Hypertension in Pregnancy --- A potential window to later years in life.

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%2815%2900035-5/abstract

http://www.pregnancyhypertension.org/article/S2210-7789%2815%2900103-8/abstract

http://www.pregnancyhypertension.org/article/S2210-7789%2814%2900172-X/abstract

http://www.pregnancyhypertension.org/article/S2210-7789%2814%2900213-X/abstract

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%2814%2900228-1/abstract

http://www.pregnancyhypertension.org/article/S2210-7789%2814%2900246-3/abstract

http://www.pregnancyhypertension.org/article/S2210-7789%2814%2900240-2/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%2812%2900344-3/abstract

http://www.pregnancyhypertension.org/article/S2210-7789%2813%2900053-6/abstract

http://www.pregnancyhypertension.org/article/S2210-7789%2814%2900219-0/abstract

http://www.ncbi.nlm.nih.gov/pubmed/20516394

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392819/

http://www.medicalnewstoday.com/articles/299748.php

Hannaford P, Ferry S, Hirsch S. 1997 Cardiovascular sequelae of toxemia of pregnancy. Heart. 77:154–158