Obstetric Medicine (MDP) Workshop
CSIM Annual Meeting, October 1, 2014
Hypertension, Cardiac Disease, Approach to
Abnormal Liver Enzymes, VTE
 Dr. Paul Gibson (Calgary) – GIM & OB Internal Medicine
 Dr. Jonathan Windram (Edmonton) – Cardiology
 Dr. Rshmi Khurana (Edmonton) - GIM & OB Internal
Medicine
 Dr. David Sam (Calgary) - GIM & OB Internal Medicine
Audience Interaction
 Text response code to: 37607
 Or use your web browser and go to:
pollev.com/obmedcsim
Hypertension in Pregnancy
Paul S. Gibson, MD, FRCPC
Associate Professor of Medicine
and Obstetrics & Gynecology
University of Calgary
Recent Sources of Information
ACOG, 2013
SOGC, 2014
What We Will Cover
1. Why hypertensive disorders in pregnancy (HDPs)
matter
2. Preconception evaluation
i.
Risk factors for preeclampsia
ii.
Choice of medications
3. In-pregnancy evaluation
i.
Classification of HDPs
ii.
Pharmacologic treatment and BP targets
4. Postpartum evaluation
i.
Recognition and treatment of ‘postpartum preeclampsia’
ii.
Implications of HDPs on women’s future health
Why do hypertensive disorders in
pregnancy (HDPs) matter ?
 Hypertensive disorders of pregnancy are a leading cause
of maternal and fetal morbidity and mortality
 They are common (~10%):
 ~ 1% of pregnancies are complicated by pre-existing
hypertension
 5-6% of pregnancies result in gestational hypertension
without proteinuria
 2-4% of pregnancies result in pre-eclampsia
* It can be expected that these numbers will
increase given the trend towards an older and more
obese obstetric population
Maternal Mortality in Canada:
Diagnoses associated with maternal deaths in Canada (excluding Quebec),
2002/03-2009/10.
Canadian Institute for Health Information.
Public Health Agency of Canada, 2011.
http://www.phac-aspc.gc.ca
Maternal Mortality due to HTN - USA
Causes of Maternal Mortality
in the UK: 2006-8
Centre for Maternal and Child Enquiries (CMACE).
Saving Mothers’ Lives. BJOG 2011;118(Suppl. 1):1–
203.
Saving Mothers’ Lives (2011)
 “It is disappointing that in this triennium … the
single most serious failing in the clinical care
provided for mothers with pre-eclampsia was the
inadequate treatment of their systolic
hypertension
 In several cases, this resulted in fatal intracranial
haemorrhage
 Systolic hypertension was also a key factor in most
of the deaths from aortic dissection”
Case #1
 23 y.o. woman, G0P0
 Referred to her local General Internist for review re:
HTN & proteinuria
 PMH:






