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A study from Denmark leveraging more than 40 million years of follow-up data from patients dating back to the 1950s offers insight into the apparent increase in the risk of myocardial infarction associated with pregnancy loss in women and whether this same effect is observed in male partners.
An analysis of data from more than 1.1 million women and their male partners is providing new insight into differences in risk of myocardial infarction and all-cause mortality following pregnancy loss.
A register-based cohort study including all people born in Denmark between 1957 and 1997, results indicate experiencing pregnancy loss was associated with an increased risk of myocardial infarction, but not all-cause mortality, among women, with investigators noting no apparent increase in risk for either outcome among male partners.1
“This nationwide cohort study found that pregnancy loss or stillbirth was significantly associated with incident myocardial infarction and stroke, but not all-cause mortality, in women,” wrote investigators.1
Despite this renewed emphasis, recent reports indicate women were receiving suboptimal cardiovascular care, with a July 2023 study out of Northwestern University Feinberg School of Medicine suggesting just 60% of at-risk women reported receiving counseling on cardiovascular health at their postpartum visit.2 Led by Anders Pretzmann Mikkelsen, MD, PhD, of the Department of Gynaecology at Copenhagen University Hospital-Rigshospitalet, along with colleagues from this institution and others in Denmark, the current study was launched with the intent of better understanding associations of increased cardiovascular risk among women and their male partners following pregnancy loss.1
With this in mind, investigators designed their study as register-based cohort study of all people born between 1957 and 1997, residing in Denmark between 1977 and 2017, and with a registered partner of the opposite sex. Using national registry data, investigators identified 1,112,563 women eligible for inclusion. Of these, 1,112,507 were considered eligible for analysis of myocardial infarction. Investigators identified 1,120,532 male partners eligible for inclusion. Of these, 1,120,029 were included.1
Investigators defined pregnancy loss as a registered spontaneous abortion, missed abortion, or blighted ovum in the National Patient Register. For the purpose of analysis, pregnancy loss was categorized as 0, 1, 2, or 3 or more pregnancy losses. The primary outcomes of interest for the analysis were myocardial infarction, stroke, and all-cause mortality. Investigators assessed risk for each using Cox proportional hazards model adjusted for age calendar year, parity, and parental history of myocardial infarction or stroke.1
Upon analysis, results suggested women with 1 (Hazard ratio [HR], 1.1; 95% Confidence interval [CI], 1.0–1.2), 2 (HR, 1.3; 95% CI, 1.1–1.5), and 3 or more pregnancy losses (HR, 1.4; 95% CI, 1.1–1.8) relative to their counterparts with no pregnancy losses. Among the male partners, results suggested estimates of risk were 1.0 (95% CI, 1.0–1.1), 1.1 (95% CI, 1.0–1.2), and 1.0 (95% CI, 0.8–1.2), for those with 1, 2, or 3 or more pregnancy losses, respectively. When examining risk of stroke, investigators found the adjusted HR was significantly elevated after 1 or 3 pregnancy losses and borderline significant after 2 pregnancy losses, compared with no pregnancy losses for the female cohort. Among male partners, the risk of stroke was not significantly elevated after a partner experienced pregnancy loss.1
During the follow-up period, 1,644 women and 29,051 male partners died. However, in adjusted analysis, there was no increase in risk observed for all-cause mortality following pregnancy loss or stillbirth in either cohort. Investigators noted having at least 1 live birth was associated with a large protective effect against all-cause mortality in both cohorts.1
Before concluding, investigators noted multiple limitations within their study to consider before over interpretation of results as well as the need for further study into causes or mechanisms for this apparent increase in risk.1
“Likely, the cause is multifactorial and complex, and further studies should aim to assess the additional benefit of using pregnancy history in addition to traditional risk factors for cardiovascular disease when predicting future cardiovascular morbidity and mortality,” investigators wrote.1