Early detection of cardiovascular risk factors after pregnancy complicated by hypertensive disorders or spontaneous preterm birth

Cardiovascular disease is the most important cause of death for women in the
Western world. Since there is a lack of sensitive and specific tests for women,
predicting cardiovascular disease remains challenging. Hypertensive disorders
are a common complication of pregnancy. Epidemiological studies have described
an association between hypertensive disorders in pregnancy and the development
of cardiovascular disease later in life. Recently, we found that women with
previous pregnancies complicated by hypertension have increased modifiable risk
factors for cardiovascular disease, years after pregnancy compared to women
with previous uncomplicated pregnancies. This implies that pregnancy can
potentially be a tool as *stress test* unmasking underlying defects, thus
identifying women at increased risk for cardiovascular events at young age.
Since both women who have a pregnancy complicated by preeclampsia and women
with cardiovascular disease show signs of (micro) vascular dysfunction, we
hypothezise that both hypertension in pregnancy and cardiovascular disease in
later life share pathophysiological features of vascular dysfunction and they
might share, at least partly, the same pathomechanism. It is known that
endothelial dysfunction is a predictor of cardiovascular disease and has a
negative effect on microcirculation and compliance of the great arteries.
Without intervention this will eventually lead to increased sytolic blood
pressure, left ventricular hypertrophy, impaired coronary perfusion and heart
failure and hereby it contributes to morbidity and mortality.

Accumulating evidence from epidemiologic studies now suggests that women with a
history of preterm birth are at increased cardiovascular risk as well. Also for
spontaneous preterm birth (SPTB) this seems to be the case. It is hypothesized
that spontaneous preterm birth has a vascular component, analogous to
preeclampsia. This is supported by shared risk factors indicating abnormal
placentation and placental insufficiency in both patients with SPTB and
patients with preeclampsia. This implies that pregnancy complicated by
spontaneous preterm birth, can potentially be used as a *stress test* as well,
thus identifying women at increased risk for cardiovascular events at
relatively young age, like hypertensive disorders of pregnancy.

This study focuses on the early detection of cardiovsacular risk factors after
pregnancy complicated by hypertensive disorders or spontaneous preterm birth.
By screening for risk factors in individuals on a local tissue and systemic
level we provide an insight in risk profiles for cardiovascular disease after
pregnancy complicated by hypertension or spontaneous preterm birth. This will
contribute to a better understanding of the pathophysiological link between
both disorders, with the ultimate aim to develop a highly sensitive and
specific test to predict an individual*s cardiovascular risk later in life
using pregnancy as a stress test and hereby creating opportunities for early
intervention and secondary prevention at a relatively young age.

We hypothezise that hypertension in pregnancy, spontaneous preterm birth and
cardiovascular disease in later life share pathophysiological features of
endothelial dysfunction. We will investigate this on two levels including local
on tissue level and systemic level:

I: Identification of (micro) vascular dysfunction in women with a history of
pregnancy complicated by early preeclampsia or spontaneous preterm birth, in
which a proposed higher prevalence of hypertension and the metabolic syndrome
will be seen. Besides, the total number of circulating microparticles and the
cellular origin of the microparticles will be analyzed.

II: Identification of diastolic heart dysfunction in women with a history of
pregnancy complicated by early preeclampsia or spontaneous preterm birth.
Diastolic dysfunction is one of the earliest signs of cardiac failure
especially in *asymptomatic* women.

For the identification of the endothelial dysfunction and diastolic dysfunction
we designed an observational cohort study. Women will be invited 9-16 years
after they gave labor in a University Medical Center in the Netherlands. The
cases consist of 1. a group of women with a history of pregnancy complicated by
preeclampsia (before 34 weeks gestation) and 2. a group of women with a history
of spontaneous preterm birth (before 37 weeks of gestation). The controls will
be matched on time of labor (+/- 3 monts), parity, ethnicity and maternal age
and are women without any vascular complications of their pregnancy who gave
labor after 37 weeks of gestation in the same University Medical Center in the
Netherlands. These women will be screened for the metabolic syndrome and other
cardiovascular risk factors by answering a questionnaire, antroprometrics,
venous blood samples which will be used in a subpopulation for investigating
the number of circulating microparticles and cardiac ultrasonography.

Both parts of the study will result in basic knowledge of the
pathophysiological process of cardiovascular disease in general and in
particularly in women. More specifically this study will result in an increase
of knowledge of the relationship between hypertensive disorders in pregnancy,
spontaneous preterm birth and cardiovascular disease development in later life.
The methods of research we use (including questionnaires, anthropometrics,
venous blood sampling, ultrasonography) are safe and hardly invasive. The
venous blood sampling can result in a hematoma or vasovagal reaction.
Hereby most of the burden for the patient will be time related since patients
have to invest half a day for the research.
We believe that the scientific gain that this study intends, outweighs the
temporarily discomfort that may occur.