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 MS 1 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
Preeclampsia: a complex disorder 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 Mongraw-Chaffin et al., Hypertension, 2010 Jong Shiuan Yeh et al. J Am Heart Assoc 2014;3:e001008 Hammer & 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%)
Demographics Mean age at start of study (range) Preeclampsia (n=4072) No preeclampsia (n=79,718) 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 60 31 (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 Bernstein Mentors and Collaborators: Josh Willey, Randy Marshall, Mitch Elkind, Amelia Boehme, Jeanine Genkinger, Ronald Wapner, Kirsten Cleary, Mary D alton, Natalie Bello