Effects of reproductive period duration and number of pregnancies on midlife ECG indices: a secondary analysis from the Women’s Health Initiative Clinical Trial

Abstract

ObjectivesPregnancy, menses and menopause are related to fluctuations in endogenous sex hormones in women, which cumulatively may alter cardiac electrical conduction. Therefore, we sought to study the association between number of pregnancies and reproductive period duration (RD, time from menarche to menopause) with ECG intervals in the Women’s Health Initiative Clinical Trials.DesignSecondary analysis of multicentre clinical trial.SettingUSA.Primary outcome measuresECGintervals: PR interval, P-wave duration, P-wave dispersion, QTc interval.Participantsn=40 687 women (mean age=62 years) participating in the Women’s Health Initiative Clinical Trials. 82.5% were white, 9.3% black, 4% Hispanic and 2.7% Asian.MethodsIn primary analysis, we employed multivariable linear regression models relating number of pregnancies and RD with millisecond changes in intervals from enrolment ECG. We studied effect modification by hormone therapy use.ResultsAmong participants, 5+ live births versus 0 prior pregnancies was associated with a 1.32 ms increase in PR interval (95% CI 0.25 to 2.38), with a graded association with longer QTc interval (ms) (none (prior pregnancy, no live births)=0.66 (–0.56 to 1.88), 1=0.15 (–0.71 to 1.02), 2–4=0.25 (–0.43 to 0.94) and 5+ live births=1.15 (0.33 to 1.98), p=0.008). RD was associated with longer PR interval and maximum P-wave duration (but not P-wave dispersion) among never users of hormone therapy: (PR (ms) per additional RD year: 0.10 (0.04 to 0.16); higher P-wave duration (ms): 0.09 (0.06 to 0.12)). For every year increase in reproductive period, QTc decreased by 0.04 ms (−0.07 to –0.01).ConclusionsAn increasing number of live births is related to increased and RD to decreased ventricular repolarisation time. Both grand multiparity and longer RD are related to increased atrial conduction time. Reproductive factors that alter midlife cardiac electrical conduction system remodelling in women may modestly influence cardiovascular disease risk in later life.Trial registration numberNCT00000611; Post-results.

Association of Number of Live Births With Electrocardiographic and Cardiac Structural Changes

“…There has only been 1 other study to show an association between parity and electrocardiographic parameters. 27 The authors reported that grand multiparity (≥5 live births) was associated with a 1.32‐ms increase in PR interval, supporting the plausibility of our findings. Pregnancy has been associated with increase in P‐wave parameters (P‐wave duration and P‐wave dispersion) when compared with controls , 28 with exaggerated changes in pathologic states, such as preeclampsia.…”

“…A large‐scale study reported that prolonged reproductive duration (age from menarche to menopause) is associated with a prolonged PR interval, suggesting a hormonal effect on cardiac conduction. 27 …”

Infertility and Risk of Heart Failure in the Women’s Health Initiative

“…For ASCVD risk score analyses, we performed multiple imputation to impute missing total cholesterol and high-density lipoprotein values because of significant missingness. 18 Total cholesterol and high-density lipoprotein along with all CHD risk factors were used in an fully conditional specification regression model, and the final results were summarized from 20 iterations of the imputation process using PROC MIANALYZE. All crosssectional models were also adjusted for cohort to reduce selection bias from the HF subcohort.…”

Sex-related electrocardiographic differences in patients with different types of atrial fibrillation: Results from the SWISS-AF study

“…Parikh et al studied the effects of reproductive period duration and number of pregnancies on midlife ECG indices, reporting small but significant changes in Pwave characteristics. However, they also stated that many factors could contribute to this behavior, thus the role of sex hormones is not clear [17].…”