Hypertensive disorders in Pregnancy (HDP) have a prevalence
of 10% of all pregnancies and account for 5-10% of maternal mortality in
developed countries!
It also accounts for increased perinatal mortality (2- to
3-fold) and women with early-onset preeclampsia have a 4-fold increased risk of
stillbirth. It is also a major risk factor for iatrogenic preterm birth (PTB).
Because women with a history of
hypertension in pregnancy make up 6–8% of the female population, more
investigation is warranted into the implications of hypertension in pregnancy
beyond the pregnancy itself.
With more women delaying childbirth to later years, we are
seeing more percentage of antenatal patients who have already developed
essential hypertension.
Pregnancy itself act as an natural “physiological stress
test” unmasking underlying pathologies such
as endothelial dysfunction, insulin resistance
that will ultimately lead to metabolic syndrome later in life.
There has never been
a consensus on the classification and diagnostic criteria for HDP, but it does
comprises a wide spectrum of diseases ranging from essential hypertension
before pregnancy to full blown eclampsia.
The revised International Society for the Study of Hypertension in
Pregnancy (ISSHP) classification (2013) for hypertensive disorders in pregnancy.
1. Chronic hypertension
2. Gestational hypertension
3. Pre-eclampsia – de novo or superimposed on chronic hypertension
4. Other hypertensive
effects—
- Transient
hypertensive effect--- Elevated BP may be due to environmental stimuli or
the pain of labour, for example
- White
coat hypertensive effect--- BP that is elevated in the office (sBP > 140 mmHg
or dBP > 90 mmHg)
but is consistently normal outside of the office (<135/85 mmHg)
by ABPM or HBPM
- Masked
hypertensive effect--- BP that is consistently normal in the office (sBP < 140 mmHg
or dBP < 90 mmHg)
but is elevated outside of the office (>135/85 mmHg
< 90 mmHg) .
With the emerging focus on the
importance of cardiovascular disease as the leading cause of death in women
many studies and research group from different parts of world are
beginning to unravel the link between preeclampsia and emerging cardiovascular
and other diseases later in life.
Some salient
features of various studies are:
Strong association has been documented in nation wide
registry and other observational studies between HDP and cerebrovascular, cardiac
and renal diseases. Furthermore, it is now clear that women who have had
preeclampsia have an increased risk of cardiovascular events over the next
10–15 years.
These results further establish the predisposition to CVD in
women with previous pre-eclampsia or PIH. (Early onset Preeclampsia) EOPE is
associated with a more pronounced CVD risk factor profile than (Late onset
Preeclampsia) LOPE or PIH.
A large population based cohort study by Mannisto et al used
The Northern Finland Birth Cohort 1966, followed the patients for 39.4 years
with an average age at the end of follow-up of 66.7 years. This study provides
evidence that isolated hypertension during pregnancy, either indicative of an
elevation in systolic or diastolic blood pressure, is sufficient to increase
future risk of chronic disease in the mother.
Data analyzed by researchers at the Public Health
Institute's Child Health and Development Studies (CHDS) at Berkeley, CA.
This large study by Cohn B.A. et al enrolled 15,528 pregnant women between 1959
and 1967 and followed them till 2010. By 2010, a total of 368 of these women,
with an average age of 66, had died of CVD. All women with a previous history of preeclampsia had 5–10 mmHg
higher peripheral and central BP (P < 0.001) as
well as elevated total: HDL cholesterol (P < 0.003),
insulin resistance (P < 0.04) and
circulating TNFα (P < 0.007).
They also had increased arterial stiffness (P < 0.04) and
cIMT (P < 0.005).
The 2011 update of the American Heart Association Risk
classification for women listed preeclampsia as a risk factor for heart disease
and stroke. Indeed, preeclampsia is associated with a fourfold increased risk
of hypertension and double the risk of fatal and non fatal ischaemic heart
disease and stroke.
Women who have had preeclampsia seem to be at higher risk of
premature death, mortality from ischemic heart disease, cardiovascular diseases
including ischemic heart disease and hypertension, fatal and non-fatal stroke,
venous thromboembolism, renal failure, type 2 diabetes mellitus,
hypothyroidism, and cognitive defects, although they appear surprisingly
protected from cancer.
