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Background Hypertensive disorders of pregnancy (HDP) are a leading global cause of maternal and fetal morbidity/mortality. Most estimates of HDP occurrence are reported for composite exposures of HDP or preeclampsia alone, with limited disaggregation by obstetrical subgroup (eg, multi‐fetal deliveries). Consequently, our understanding of HDP prevalence and temporal trends remains limited, and methods for identifying specific diagnoses in administrative data remain underexamined. This population‐based descriptive study assessed how enhanced administrative case‐finding definitions influence prevalence estimates of HDP in pregnancy and postpartum. Methods Included were individuals aged ≥18 years discharged from an Ontario hospital following their first obstetrical delivery between April 1, 2002, and December 31, 2017. We calculated overall and annual prevalence estimates and assessed temporal trends for any HDP and major subtypes by case‐finding definitions, stratified by plurality (singleton versus multi‐fetal deliveries). Results Most subjects had a singleton first delivery (n=781 258; 98%); however, HDP was 2.2 to 2.4 times more prevalent in multi‐fetal deliveries. When pre‐pregnancy hypertension was considered during case‐finding, HDP prevalence increased from 193.6 to 207.6 per 1000 multi‐fetal deliveries and from 79.9 to 92.6 per 1000 singleton deliveries. Gestational hypertension was the most common diagnosis in both populations but was nearly twice as common in those who delivered a multiple gestation (94.4–100.0 versus 49.7–53.4 per 1000 deliveries). Prevalence trends differed by coding strategy and plurality. Conclusions Although informative, data from discharge abstracts alone are insufficient for HDP surveillance, particularly for chronic hypertension in pregnancy. Validation studies should assess the accuracy of our case‐finding definitions against suitable reference standards.

TPS3184 Background: Replication stress (RS) creates cancer cell vulnerability to which the critical DNA damage response kinase, ATR (Ataxia-Telangiectasia and Rad3-related) responds. ATR senses the stress, halts the cell cycle, and promotes DNA repair to allow proliferation. Alnodesertib is an ATR inhibitor developed to prevent cancer cells from successfully repairing RS and proliferating further. In earlier stages of alnodesertib development, preclinical and translational research demonstrated that tumor cells experience three combined biological insults: irinotecan-induced RS, endogenous RS via ataxia-telangiectasia mutated (ATM) loss, and RS rescue prevention by ATR inhibition. Data from the dose escalation and initial dose expansion cohorts of this trial in a tumor agnostic population showed encouraging results in ATM-negative cancers (confirmed Overall Response Rate of 50% in 20 patients with ATM negative cancers and responses across 8 cancer types including complete responses, Ulahannan et al, AACR 2025). Tumor-specific dose expansion cohorts are now enrolling, including colorectal cancer (CRC) and pancreas ductal adenocarcinoma (PDAC). Methods: Two tumor-specific cohorts are now open, each enrolling approximately 50 patients (pts): ATM-negative CRC and ATM-negative PDAC. Pts will receive the recommended dose of alnodesertib 200mg orally on days 1-3 and 8-10 combined with low-dose irinotecan 60mg/m 2 IV on days 1 and 8, of each 21-day cycle. Tumor tissue is prescreened by immunohistochemistry for ATM protein loss (H score 0) for enrollment eligibility. Pts with CRC must have received a maximum of 2 prior chemotherapies excluding prior trifluridine/tipiracil, fruquintinib, or regorafenib, and pts with PDAC must have received a maximum of 1 prior chemotherapy for advanced disease. Prior targeted agents are allowed and do not count as prior lines of therapy. Key objectives include safety, tolerability, and preliminary efficacy. Clinical trial information: NCT04657068 .

