Metabolomics of Right Ventricular Function in Pulmonary Hypertension
The findings suggest that steroid hormone pathways, vitamin A metabolism, glutathione-related pathways, fatty acid metabolism, and polyamine metabolism may play important roles in RV adaptation and dysfunction. The observation that androgenic steroid metabolites have stronger associations with RV function in females highlights the potential importance of sex-specific biological mechanisms.
KEY FINDINGS: This study provides one of the most comprehensive metabolomic characterizations of RV systolic function across the spectrum of pulmonary hypertension. The findings suggest that steroid hormone pathways, vitamin A metabolism, glutathione-related pathways, fatty acid metabolism, and polyamine metabolism may play important roles in RV adaptation and dysfunction. The observation that androgenic steroid metabolites have stronger associations with RV function in females highlights the potential importance of sex-specific biological mechanisms. The results also indicate that RV metabolic signatures appear relatively consistent across different PH subtypes and levels of pulmonary vascular resistance, supporting the concept of shared metabolic pathways in RV remodeling. These findings may contribute to future biomarker development and therapeutic targeting strategies aimed at preserving RV function in pulmonary hypertension.
BACKGROUND: Right ventricular (RV) dysfunction is a major determinant of outcomes in patients with pulmonary hypertension (PH), yet the metabolic mechanisms underlying RV impairment remain incompletely understood. Previous research has primarily focused on pulmonary vascular disease, while the metabolic pathways contributing to RV adaptation or failure across different forms of PH have received less attention. This study sought to identify circulating metabolites and metabolic pathways associated with RV systolic function and to determine whether these associations vary according to pulmonary vascular resistance, PH subtype, or sex.
DETAILS: Investigators analyzed data from the multicenter PVDOMICS (Pulmonary Vascular Disease Phenomics) cohort. The study evaluated RV systolic performance using echocardiographic fractional area change, global longitudinal strain, and cardiac magnetic resonance-derived ejection fraction. Plasma metabolomic profiling was performed, and statistical analyses were adjusted for age, sex, body mass index, and PH classification. Pathway enrichment analyses were used to identify biologically relevant metabolic networks associated with RV function. The investigators also assessed whether metabolite associations differed according to pulmonary vascular resistance, Group 1 PH status, or sex. In addition, metabolite-based predictive scores were developed and evaluated for prognostic utility. The study included 979 participants with available plasma metabolomic and RV functional data. Analysis identified 170 metabolites that demonstrated significant associations across all three RV function measurements. Metabolic pathways most strongly linked to RV systolic performance included androgenic steroid metabolism, gamma-glutamyl amino acid metabolism, polyamine metabolism, vitamin A metabolism, fatty acid metabolism, and sterol pathways. Only 2 metabolites showed significant interaction with Group 1 PH status, while 6 metabolites demonstrated interaction with pulmonary vascular resistance. Four androgenic steroid metabolites exhibited stronger associations with RV systolic function in women than in men. Metabolite-derived scores demonstrated prognostic performance comparable to RV functional measurements but were less accurate than REVEAL Lite 2 risk scores.
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Source: Chacon-Barahona, J., Chung, S. J., Garry, J. D., et al. Metabolomics of Right Ventricular Function in Pulmonary Hypertension. Circulation Research. 138(11): e328512. Published: April 15, 2026. DOI: 10.1161/CIRCRESAHA.125.327342
Somatic Diseases May Affect the Brain Primarily Through Vascular Injury and Neuronal Loss
A narrative review found that common age-related somatic diseases were consistently associated with brain atrophy, neuronal loss, and cerebrovascular lesions. Evidence linking these diseases to amyloid and tau pathology was limited and inconsistent. The findings suggest that systemic diseases may contribute to dementia primarily through non-Alzheimer's mechanisms, particularly vascular injury and neuronal loss. The review underscores the importance of recognizing mixed dementia and considering systemic health in the assessment of cognitive decline.
KEY FINDINGS: Common age-related somatic diseases appear to be more consistently associated with cerebrovascular injury, brain atrophy, and neuronal loss than with amyloid or tau pathology. These findings suggest that the relationship between systemic disease and dementia may involve multiple non-AD pathways rather than a direct effect on classical AD pathology. The review highlights the importance of recognizing mixed dementia and considering systemic health when evaluating brain aging and cognitive decline.
