Kwak S, Park CS, Park Y
… +6 more, Rhee TM, Lee H, Kim HK, Kim YJ, Han K, Park JB
JAMA Intern Med
· 2026 Apr · PMID 41627823
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IMPORTANCE: Hypertensive disorders of pregnancy (HDPs) are associated with an increased long-term risk of cardiovascular disease, but the risks across different HDP subtypes, particularly those other than preeclampsia, r...IMPORTANCE: Hypertensive disorders of pregnancy (HDPs) are associated with an increased long-term risk of cardiovascular disease, but the risks across different HDP subtypes, particularly those other than preeclampsia, remain unclear. OBJECTIVE: To examine whether the risk and distribution of specific cardiovascular outcomes differ across HDP subtypes. DESIGN, SETTING, AND PARTICIPANTS: This nationwide cohort study retrospectively analyzed women with deliveries in South Korea from 2010 to 2018 using the National Health Insurance Service database. HDPs were classified into 5 subtypes: chronic hypertension, gestational hypertension, superimposed preeclampsia, preeclampsia/eclampsia, and unspecified hypertension. Events were verified through December 2022. Data were analyzed from June 1 to October 31, 2025. EXPOSURES: HDPs and their subtypes. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of cardiovascular events, including cardiovascular death, heart failure, myocardial infarction, stroke, and atrial fibrillation. Adjusted hazard ratios (AHRs) were estimated using Cox models accounting for age, cardiovascular comorbidities, demographic, lifestyle, and pregnancy-related factors. RESULTS: Among 570 843 women (mean [SD] age, 32.7 [4.0] years), 22 876 (4.0%) had HDPs. HDPs were associated with a higher incidence of cardiovascular events compared with women without HDPs (AHR, 1.62; 95% CI, 1.49-1.76; P < .001). The absolute risk increase was approximately 2.10 additional cardiovascular events per 1000 person-years over a median follow-up of 6.5 years (IQR, 4.7-8.7 years; incidence rate, 4.39 vs 2.29 per 1000 person-years). Among those with HDPs, 34.8% had gestational hypertension, 32.4% had preeclampsia or eclampsia, 17.7% had unspecified hypertension, 12.3% had chronic hypertension, and 2.8% had superimposed preeclampsia. All subtypes were independently associated with higher cardiovascular risk, with the highest risk observed in superimposed preeclampsia compared with women without HDPs (AHR, 2.93; 95% CI, 2.15-3.99; P < .001). All subtypes were associated with increased risks of heart failure and stroke, and most subtypes were associated with higher cardiovascular mortality. Unspecified hypertension was associated with myocardial infarction, and chronic hypertension and unspecified hypertension were associated with atrial fibrillation. CONCLUSIONS AND RELEVANCE: In this cohort study, all HDP subtypes were associated with modest increases in long-term cardiovascular risk, except superimposed preeclampsia, which was associated with a markedly higher risk. These findings suggest that women with superimposed preeclampsia may benefit from closer postpartum cardiovascular surveillance.
Pop-Busui R, Rasmussen S, Deanfield JE
… +21 more, Buse JB, Marx N, Mulvagh SL, Inzucchi SE, Mann JFE, Emerson SS, Poulter NR, Engelmann MDM, Hovingh GK, Bayer Tanggaard K, Birkenfeld AL, Connelly KA, Haluzik M, Cavender MA, Kellerer M, Jhund PS, Gregersen S, Nielsen OW, Lam CSP, McGuire DK, SOUL Study Group
JAMA Intern Med
· 2026 Apr · PMID 41627802
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IMPORTANCE: Heart failure (HF) is a common complication of type 2 diabetes (T2D). Oral semaglutide reduced the risk of major adverse cardiovascular (CV) events (MACE; comprising CV death, nonfatal myocardial infarction,...IMPORTANCE: Heart failure (HF) is a common complication of type 2 diabetes (T2D). Oral semaglutide reduced the risk of major adverse cardiovascular (CV) events (MACE; comprising CV death, nonfatal myocardial infarction, or nonfatal stroke) in people with T2D in the SOUL trial, but the impact on HF outcomes in these participants is unknown. OBJECTIVE: To evaluate the effect of oral semaglutide on HF events, MACE, and safety among participants with or without HF at baseline. DESIGN, SETTING, AND PARTICIPANTS: This is a secondary analysis of the double-blind, placebo-controlled, event-driven, phase 3b SOUL randomized clinical trial, which was conducted at 444 centers in 33 countries. Participants were enrolled from June 17, 2019, to March 24, 2021, and had T2D and atherosclerotic CV disease and/or chronic kidney disease, stratified according to the presence or absence of HF history at baseline. Data were analyzed from December 2024 to August 2025. INTERVENTION: Once-daily oral semaglutide or placebo in addition to standard of care. MAIN OUTCOMES AND MEASURES: Prespecified