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a major cause of maternal morbidity and mortality and are associated with acute cardiac events in the peripartum period, as well as cardiovascular disease later in life. Despite the robust association between hypertension and atrial fibrillation (AFib), comparatively little is known about HDP and its subtypes as sex-specific risk factors for AFib. METHODS: A population-based retrospective cohort study was conducted, including 771 521 nulliparous women discharged for obstetrical delivery of their first live or stillborn singleton infant between 2002 and 2017 in Ontario, Canada. Data were obtained from record-level, coded, and linked population-based administrative databases housed at ICES. Using competing risks Cox proportional hazards regression, we estimated crude and multivariable-adjusted cause-specific hazard ratios and 95% CIs for associations between history of any HDP (and its 6 subtypes), and AFib before death, as well as all-cause mortality without a previous AFib diagnosis. RESULTS: Approximately 8% of women were diagnosed with HDP during the 16-year exposure accrual period. The total person-time of follow-up was 7 380 304 person-years, during which there were 2483 (0.3%) incident AFib diagnoses and 2951 (0.4%) deaths. History of any HDP was associated with an increased cause-specific hazard ratios of incident AFib and death without a previous AFib diagnosis (adjusted cause-specific hazard ratios, 1.45 [95% CI, 1.28–1.64] and 1.31 [95% CI, 1.16–1.47], respectively). These associations were observed in relatively young women (median time to event, 7 years postpartum). Associations suggestive of a dose-response relationship were observed, with more severe HDP subtypes and prepregnancy chronic hypertension associated with a 1.5 to 2.2 times higher cause-specific rate of AFib, and a 1.4 to 2.1 times higher cause-specific rate of death compared with no hypertension in pregnancy. CONCLUSIONS: Women exposed to HDP in their first delivery have a significantly increased cause-specific hazard ratios of incident AFib compared to their unexposed counterparts, with higher rates observed in subjects exposed to more severe de novo HDP diagnoses as well as chronic hypertension in pregnancy. These findings underscore the need to consider HDP history in risk calculation/stratification for arrhythmic and nonarrhythmic cardiovascular diseases, improve surveillance of traditional and female-specific cardiovascular disease risk factors, and develop targeted prevention strategies to reduce the occurrence and burden of HDP.

AbstractBackgroundHypertensive disorders of pregnancy (HDP) are a major cause of maternal morbidity and mortality, and their association with increased cardiovascular disease (CVD) risk represents a major public health concern. However, assessing CVD risk in women with a history of these conditions presents unique challenges, especially when studies are carried out using routinely collected data.ObjectivesTo summarise and describe key challenges related to the design and conduct of administrative studies assessing CVD risk in women with a history of HDP and provide concrete recommendations for addressing them in future research.MethodsThis is a methodological guidance paper.ResultsSeveral conceptual and methodological factors related to the data‐generating mechanism and study conceptualisation, design/data management and analysis, as well as the interpretation and reporting of study findings should be considered and addressed when designing and carrying out administrative studies on this topic. Researchers should develop an a priori conceptual framework within which the research question is articulated, important study variables are identified and their interrelationships are carefully considered.ConclusionsTo advance our understanding of CVD risk in women with a history of HDP, future studies should carefully consider and address the conceptual and methodological considerations outlined in this guidance paper. In highlighting these challenges, and providing specific recommendations for how to address them, our goal is to improve the quality of research carried out on this topic.

Beyond conventional risk factors for cardiovascular disease, women face an additional burden of sex-specific risk factors. Key stages of a woman’s reproductive history may influence or reveal short- and long-term cardiometabolic and cardiovascular trajectories. Early and late menarche, polycystic ovary syndrome, infertility, adverse pregnancy outcomes (eg, hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, and intrauterine growth restriction), and absence of breastfeeding are all associated with increased future cardiovascular disease risk. The menopause transition additionally represents a period of accelerated cardiovascular disease risk, with timing (eg, premature menopause), mechanism, and symptoms of menopause, as well as treatment of menopause symptoms, each contributing to this risk. Differences in conventional cardiovascular disease risk factors appear to explain some, but not all, of the observed associations between reproductive history and later-life cardiovascular disease; further research is needed to elucidate hormonal effects and unique sex-specific disease mechanisms. A history of reproductive risk factors represents an opportunity for comprehensive risk factor screening, refinement of cardiovascular disease risk assessment, and implementation of primordial and primary prevention to optimize long-term cardiometabolic health in women.