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Is Preeclampsia and Spontaneous Preterm
Delivery Associated with Vascular and
Cardiac Function
Margo B. Minissian, PhD, ACNP-BC, RN, NEA-BC, FAHA, FAAN
Executive Director, Nursing Innovation and Research
Cedars Sinai Health System
Simms Mann Family Foundation Chair in Nurse Education, Innovation and Research
Leah Spiro, DNP, FNP-C
Clinical Research Nurse Scientist, Nurse Practitioner
Nursing Innovation and Research, Postpartum Heart Health Program
Cedars Sinai Health System
Cardiovascular Disease Risk Factors Unique to Women
Traditional Factors
Age, HTN, HLD,
Smoking, DM
Inactivity, Poor diet,
Family history
Other Factors
APO, Autoimmune
disorders, CKD, Chest
wall radiation, Cardio-
toxic chemotherapy
Hormonal Factors
Premature menopause,
Hormone therapy,
PCOS, Obesity, Cardio-
metabolic risk
Social Determinants
of Health
Race/ethnicity, Education,
Income, Zip code
Psychological Risk
Factors
Depression, Anxiety,
Loneliness, Perceived stress
Inflammation
Endothelial dysfunction, Subclinical Atherosclerosis,
Autonomic Dysfunction, Immune Dysfunction
Cardiovascular Disease
MI, Heart Failure, Stroke, Sudden cardiac death
Cho, L. et al. J Am Coll Cardiol. 2020; 75(20):2602-18.
Risk Enhancing Factors
Hemodynamic Changes During Normal Pregnancy
Liu L, Arany Z et al. Cardiovascular Research. 2014; 101:545-553
Hall et al. Rev Esp Cardiol. 2011 November; 64(11): 1045-1050
Khalil et al. Ultrasound in obstetrics & gynecology: 2012; 40:35-9
Minissian, MB. 2017; https://scholarship.org/uc/item/39h203jp
Foundation Work: Association of sPTD and Maternal ASCVD Risk
• Prior Study Aim: Assess vascular function of sPTD women against term
controls 24-72 hours postpartum
• Vascular assessments measured Augmentation Index (AIx75), central
pulse pressure (CPP), and pulse wave velocity (PWV)
• sPTD women had lower AIx75 vs controls (24.10 ± 16.10% vs. 39.90 ±
15.2%, p=0.001)
• sPTD women had lower CPP vs controls (29.1 ± 5 mmHg vs 34.6 ± 6
mmHg, p=0.004)
Foundation Work: Vascular Function is Different in Women with sPTD vs
Full-Term Controls at 24-72 Hours (Visit 1) vs. 6 Months (Visit 2) Postpartum
39.9 ± 15.2 vs 21.4 ± 16.1, p<0.001 26.3±9.8 vs 26.9 ± 13, p=0.887
Results support follow up of APO patients’
vascular tone to assess ASCVD risk
PE and sPTD women may have endothelial
dysfunction after pregnancy related to APO
Mean brachial SBP and mean central SBP are
potential ASCVD risk screening tools for PE
women
Vascular function in sPTD is likely
mechanistically different than hypertensive
disorders of pregnancy such as PE
Is it potentially beneficial for a woman to go
through the “vascular exercise” of a full-term
pregnancy?
Discussion and Limitations
6
Currently NINR Funded
7
Comparative, longitudinal study in 4 groups of women:
1. Women with preterm PreE (<37weeks)
2. sPTD (≤34 weeks)
3. TPre (≥37 weeks)
4. Full-term delivery (≥ 39 weeks)
Women give informed consent, will be enrolled, and complete baseline
study procedures up to 3 months postpartum (K99). Measurements will be
repeated at 1-2 years postpartum (R00).
Aims
8
Aim 1: Investigate group differences (N=120) in vascular function measured by augmentation index and
pulse wave velocity at entry (1- 3 months) and at 1-2 years (+/- 3 months) and 2-3 years (+/- 3 months)
postpartum.
Hypothesis: both spontaneous preterm delivery, preterm preeclampsia and term preeclampsia groups will
experience vascular dysfunction compared to full-term controls at 24-72 hours postpartum. Preterm
preeclampsia group will display continued vascular dysfunction and at 1-2 years follow up.
Aim 2: Investigate group differences (N=80) in cardiac structure and function measured by CMRI utilizing
Cine, Tissue Tagging (left ventricular systolic and diastolic function including strain), T1 mapping (fibrosis),
at 1-2 years (+/- 3 months) and 2-3 years (+/- 3 months) postpartum.
