1. Cochrane ALK, Murphy MP, Ozanne SE, Giussani DA. Pregnancy in obese women and mechanisms of increased cardiovascular risk in offspring. Eur Heart J 2024;45:5127–45. Pregnancy complicated by maternal obesity contributes to an increased cardiovascular risk in offspring, which is increasingly concerning as the rates of obesity and cardiovascular disease are higher than ever before and still growing. There has been much research in humans and preclinical animal models to understand the impact of maternal obesity on offspring health. This review summarizes what is known about the offspring cardiovascular phenotype, describing a mechanistic role for oxidative stress, metabolic inflexibility, and mitochondrial dysfunction in mediating these impairments. It also discusses the impact of secondary postnatal insults, which may reveal latent cardiovascular deficits that originated in utero. Finally, current interventional efforts and gaps of knowledge to limit the developmental origins of cardiovascular dysfunction in offspring of obese pregnancy are highlighted.
2. Zhang Y, Yu S, Chen Z, et al. Gestational diabetes and future cardiovascular diseases: associations by sex-specific genetic data. Eur Heart J 2024;45: 5156–67. This study demonstrated a suggestive causal relationship between genetic predisposition to gestational diabetes mellitus and the risk of coronary artery disease, which was mainly mediated by Type 2 diabetes and hypertension. These findings highlight targeting modifiable cardiometabolic risk factors may reduce the risk of coronary artery disease in women with a history of gestational diabetes mellitus.
3. Di Pietrantonio N, Sánchez-Ceinos J, Shumliakivska M, Rakow A, Mandatori D, Di Tomo P, et al. The inflammatory and oxidative phenotype of gestational diabetes is epigenetically transmitted to the offspring: role of methyltransferase MLL1-induced H3K4me3. Eur Heart J 2024;45:5171–85. Such proof-of-concept study shows persistence of MLL1-dependent H3K4me3 in offspring born to GD women, suggesting an epigeneticdriven transmission of maternal phenotype. These findings may pave the way for pharmacological reprogramming of adverse histone modifications to mitigate abnormal phenotypes underlying early ASCVD.
4. Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med 2024;391:109–21. Among patients with complex coronary-artery bifurcation lesions, OCT-guided PCI was associated with a lower incidence of MACE at 2 years than angiography-guided PCI.
5. Mahaffey KW, Tuttle KR, Arici M, et al. Cardiovascular outcomes with semaglutide by severity of chronic kidney disease in type 2 diabetes: the FLOW trial. Eur Heart J 2025;46:1096–108. In this individual patient data meta-analysis, DAPT-based de-escalation was associated with both decreased ischaemic and bleeding endpoints. Reduction in bleeding endpoints was more prominent for the unguided than the guided de-escalation strategy.
6. Badve SV, Bilal A, Lee MMY, et al. Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a metaanalysis of randomised controlled trials. Lancet Diabetes Endocrinol 2025;13:15–28. We found evidence that GLP-1 receptor agonists significantly reduce clinically important kidney events, kidney failure, and cardiovascular events.
7. Pratley RE, Tuttle KR, Rossing P, et al. Effects of semaglutide on heart failure outcomes in diabetes and chronic kidney disease in the FLOW trial. J Am Coll Cardiol 2024;84:1615–28. We found evidence that GLP-1 receptor agonists significantly reduce clinically important kidney events, kidney failure, and cardiovascular events.
8. Butler J, Shah SJ, Petrie MC, et al. Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials. Lancet 2024;403:1635–48. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide was superior to placebo in improving heart failure-related symptoms and physical limitations, and reducing bodyweight in participants with obesity-related heart failure with preserved ejection fraction. These effects were largely consistent across patient demographic and clinical characteristics. Semaglutide was well tolerated.
9. Kosiborod MN, Deanfield J, Pratley R, et al. Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. Lancet 2024;404:949–61. In patients with HFpEF, semaglutide reduced the risk of the combined endpoint of cardiovascular death or worsening heart failure events, and worsening heart failure events alone, whereas its effect on cardiovascular death alone was not significant. These data support the use of semaglutide as an efficacious therapy to reduce the risk of clinical heart failure events in patients with HFpEF, for whom few treatment options are currently available.
10. Neuen BL, Fletcher RA, Heath L, et al. Cardiovascular, kidney, and safety outcomes with GLP-1 receptor agonists alone and in combination with SGLT2 inhibitors in type 2 diabetes: a systematic review and meta- analysis. Circulation 2024;150:1781–90. In people with type 2 diabetes, the cardiovascular and kidney benefits of GLP-1 receptor agonists are consistent regardless of SGLT2 inhibitor use.
11. Apperloo EM, Neuen BL, Fletcher RA, et al. Efficacy and safety of SGLT2 inhibitors with and without glucagon-like peptide 1 receptor agonists: a SMART-C collaborative meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol 2024;12: 545–57. The effects of SGLT2 inhibitors on cardiovascular and kidney outcomes are consistent regardless of the background use of GLP-1 receptor agonists. These findings suggest independent effects of these evidence-based therapies and support clinical practice guidelines recommending the use of these agents in combination to improve cardiovascular and kidney metabolic outcomes.
12. Bi Y, Li M, Liu Y, et al. Intensive blood pressure control in patients with type 2 diabetes. N Engl J Med 2025;392:1155–67. Among patients with type 2 diabetes, the incidence of major cardiovascular events was significantly lower with intensive treatment targeting a systolic blood pressure of less than 120 mm Hg than with standard treatment targeting a systolic blood pressure of less than 140 mm Hg.
13. Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med 2024;391:1193–205. Among persons with moderate-to-severe obstructive sleep apnea and obesity, tirzepatide reduced the AHI, body weight, hypoxic burden, hsCRP concentration, and systolic blood pressure and improved sleeprelated patient-reported outcomes.
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