Uncontrolled HTN at age 13
Proteinuria – Bx = TBMD
Ongoing anti-HTN meds since
Home BP = 115-130 / 72-80 on lisinopril 10 mg/d
Serum Cr = 105
Urine PCR = 40 mg/mmol, 24h urine = 500 mg/d
Case #1 - continued
 Announces that she had just stopped her
OCP, hoping to achieve pregnancy ASAP!
Preconception Issues?
 Medication changes?
 Risks in pregnancy?
 Preeclampsia prevention?
ACE-inhibitors in pregnancy
 Use in the 2nd & 3rd trimesters long known to cause
fetal renal toxicity, leading to: oligohydramnios, IUGR,
hypocalvaria, renal dysplasia, anuria, renal failure, and
IUFD
N Engl J Med 2006;354:2443-51
Infants exposed to ACE inhibitors in the first
trimester were at increased risk for
malformations of the:
• cardiovascular system (risk ratio, 3.72)
• central nervous system (risk ratio, 4.39)
 Concern that these finding were due to
higher prevalence of undiagnosed DMII,
rather than true medication effect
What is this woman’s risk of
developing preeclampsia?
1. 2%
2. 5%
3. 10%
4. 25%
5. 50%
What is this woman’s risk of
developing preeclampsia?
 Other risks of cHTN include IUGR, placental abruption,
preterm delivery & prematurity
 Most of the morbidity and mortality are from preeclampsia
What would you suggest to
reduce her risk of preeclampsia?
1. Keep BP < 120/80 throughout
2. Fish oil supplements > 1000 mg/d
3. Maternal sodium intake < 2.0 g/d
4. Low-dose aspirin
5. Antioxidant vitamins (Vits C & E)
Preeclampsia Prevention?
SOGC Recommends (for women at increased risk):
 ASA 75-162 mg/d, taken at bedtime, started before 16 weeks
GA and continued until delivery (for women at increased risk)
 Calcium supplementation (>= 1 g/d)
 Recommended for other established beneficial effects in
pregnancy: abstention from alcohol, periconceptual use of a
folate-containing multivitamin, and smoking cessation
 The following are not recommended: prostaglandin
precursors, dietary salt restriction, calorie restriction in
overweight women (during pregnancy), antihypertensive
therapy specifically to prevent preeclampsia, and vitamins C
and E
 WE GENERALLY recommend Vitamin D (1000-2000 IU/d)
BP Monitoring Using Automated Devices
in Pregnancy & Preeclampsia
 Due to altered hemodynamics in pregnancy, it is
recommended that automated devices are
validated specifically in pregnant women
 Further profound changes in hemodynamics can
occur in pregnancies complicated by pre-eclampsia
 Some investigators have found large discrepancies
between oscillometric devices and auscultation by
observers, particularly in pre-eclampsia
Devices for home BP monitoring?
A comprehensive list of approved devices for HBPM can
be found at:
 http://www.dableducational.org
 http://www.bhsoc.org/default.stm
 http://www.hypertension.ca/devices-endorsed-byhypertension-canada-dp1.
What about home BP monitoring?
A comprehensive list of approved devices for HBPM can
be found at:
 http://www.dableducational.org
 http://www.bhsoc.org/default.stm
 http://http://hypertension.ca/en/hypertension/wha
t-do-i-need-to-know/how-to-measure-my-bloodpressure/918-public/landing/249-devices-endorsedby-hypertension-canada
Case #1 - continued
 Pt is switched to Labetalol 200 mg BID
 BP initially 140/90, then drops and remains ~ 130/80
 Prenatal care arranged with an OB/GYN
 Periodic follow-up with GIM every 6-8 weeks
 At 31 weeks GA she is hospitalized with worsening HTN,
despite labetalol 400 TID
 BPs exceeding 160/105
 Hb=132, Plt=309, Cr=50, ALT=7, UA=380, LD=238
 Repeat urine Prot:Cr = 234 mg/mmol (was 40)
Diagnosis of HTN
During Pregnancy
 HTN in pregnancy is defined as:
 SBP ≥ 140mmHg or DBP
≥90mmHg
 Severe hypertension is defined
as:
 systolic BP of ≥ 160mmHg or
a diastolic BP of ≥ 110mmHg
* based on the average of at least two
measurements, taken in the same arm at least
15 minutes apart
What is “abnormal
proteinuria” in
pregnancy

All pregnant women should be assessed for proteinuria



Urinary dipstick testing may be used for screening for
proteinuria when the suspicion of preeclampsia is low
Proteinuria is highly suspect when urinary dipstick proteinuria
is ≥ 1+
Proteinuria is defined as:


Protein ≥ 30 mg/mmol urinary creatinine (0.03 g/mmol) in a
spot urine (protein:creatinine) sample or
≥ 0.3g (300mg) in a 24-hour urine collection
Classification of HTN in Pregnancy
SOGC
Preexisting hypertension
-With Comorbid Conditions
-With Preeclampsia
Gestational hypertension
-With Comorbid Conditions
-With Preeclampsia
Preeclampsia
Other Hypertensive Effects
Classification of HTN in
Pregnancy: Co-morbid Conditions
1.
Preexisting Hypertension

2.
with Co-morbid Conditions
Gestational Hypertension

with Co-morbid Conditions
Co-morbid conditions:

•
•

Conditions such as type I or II diabetes mellitus and renal or
vascular disease
Strong indications for more aggressive antihypertensive
therapy outside of pregnancy
warrant special BP treatment thresholds and goals in
pregnancy
Classification of HTN in
Pregnancy
1.
Preexisting Hypertension