Hypothesis: Preterm preeclampsia will experience cardiac structural/ functional anomalies compared to
full-term controls at 1-2 years (+/- 3 months) and 2-3 years (+/- 3 months) postpartum.
Significance
9
Significance: Results will provide important information regarding group
differences in pre-clinical ASCVD pathways of adverse pregnancy outcomes
that will inform future interventions to identify and address alterations in
peripartum vascular and cardiac function associated with ASCVD risk in women.
I have 4 publications on this topic including a publication in Circulation. These
data will inform innovative solutions in the field symptom science which
specifically address symptom precursors and how they contribute to the
physiology of symptom risk, severity, duration, and response to future treatment.
Pregnancies Middle age
Population with complicated pregnancy, e.g. PE
Healthy population
Threshold for clinical vascular or metabolic disease
Vascular
dysfunction
Targeted screening, lifestyle modification, early treatment
Courtesy of Dr. Janet Rich Edwards
Future Clinical Implications

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Is preeclampsia and spontaneous preterm delivery associate with vascular and cardiac function

  • 1. cedars-sinai.org Is Preeclampsia and Spontaneous Preterm Delivery Associated with Vascular and Cardiac Function Margo B. Minissian, PhD, ACNP-BC, RN, NEA-BC, FAHA, FAAN Executive Director, Nursing Innovation and Research Cedars Sinai Health System Simms Mann Family Foundation Chair in Nurse Education, Innovation and Research Leah Spiro, DNP, FNP-C Clinical Research Nurse Scientist, Nurse Practitioner Nursing Innovation and Research, Postpartum Heart Health Program Cedars Sinai Health System
  • 2. Cardiovascular Disease Risk Factors Unique to Women Traditional Factors Age, HTN, HLD, Smoking, DM Inactivity, Poor diet, Family history Other Factors APO, Autoimmune disorders, CKD, Chest wall radiation, Cardio- toxic chemotherapy Hormonal Factors Premature menopause, Hormone therapy, PCOS, Obesity, Cardio- metabolic risk Social Determinants of Health Race/ethnicity, Education, Income, Zip code Psychological Risk Factors Depression, Anxiety, Loneliness, Perceived stress Inflammation Endothelial dysfunction, Subclinical Atherosclerosis, Autonomic Dysfunction, Immune Dysfunction Cardiovascular Disease MI, Heart Failure, Stroke, Sudden cardiac death Cho, L. et al. J Am Coll Cardiol. 2020; 75(20):2602-18. Risk Enhancing Factors
  • 3. Hemodynamic Changes During Normal Pregnancy Liu L, Arany Z et al. Cardiovascular Research. 2014; 101:545-553 Hall et al. Rev Esp Cardiol. 2011 November; 64(11): 1045-1050 Khalil et al. Ultrasound in obstetrics & gynecology: 2012; 40:35-9 Minissian, MB. 2017; https://scholarship.org/uc/item/39h203jp
  • 4. Foundation Work: Association of sPTD and Maternal ASCVD Risk • Prior Study Aim: Assess vascular function of sPTD women against term controls 24-72 hours postpartum • Vascular assessments measured Augmentation Index (AIx75), central pulse pressure (CPP), and pulse wave velocity (PWV) • sPTD women had lower AIx75 vs controls (24.10 ± 16.10% vs. 39.90 ± 15.2%, p=0.001) • sPTD women had lower CPP vs controls (29.1 ± 5 mmHg vs 34.6 ± 6 mmHg, p=0.004)
  • 5. Foundation Work: Vascular Function is Different in Women with sPTD vs Full-Term Controls at 24-72 Hours (Visit 1) vs. 6 Months (Visit 2) Postpartum 39.9 ± 15.2 vs 21.4 ± 16.1, p<0.001 26.3±9.8 vs 26.9 ± 13, p=0.887
  • 6. Results support follow up of APO patients’ vascular tone to assess ASCVD risk PE and sPTD women may have endothelial dysfunction after pregnancy related to APO Mean brachial SBP and mean central SBP are potential ASCVD risk screening tools for PE women Vascular function in sPTD is likely mechanistically different than hypertensive disorders of pregnancy such as PE Is it potentially beneficial for a woman to go through the “vascular exercise” of a full-term pregnancy? Discussion and Limitations 6
  • 7. Currently NINR Funded 7 Comparative, longitudinal study in 4 groups of women: 1. Women with preterm PreE (<37weeks) 2. sPTD (≤34 weeks) 3. TPre (≥37 weeks) 4. Full-term delivery (≥ 39 weeks) Women give informed consent, will be enrolled, and complete baseline study procedures up to 3 months postpartum (K99). Measurements will be repeated at 1-2 years postpartum (R00).
