardiac Death? The Atherosclerosis Risk in Communities (ARIC) Study

2019 ◽  
Author(s):  
Stacey J. Howell ◽  
David German ◽  
Aron Bender ◽  
Francis Phan ◽  
Srini V. Mukundan ◽  
...  

AbstractBackgroundSex is a well-recognized risk factor for sudden cardiac death (SCD). Sex differences in electrophysiological (EP) substrate of SCD are known. However, it remains unknown whether sex can modify an association of EP substrate with SCD.MethodsParticipants from the Atherosclerosis Risk in Communities study with analyzable ECGs (n=14,725; age, 54.2±5.8 yrs; 55% female, 74% white) were included. EP substrate was characterized by traditional 12-lead ECG (heart rate, QRS, QTc, Cornell voltage), spatial ventricular gradient (SVG) and sum absolute QRST integral (SAI QRST) metrics. Two competing outcomes were adjudicated SCD and nonSCD. Interaction of ECG metrics with sex was studied in Cox proportional hazards and Fine-Gray competing risk models. Relative hazard ratio (RHR) and relative sub-hazard ratio (RSHR) with a 95% confidence interval for SCD and nonSCD risk for women relative to men were calculated. Model 1 was adjusted for prevalent cardiovascular disease (CVD) and risk factors. Time-updated model 2 was additionally adjusted for incident non-fatal CVD.ResultsOver a median follow-up of 24.4 years, there were 530 SCDs (incidence 1.72 (1.58-1.88)/1000 person-years) and 2,178 nonSCDs (incidence 7.09; (6.80-7.39)/ 1000 person-years). Women experienced a greater than men risk of SCD associated with Cornell voltage (RHR 1.18(1.06-1.32); P=0.003), SAI QRST (RHR 1.16(1.04-1.30); P=0.007), area SVG magnitude (RHR 1.24(1.05-1.45); P=0.009), and peak SVG magnitude (RHR 1.22(1.04-1.44); P=0.018), independently from incident CVD. Greater risk of SCD for women than men associated with QRS duration (RHR 1.24(1.07-1.44); P=0.004) and QTc (RSHR 1.15(1.02-1.30); P=0.025) was explained by incident CVD. Furthermore, women had greater odds of SCD associated with heart rate (RSHR 1.19(1.01-1.40); P=0.036), independently of incident CVD.ConclusionsSex modifies an association of EP substrate with SCD. In women, global EP substrate is associated with up to 27% greater risk of SCD than in men. Development of sex-specific risk scores of SCD is necessary. Further studies of mechanisms behind sex differences in EP substrate of SCD are warranted.

2019 ◽  
Author(s):  
Kelly Jensen ◽  
Stacey J. Howell ◽  
Francis Phan ◽  
Maedeh Khayyat-Kholghi ◽  
Linda Wang ◽  
...  

AbstractRace is an established risk factor for sudden cardiac death (SCD). We sought to determine whether the association of electrophysiological (EP) substrate with SCD varies between black and white individuals. Participants from the Atherosclerosis Risk in Communities study with analyzable ECGs (n=14,408; age 54±6 y; 74% white) were included. EP substrate was characterized by traditional 12-lead ECG and vectorcardiographic metrics. Two competing outcomes were adjudicated SCD and non-sudden cardiac death (nonSCD). Interaction of ECG metrics with race was studied in Cox proportional hazards and Fine-Gray competing risk models, adjusted for prevalent cardiovascular disease (CVD), risk factors, and incident non-fatal CVD. At the baseline visit linear regression analysis, adjusted for age, sex, and study center, showed black individuals had larger Spatial Ventricular Gradient magnitude by 0.30 (95%CI 0.25-0.34) mV, SAI QRST by 18.4 (13.7-23.0) mV*ms, Cornell voltage by 0.30 (95%CI 0.25-0.35) mV than white individuals. Over a median follow-up of 24.4 years, SCD incidence was higher in black (2.86; 95%CI 2.50-3.28 per 1000 person-years) than white individuals (1.37; 95%CI 1.22-1.53 per 1000 person-years). Black individuals with hypertension had the highest rate of SCD: 4.26; 95%CI 3.66-4.96 per 1000 person-years. Race did not modify associations of EP substrate with SCD and nonSCD. EP substrate does not explain racial disparities in SCD rate.


Heart ◽  
2017 ◽  
Vol 104 (5) ◽  
pp. 423-429 ◽  
Author(s):  
Brittany M Bogle ◽  
Nona Sotoodehnia ◽  
Anna M Kucharska-Newton ◽  
Wayne D Rosamond

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.


Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Srini V Mukundan ◽  
Muammar M Kabir ◽  
Jason Thomas ◽  
Golriz Sedaghat ◽  
Jonathan W Waks ◽  
...  

