About the Authors
Sheila Rodger is with the Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Winnie Sia is with the Department of Medicine and Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.
Corresponding author: Winnie Sia Winnie.Sia@albertahealthservices.ca
Submitted: April 10, 2017; Accepted: June 10, 2018. Published: August 27, 2018.
Dyslipidemia Management after Pre-eclampsia:
What is the Threshold for Treatment Due to
Increased Cardiovascular Risk?
Sheila J Rodger MD, Winnie Sia MD
Abstract
Growing evidence shows that women with a history of pre-eclampsia, pregnancy-induced
hypertension or gestational diabetes are at increased long-term risk of cardiovascular disease
(CVD). This was incorporated in the American Heart Associations 2011 guideline on the
prevention of CVD in women and was recently reflected in the 2016 Canadian Cardiovascular
Society’s guidelines, suggesting that young women who would not formerly have been considered
for primary CVD prevention may benefit from screening for dyslipidemia. However, the
indications and targets for medical treatment of dyslipidemia postpartum remain unclear
and in fact differ amongst guidelines. We present the case of a 31-year-old G1P1L2 woman
with pre-eclampsia, preterm delivery and dyslipidemia who had active vascular risk reduction
postpartum, including adjustment of antihypertensives, diet and exercise counselling for low-
density lipoprotein cholesterol reduction and weight loss promotion, and consideration of an
HMG-CoA reductase inhibitor, which was ultimately decided against given the improvements
seen with lifestyle modifications.
RESUME
Des preuves de plus en plus nombreuses montrent que les femmes ayant des antécédents de
pré-éclampsie, d’hypertension induite par la grossesse ou de diabète gestationnel sont exposées
à un risque accru de maladie cardiovasculaire (MCV) à long terme. Elle a été incorporée dans
les lignes directrices de 2011 de lAmerican Heart Association sur la prévention des maladies
cardiovasculaires chez les femmes et a récemment été reflétée dans les lignes directrices de
2016 de la Société canadienne de cardiologie, suggérant que les jeunes femmes qui nauraient
jamais été considérées comme prévention primaire des MCV pourraient bénéficier du dépistage
de la dyslipidémie. Cependant, les indications et les cibles pour le traitement médical de la
dyslipidémie post-partum restent peu claires et en fait diffèrent des lignes directrices. Nous
présentons le cas dune femme G1P1L2 âgée de 31 ans avec pré-éclampsie, accouchement
prématuré et dyslipidémie ayant une réduction active du risque vasculaire post-partum, y
compris lajustement des antihypertenseurs, un régime alimentaire et des exercices pour la
réduction du cholestérol à lipoprotéines de basse densité et la prise en compte dun inhibiteur
de la HMG-CoA réductase, qui a finalement été rejeté compte tenu des améliorations observées
avec les modifications du mode de vie.
Canadian Journal of General Internal Medicine
Volume 13, Issue 3, 2018 25
Case Report
Case
Our non-smoking 31-year-old G1P1L2 female patient had a
pre-pregnancy body mass index (BMI) of 40.1, dyslipidemia,
and a family history of dyslipidemia and pre-eclampsia. Two
years prior to pregnancy, her total cholesterol was 6.06mmol/L,
low-density lipoprotein cholesterol (LDL-C) 4.81mmol/L and
ratio of total cholesterol to high-density lipoprotein cholesterol
(HDL-C) 6.6. After treatment with a low-dose HMG-CoA
reductase inhibitor (statin), her LDL dropped to 2.06. Prenatal
labwork was otherwise normal, and an oral glucose tolerance
test was negative for gestational diabetes. When she became
pregnant, she was taking omega-3 fatty acids, but had stopped
her statin for pregnancy.
At 30 weeks into her diamniotic, dichorionic twin pregnancy,
she developed pre-eclampsia, with hypertension, proteinuria,
headache, vision changes, thrombocytopenia and elevated
transaminases. Her twins were delivered 5 days later by Caesarean
section for pre-eclampsia and breech/breech presentation. Her
symptoms resolved and laboratory markers normalized soon
after delivery; however, she still required medications for blood
pressure control.
She was referred to the Postpartum Pre-eclampsia Clinic
(PPPC), a Specialty Vascular Risk Reduction clinic run by a
general internist dedicated to women who have developed
pre-eclampsia,
1–3
for education and active management advice
regarding the patients long-term risk of vascular disease following
preterm pre-eclampsia and her future risk of pre-eclampsia in
subsequent pregnancies.
4
At her initial visit 3 months postpartum
she was assessed by the multidisciplinary team consisting of
a physician, nurse practitioner, pharmacist and dietitian; her
BMI at that time was 40. An action plan was developed which
included limiting saturated fat intake and beginning a program
of exercise 3 times per week.
