Association between pregnancy losses in women and risk of atherosclerotic disease in their relatives: a nationwide cohort study†.
OBJECTIVE
A common underlying mechanism with a genetic component could link pregnancy losses with vascular disease. We examined whether pregnancy losses (miscarriages and stillbirths) and atherosclerotic outcomes co-aggregated in families.


RESULTS
Using Danish registers, we identified women with pregnancies in 1977-2008, and their parents (>1 million) and brothers (>435 000). We followed parents for incident ischaemic heart disease (IHD), myocardial infarction (MI), and cerebrovascular infarction (CVI), and brothers for a broader combined atherosclerotic endpoint. Using Cox regression, we estimated hazard ratios (HRs) for each outcome by history of pregnancy loss in daughters/sisters. Overall, parents whose daughters had 1, 2, and ≥3 miscarriages had 1.01 [95% confidence interval (CI) 0.99-1.04], 1.07 (95% CI 1.02-1.11), and 1.10 (95% CI 1.02-1.19) times the rate of MI, respectively, as parents whose daughters had no miscarriages. For parents with ≥3 daughters, the HRs were 1.12 (95% CI 1.02-1.24), 1.29 (95% CI 1.13-1.48), and 1.33 (95% CI 1.12-1.57). Effect magnitudes did not differ for fathers and mothers. We observed similar patterns for IHD and CVI (parents) and the atherosclerotic endpoint (brothers). Parents whose daughters had stillbirths had 1.14 (95% CI 1.05-1.24) and 1.07 (95% CI 0.96-1.18) times the rates of MI and CVI, respectively, as parents whose daughters had no stillbirths.


CONCLUSIONS
Certain pregnancy losses and atherosclerotic diseases in both heart and brain may have a common aetiologic mechanism. Women in families with atherosclerotic disease may be predisposed to pregnancy loss; conversely, pregnancy losses in first-degree relatives may have implications for atherosclerotic disease risk.
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Mattis Flyvholm
MF
Ranthe
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Lars Jorge
LJ
Diaz
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Ida
I
Behrens
Unit for Inherited Cardiac Diseases, Heart Centre, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
Henning
H
Bundgaard
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Jacob
J
Simonsen
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Mads
M
Melbye
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark hoy@ssi.dk.
Heather Allison
HA
Boyd
D000022:Abortion, Spontaneous / Q000453:epidemiology / Q000235:genetics*; D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics*; D002544:Cerebral Infarction / Q000453:epidemiology / Q000235:genetics; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005190:Family; D005260:Female; D020073:Gravidity; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000235:genetics; D009679:Nuclear Family; D010375:Pedigree; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000453:epidemiology / Q000235:genetics; D035781:Siblings; D050497:Stillbirth / Q000453:epidemiology / Q000235:genetics*
Atherosclerosis; Epidemiology; Familial aggregation; Ischaemic disease; Pregnancy loss