2.
Gestational Hypertension


3.
with Co-morbid Conditions
with Pre-eclampsia
with Co-morbid Conditions
with Pre-eclampsia
Preeclampsia
Pre-eclampsia
• Preeclampsia
 Gestational HTN PLUS
 New proteinuria, or
 One or more ‘adverse conditions’ or ‘severe
complications’
• Gestational Hypertension with Pre-eclampsia
 New proteinuria, or
 One or more ‘adverse conditions’ or ‘severe
complications’
 Preexisting Hypertension with Pre-eclampsia
 Resistant hypertension (>2 drugs), or
 New or worsening proteinuria, or
 One or more ‘adverse conditions’ or ‘severe
complications’
Severe Preeclampsia (SOGC)
Pre-eclampsia complicated by one or more
severe complications
 Severe preeclampsia is an indication to
move to delivery (regardless of gestational
age)
What is your target BP (range)
when treating HTN in pregnancy?
1. Anything less than 170/110
2. Less than 150/95
3. 130-155/80-105
4. 120-140/80-90
5. Less than 130/80
Pharmacologic Treatment
 Treatment of mild to moderate
hypertension in pregnancy is controversial
o Until recently, aggressive treatment has not been
shown to improve major maternal and neonatal
outcomes
o There is concern that treatment of hypertension
during pregnancy will impair fetal growth
Pharmacologic Treatment
 Control of Hypertension In Pregnancy Study (CHIPS)
International, multicentre (94 sites) RCT
Women with chronic and gestational HTN
Randomized to target diastolic BP of 85 vs. 100 mmHg
Evaluating maternal and perinatal outcome
Enrolled 1030 women
Primary outcome: pregnancy loss or high level neonatal
care for >48 h in the first 28d of life
 Secondary outcome: one/more serious maternal comps






 results not yet published, abstract only
Arch Dis Child Fetal Neonatal Ed. 2014 Jun;99(Suppl 1):A5-A6. doi:
10.1136/archdischild-2014-306576.15.
CHIPS – preliminary results
 75% had pre-existing hypertension, 25% gHTN
 Women in 'less tight' (n=497) [vs. 'tight' (n = 490)] control had:
 higher mean dBP by 4.5 mmHg (95% CI 3.6, 5.4)
 similar rates of the primary (perinatal) outcome [31.4% vs. 30.7%;
aOR 1.03]
 similar rates of secondary (maternal) outcome [3.7% vs. 2.0%; aOR
1.74].
 Women receiving 'less tight' control more frequently developed BP
≥160/110mmHg (40.4% vs. 27.5%; aOR 1.78)
 'Tight' control is safer for the mother, with no adverse effects for
the baby
 Investigators: “A target dBP of 85mmHg should be aimed for”
 We should await the full published details before changing Rx
Arch Dis Child Fetal Neonatal Ed. 2014 Jun;99(Suppl 1):A5-A6. doi:
10.1136/archdischild-2014-306576.15.
Treatment of non-severe HTN (SOGC)

For women without co-morbid conditions:


For women with co-morbid conditions:


drug therapy should be used to keep sBP at 130155mmHg and dBP at 80-105mmHg
goal sBP < 140 mmHg and dBP at < 90 mmHg
Initial therapy can be with one of a variety of
antihypertensive agents:




Methyldopa
Labetalol
Calcium channel blockers (nifedipine)
Other beta-blockers (acebutolol, metoprolol, pindolol,
and propranolol)
Classification – our patient
1. Preexisting Hypertension


with Co-morbid Conditions
with Pre-eclampsia
 Resistant hypertension, or
 New or worsening proteinuria, or

One or more ‘adverse conditions’ or “severe
complications”
Case # 1- continued
 In hospital x 6 days, antenatal steroids given
 BP initially controlled to < 160/100 with addition of
Nifedipine XL (30mg BID)
 Seen Saturday morning





