Key result
In women, electrophysiological substrate metrics like QRS duration were associated with a significantly greater risk of sudden cardiac death compared to men (RHR 1.24; 95% CI 1.07-1.44; P=0.004).
Why the study?
Sex is a recognized risk factor for sudden cardiac death with known differences in electrophysiological substrate, but whether sex modifies the association of this substrate with sudden cardiac death remained unknown.
Does sex modify the association of electrophysiological substrate with sudden cardiac death?
Cohort (n=14,725)
Yes
Does sex modify the association of electrophysiological substrate with sudden cardiac death?
Effect estimate: RHR 1.24 (95% CI 1.07-1.44)
p-value: p=0.004
Sex significantly modifies the association of electrophysiological substrate with sudden cardiac death, with women facing up to a 27% greater relative risk from global EP abnormalities than men.
EP substrate metrics may confer higher SCD risk in women; leaves open sex-specific thresholds pending prospective validation.
Background Sex 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. 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 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. Results Over 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. Conclusions Sex 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.
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Howell et al. (2019) conducted a cohort in Sudden cardiac death (n=14,725). Electrophysiological substrate (ECG metrics) vs. Men was evaluated on Adjudicated sudden cardiac death (SCD) (RHR 1.24, 95% CI 1.07-1.44, p=0.004). In women, electrophysiological substrate metrics like QRS duration were associated with a significantly greater risk of sudden cardiac death compared to men (RHR 1.24; 95% CI 1.07-1.44; P=0.004).
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