Preeclampsia Increases Risk of Early Stroke Incidence:

The California Teachers Study

Eliza C. Miller MD,1 Amelia K. Boehme PhD MSPH, 1 Nadia T. Chung MPH,2 James V. Lacey, Jr. PhD, 2 Jeanine Genkinger PhD,3 Yeseon Park

Moon MS, 1 Leslie Bernstein PhD, 2 Sophia S. Wang PhD, 2 Mary D’Alton MD,4 Mitchell S.V. Elkind MD MS, 1,3 Ronald Wapner MD, 4 Joshua Z.

Willey MD MS1

1. Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY. 2. City of Hope National Medical Center, Duarte, CA.3. Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY. 4. Department of Obstetrics and Gynecology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY.

Disclosures: None

Funding: NIH NINDS StrokeNet Training Core

Some recent patients

• Common and under-recognized CV risk factor

• Severe effects on cerebral vasculature

• Quadruples risk of hypertension & heart failure, doubles long term stroke risk

• Associated with metabolic syndrome later in life

• Increased white matter hyperintensities and carotid intima-media thickening years later

Preeclampsia: a complex disorder

Mongraw-Chaffin et al., Hypertension, 2010Jong Shiuan Yeh et al. J Am Heart Assoc 2014;3:e001008Hammer & Cipolla, Current Hypertension Reports, 2015

Aspirin and preeclampsia

• ASPRE trial, NEJM 2017: aspirin 150 mg started at 11-14 wks gestation reduced incidence of preterm preeclampsia in high risk women (1.6% vs 4.3%; NNT 38)

• USPSTF/ACOG guidelines recommend low dose aspirin starting in first trimester for high risk women

• No recommendations for aspirin use after preeclampsia

• Obstetric history not incorporated into CV risk calculators

Rolnick et al, ASPRE trial NEJM 2017

Hypotheses:

1. Women with history of preeclampsia have higher risk of stroke before age 60

2. Risk is modified by aspirin use

Jean-Auguste-Dominique Ingres, Comtesse d’Haussonville, 1845 (Frick Collection)

Methods

• Prospective longitudinal cohort study

• Serial questionnaires since 1995, outcomes via linkage with CA hospitals/death records

Total n=133,479

n=83,790 4,072 with preeclampsia (4.9%)

DemographicsPreeclampsia

(n=4072)

No preeclampsia

(n=79,718)

Mean age at start of study

(range)44.2 (23.5-59.9) 45.8 (22.1-59.9)

Mean age at first pregnancy (SD) 25.8 (5.1) 25.7 (4.9)

Average # of pregnancies (SD) 2.6 (1.4) 2.0 (1.5)

Race/ethnicity (self-identified)

White 3424 (84.1%) 67,684 (84.9%)

Black 119 (2.9%) 2079 (2.6%)

Hispanic 240 (5.9%) 4384 (5.5%)

Asian/Pacific Islander 157 (3.9%) 3311 (4.2%)

Native American 45 (1.1%) 482 (.6%)

Other/mixed 59 (1.5%) 1241 (1.6%)

Unknown 28 (.69%) 537 (.67%)

Patient characteristics

Preeclampsia

(n=4072)

No preeclampsia

(n=79,718)

Obesity 881 (21.6%) 10,658 (13.4%)

Smoking 1052 (25.8%) 22,053 (27.7%)

Migraine 1090 (26.8%) 17,041 (21.4%)

Diabetes 459 (11.3%) 4482 (5.6%)

Hypertension 1662 (40.8%) 17,310 (21.7%)

Chronic kidney disease 101 (4%) 865 (1.9%)

Reported aspirin use 1069 (26.3%) 19,369 (24.3%)

Results: Risk of stroke before age 60

• Preeclampsia: 38 of 4072 women (.93%)

• No preeclampsia: 495 of 79,718 women (0.62%)

• Cox PH time-to-event analysis: • Unadjusted HR 1.5 (1.1-2.1)• Adjusted for age, race, tobacco use: HR 1.5 (1.1-2.1)• Additional adjustments for hypertension, diabetes and

obesity: HR 1.2 (.87-1.7)

Stroke before 60 in women with and without history of preeclampsia, stratified by aspirin use

No aspirin Aspirin

PEC

(n=3003)

No PEC

(n=60,349)

PEC

(n=1069)

No PEC

(n=19,369)

Stroke

before 6031 (1.03%) 359 (0.59%) 7 (0.65%) 136 (0.70%)

Unadjusted

HR (95%CI)1.7 (1.2-2.5) 0.9 (0.4-2.0)

Adjusted* HR

(95%CI)1.4 (1.0-2.1) 0.7 (0.32-1.5)

*adjusted for age, race, smoking, obesity, diabetes, hypertension

PEC: preeclampsia

Conclusions

• Preeclampsia: sex-specific risk factor for stroke in young and middle aged women

• Risk may be mediated by, but is not entirely explained by hypertension and other comorbidities

• Aspirin may modify risk

Emilie du Chatelier, physicist, mathematician and natural philosopher, died in childbirth in 1749 at age 42

Portrait by Maurice Quentin de la Tour

Next steps

• Confirm results in more diverse cohorts

• Develop cardiovascular risk scores that incorporate obstetric history

• Early intervention opportunity (especially postpartum)?

• Time for a prevention trial?

Vincent van Gogh, Sien Nursing Baby, 1882

Thank you!

CTS team: Jim Lacey, Sophia Wang, Nadia Chung, Leslie BernsteinMentors and Collaborators: Josh Willey, Randy Marshall, Mitch Elkind,

Amelia Boehme, Jeanine Genkinger, Ronald Wapner, Kirsten Cleary, Mary D’alton, Natalie Bello