  • 8. Aims 8 Aim 1: Investigate group differences (N=120) in vascular function measured by augmentation index and pulse wave velocity at entry (1- 3 months) and at 1-2 years (+/- 3 months) and 2-3 years (+/- 3 months) postpartum. Hypothesis: both spontaneous preterm delivery, preterm preeclampsia and term preeclampsia groups will experience vascular dysfunction compared to full-term controls at 24-72 hours postpartum. Preterm preeclampsia group will display continued vascular dysfunction and at 1-2 years follow up. Aim 2: Investigate group differences (N=80) in cardiac structure and function measured by CMRI utilizing Cine, Tissue Tagging (left ventricular systolic and diastolic function including strain), T1 mapping (fibrosis), at 1-2 years (+/- 3 months) and 2-3 years (+/- 3 months) postpartum. Hypothesis: Preterm preeclampsia will experience cardiac structural/ functional anomalies compared to full-term controls at 1-2 years (+/- 3 months) and 2-3 years (+/- 3 months) postpartum.
  • 9. Significance 9 Significance: Results will provide important information regarding group differences in pre-clinical ASCVD pathways of adverse pregnancy outcomes that will inform future interventions to identify and address alterations in peripartum vascular and cardiac function associated with ASCVD risk in women. I have 4 publications on this topic including a publication in Circulation. These data will inform innovative solutions in the field symptom science which specifically address symptom precursors and how they contribute to the physiology of symptom risk, severity, duration, and response to future treatment.
  • 10. Pregnancies Middle age Population with complicated pregnancy, e.g. PE Healthy population Threshold for clinical vascular or metabolic disease Vascular dysfunction Targeted screening, lifestyle modification, early treatment Courtesy of Dr. Janet Rich Edwards Future Clinical Implications

Editor's Notes

  1. As cardiac output and blood volume increase during gestation, systemic vascular resistance decreases causing decreases in vascular stiffness and vasodilation, reaching nadir in the second to early third trimester. At the time of delivery, arterial stiffness increases as cardiac output and blood volume decrease- to maintain homeostasis. During preeclampsia, vascular stiffness is INCREASED and continues up to 6 months postpartum compared to normal pregnancy. On the contrary, We have previously described decreased vascular stiffness in women with sPTD compared to their matched term controls at 24-72 hours postpartum
  2. We have previously described decreased vascular function in women with sPTD compared to their matched term controls at 24-72 hours postpartum (Citation is above). The aim of this study was to assess vascular function over time in women who experience sPTD compared to matched, term delivery controls.
  3. At 24-72 hours postpartum, women with sPTD had significantly lower AIx75 compared to term controls (39.9 ± 15.2 vs 21.4 ± 16.1, p<0.001). At 6 months, women with sPTD had no significant difference in AIx75 compared to term controls (26.3±9.8 vs 26.9 ± 13, p=0.887). In simpler terms, at 6 months: sPTD women had no sig changes in augmentation index. Term controls had sig. lower AIx75
  4. A possible explanation to our findings is that sPTD deliveries have a much lower AIx75 at the 24-72 hour timepoint due to the timing of the delivery. In full-term deliveries, there is a u-shaped curve to AIx75 with the lowest AIx75 occurring between late-second and early third trimester when our sPTD would deliver. During term pregnancy AIx75 increases in the third trimester and then postpartum, hence having a higher AIx75 in term pregnancies as these deliveries are further along.25, 26 They both then return to baseline at 6 months postpartum. Our data may have important clinical implications as it may suggest that adverse pregnancy outcomes may have different vascular mechanistic pathways. Medically indicated preterm delivery (preeclampsia and hypertension disorders in pregnancy) has been associated with increased AIx75 up to 6 months postpartum. Where our data suggested initial vasodilation likely related to the early delivery and then returns to baseline by 6 months. However, implications are unknown for women with sPTD in relation to their vasculature not experiencing augmentation of their vascular tone during late pregnancy and immediately postpartum in a similar fashion as the matched full-term control group. Future research questions include: Is it potentially beneficial for a woman to go through the “vascular exercise” of a full-term pregnancy? Is her vascular function contributing to the preterm delivery itself? Is she therefore unable to complete her first physiological stress test?
  5. Clinical Implications: Assess and document pregnancy history Early ASCVD risk factor modification Improve home BP monitoring technique and measurement frequency Optimal medical therapy for treatment of postpartum and essential HTN