At the 7 months postpartum follow-up visit, our patient
was exercising aerobically 3 to 5 times weekly and her BMI had
decreased to 39.3; her antihypertensive medications were weaned
and discontinued by 4 months post-partum. Her fasting lipids after
stopping lactation were: triglycerides (TG) 1.27 mmol/L (normal
<1.70 mmol/L), total cholesterol 5.03 mmol/L (<6.20 mmol/L),
HDL-C 0.75 mmol/L (>1.10mmol/L) and LDL-C 3.7mmol/L.
Her LDL-C would be considered acceptable according to the
current Canadian Cardiovascular Society (CCS) guidelines
2
(see Table 1); however, given her history of pre-eclampsia, the
American Heart Associations (AHA) 2011 Guidelines for the
Prevention of Cardiovascular Disease (CVD) in Women and the
Pre-eclampsia Foundation recommend a lower target of LDL-C
<2.6mmol/L.
1,5
The clinic dietician therefore provided dietary
recommendations for LDL-C reduction, including increasing
fiber and whole grains and reducing prepackaged food intake.
From 7 to 12 months postpartum, our patients weight had
decreased by 1.1 kg and her BMI was 38.5. Unfortunately, her
total cholesterol increased to 5.62 mmol/L and LDL-C increased
to 4.3 mmol/L. Hence, not only was it unclear whether or not
she met criteria for “dyslipidemia” as the CCS and AHA/Pre-
eclampsia guidelines differ in this population, it was even less
clear if this possible dyslipidemia should be treated aggressively,
such as with pharmacological therapy.
The PPPC team decided to further investigate her possible
dyslipidemia with bloodwork. Her lipoprotein(a) was slightly
elevated at 0.43 g/L (<0.30 g/L); as per the CCS 2016 guidelines,
this indicates an increased risk for CVD.
2
Apolipoprotein B100
(Apo B) was also slightly elevated at 1.21g/L (<1.20 g/L), but
her LDL-C had decreased to 3.73 mmol/L. Given both the
improvement in LDL-C with lifestyle modifications and the finding
that her lipoprotein(a) and Apo B levels were not significantly
elevated, no pharmacological treatment was recommended
by the clinic. At this time, her 10-year risk of CVD as per the
American College of Cardiology (ACC)/AHA risk calculator was
1.7% or “low risk,” although the clinic was fully aware that the
Fragminham 10-year risk prediction in such a young woman in
this population is not valid. She was discharged from the PPPC
back to her family physician with the recommendation to check
her lipid panel every 1–2 years, although the optimal frequency
of screening in this population is also not well-defined in any
guidelines. The clinic suggested for the family physician to aim
for an LDL of low 3 or high 2 range, until future guidelines can
clarify the threshold.
Discussion
To our knowledge, this is the first published case of a woman
with pre-eclampsia and preterm delivery who had active vascular
risk reduction postpartum, despite the fact that women with a
history of pre-eclampsia have been shown to be at increased risk of
CVD.
6–9
It brings to light the clinical challenges regarding: (1) the
establishment of an appropriate LDL-C target in this population,
and (2) the aggressiveness of dyslipidemia management. There
has been emerging literature on the association between the
history of pre-eclampsia and long-term vascular risk: a prospective
longitudinal cohort study and two systemic reviews with meta-
analyses have shown that women with pre-eclampsia have a
higher long-term risk of CVD (2 to 5.6 times), hypertension (3.7
times) and stroke (1.8 times).
6–8
In addition, these women are
at risk for premature CVD: a population-based study showed
that the mean age of a first cardiovascular event was 38.3 years
in women with a history of maternal placental syndromes.
9
While there is some evidence that lifestyle interventions help
to reduce cardiovascular risk in women with a history of pre-
eclampsia,
7
the thresholds for starting what will likely be lifelong
Canadian Journal of General Internal Medicine
26 Volume 13, Issue 3, 2018
Dyslipidemia Management after Pre-eclampsia
medication and the potential targets of medical management
have not been clear.
The 2011 AHA Guidelines for the Prevention of CVD in
Women
1
reflects the above evidence by including pre-eclampsia,
pregnancy-induced hypertension and gestational diabetes mellitus
as factors that put women in the “at risk” category for CVD,
along with smoking, hypertension, dyslipidemia, obesity, poor
diet, physical inactivity, family history, metabolic syndrome,
advanced subclinical atherosclerosis, and systemic autoimmune
collagen-vascular diseases such as lupus or rheumatoid arthritis.
Both these guidelines and the Pre-eclampsia Foundation suggest
a target LDL of <2.6mmol/L
5
(based on expert opinions as
currently there is no data on this issue) through lifestyle changes
as well as medication if required.
The 2016 Canadian guidelines have now included hypertensive
diseases of pregnancy as an indication to screen for dyslipidemia.
