Key words
hypertensive disorders of pregnancy - arterial hypertension - cardiovascular risks
- follow-up - prevention
Schlüsselwörter
hypertensive Schwangerschaftserkrankungen - arterielle Hypertonie - kardiovaskuläres
Risiko - Follow-up - Prävention
Introduction
The group of cardiovascular diseases is the most frequent cause of death in the
industrialised nations. One of the major reasons for death due to cardiovascular
problems is arterial hypertension.
About one quarter of the worldʼs population suffers from arterial hypertension.
Although on the whole men and women are equally affected, postmenopausal women
suffer increasingly more often from hypertension than men [1].
Early recognition of and therapy for arterial hypertension can markedly reduce the
long-term cardiovascular sequelae. Furthermore, prevention in the form of lifestyle
changes can delay the occurrence of hypertension and reduce its severity.
It is important that the occurrence of a hypertensive disorder of pregnancy – and
this includes, among others, hypertension induced by pregnancy, preeclampsia as well
as HELLP syndrome – at a young age can be considered as a relevant indication for
the later development of chronic hypertension [2]. If this
knowledge would be consequently implemented in strategies for early detection and
prevention, the cardiovascular risks and the subsequent cardiovascular mortality
could be reduced for the afflicted women.
The aim of the present review is to help reduce the morbidity and mortality for women
who have suffered from hypertensive disorders of pregnancy by demonstrating in
principle the relationships between hypertensive disorders of pregnancy with later
cardiovascular diseases and by emphasising the significance of an adequate
follow-up.
Materials and Methods
Selective literature searches (Medline, Cochrane Library) were carried out on the
basis of the key words “pregnancy” and “hypertensive”, individually combined with
the further key words “preeclampsia”, “hypertension”, “cardiovascular”, “mortality”,
“risk” and “prevention” and with exclusion of those references that investigated the
pathogenesis of hypertensive diseases of pregnancy. Also included were the cited
reference articles as well as basic references and national as well as international
guidelines.
Arterial Hypertension and Women
Arterial Hypertension and Women
Arterial hypertension is one of the most important risk factors for morbidity and
mortality due to cardiovascular problems. 26.4 % of the world population, more or
less equally distributed between men and women suffer, from arterial hypertension:
26.1 % of all women and 26.6 % (26.0–27.2 %) of all men [3]. However, there are age-dependent and gender-specific differences. Up
to 45 years of age men suffer more frequently from hypertension than women, between
the ages of 46 and 65 years the gender-specific difference is almost non-existent,
from 65 years onwards women suffer more than men from elevated blood pressure [1]. Due to demographic developments and the increasing
average age of the central European population an increase in the number of
afflicted women is to be expected in the future [4].
Cardiovascular sequelae of hypertension such as myocardial infarction, heart failure
and cerebral insult constitute the main causes of all deaths in the industrialised
nations. In Germany cardiovascular causes are responsible for 45.1 % of all deaths
among women. In comparison 26.7 % of all deaths among women are due to cancer [5]. International data show that therapy for arterial
hypertension is often inadequate. This applies especially for elderly women. The
rates for guideline-conform therapy for hypertension in men and women are, according
to age groups (p < 0.01) [6]:
-
< 60 years: 38 % for men and women
-
60–79 years: 36 % for men vs. 29 % for women
-
≥ 80 years: 38 % for men vs. 23 % for women
Thus arterial hypertension together with its clinical consequences is of enormous
health-care political importance. Primary prevention of hypertension, early
diagnosis of hypertension and adequate non-drug as well as pharmacological therapies
are decisive cornerstones for the prevention of morbidity and mortality due to
cardiovascular problems.
Since there is a direct association between hypertensive disorders of pregnancy and
a
later cardiovascular risk, the case histories and courses of previous pregnancies
should be an essential part of general and internal medical examinations. Pregnancy
is so to speak a general medical stress test and should thus be considered as a
suitable medical window for the future.
Hypertensive Disorders of Pregnancy
Hypertensive Disorders of Pregnancy
Among the hypertensive disorders of pregnancy – including hypertension induced by
pregnancy, preeclampsia and HELLP syndrome – there are various clinical pictures
with in part widely differing clinical courses and severities ([Table 1]).
