History of Stillbirth, Many Miscarriages Ups CVD Risk

November 07, 2012

LOS ANGELES — The largest study ever to look at atherosclerotic disease following pregnancy loss--either in the form of miscarriage or stillbirth--has found a strong association between these adverse pregnancy outcomes and three different end points: MI, cerebral infarction, and renovascular hypertension. Dr Mattis F Ranthe (Statens Serum Institute, Copenhagen, Denmark) reported the findings from a nationwide cohort study of one million women in Denmark at the American Heart Association 2012 Scientific Sessions yesterday.

The association was strongest in younger women and for stillbirths. For miscarriage, there was a dose-response relationship: the more pregnancy losses someone had suffered, the greater their risk, he told the meeting.

For those who had had four or more miscarriages or a previous stillbirth, there was an approximately twofold increase in the risk of the three different atherosclerotic end points, "supporting the concept that this is a common pathology," said Ranthe.

Danish Citizens All Tracked From Birth With Personal ID Number

Ranthe says previous studies have confirmed a link between preeclampsia during pregnancy and an increased risk of cardio- and cerebrovascular conditions. "But regarding pregnancy loss or miscarriage, the evidence is not so clear," he observed.

"If a common underlying pathology links adverse pregnancy events and atherosclerosis, we would expect to find an increased risk of the different atherosclerotic end points in women experiencing pregnancy losses, so that was the aim of our study."

He explained that, in Denmark, all citizens are assigned a 10-digit personal-identification number at birth, and this number is used in a variety of health registries, including those that track pregnancies. His team examined a cohort of women over the age of 12 in the study period ranging from 1997 to 2008. These women either had to have given birth to a live singleton or experienced a miscarriage or stillbirth.

"We followed these women for MI, cerebral infarction, or renovascular hypertension, all defined as discharge diagnoses in the national discharge registry, and used incident rate ratios (IRRs) for an average follow-up of 15 years."

The figures were adjusted for calendar period, current age, and number of live births, and in a subset of the cohort they also had information on smoking and the use of lipid-lowering and antihypertensive drugs, Ranthe said.

There were 1 031 279 women in the cohort, 842 616 of whom experienced live births only. Of those who had a miscarriage or stillbirth, 151 880 experienced one miscarriage; 28 398 had two; 5979 lost three pregnancies; 2406 women had four or more miscarriages; and 8191 had one or more stillbirths.

Over the follow-up period there were 2798 MIs, 4053 cerebral infarctions and 1269 diagnoses of renovascular hypertension in the cohort.

"For all three outcomes, the risk is increased roughly twofold given a history of any stillbirth," Ranthe said. "Given a history of any miscarriage, the association was more modest, although highly significant for all three end points, and there is a dose-response, which was robust to additional adjustment for confounders--such as smoking and diabetes." The risk associated with miscarriage was highest among younger women, he noted

Risk of Atherosclerotic Outcomes by History of Pregnancy Lossesa

Outcome

MI IRR

p

Cerebral infarctions

IRR

p

Renovascular hypertension

IRR

p

History of stillbirth

           

No

1 (ref)

 

1 (ref)

 

1 (ref)

 

Yes

2.69

<0.001

1.74

<0.001

2.42

<0.001

Number of miscarriages

           

0

1 (ref)

 

1 (ref)

 

1 (ref)

 

1

1.11

 

1.13

 

1.15

 

2

1.18

0.02

1.22

<0.001

1.12

<0.001

3

0.85

 

1.43

 

1.78

 

4

2.98

 

1.89

 

3.78

 

Trend for miscarriages b

1.09

0.007

1.13

<0.001

1.19

<0.001

a. All analyses adjusted for age, calendar period, and number of live births

b. Additional risk that a woman has by experiencing one additional miscarriage, all other variables held even

"This research, taken together with previous studies, implies a possible common underlying pathology linking pregnancy losses and atherosclerosis," he concluded.

Ranthe reports no conflicts of interest.

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