2
The pharmacological treatment indications for primary prevention
include: (1) high Framingham Risk Score (FRS) ≥20%, regardless
of LDL-C level, and (2) intermediate FRS (10–19%) with LDL-C
≥3.5 mmol/L, non-HDL-C ≥4.3 mmol/L, Apo B ≥1.2 g/L, or
men ≥50 and women ≥60 years old with 1 additional CVD risk
factor. Conditions for which a statin is indicated as initial therapy
include: clinical atherosclerosis, abdominal aortic aneurysm,
diabetes mellitus (age ≥40 years, 15-year duration for age ≥ 30
(DM 1) or microvascular disease), chronic kidney disease (age
≥50 years with estimated glomerular filtration rate <60 mL/
min/1.73 m
2
or albumin-to-creatinine ratio >3 mg/mmol),
or LDL-C ≥5.0 mmol/L. With the exception of LDL-C ≥ 5.0
mmol/L, the treatment targets for all of the above are LDL-C
<2.0 mmol/L or >50% decrease, ApoB <0.8 g/L, or non-HDL-C
<2.6 mmmol/L. The target for LDL-C ≥ 5.0 mmol.L is >50%
decrease in LDL-C. Of note, our patient would not have met
any of these CCS 2016 criteria for pharmacological treatment.
In comparison, the 2013 ACC/AHA Guideline on the
Treatment of Blood Cholesterol to Reduce Atherosclerotic
Cardiovascular Risk in Adults,
10
which does not specifically
address pre-eclampsia, recommends primary prevention with
a high intensity statin for adults aged 21 and older with LDL-C
≥4.91 mmol/L, with the goal of at least a 50% reduction in LDL-C.
For individuals <40 years of age with LDL-C <4.91mmol/L,
these guidelines state that statin therapy for primary prevention
may be considered in select individuals with risk factors such
as LDL-C ≥4.14 mmol/L, which would include patients such as
ours. As such, the current guidelines differ on the threshold of
lipids for treatment in young women who had a history of pre-
eclampsia, or hypertensive disorder of pregnancy. This makes
it very challenging for General Internists to actively reduce the
vascular risks in these young women who have an increased
long-term risk.
Conclusion
This case of a postpartum woman with dyslipidemia and a
history of pre-eclampsia illustrates the challenges involved in
determining the optimal management for cardiovascular risk
reduction in the context of increasing evidence that pregnancy
complications such as pre-eclampsia, pregnancy-induced
hypertension and gestational diabetes lead to an increased risk
of CVD later in life. Early identification of such women in the
peri- and postpartum period and active follow-up by a general
internist or referral to a Specialty Vascular Risk Reduction clinic
Table 1. LDL-C Target for Women with History of Hypertensive Disorders of Pregnancy and Pre-eclampsia
Guidelines LDL-C Target or Indication for Therapy in mmol/L (mg/dL)
AHA 2011
1
Target LDL-C <2.6 (<100) in women with history of pre-eclampsia, gestational diabetes, or pregnancy-
induced hypertension
Pre-eclampsia Foundation
5
Target LDL-C <2.6 (<100)
AHA/ACC 2013
10
After ruling out secondary causes of hyperlipidemia, treat if age ≥21 and LDL-C ≥ 4.91 (≥190), with goal
of ≥50% reduction
Consider treating if LDL-C ≥4.14 (≥160); no specific reference to pre-eclampsia
CCS 2016
2
In “intermediate” risk group, treat if LDL-C ≥3.5 (≥135) with target of >50% LDL-C reduction or LDL-C
<2.0 (<77)
In “low” risk group, treat if LDL-C ≥5.0 (≥193) with goal of 50% reduction
AHA = American Heart Association; ACC = American College of Cardiology; CCS = Canadian Cardiovascular Society; LDL-C = Low-density lipoprotein cholesterol; HDL-C = High-density
lipoprotein cholesterol; TC = Total cholesterol.
Canadian Journal of General Internal Medicine
Volume 13, Issue 3, 2018 27
Roger and Sia
(if available) can help to connect women with the resources and
support needed for lifestyle interventions and medical treatment
if appropriate. Work remains to be done in defining thresholds
for starting potentially lifelong medications in these young
women, as well as optimal targets for treatment.
We hope to make physicians aware that older women should
also be screened for a history of maternal placental syndromes
and pregnancy complications, as these factors have not typically
been included outside of the obstetrics and gynecology setting
when teaching trainees to take a past medical history. Validated
education tools exist
5
and practitioners can share these tools with
both patients and colleagues to increase awareness.
Finally, this case highlights the need for knowledge translation
of pre-eclampsia as a long-term vascular risk factor into lipid
guidelines for arguably secondary prevention in this often
under-recognized population.
Declarations
The authors declare this case report to be original work, and do
not have any commercial interests in this subject.
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