Persistence of Cardiovascular Risk Factors in Women With Previous Preeclampsia: A Long-term Follow-up Study Fatma Aykas, MD,* Yalcin Solak, MD,† Abdulsamet Erden, MD,* Kadir Bulut, MD,* Selcuk Dogan, MD,‡ Bahadır Sarli, MD,‡ Gokhan Acmaz, MD,§ Baris Afsar, MD,k Dimitrie Siriopol, MD,¶ Adrian Covic, MD,¶ Shailendra Sharma, MD,** Richard J. Johnson, MD,** and Mehmet Kanbay, MD†† Background: Preeclampsia is a cardiovascular (CV) disease risk factor, and lifestyle modifications are recommended. It was suggested that pre- eclampsia may increase the prevalence of various CV disease risk factors such as metabolic syndrome, hypertension, insulin resistance, microalbuminuria, and endothelial dysfunction, among others. Here, we investigate the role of serum uric acid in preeclampsia in the development of CV complications. Materials and Methods: This was an observational case-control study that compared women with history of preeclampsia (n = 25) with age- matched controls with uncomplicated pregnancies (n = 20) who were followed for at least 5 years. Measurements included clinical and ambula- tory blood pressure monitoring, ultrasound-measured flow-mediated dila- tation (FMD), microalbuminuria, carotid intima-media thickness (CIMT) and serum uric acid, as well as clinical and demographic features. Cardio- vascular disease risk factors were compared in women with and without previous preeclampsia. Results: At the time of index gestation, preeclamptic women had higher serum uric acid values (4.36 ± 0.61 vs 2.27 ± 0.38 mg/dL, P < 0.001). Five years after pregnancy, the patients who had preeclampsia were more likely to have hypertension and had higher serum uric acid levels, higher microalbuminuria and CIMT levels, and lower FMD values than did the patients who did not have preeclampsia. The 2 groups were similar with re- gard to various ambulatory blood pressure parameters. Univariate associ- ates of FMD were history of preeclampsia and the current hypertension status. Microalbuminuria correlated with gestational uric acid levels (coef- ficient of correlation of 0.40, P = 0.01 for FMD and coefficient of correla- tion of 0.37, P = 0.01 for CIMT, respectively). Conclusions: Preeclampsia might be a risk factor for the development of cardiovascular risk factors at least 5 years after index pregnancy. Serum uric acid and microalbuminuria may be mechanistic mediators of height- ened risk, along with impaired endothelial function in preeclampsia. Key Words: preeclampsia, cardiovascular disease, risk factor, endothelial dysfunction, uric acid, microalbuminuria (J Investig Med 2015;63: 00–00) P reeclampsia is a multisystem disorder characterized by mater- nal endothelial dysfunction. The disease is characterized by hypertension, proteinuria, and edema that develop after 20 weeks of gestation. Preeclampsia complicates 2% to 8% of all pregnan- cies and is associated with increased morbidity and immediate mortality of both the mother and the fetus. 1 Women with pre- eclampsia have increased long-term risks for developing hyper- tension and cardiovascular (CV) disease. 2,3 Thus, preeclampsia is a CV disease risk factor, and women with a history of pre- eclampsia are recommended to undergo lifestyle modification to reduce CV disease risk. 4 Several studies have evaluated the role of microalbuminuria, endothelial dysfunction (through flow-mediated dilatation [FMD] and soluble markers of vascular function), carotid intima-media thickness (CIMT), and increased blood pressure as risk factors for future CV 5–7 events. However, serum uric acid has been seldom studied to date in studies investigating future risk for developing CV disease in preeclampsia despite it being characteristically high in this condi- tion and despite its strong association with CV disease in nonpreg- nant subjects. 8 We therefore evaluated the role of uric acid in preeclamptic patients with a future history of metabolic and cardiorenal disease including blood pressure, microalbuminuria, endothelial function, CIMT, and uric acid in a case-control study design. MATERIALS AND METHODS Study Design and Participants This is an observational case-control study that recruited pa- tients with preeclampsia during their pregnancy and women whose pregnancies were not complicated by preeclampsia as con- trol subjects. Case patients and control subjects were recruited from the Department of Obstetrics and Gynecology of Kayseri Education and Research Hospital, Turkey. The primary aim of this study was to investigate the effects of previous preeclampsia and uric acid on the future development of hypertension, kidney func- tion, CIMT, and endothelial function. We included all available patients who had experienced a pregnancy complicated by pre- eclampsia from before January 2008. A total of 44 eligible pa- tients with preeclampsia were initially examined in the study. Seven patients had a previous history of hypertension, 3 patients had chronic kidney disease, 8 patients were lost to follow-up, and 1 patient withdrew consent. Twenty-five patients with a his- tory of preeclampsia were included in the final analysis. Preeclampsia is diagnosed when blood pressure is 140 mm Hg systolic or greater or 90 mm Hg diastolic or greater on 2 From the *Department of Medicine, Kayseri Training and Research Hospital, Kayseri; †Department of Medicine, Division of Nephrology, Sakarya University Training and Research Hospital, Sakarya; Departments of ‡Cardiology, and §Gynecology, Kayseri Training and Research Hospital, Kayseri; kDepartment of Nephrology, Konya Numune State Hospital, Konya, Turkey; ¶Nephrology Clinic, Dialysis and Renal Transplant Center, C.I. Parhon University Hospital and Grigore T. Popa University of Medicine, Iasi , Romania; **Division of Renal Diseases and Hypertension, University of Colorado, Denver, CO; and ††Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey. Received September 24, 2014, and in revised form January 21, 2015. Accepted for publication January 22, 2015. Reprints: Mehmet Kanbay, MD, Department of Medicine, Division of Nephrology, Koc University School of Medicine, 03490, Sariyer, Istanbul, Turkey. E-mail:drkanbay@yahoo.com; mkanbay@ku.edu.tr. Conflict of interest: Dr. Johnson is an inventor on several patent and patent applications related to lowering uric acid in the treatment of metabolic and renal diseases that have been licensed to XORT Therapeutics. The other authors state that they have no proprietary interest in the products named in this article. Copyright © 2015 by The American Federation for Medical Research ISSN: 1081-5589 DOI: 10.1097/JIM.0000000000000189 ORIGINAL ARTICLE Journal of Investigative Medicine • Volume 63, Number 4, April 2015 1 Copyright © 2015 American Federation for Medical Research. Unauthorized reproduction of this article is prohibited.