composite HF outcome (time to first occurrence of HF hospitalization, urgent HF visit, or CV death). RESULTS: Overall, 9650 participants (median [IQR] age, 66.0 [61.0-72.0] years; 2790 [28.9%] female) were randomized, with a mean (SD) follow-up of 47.5 (10.9) months. Of these participants, 2229 (23.1%) had HF history (991 [10.3%] with preserved ejection fraction, 592 [6.1%] with reduced ejection fraction, and 646 [6.7%] with unknown subtype). For participants with HF at baseline, the hazard ratio (HR) for risk of the composite HF outcome with oral semaglutide vs placebo was 0.78 (95% CI, 0.63-0.96) and was 1.01 (95% CI, 0.84-1.20) in those without HF at baseline (P for interaction = .06). Among participants with HF, the HR was 0.59 (95% CI, 0.39-0.86) in those with preserved ejection fraction and 0.98 (95% CI, 0.70-1.38) in those with reduced ejection fraction. There was no heterogeneity in the risk reduction of MACE with oral semaglutide in participants with HF history (HR, 0.83; 95% CI, 0.68-1.01) or without HF history (HR, 0.86; 95% CI, 0.75-0.98) (P for interaction = .77). Serious adverse event occurrence among participants with HF was similar with oral semaglutide (594 [53.8%]) and placebo (642 [57.1%]). CONCLUSIONS AND RELEVANCE: In this secondary analysis of the SOUL randomized clinical trial, among individuals with T2D, atherosclerotic CV disease, and/or chronic kidney disease, a reduction of HF events was observed with use of oral semaglutide compared with placebo in those with a history of HF, without increasing the risk of serious adverse events. These data support the potential benefit of oral semaglutide in reducing HF events in people with T2D and HF. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03914326.
Cipolletta E, Zverkova Sandström T, Rozza D
… +8 more, Leyrat C, Nakafero G, Drivelegka P, Avery AJ, Mamas MA, Tata LJ, Dehlin M, Abhishek A
JAMA Intern Med
· 2026 Mar · PMID 41587055
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IMPORTANCE: Gout is associated with increased cardiovascular risk. Whether achieving a target serum urate level lower than 6 mg/dL with urate-lowering treatment (ULT) would reduce cardiovascular risk in patients with gou...IMPORTANCE: Gout is associated with increased cardiovascular risk. Whether achieving a target serum urate level lower than 6 mg/dL with urate-lowering treatment (ULT) would reduce cardiovascular risk in patients with gout is unknown. OBJECTIVES: To evaluate the association between achieving a serum urate treatment target lower than 6 mg/dL and cardiovascular events among patients with gout who were newly prescribed ULT. DESIGN, SETTING, AND PARTICIPANTS: This new-user cohort study using emulated target trial framework with up to 5-year follow-up was performed using primary care data from the Clinical Practice Research Datalink Aurum linked to hospitalization and mortality records from January 1, 2007, to March 29, 2021. Patients were 18 years or older, diagnosed with gout, had a pretreatment serum urate level higher than 6 mg/dL, and were newly prescribed ULT. Data were analyzed from May 2024 to January 2025. EXPOSURE: Patients were assigned to the treat-to-target (T2T) ULT arm or the non-T2T ULT arm if they achieved or did not achieve a serum urate level lower than 6 mg/dL, respectively, within 12 months of their first ULT prescription. MAIN OUTCOMES AND MEASURES: The primary outcome was first major adverse cardiovascular event within 5 years of first ULT prescription. Gout flare was the positive control outcome. Acute bronchitis, cataract, and appendicitis were included as negative control outcomes. Weighted absolute 5-year event-free survival and weighted hazard ratios (HRs) with 95% CIs were estimated. RESULTS: Of 109 504 patients included, the mean (SD) age was 62.9 (15.2) years, 22.2% were female, the mean (SD) disease duration was 2.5 (3.6) years, and 27.3% were included in the T2T ULT arm. Patients in the T2T ULT arm had a higher 5-year survival (weighted survival difference, 1.0%; 95% CI, 0.5%-1.6%) and lower risk of major adverse cardiovascular events (weighted HR, 0.91; 95% CI, 0.89-0.92) than those in the non-T2T ULT arm. There was a greater association for people at high and very high cardiovascular risk than those with moderate risk. Patients who achieved a lower serum urate target of less than 5 mg/dL had a larger risk reduction (weighted survival difference, 2.6%; 95% CI, 0.9%-3.6%; weighted HR, 0.77; 95% CI, 0.72-0.81). Patients in the T2T ULT arm had fewer gout flares. No differences were observed for negative control outcomes. CONCLUSIONS AND RELEVANCE: In this cohort study among patients with gout who were newly prescribed ULT, achieving serum urate levels lower than 6 mg/dL within 12 months was associated with a lower 5-year risk of major adverse cardiovascular events.