BACKGROUND: Several common age-related somatic diseases are associated with an increased risk of dementia, but the neuropathological pathways underlying these associations remain incompletely understood. This narrative review examined evidence linking heart disease, type 2 diabetes, kidney disease, liver disease, lung disease, and anemia with brain pathology, including Alzheimer's disease (AD)-related amyloid and tau pathology and non-AD changes such as neuronal loss, brain atrophy, cerebrovascular lesions, neuroinflammation, and non-AD proteinopathies.
DETAILS: The authors conducted a PubMed search for human studies investigating associations between somatic diseases and brain pathology using postmortem examinations, brain imaging, or cerebrospinal fluid biomarkers. The available evidence was qualitatively synthesized and graded according to its strength. The review specifically evaluated whether common systemic diseases were associated with AD-related pathology or with other forms of brain injury that may contribute to cognitive impairment and dementia.
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Across the conditions examined, the strongest and most consistent associations were between somatic diseases and global neuronal loss or brain atrophy, as well as cerebrovascular lesions. In contrast, associations between somatic diseases and amyloid or tau deposition were limited and inconsistent. The review found no systematic studies examining neuroinflammation or non-AD proteinopathies in relation to somatic diseases.
Overall, the available evidence suggests that systemic diseases may contribute to brain damage predominantly through non-AD mechanisms, particularly cerebrovascular injury and diffuse neuronal loss, rather than by directly driving the characteristic amyloid and tau pathology of AD. The authors emphasize that these processes may contribute to the complex combination of pathologies frequently underlying dementia in older adults.
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Source: Grande, G., Valletta, M., Gasparini, F., et al. Brain pathology in relation to somatic diseases: Exploring the body–brain crosstalk. Journal of Internal Medicine. 2026; 300(3): 223–237. Published: June 2, 2026. DOI: 10.1111/joim.70119.
Hypertension at 5 Months Postpartum in Women With Gestational Diabetes
Among 678 women with recent gestational diabetes mellitus, 26.4% developed hypertension by 5 months postpartum. Higher early-pregnancy weight and blood pressure, Black or mixed ethnicity, and gestational hypertension or pre-eclampsia were associated with increased risk. Postpartum hypertension was also associated with greater adiposity and dyslipidemia. The findings support structured postpartum screening for blood pressure and broader cardiometabolic risk after GDM.
KEY FINDINGS: Approximately one in four women with recent GDM developed hypertension by 5 months postpartum. Higher maternal weight and blood pressure early in pregnancy, as well as Black or mixed ethnicity, were associated with increased risk, while gestational hypertension or pre-eclampsia was also associated with postpartum hypertension. Women with postpartum hypertension had greater adiposity and more frequent dyslipidemia, highlighting the broader cardiometabolic abnormalities present after GDM. Because early-pregnancy characteristics provided only modest prediction, the findings support structured postpartum assessment that includes blood pressure and broader cardiometabolic risk evaluation rather than focusing solely on dysglycemia.
BACKGROUND: Gestational diabetes mellitus (GDM) is associated with an increased risk of later cardiometabolic disease, including hypertension. However, the occurrence and determinants of hypertension soon after pregnancy complicated by GDM have not been well defined. This prospective study evaluated the incidence and predictors of hypertension at 5 months postpartum and examined its relationship with other cardiometabolic abnormalities in women with recent GDM.
DETAILS: This single-center observational prospective cohort study was conducted at King's College Hospital, London, between September 2023 and January 2025. Women with GDM who received routine prenatal care at 12 weeks' gestation were invited for a postpartum assessment at approximately 5 months after delivery; women with chronic hypertension were excluded. The assessment included blood pressure, BMI, waist circumference, glucose status, lipid profile, and renal function. Hypertension was defined as systolic BP ≥ 130 mmHg, diastolic BP ≥ 80 mmHg, or receipt of antihypertensive treatment. Of 912 women with GDM invited for postpartum review, 696 (76.3%) attended. After excluding 18 women with chronic hypertension, 678 women constituted the study cohort. Follow-up occurred at a median of 5.1 (IQR, 4.4-6.7) months after birth.