Constitutional differences when becoming pregnant, number of
preeclamptic episodes, obesity, as well as lifestyle may all influence the risk
for later CVD
Children born from preeclamptic pregnancies are more prone
to hypertension, insulin resistance and diabetes mellitus, neurological
problems, stroke, and mental disorders along their life.
Hypertensive pregnancy disorders, especially PIH, were
associated with adverse metabolic outcomes and an increased risk of clustering
of metabolic risk factors six years after pregnancy compared to normotensive
women.
Strong associations between blood pressure levels during
pregnancy and the development of both hypertension and hyperlipidemia in later
life were observed.
Among 61% of women who had hypertensive pregnancy disorders
at term, high blood pressure at six weeks postpartum indicated chronic hypertension.
This warrants the importance of identification of hypertension 6 weeks
postpartum for women’s future health
Impaired endothelial vasoreactivity and increased carotid
artery intima-media thickness (CA-IMT) are prevalent in women with a history of
PE and PIH and are associated with traditional risk factors that strongly
suggest that PE and PIH could be non-traditional cardiovascular risk factors
A recent prospective cohort study by Royal college of
General Practitioner recruited 23,000 patients showed that women with a history
of HDP have a significantly increased risk of hypertensive disease (relative
risk (RR) 2.35), acute myocardial infarction (RR 2.24), chronic ischaemic heart
disease (RR 1.74), angina pectoris (RR 1.53), all ischaemic heart disease (RR
1.65), and venous thromboembolism (RR 1.62) as compared to normotensive women.
The rates for all cerebrovascular disease and peripheral vascular disease were
also increased but not significantly. This study
supports the concept that pregnancy can be a predictor of not only increased
but also decreased long-term cardiovascular risk for women.
Follow-up of kidney function is relevant for about 16% of
all women with a history of preeclampsia. Kidney function should be part of
cardiovascular risk assessment after preeclampsia, with special emphasis to be
directed on the postpartum disappearance of the preeclampsia-induced
albuminuria. Systematic assessment of renal risk factors 6 weeks after
preeclampsia allows identification of high-risk women and early implementation
of preventive and therapeutic strategies.
A Japanese cohort study predicted that BP at one month post
delivery of the index case predicts subsequent hypertension 5 years
after, independent of HDP.
Women with preeclamptic pregnancies 10 years earlier tended
to have higher pulse wave velocity compared to women with previous normotensive
pregnancies.
As the long term cardiovascular risk to both mother and
child is known from delivery there is increasing interest in key phenotypic
variations that are identifiable in mothers and children during the years
between the episode of preeclampsia and the emergence of established
cardiovascular disease. These might help explain the link between the two
conditions, provide a means to identify subjects at greatest risk of later
cardiovascular disease and establish intermediate endpoints for future
preventative interventions.
A recent meta-analysis found 8 genetic variants associated
with preeclampsia. Most of these variants are in the renin-angiotensin and the
coagulation system. Importantly, many of the variants that were associated with
preeclampsia are known to be risk factors for the development of cardiovascular
disease, indicating that preeclampsia and cardiovascular disease have shared
genetic risk factors. The relative contribution and relevance of the identified
genes in the pathogenesis of preeclampsia should be the focus of future
studies.
Many studies also identified causal genetic risk factors for
preeclampsia at the 2q22 risk locus.
This increased understanding allows both better characterization of long term cardiovascular outcomes and better identification
of optimal approaches to improve long term outcomes. According to Dutch
Obstetric and Gynecological society evidence based medicine a cardiovascular
risk profile should be offered to all women with history of HDP at the age of
50 years.
References:
http://www.pregnancyhypertension.org/article/S2210-7789%2812%2900172-9/abstract
http://www.pregnancyhypertension.org/article/S2210-7789%2814%2900246-3/abstract
http://www.pregnancyhypertension.org/article/S2210-7789%2812%2900241-3/abstract
http://www.pregnancyhypertension.org/article/S2210-7789%2815%2900105-1/abstract
http://www.pregnancyhypertension.org/article/S2210-7789%2813%2900053-6/abstract
Hannaford P, Ferry S, Hirsch S. 1997
Cardiovascular sequelae of toxemia of pregnancy. Heart. 77:154–158