Table 1 Classification of the hypertensive disorders of
pregnancy (data taken from DGGG guideline, stand 2010 [15]).
|
Gestational hypertension
|
RR ≥ 140/90 mmHg after 20th week of pregnancy in patient without
pre-existing hypertension
|
within 12 weeks return to normotensive blood pressure values, no
proteinuria ≥ 300 mg/24 h
|
|
Preeclampsia
|
RR ≥ 140/90 mmHg after 20the week of pregnancy in patient without
pre-existing hypertension plus proteinuria ≥ 300 mg in 24-h
urine
|
|
|
HELLP syndrome
|
haemolysis
elevated liver
enzymes
low platelets
(< 100,000/µL)
|
special form of preeclampsia
hypertension and proteinuria
may be lacking
|
|
Eclampsia
|
tonic-clonic seizures in cases of preeclampsia
|
hypertension and proteinuria may be lacking
|
|
Pre-existing hypertension
|
RR ≥ 140/90 mmHg pre-conception or before 20th week of
pregnancy
|
hypertension persisting beyond 12 weeks post partum
|
|
Preeclampsia superimposed on chronic hypertension
|
RR ≥ 140/90 mmHg pre-conception or before 20th week of pregnancy
plus de-novo proteinuria ≥ 300 mg in 24-h
urine
or
RR ≥ 140/90 mmHg and proteinuria
pre-conception of before 20th week of pregnancy and sudden
elevation of hypertension or proteinuria ≥ 20th week of
pregnancy
|
hypertension persisting beyond 12 weeks post partum
|
The incidence of hypertensive disorders of pregnancy varies in the literature and
according to recent data amounts to 6–8 % [7], [8], [9]. Since the incidence
increases with increasing maternal age, body mass index and associated accompanying
diseases, an increase must be expected in the course of time due to the demographic
developments. In central Europe hypertensive disorders of pregnancy represent one
of
the three most frequent causes of death among pregnant women after haemorrhages and
thromboembolisms [10], [11].
Preeclampsia is of particular importance as it is to a large extent responsible not
only for increased maternal but also for increased perinatal morbidity and
mortality. The frequency of preeclampsia including the HELLP syndrome, which is
considered to be a variant of preeclampsia, amounts to 2–4 %. Primiparous women are
afflicted about 2- to 3-times more frequently than multiparous women [12].
Possible complications of preeclampsia are eclamptic seizures or the occurrence of
a
cerebral insult.
Cerebral insults are very rare and can be both haemorrhagic (92.6 %) as well as
ischaemic (7.4 %). In such cases the systolic blood pressure is of more significance
than the diastolic value. A cerebral insult is not to be expected below a systolic
blood pressure of 155 mmHg, according to the literature most insults occur at a
systolic value above 160 mmHg [13]. According to the ACOG
systolic blood pressure values of more than 160 mmHg should be reduced by drug
therapy [14]. The guidelines of the DGGG state that
systolic blood pressures above 170 mmHg should be reduced by drug therapy and – in
cases with pre-existing vascular diseases – even for systolic values above 160 mmHg
[15]. The maternal mortality amounts to 53.6 % after
an insult, and the morbidity is high among the survivors. In the literature merely
11 % of the women remain without significant late sequelae after a cerebral insult
in the course of hypertensive disorders of pregnancy [13].
The full clinical picture of a hypertensive disorder of pregnancy can develop during
the antepartal, intrapartal and even during the first postpartal days. In up to 30 %
a HELLP syndrome can show first manifestations in the postpartal period [16], an eclamptic seizure in up to 44 % [17]. For this reason maternal monitoring and therapy are
also mandatory in the lying-in period after delivery.
Foetal consequences consist on the one hand of growth retardation and an increased
rate of IUFT due to placentation disorders and on the other hand the associated
premature birth [18]. Thus, management of preeclampsia is
always a compromise between pregnancy prolongation and delivery, between foetus and
mother [19].
Association of Hypertensive Disorders of Pregnancy with Later Hypertension and
Cardiovascular Risks
Association of Hypertensive Disorders of Pregnancy with Later Hypertension and
Cardiovascular Risks
After the occurrence of a hypertensive disorder of pregnancy there is not only a
demonstrated increased risk for a recurrence in subsequent pregnancies [20] but also – staggered in time – a significantly higher
risk for cardiovascular diseases than in a comparable collective of women without
hypertensive disorders of pregnancy [21], [22].
