A new era in reducing obesity and the risk of cardiovascular disease events in preeclampsia

Women with preeclampsia have increased short-term risks to the foetus (intrauterine growth restriction, preterm delivery) and themselves [renal failure, HELLP syndrome, disseminated intravascular coagulation (DIC), cerebral haemorrhage]. They also have a doubling in the long-term risk of cardiovascular disease (CVD) and stroke, attributed to endothelial dysfunction and inflammation. In addition to preeclampsia, stillbirth, preterm birth, gestational hypertension, gestational diabetes, polycystic ovary syndrome and shorter length of breastfeeding are also associated with an increased risk of CVD; and oral contraceptive use, gestational diabetes and polycystic ovary syndrome are associated with increased risk of stroke [1]. However, none of these factors can be modulated, and lowering blood pressure (BP) is not viable in young women who may wish to conceive again. Barbosa et al. have undertaken a retrospective case-cohort study to reveal that central obesity promotes an increase in ambulatory and day-time BP, arterial stiffness and incidence of stroke in young women with preeclampsia. The authors suggest ‘targeted prevention strategies’ but do not elaborate on what this might entail. Most would endorse diet and exercise, but the reality is this achieves moderate short-term weight loss at best, is not maintained in the long-term and has no benefit on CVD events [2,3]. However, we are now in a new era in the management of obesity with several highly efficacious approved therapies and multiple new treatments undergoing evaluation in phase I/II/III clinical trials [4]. Weekly subcutaneous Semaglutide 2.4 mg (-13.7% body weight) [5], a glucagon-like peptide-1 (GLP-1)-mono-agonist, oral Semaglutide 25 mg (-11.4% body weight) [6], a small-molecule, nonpeptide oral GLP-1 receptor agonist-Orfoglipron (-11.2% body weight) [7]; dual GLP1/GIP agonists (Tirzepatide-15 mg) (-20.2% body weight) [5]; Cagrisema (Semaglutide-2.4 mg/Cagrilintide-long acting amylin-analog-2.4 mg) (-17% body weight) [8] and Mazdutide (GLP-1/glucagon receptor dual agonist) (-12% body weight) [9] as well as the GLP1/GIP/glucagon receptor triple agonist- Retatrutide (-24.2% body weight) [10] have shown robust weight loss. These therapies reduce central adiposity, SBP and DBP and insulin resistance, resulting in remission of prediabetes and type 2 diabetes [11] and a significant reduction in the incidence of CVD events and stroke. This pipeline of innovative and highly effective therapies for obesity could have a transformative effect in altering the trajectory of long-term adverse outcomes of preeclampsia. Clinical trial data is now required to provide definitive proof of their benefits in women with a history of preeclampsia. Alternatively, leveraging powerful platform technologies like TrinetX with their integrated analytics could provide robust evidence to endorse their use in clinical practice [12]. ACKNOWLEDGEMENTS None. Conflicts of interest None.