BP = variable up to 180/115
Chest tightness and SOB onset overnight
Orthopnea
Sats 92% on room air
JVP 3-4 cms, HR 130 with gallop, crackles
Case # 1- continued
 CXR: ? Early interstitial changes
 Report: “low lung volumes, patchy opacities in lingula and
LLL, likely related to atelectasis, pneumonia cannot be r/o”
 CT: No PE, interstitial/alveolar edema!
 Fetus doing OK
 BPs up to 180/115 !!!
Treatment of Severe Hypertension
(SBP >160 mmHg or DBP ≥110mmHg)
Severe hypertension should always be treated
to prevent acute end-organ damage
 BP should be promptly lowered to < 160 mmHg
systolic and < 110 mmHg diastolic
 Initial therapy should be with:
• Labetalol IV
• Hydralazine IV
• Nifedipine PO (capsules or PA tablets)
Meds for Acute BP Lowering
Agent
Dosage
Labetalol
Start with 20mg iv; repeat 20-80mg iv q
30min, or 1-2 mg/min, max 300mg (then
switch to oral)
Nifedipine
5-10mg capsule to be bitten and swallowed,
or just swallowed, every 30min
10mg PA tablet every 45min to a maximum of
80 mg/d
Hydralazine
Start with 5mg iv; repeat 5-10mg iv every
30min, or 0.5-10mg/hr iv, to a maximum of
20mg/hr iv (or 30mg IM)
Case # 1- continued
 BP lowered to < 160/100 with IV labetalol
 Pulmonary edema = Severe Complication
 Decision to move to delivery!
 Poor fetal tolerance of labour induction
 C/S performed
 Neonatal respiratory distress – in NICU x weeks
 Mother and baby doing well in follow-up
Case #2
• 37 y.o. African-Canadian woman, G2P2
• Uneventful pregnancy, no HTN or GDM, BPs ~ 110/70
• Induced vaginal delivery at 41 wks with epidural, sent
home on PP day #2
• Progressive headache over 7 days postpartum
• Taken to ER
• Initial BP = 155/107
• Evaluated by MD, no labs
• Given morphine, BP settled to 145/95
• Told she had a ‘migraine’
• Sent home with NSAIDs
Case #2- continued
• Returned to ER the next day, worse h/a, c/o visual deficits
• Initial BP=170/115,
• given morphine & IV labetalol x 3
• Labs: ALT 176, LD 398, 24hr U protein 1.62 g/day
• Exam revealed L homonymous hemianopsia
• CT head – small R occipito-parietal ICH
• Admitted to Stroke service
• BP controlled with nifedipine XL 60 OD
• Remained on antihypertensives for 9 weeks
• Aggressive rehab for vision and balance
• At 9 weeks postpartum, mild visual defect remaining
but otherwise normal (proteinuria resolved)
Etiology of Postpartum HTN
Up to 2/3 of women with postpartum
preeclampsia had no HTN during pregnancy
BMJ 2013;346:f894 doi: 10.1136/bmj.f894
Postpartum Preeclampsia - Symptoms
Symptom
Prevalence
Headache
62-82
Visual Changes
19-31
Shortness of Breath/Chest Pain
13-30
Nausea
12.5-18
Vomiting
11.2-14
Abdominal Pain
7-14
Edema
9-10.5
Neurological Deficits
5.3
Al-Safi et al. Obstet Gynecol 2011;118:1102-7.
Postpartum Preeclampsia - Labs
•
•
•
•
•
•
•
•
Hemoconcentration (elevated Hg & Hct)
Mild thrombocytopenia (plt 100-150 109/L)
HELLP: hemolysis, transaminitis, thrombocytopenia
Uric Acid >300 μmol/L
Creatinine >70 μmol/L
AST/ALT elevated
LDH >235 U/L
In & out cath for random urine Protein:Creatinine ratio
(≥30 mg/mmol)
ER
Protocol
Persistent Hypertension Postpartum
Systolic ≥155 mmHg & 1 of
(Symptoms/HTN within 4 weeks of delivery)
Headache
Visual changes
SOB/CP
Nausea/Vomiting
Abdo pain
Edema
Neuro deficits
Fast track to MD
Assessment
• detailed History & Physical
• Labs: CBC, lytes, Cr, ALT, urate, LD, random U PCr
• ECG, CXR
Treat to sBP <155 mmHg
• labetalol iv/PO or nifedipine fast then XL
PP Preeclampsia &:
Neurological Deficits
PP Preeclampsia &:
Pulm Edema/CP
PP Preeclampsia &:
HELLP
MgSO4 infusion
CT/CT-A Brain
MRI Brain
Troponins
Echo
Neuro/Stroke/ICU
OB/MDP
Cardio/MTU
OB/MDP
Full liver panel
Including AST,
Bili, BG q1h,
DIC w/u
If eclampsia/on Mag:
ICU/OB to admit
Cardio/MTU
to admit
OB/MTU to
admit
If stroke:
Neuro to admit
Avoid fluids
Diuretic trial
ACE-I
OB to decide
If MgSO4
*Supportive
Care*
If imaging N, no Mag:
MTU to admit
OB/MTU/MDP
If worsening:
-TTP/HUS
-SLE
-APAS
-AFLP
PP Preeclampsia &:
Hypertension
w/u for 2nd
Cause HTN
MTU/MDP
MTU to admit
(≥24 hrs)
Postpartum Preeclampsia
 Be alert to this possible diagnosis, even if BP elevation
not very ‘severe’ initially
 Most important to recognize and treat HTN
 Goal < 155/105 acutely, then < 140/90
 Admit for observation for 24-48h and anticipate further
worsening over first 7 days PP
 Avoid exacerbating with IVF and/or NSAIDs
Does her HDP have future
health implications for
this woman?
Evidence is accumulating
that women who develop
hypertensive disorders of
pregnancy are at
subsequent increased
lifetime risk of vascular
complications
Two recent meta-analyses
Bellamy et al. BMJ 2007;335:974-86.
McDonald et al. AHJ 2008;156:918-30.
Preeclampsia and Hypertension:
RR = 3.7
Bellamy et al. BMJ 2007;335:974-86.
Preeclampsia and Ischemic Heart Disease:
RRs = 2.33
McDonald et al. AHJ 2008;156:918-30.
Preeclampsia and Stroke
RRs ≈ 2.0
McDonald et al. AHJ 2008;156:918-30.
It is clear from a review of multiple
recent studies that …
Women with a history of preeclampsia have an
increased risk for the later development of (RR):
• HTN: 3.7
• IHD: 2.3
• Stroke: 2.0
• PVD: 1.9
• DVT: 1.2
• CV Death: 2.3
• Death: 1.5
Risk of Future CVD is Proportional to
Timing/Severity of Preeclampsia
McDonald et al. AHJ 2008;156:918-30.
Chicken vs Egg
Is the preeclampsia a CAUSE OF
increased systemic vascular risk,
or
is the preeclampsia a RESULT OF an underlying
systemic vasculopathy (unmeasured ?)
CHAMPS study:
Link with Metabolic Syndrome
• CHAMPS identified higher risk of future CVD
in women with a MATERNAL PLACENTAL
SYNDROME who develop elements of
metabolic syndrome (obesity, HTN, DM,
dyslipidemia)
• 1-2 features: AHR = 4.5
• 3-4 features: AHR = 11.7
Ray et al. Lancet 2005;366:1797-803.
CV Risk with MPS
and features of
Metabolic Syndrome
History of
preeclampsia/MPS
adds to CV Risk of
traditional CV Risk
Factors
Some women who experience a HDP also have
(or develop) features of the METABOLIC
SYNDROME (obesity, hypertension, diabetes,
dyslipidemia)
Women with these features are at MUCH HIGHER
risk of vascular complications
How does this all tie together?
Microvascular dysfunction, metabolic disturbance,
endothelial dysfunction and inflammation