The question as to how the increased cardiovascular risk arises after a hypertensive
disorder of pregnancy has not been answered unequivocally. Is the endothelial
dysfunction a common risk factor not only for pregnancy-induced high blood pressure
disease but also for later cardiovascular diseases or is possibly a change first
induced or potentiated by the occurrence of the hypertensive disorder of pregnancy
which is ultimately partially or wholly responsible for the markedly increased risk
for the afflicted women?
At present the former hypothesis is rather more favoured, i.e., it appears that, even
before the onset of pregnancy, some young women have a predisposition that can lead
to a preeclampsia and later, after a symptom-free period, favour the development of
arterial hypertension and cardiovascular diseases.
A hint for such a predisposition in the first line is the presence of elevated,
albeit still guideline-conform as normotensive, systolic and diastolic blood
pressure values prior to conception, higher than in those in women without such a
predisposition [23]. The existence of higher levels of
triglycerides, LDL and an unfavourable HDL/LDL ratio does not appear to represent
a
further hint for a predisposition for hypertensive disorders of pregnancy and
cardiovascular diseases in later life, but is rather a coincidence with a higher BMI
([Table 2]) [23].
Table 2 Pre-conceptional differences between women with and
without subsequent hypertensive disorders of pregnancy (data taken from
Romundstad et al. 2010 [23]).
|
|
No hypertensive disorder of pregnancy
|
Hypertensive disorder of pregnancy
|
Mean difference (adjusted)
|
|
Average BMI (kg/m2)
|
22.5
|
24.1
|
0.8 (0.5–1.1)
|
|
Average systolic blood pressure (mmHg)
|
117
|
126
|
6.2 (4.7–7.8)
|
|
Average diastolic blood pressure (mmHg)
|
74
|
81
|
3.5 (2.4–4.6)
|
|
Antihypertensive drugs in case history (%)
|
1
|
8
|
no data
|
After the occurrence of preeclampsia, in comparison to women without hypertensive
disorders of pregnancy, there is a markedly higher risk to develop arterial
hypertension, to suffer from an ischaemic heart disease with or without lethal
outcomes, to experience an ischaemic or haemorrhagic cerebral insult, or to be
afflicted by a thromboembolic incident ([Table 3]) [21], [24], [25].
Table 3 Increase of risk for cardiovascular diseases after
preeclampsia (RR = rel. risk) (data taken from Bellamy et al. 2007 [25]).
|
|
RR after preeclampsia (95 % confidence interval)
|
Average follow-up time (in years)
|
|
Arterial hypertension
|
3.70 (2.70–5.05)
|
14.1
|
|
Ischaemic heart disease
|
2.16 (1.86–2.52)
|
11.7
|
|
Cerebral insult
|
1.81 (1.45–2.27)
|
10.4
|
|
Thromboembolic event
|
1.79 (1.37–2.33)
|
4.7
|
In addition, there is an inverse correlation between an early manifestation of
preeclampsia and the probability of a later hypertension or, respectively, a later
cardiovascular risk – in other words: the earlier (referred to weeks of pregnancy)
the preeclampsia occurs, the higher is the later risk of cardiovascular disease
[25].
The severity of preeclampsia as well as the repeated occurrence of preeclampsia in
several pregnancies also correlate with the cardiovascular risk [24], [25], [48], [49]: the risk for an
ischaemic heart disease after the occurrence of preeclampsia is increased by a
factor of 2.2 in comparison to healthy women. After an early manifestation of
preeclampsia before the 37th week of pregnancy the risk for an ischaemic heart
disease is even increased by a factor of 7.7 in comparison to healthy women ([Table 4]). The risk to suffer from a cerebral insult is
increased by a factor of 5.1 after occurrence of an early preeclampsia before the
37th week of pregnancy in comparison to that for women who develop preeclampsia
after the 37th week of pregnancy. In cases of severe preeclampsia the risk for a
venous thromboembolism increases by a factor of 2.3 in comparison to cases of mild
preeclampsia.
