LOS ANGELES – Pregnancy loss is strongly associated with increased risks of three different clinical forms of atherosclerotic disease over the subsequent 15 years, a study of more than 1 million Danish pregnant women has shown.
"This is the largest-ever study on the occurrence of atherosclerotic disease after pregnancy loss. This study, taken together with previous studies, implies a possible common underlying pathology linking pregnancy losses and atherosclerosis," said Dr. Mattis F. Ranthe of the Statens Serum Institute, Copenhagen.
Dr. Mattis F. Ranthe
The study used Denmark’s comprehensive national cradle-to-the-grave health care registry to track all 1,031,279 Danes who were free of a history of cardiovascular disease at the time they became pregnant during 1977-1988. A total of 8,191 women had one or more stillbirths. There were 151,808 women with one miscarriage, 28,398 with two miscarriages, 5,979 with three, and 2,406 women with four or more miscarriages.
The three expressions of atherosclerosis under study were acute MI, cerebral infarction, and renovascular hypertension. During more than 15 million person-years of follow-up through the registry, there were 2,798 cases of MI, 4,053 cerebral infarcts, and 1,269 diagnoses of renovascular hypertension, Dr. Ranthe reported at the annual scientific sessions of the American Heart Association.
A history of even a single stillbirth was associated with a 2.69-fold increased incidence rate ratio for subsequent MI, a 1.74-fold increase in cerebral infarction, and a 2.42-fold increase in renovascular hypertension after adjustment for age, number of live births, and calendar year.
A robust dose-response relationship was evident between the number of miscarriages and atherosclerotic disease risk. Women with a history of a single miscarriage had an adjusted 1.11-fold increased risk of MI, a 1.13-fold increase in cerebral infarction, and a 1.15-fold greater risk of developing renovascular hypertension during follow-up than did women with no miscarriages. These 11%-15% increases in relative risk were all strongly significant, given the large numbers.
With two miscarriages, the risks of MI, cerebral infarct, and renovascular hypertension were increased 1.18-fold, 1.22-fold, and 1.12-fold, respectively. With a history of three miscarriages, the risks were 0.85, 1.43, and 1.78. And with 4 or more miscarriages, the incidence rate ratio for MI was increased 2.08-fold, that for cerebral infarct was 1.89-fold, and for renovascular hypertension it was 3.78-fold greater than in women with no miscarriages.
Further adjustment for diabetes, smoking, thrombophilia, and polycystic ovarian syndrome left these estimates unchanged.
The risk of each of the three forms of atherosclerosis climbed by 10%-20% with each additional miscarriage. However, the risk wasn’t evenly spread across all age groups. Rather, the risk of developing atherosclerotic disease within the next 15 years was greatest in the youngest women who miscarried. The risk associated with miscarriage late in the period of childbearing potential was far less, the physician noted.
That observation raised a red flag for one audience member.
"If you have younger women of childbearing years having myocardial infarctions earlier on, one tends to think that mechanistically it may be atherosclerosis, but it may actually be due to other issues involving connective tissue diseases. I’d be cautious in using atherosclerosis as a broad pathophysiologic explanation," she said.
Dr. Ranthe agreed.
He reported having no financial conflicts related to this study, which was funded by the Danish Heart Foundation.