Browsing by Author "Patel, Aniruddh P."

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    Association of premature menopause with incident pulmonary hypertension: A cohort study
    (PLOS, 2021-03-10) Honigberg, Michael C.; Patel, Aniruddh P.; Lahm, Tim; Wood, Malissa J.; Ho, Jennifer E.; Kohli, Puja; Natarajan, Pradeep; Medicine, School of Medicine
    Background: Several forms of pulmonary hypertension (PH) disproportionately affect women. Animal and human studies suggest that estradiol exerts mixed effects on the pulmonary vasculature. Whether premature menopause represents a risk factor for PH is unknown. Methods and findings: In this cohort study, women in the UK Biobank aged 40-69 years who were postmenopausal and had complete data available on reproductive history were included. Premature menopause, defined as menopause occurring before age 40 years. Postmenopausal women without premature menopause served as the reference group. The primary outcome was incident PH, ascertained by appearance of a qualifying ICD code in the participant's UK Biobank study record. Of 136,715 postmenopausal women included, 5,201 (3.8%) had premature menopause. Participants were followed up for a median of 11.1 (interquartile range 10.5-11.8) years. The primary outcome occurred in 38 women (0.73%) with premature menopause and 409 (0.31%) without. After adjustment for age, race, ever-smoking, body-mass index, systolic blood pressure, antihypertensive medication use, non-high-density lipoprotein cholesterol, cholesterol-lowering medication use, C-reactive protein, prevalent type 2 diabetes, obstructive sleep apnea, heart failure, mitral regurgitation, aortic stenosis, venous thromboembolism, forced vital capacity (FVC), the forced expiratory volume in 1 second-to-FVC ratio, use of menopausal hormone therapy, and hysterectomy status, premature menopause was independently associated with PH (hazard ratio 2.13, 95% CI 1.31-3.23, P<0.001). In analyses of alternate menopausal age thresholds, risk of PH appeared to increase progressively with younger age at menopause (Ptrend <0.001), with 4.8-fold risk in women with menopause before age 30 years (95% CI 1.82-12.74, P = 0.002). Use of menopausal hormone therapy did not modify the association of premature menopause with PH. Conclusions: Premature menopause may represent an independent risk factor for PH in women. Further investigation of the role of sex hormones in PH is needed in animal and human studies to elucidate pathobiology and identify novel therapeutic targets.
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    Genetic Risk and First-Trimester Cardiovascular Health Predict Hypertensive Disorders of Pregnancy in Nulliparous Women
    (Elsevier, 2025) Mathew, Vineetha; Khan, Raiyan R.; Jowell, Amanda R.; Yan, Qi; Pe'er, Itsik; Truong, Buu; Natarajan, Pradeep; Yee, Lynn M.; Khan, Sadiya S.; Sharma, Garima; Patel, Aniruddh P.; Cho, So Mi Jemma; Pabon, Maria A.; McNeil, Rebecca B.; Spencer, Jillyn; Silver, Robert M.; Levine, Lisa D.; Grobman, William A.; Catov, Janet M.; Haas, David M.; Honigberg, Michael C.; Obstetrics and Gynecology, School of Medicine
    Background: Hypertensive disorders of pregnancy (HDPs) (preeclampsia/eclampsia and gestational hypertension) are a leading cause of maternal and perinatal morbidity and mortality and are associated with long-term maternal cardiovascular disease. High genetic risk and poor cardiovascular health (CVH) are each associated with HDPs, but whether genetic risk for HDP is modified by CVH status in early pregnancy is unknown. Objectives: In this study, the authors sought to test the independent and joint associations of genetic risk and first-trimester CVH with development of HDP. Methods: We examined genotyped participants from the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be), a prospective observational cohort that enrolled nulliparous individuals with singleton pregnancies from 2010 to 2013 at 8 U.S. clinical sites. Genetic risk was calculated according to a validated genetic risk score for HDP. A first-trimester CVH score was closely adapted from the American Heart Association Life's Essential 8 model. Genetic risk and CVH were each categorized as low (bottom quintile), intermediate (quintile 2-4), or high (top quintile). The primary outcome was development of HDP. Multivariable-adjusted logistic regression was used to test the independent and joint associations of genetic risk and CVH with development of HDPs. Results: Among 7,499 participants (mean age 27.0 years), the median first-trimester CVH score was 77.1 (Q1-Q3: 67.1-85.7). Overall, 1,032 participants (13.8%) developed an HDP (487 [6.5%] preeclampsia, 545 [7.3%] gestational hypertension). Genetic risk and CVH were each independently and additively associated with HDP (high vs low genetic risk: adjusted OR [aOR]: 2.21 [95% CI: 1.78-2.77; P < 0.001]; low vs high CVH: aOR: 2.92 [95% CI: 2.28-3.74; P < 0.001]). There was no significant interaction between genetic risk and CVH regarding risk of HDPs (Pinteraction > 0.05). HDP incidence ranged from 4.5% (low genetic risk, high CVH) to 25.7% (high genetic risk, low CVH). Compared with low CVH, high CVH was associated with 53%-74% lower risk of HDP across genetic risk strata. Findings were consistent when examining preeclampsia/eclampsia and gestational hypertension separately. Conclusions: Lower genetic risk and higher first-trimester CVH were independently and additively associated with lower risk of developing HDPs in nulliparous individuals. Favorable CVH in early pregnancy may mitigate high genetic risk for HDP.
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    Polygenic prediction of preeclampsia and gestational hypertension
    (Springer Nature, 2023) Honigberg, Michael C.; Truong, Buu; Khan, Raiyan R.; Xiao, Brenda; Bhatta, Laxmi; Vy, Ha My T.; Guerrero, Rafael F.; Schuermans, Art; Selvaraj, Margaret Sunitha; Patel, Aniruddh P.; Koyama, Satoshi; Cho, So Mi Jemma; Vellarikkal, Shamsudheen Karuthedath; Trinder, Mark; Urbut, Sarah M.; Gray, Kathryn J.; Brumpton, Ben M.; Patil, Snehal; Zöllner, Sebastian; Antopia, Mariah C.; Saxena, Richa; Nadkarni, Girish N.; Do, Ron; Yan, Qi; Pe’er, Itsik; Verma, Shefali Setia; Gupta, Rajat M.; Haas, David M.; Martin, Hilary C.; van Heel, David A.; Laisk, Triin; Natarajan, Pradeep; Obstetrics and Gynecology, School of Medicine
    Preeclampsia and gestational hypertension are common pregnancy complications associated with adverse maternal and child outcomes. Current tools for prediction, prevention and treatment are limited. Here we tested the association of maternal DNA sequence variants with preeclampsia in 20,064 cases and 703,117 control individuals and with gestational hypertension in 11,027 cases and 412,788 control individuals across discovery and follow-up cohorts using multi-ancestry meta-analysis. Altogether, we identified 18 independent loci associated with preeclampsia/eclampsia and/or gestational hypertension, 12 of which are new (for example, MTHFR-CLCN6, WNT3A, NPR3, PGR and RGL3), including two loci (PLCE1 and FURIN) identified in the multitrait analysis. Identified loci highlight the role of natriuretic peptide signaling, angiogenesis, renal glomerular function, trophoblast development and immune dysregulation. We derived genome-wide polygenic risk scores that predicted preeclampsia/eclampsia and gestational hypertension in external cohorts, independent of clinical risk factors, and reclassified eligibility for low-dose aspirin to prevent preeclampsia. Collectively, these findings provide mechanistic insights into the hypertensive disorders of pregnancy and have the potential to advance pregnancy risk stratification.