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
Hypertension in Pregnancy Paul S. Gibson, MD, FRCPC Associate Professor of Medicine and Obstetrics & Gynecology University of Calgary
Recent Sources of Information SOGC, 2014 ACOG, 2013
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
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 2 nd & 3 rd 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%
Other risks of cHTN include IUGR, placental abruption, preterm delivery & prematurity Most of the morbidity and mortality are from preeclampsia What is this woman’s risk of developing 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-by- hypertension-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-blood- pressure/918-public/landing/249-devices-endorsed- by-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 with Co-morbid Conditions 2.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 with Co-morbid Conditions with Pre-eclampsia 2.Gestational Hypertension with Co-morbid Conditions with Pre-eclampsia 3.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’
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: drug therapy should be used to keep sBP at 130- 155mmHg and dBP at 80-105mmHg For women with co-morbid conditions: 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
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 !!! Case # 1- continued
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 AgentDosage 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)
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 # 1- continued
37 y.o. African-Canadian woman, G 2 P 2 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
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) Case #2- continued
Etiology of Postpartum HTN BMJ 2013;346:f894 doi: 10.1136/bmj.f894 Up to 2/3 of women with postpartum preeclampsia had no HTN during pregnancy
Postpartum Preeclampsia - Labs Hemoconcentration (elevated Hg & Hct) Mild thrombocytopenia (plt 100-150 10 9 /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)
Persistent Hypertension Postpartum Systolic ≥155 mmHg & 1 of 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 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 Treat to sBP <155 mmHg labetalol iv/PO or nifedipine fast then XL (Symptoms/HTN within 4 weeks of delivery) ER Protocol
PP Preeclampsia &: Neurological Deficits PP Preeclampsia &: Neurological Deficits MgSO4 infusion CT/CT-A Brain MRI Brain Neuro/Stroke/ICU OB/MDP If eclampsia/on Mag: ICU/OB to admit If stroke: Neuro to admit If imaging N, no Mag: MTU to admit PP Preeclampsia &: Pulm Edema/CP PP Preeclampsia &: Pulm Edema/CP Troponins Echo Cardio/MTU OB/MDP Cardio/MTU to admit Avoid fluids Diuretic trial ACE-I PP Preeclampsia &: HELLP PP Preeclampsia &: HELLP Full liver panel Including AST, Bili, BG q1h, DIC w/u OB/MTU/MDP OB/MTU to admit OB to decide If MgSO4 *Supportive Care* If worsening: -TTP/HUS -SLE -APAS -AFLP PP Preeclampsia &: Hypertension PP Preeclampsia &: Hypertension w/u for 2 nd 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
Bellamy et al. BMJ 2007;335:974-86. McDonald et al. AHJ 2008;156:918-30. Two recent meta-analyses
Preeclampsia and Hypertension: Bellamy et al. BMJ 2007;335:974-86. RR = 3.7
Preeclampsia and Ischemic Heart Disease: McDonald et al. AHJ 2008;156:918-30. RRs = 2.33
Preeclampsia and Stroke McDonald et al. AHJ 2008;156:918-30. RRs ≈ 2.0
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 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.
History of preeclampsia/MPS adds to CV Risk of traditional CV Risk Factors CV Risk with MPS and features of Metabolic Syndrome
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
Powe et al. Circulation 2011;123:2856-2869. Pregnancy is a metabolic stress test
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! THANK YOU for your time and attention! Questions during the Panel Discussion