Table 4 Ischaemic heart disease after preeclampsia in
dependence on time of onset and severity of the preeclampsia (RR = rel.
risk) (data taken from Bellamy et al. 2007 [25]).
|
|
Ischaemic heart disease
relative risk (95 % confidence
interval)
|
|
RR after preeclampsia (95 % confidence interval)
|
2.16 (1.86–2.52)
|
|
RR after preeclampsia < 37th week of pregnancy (95 %
confidence interval)
|
7.71 (4,4–13.52)
|
|
RR after severe preeclampsia (95 % confidence interval)
|
2.86 (2.25–3.65)
|
|
RR after mild preeclampsia (95 % confidence interval)
|
1.92 (1.65–2.24)
|
The study situation with regard to cardiovascular risk after gestational hypertension
without preeclampsia is less homogeneous than that for the cardiovascular risk after
preeclampsia [25], [26], [27]. But even here a significant relationship with an
increased incidence of later arterial hypertension can be demonstrated: relative
risk 5.3 (4.90–5.75). Furthermore, there is an unambiguous indication for a more
frequent occurrence of diabetes mellitus after gestational hypertension and
preeclampsia [26].
The mortality after preeclampsia is increased by a factor of 1.49 (1.05–2.12) or,
respectively by a factor of 2.71 (1.99–3.68) after early preeclampsia (< 37th
week of pregnancy). After a hypertensive disorder of pregnancy an increased
mortality due to cancer (all cancers) as well as an increased breast
cancer-associated mortality can be excluded. The increase in mortality can thus be
attributed mainly to cardiovascular causes [25], [28].
Medical Knowledge with Regard to Late Cardiovascular Manifestations after
Hypertensive Disorders of Pregnancy
Medical Knowledge with Regard to Late Cardiovascular Manifestations after
Hypertensive Disorders of Pregnancy
A recent study was concerned with the knowledge about the relationships between
hypertensive disorders of pregnancy and later cardiovascular risks and came to the
following results: 56 % of the internal medicine specialists and 23 % of the
gynaecologists were not, or were only insufficiently, aware of the association of
preeclampsia with later ischaemic heart disease, 48 % of the internal medicine
specialists and 38 % of the gynaecologists did not know about the association with
later stroke and 79 % and, respectively, 77 % about the association with a lower
life expectancy [29].
Lying-in and Postpartum Course
Lying-in and Postpartum Course
In most women with hypertensive disorders of pregnancy the elevated blood pressure
normalises within a few days after birth, in cases of pure gestational hypertension
on average after 6 days, in cases of preeclampsia after 16 days [30]. However, this is not the case in about 5 % of all
patients with pregnancy-associated hypertensive diseases, in other words these
patients remain hypertensive. It may be assumed that the major proportion of these
women were suffering from an undiagnosed chronic hypertension already prior to the
pregnancy. On account of the fall in blood pressure during the first half of
pregnancy a pre-existing hypertension is at first often not recognised.
Not only does the blood pressure mostly return to normal rapidly postpartum but also
the laboratory parameters and – if present – the patientʼs subjective complaints
normalise. Subclinical changes, however, remain and above all for women afflicted
with hypertensive disorders of pregnancy in common there is the higher
cardiovascular risk.
Comprehensive information for the patient before release of the afflicted women from
the hospital is very important. The value of the transmission of information about
the nature and severity of the hypertensive disorder of pregnancy to the patientʼs
subsequently responsible gynaecologist, general practitioner or internist should be
emphasised with the aims of early detection of a later hypertension and its adequate
therapy in order to reduce the cardiovascular risks.
Follow-up: Primary Prophylaxis, Diagnostics and Therapy
Follow-up: Primary Prophylaxis, Diagnostics and Therapy
A renewed occurrence of arterial hypertension should be diagnosed as early as
possible in order to avoid end organ damage. For this purpose the patients are
recommended to undergo an annual outpatient 24-h blood pressure control [31]. In addition an outpatient, protocolled self-control
of blood pressure can be considered. Upon confirmation of hypertension the decision
concerning type and intensity of the antihypertensive therapy is made in
consideration of the cardiovascular risk and depending on the severity of the
hypertension.