play a role in the pathogenesis of preeclampsia
similar to the pathogenesis of atherosclerosis
 Preeclampsia and subsequent cardiovascular disease
may both be manifestations of the metabolic syndrome
 Women who have a predisposition for the metabolic
syndrome are more likely to:
• develop preeclampsia during pregnancy
• subsequently develop clinically evident hypertension,
obesity, atherosclerosis and type 2 diabetes
• eventually develop CV disease
Pregnancy is a metabolic stress test
Powe et al. Circulation 2011;123:2856-2869.
Can preeclampsia cause an increased risk
of vascular complications?
MAYBE
Shared risk factors, but:
• Risk of complications is higher in women
following preeclampsia than in women simply
sharing the same metabolic risk factors
• It appears that changes in vascular endothelial
function can “outlive” the preeclamptic event
 This is an important point for preconception
counseling regarding subsequent pregnancies
Population at Risk
Women who have experienced an
(early/severe) preeclamptic
pregnancy are an at risk population
who may benefit from primary prevention
regarding modifiable CV risk factors
Primary Prevention Strategies To
Consider Following Preeclampsia
• Weight control/exercise programs
•
Return to pre-pregnancy weight / BMI<25
• Hypertension screening/monitoring and
treatment
• Smoking cessation
• Diabetes screening
• Lipid monitoring +/treatment
Conclusions
 Hypertensive disorders of pregnancy are common, and
remain an important cause of maternal morbidity and
mortality
 Limited options for preeclampsia prevention in high-risk
women
 ASA and Calcium (+/- Vit D) in high-risk women
 Proteinuria
 Dipstick = screen (≥ 1+)
 Diagnosis:
 Urine protein: Cr ratio (≥ 30 mg/mmol Cr)
 24-hour collection (≥ 0.3 g/24h)
Conclusions
 HTN in Pregnancy is SBP >= 140 and/or DBP >= 90 mmHg
but treatment target is wide (130-155/80-105)
 Results from CHIPS may change practice/targets
 Preeclampsia may present/worsen within the first week
postpartum
 Recognition and prompt BP lowering is critical
 Women with a history of preeclampsia have increased
risk for vascular disease and chronic renal disease later
in life
 Opportunity for counseling, screening and possibly
enhanced primary prevention of CVD
THANK YOU
for your time and attention!
Questions during the Panel
Discussion