Introduction: Autonomic imbalance, quantified by decreased heart rate variability (HRV), is associated with increased cardiovascular mortality. It is unknown if autonomic influences on sinus and atrioventricular (AV) nodes are equally important for the risk of sudden cardiac death (SCD). Hypothesis: Autonomic influences on sinus and AV node are equally strongly associated with increased SCD, non-sudden cardiac death (non-SCD), and non-cardiac death. Methods: Baseline visit 10-second ECGs (n=14,250) of the Atherosclerosis Risk in Communities (ARIC) cohort were analyzed. Normalized variance of P-onset to P-onset intervals (PPVN) and QRS-onset to QRS-onset intervals (QQVN) was calculated to assess autonomic influence on sinus and AV node respectively. Normalized variance of Rpeak - Rpeak intervals was determined as HRV measure. Values were log-transformed to normalize distribution. SCD served as primary outcome. Secondary outcomes were non-SCD and non-cardiac death. Three Cox regression models were constructed for dichotomized at 20 th percentile predictor variables. Results: Over median follow-up of 24.4 years, there were 497 SCDs (incidence 1.66 [95%CI 1.52-1.82], 742 non-SCDs (incidence 2.48 [95%CI 2.31-2.67], and 3,753 non-cardiac deaths (incidence 12.6 [95%CI 12.1-13.0]) per 1,000 person-years. In paired analysis, LogPPVN was significantly larger than LogQQVN (-7.28±1.06 vs. -7.72±1.24; P<0.0001). There was no difference between LogQQVN and Log RRVN (-7.72±1.24 vs -7.72±1.23; P=0.364). After full adjustment, LogRRVN and LogQQVN were significantly associated with non-SCD and SCD. Association with non-SCD was stronger. LogPPVN was independently associated with non-SCD but not SCD. No value was associated with non-cardiac death. Conclusion: Autonomic imbalance at the AV node, with likely summary effect at the bundle of His, is associated with SCD and non-SCD. Autonomic imbalance at the SA node is associated with non-SCD only. Autonomic input to SA and AV node should be further studied.


Author(s):  
Paul L. Hess ◽  
Hussein R. Al‐Khalidi ◽  
Daniel J. Friedman ◽  
Hillary Mulder ◽  
Anna Kucharska‐Newton ◽  
...  

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Howell ◽  
E Perez-Alday ◽  
D German ◽  
A Bender ◽  
N Rogovoy ◽  
...  

Abstract Background Sex-based differences in sudden cardiac death (SCD) exist and screening methods for SCD are inadequate. Purpose To develop sex-specific lifetime risk prediction models using electrocardiographic (ECG) global electrical heterogeneity (GEH) and clinical characteristics. Methods Participants from the Atherosclerosis Risk in Communities study with analyzable ECGs (n=14,725; age, 54.2±5.8 yrs; 55% female, 74% white) were followed up for 24.4 years (median). Traditional ECG and GEH variables were measured on 12-lead ECGs. A Cox regression model was used to develop a prediction model. In women, the final model included race, age, coronary heart disease (CHD), stroke, hypertension, diabetes, smoking, high-density lipoprotein, albumin, uric acid, education level, heart rate, QTc, sum absolute QRST integral, spatial peak QRS-T angle. In men, the final prediction model included age, race, CHD, stroke, hypertension, diabetes, total cholesterol, physical activity, smoking, serum phosphorus, albumin, chronic kidney disease, spatial area QRS-T angle, area spatial ventricular gradient (SVG) elevation and magnitude, and peak SVG magnitude. Results There were a total of 530 SCDs. Our prediction models showed robust prediction of SCD in both sexes [(Harrell's C-statistic women 0.863 (95% CI 0.845–0.882), men 0.786 (95% CI 0.786–0.803)]. In women when ECG and GEH variables were added to clinical variables, the net reclassification improved by 9% (P=0.001) (Table). In men there was no significant reclassification improvement. Net reclassification Lifetime SCD Risk: Clinical + ECG + GEH Variables Women Men <5% 5–15% >15% Total <5% 5–15% >15% Total SCD Cases <5% 82 14 0 96 103 16 0 119 5–15% 7 59 10 76 12 116 12 140 >15% 0 0 20 20 0 5 74 79 Lifetime SCD Risk: Total 89 73 30 192 115 137 86 338 Clinical Variables Only Non-Cases <5% 6,956 131 2 7,089 4,411 264 0 4,675 5–15% 180 509 42 731 210 1,059 48 1,317 >15% 0 28 84 112 0 56 214 270 Total 7,136 668 128 7,932 4,621 1,379 262 6,262 Conclusions We were the first to develop sex-specific lifetime SCD prediction models. The addition of ECG GEH to clinical variables improved SCD risk reclassification in women, but not in men. Prediction of SCD was more accurate in women as compared to men.


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