JAMA Intern Med
· 2026 Mar · PMID 41557438
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IMPORTANCE: Approximately 25% to 40% of hospitalized adults are discharged to receive postacute care (PAC) either at home through home health (HH) or in skilled nursing facilities (SNFs), inpatient rehabilitation facilit...IMPORTANCE: Approximately 25% to 40% of hospitalized adults are discharged to receive postacute care (PAC) either at home through home health (HH) or in skilled nursing facilities (SNFs), inpatient rehabilitation facilities (IRFs), or long-term acute care hospitals (LTACHs). An overview of various PAC settings is needed to help hospital-based clinicians collaborate most effectively with patients, caregivers, and an interdisciplinary care team to promote high-quality PAC and facilitate better PAC transitions. OBSERVATIONS: PAC settings vary in their eligibility requirements and in the intensity and complexity of services they provide. HH provides intermittent in-home support for homebound individuals with skilled needs. SNFs provide housing, daily nursing care, rehabilitative services, and medical supervision, although the medical care provided is often a dramatic step down from hospital-based acute care. IRFs provide intensive rehabilitation, most commonly for individuals with specific diagnoses (eg stroke, hip fracture, or spinal cord injury). LTACHs care for patients with medically complex conditions who require prolonged hospital-level care for services (eg, ventilator weaning, complex wound management). Discharge planning to PAC should be guided by clinical needs, caregiver support, and the values and preferences of patients and caregivers; yet it is often opaque and influenced by external factors such as insurance coverage and geography. Clinicians should proactively recognize PAC needs, advocate for specific PAC settings for targeted situations, and assist on selecting an appropriate PAC facility, especially for patients with insurance restrictions. Moreover, PAC admissions frequently represent a pivotal time period for individuals with serious illness, during which a subsequent poor prognosis becomes clear. Therefore, PAC stays represent an opportunity for clinicians to revisit prognosis with patients and caregivers, engage in goals of care conversations, and clarify plans for the future. CONCLUSIONS AND RELEVANCE: To provide patient-centered care and help facilitate better transitions for patients and caregivers, hospital-based clinicians have a responsibility to understand the different types of PAC settings and actively participate in discharge planning.
Jensen SK, Heide-Jørgensen U, Andersen IT
… +4 more, Bonnesen K, Fu EL, Thomsen RW, Christiansen CF
JAMA Intern Med
· 2026 Mar · PMID 41557360
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IMPORTANCE: No randomized clinical trial has directly compared the effectiveness of sodium-glucose cotransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment in reducing acute and...IMPORTANCE: No randomized clinical trial has directly compared the effectiveness of sodium-glucose cotransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment in reducing acute and chronic kidney outcomes. OBJECTIVE: To examine the comparative effectiveness of SGLT2i and GLP-1RA treatment for acute and chronic kidney outcomes in individuals with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study with a target trial emulation design used nationwide, population-based data from Denmark. Participants were individuals with metformin-treated type 2 diabetes who initiated SGLT2i or GLP-1RA treatment from January 2014 to November 2020, with follow-up through October 2024. EXPOSURE: Initiation of an SGLT2i or a GLP-1RA. MAIN OUTCOMES AND MEASURES: The 2 coprimary outcomes were chronic kidney disease (CKD; 40% reduction in estimated glomerular filtration rate [eGFR], severe albuminuria, or kidney failure) and acute kidney injury (AKI). Secondary outcomes included the individual components of CKD, albuminuria, and death. Intention-to-treat effects were estimated using inverse probability of treatment weights, comparing risks for CKD assessed by the Aalen-Johansen estimator, and AKI burden by mean cumulative counts (MCCs; mean number of events per individual as multiple AKI events were possible). Subgroup analyses included stratification by preexisting cardiovascular or kidney disease. RESULTS: The study included 36 279 individuals who initiated an SGLT2i and 18 782 who initiated a GLP-1RA (median [IQR] age, 63 [55-71] years vs 61 [52-70] years), with comparable diabetes duration, eGFR, and urine albumin-creatinine ratios. The weighted 5-year risk of CKD was 6.7% (95% CI, 6.4%-7.0%) for SGLT2i initiators and 8.2% (95% CI, 7.8%-8.6%) for GLP-1RA initiators (risk ratio: 0.81 [95% CI, 0.76-0.87]; risk difference: -1.5% [95% CI, -2.0% to -1.0%]). The 5-year MCC of AKI per 100 individuals was 25.2 (95% CI, 24.4-26.1) for SGLT2i initiators and 28.7 (95% CI, 27.4-30.0) for GLP-1RA initiators (MCC ratio: 0.88 [95% CI, 0.83-0.93]; MCC difference: -3.5 [95% CI, -5.0 to -2.0]). In contrast, the secondary outcomes of albuminuria and mortality were slightly reduced in GLP-1RA initiators. Results were consistent across subgroups, with the most pronounced CKD and AKI reductions with SGLT2i observed among individuals without preexisting kidney disease. CONCLUSIONS AND RELEVANCE: This comparative effectiveness study found that initiation of SGLT2i vs GLP-1RA treatment in individuals with type 2 diabetes was associated with a lower 5-year risk of CKD and a lower 5-year count of AKI. These findings underscore the potential of SGLT2i treatment for primary prevention of kidney disease in individuals with type 2 diabetes.