Monitoring of renal parameters until normalisation and thereafter when signs of renal
function disorders are present is also strongly recommended. This includes the
exclusion of the persisting proteinuria and microalbuminuria (24-hour urine
collection) as well as measurement of serum creatinine [32]. In particular, a persisting or recurring microalbuminuria is the
sign for an up to 50 % increased cardiovascular risk [33]. Even in non-diabetic and normotensive patients a mild microalbuminuria
below the actual cut-off value constitutes a cardiovascular risk factor, furthermore
it is an early marker for later kidney diseases in previously preeclamptic women.
In
comparison to women after uncomplicated pregnancies, the frequency of a
microalbuminuria is increased by a factor of 4–8 in women after preeclampsia [34].
The regular performance of an oral glucose tolerance test after the occurrence of
a
hypertensive disorder of pregnancy cannot uniformly be recommended on the basis of
the current state of knowledge. However, since the risk of type 2 diabetes is
increased by a factor of 3–4 not only after gestational hypertension but also after
preeclampsia [26] and the fact that diabetes mellitus
further increases the cardiovascular risks, the performance of this screening
examination may be considered [50]. Factors that are
suspicious for the existence of a diabetic metabolic situation should be considered
and, if present, should in every case result in the performance of an oral glucose
tolerance test.
It is sufficiently well known that numerous primary prophylactic, so-called lifestyle
measures, have been demonstrated to hinder hypertension [35]. These include healthy nutrition, weight reduction in cases of high
BMI [36], [37], regular
physical exercise [38], reduction of an excessive alcohol
consumption [39] as well as cessation of smoking or other
forms of tobacco consumption [35]. Support of the
patientʼs self responsibility is an essential but often difficult to realise point
of intervention.
As secondary prophylaxis the timely and adequate initiation of an antihypertensive
therapy can markedly reduce the subsequent effects of high blood pressure on the
cardiovascular system [40]. Reduction of the diastolic
blood pressure by merely 1 mmHg, for example, leads to a 2–3 % reduced rate of
myocardial infarction. Reduction of the blood pressure by 5–6 mmHg can reduce the
insult rate within 5 years by 42 % [41]. Cofactors for
subsequent cardiovascular diseases besides hypertension, such as dyslipidosis or
diabetes mellitus, must each be treated accordingly [42].
The exploitation of all therapeutic options beginning with lifestyle changes through
to polypharmacological treatment [43] is an essential
factor.
That by far not all patients with hypertension are recognised as such and thus
especially are not receiving an adequate therapy has been demonstrated by a
comparative study in Germany: the hypertension is known in 59 % of all hypertensive
women aged between 35 and 64 years in Germany, it is being treated in 47 % and
merely 63 % of all hypertensive women under treatment are receiving an adequate
therapy. Thus, altogether only 29 % of all women with hypertension are receiving an
appropriate treatment [44]. One reason for the low
recognition rate of hypertension in the population may be the low degree of
awareness about screening examinations. Thus, for example, for all people over the
age of 35 years in Germany the statutory health insurances cover the costs for a
health check-up (“Check-Up 35+”) [45] every 2 years, but
this is much too seldom utilised (24.7 % of all women).
The participation in gynaecological screening programmes such as the nation-wide
mammography screening is currently stated as being 54 % [46], the cervical cancer screening programmes have a participation of on
average 36–51 % [47]. Thus, the responsible
gynaecologists have the possibility and the duty to inform their patients of the
significance of follow-up after hypertensive diseases of pregnancy and to implement
it in close cooperation with the patientʼs general practitioner and/or internist.
We
once again emphasize the need to provide the patient with comprehensive information
about the risks of hypertension and the associated cardiovascular consequences as
well as about the possibilities for prophylactic and, if necessary, therapeutic
interventions.
Conclusion
Arterial hypertension is one of the most important risk factors for morbidity and
mortality due to cardiovascular causes, even so only one quarter to one third of all
women with hypertension are receiving an adequate therapy.
On the one hand hypertensive disorders of pregnancy lead to direct foeto-maternal
consequences and on the other hand there is a significant relationship with a later
developing arterial hypertension, with cardiovascular morbidity and mortality.
The appropriate follow-up of women after hypertensive disorders of pregnancy leads
to
the early diagnosis of a later arterial hypertension; cardiovascular late sequelae
can be markedly reduced by an early and adequate therapy. By means of primary and
secondary prophylactic intervention post partum the occurrence of arterial
hypertension can be delayed and in the best case completely avoided.