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Among the 678 women with previous GDM, 179 (26.4%) developed hypertension at a median of 5.1 (IQR, 4.4-6.7) months postpartum. Women who subsequently developed hypertension had higher early-pregnancy weight and blood pressure. At 12 weeks' gestation, median weight was 79.3 kg versus 69.3 kg among women who remained normotensive, while median systolic BP was 121.8 versus 115.5 mmHg and median diastolic BP was 74.5 versus 70.3 mmHg, respectively. Obesity at this stage was also more frequent among women who later developed hypertension (50.3% vs 28.5%). Pregnancy hypertensive disorders were more common among women who developed postpartum hypertension. Gestational hypertension occurred in 8.4% versus 3.8%, and pre-eclampsia in 9.5% versus 1.8%, among women who developed postpartum hypertension compared with those who remained normotensive.
Multivariable analysis identified higher maternal age, Black or mixed ethnicity, higher weight, and higher systolic and diastolic BP at 12 weeks as predictors of postpartum hypertension. Black ethnicity was associated with an adjusted OR of 1.88 (95% CI, 1.19-3.00), mixed ethnicity with an adjusted OR of 2.75 (95% CI, 1.21-6.24), and weight ≥ 73 kg with an adjusted OR of 1.57 (95% CI, 1.04-2.38). Each 1-mmHg increase in systolic BP was associated with an adjusted OR of 1.04 (95% CI, 1.02-1.07), and each 1-mmHg increase in diastolic BP with an adjusted OR of 1.04 (95% CI, 1.00-1.07). Development of gestational hypertension or pre-eclampsia was associated with an adjusted OR of 3.00 (95% CI, 1.69-5.34).
At the postpartum assessment, women with hypertension had a median BMI of 30.1 (IQR, 26.7-36.8) kg/m² compared with 27.0 (IQR, 23.5-30.6) kg/m² among normotensive women. A waist-to-height ratio > 0.5 was present in 87.7% versus 69.1%, and dyslipidemia in 35.8% versus 24.4%, respectively. Dysglycemia and renal dysfunction did not differ significantly between the groups.
The prenatal prediction model had only modest discriminatory ability. The AUC was 0.723 (95% CI, 0.680-0.766) using characteristics available at 12 weeks and 0.739 (95% CI, 0.697-0.782) after adding gestational hypertension or pre-eclampsia. At a 20% false-positive rate, detection rates were 49.5% and 53.7%, respectively.
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Source: Gomez Fernández, C., Charakida, M., Moser, M., et al. Hypertension at 5 months postpartum in women with gestational diabetes. Ultrasound in Obstetrics & Gynecology. 2026; 68(2): 202-210. Published: July 17, 2026. DOI: 10.1002/uog.70291.
Potassium Binders May Support Continued RAAS Inhibitor Therapy in Chronic Kidney Disease and Heart Failure
Second-generation potassium binders were associated with greater persistence of RASi and MRA therapy than first-generation binders. Continued RASi use was associated with lower observed mortality and hospitalization, but not with a clear difference in 3P-MACE. These findings suggest potassium binders may facilitate sustained RAASi therapy in CKD and HF.
KEY FINDINGS: In this Swedish nationwide observational cohort, second-generation potassium binders were associated with greater persistence of RASi and MRA therapy at 6 months than first-generation binders. RASi persistence was also associated with lower observed all-cause mortality and hospitalization, although no clear difference in 3P-MACE was identified. The findings support the potential role of potassium binders in maintaining guideline-directed RAASi therapy in patients with CKD and/or HF.
BACKGROUND: Renin–angiotensin–aldosterone system inhibitors (RAASi) provide important cardiorenal benefits in chronic kidney disease (CKD) and heart failure (HF), but their use can increase the risk of hyperkalemia. Hyperkalemia frequently leads to RAASi discontinuation despite the benefits of continued therapy. This study evaluated whether potassium binders, particularly second-generation agents, were associated with greater persistence of RAASi and mineralocorticoid receptor antagonist (MRA) therapy.
DETAILS:
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Source: Furuland, H., Larsson, A. O., Uhde, M., et al. Potassium Binders and Continuation of Renin–Angiotensin System Inhibitors/Mineralocorticoid Receptor Antagonist in Chronic Kidney Disease and Heart Failure (the DEMONSTRATE Database. Journal of Internal Medicine. 2026; 300(2): 179-192. Published: Augusts, 2026. DOI: 10.1111/joim.70087.
2026 Dyslipidemia Guideline Expands Eligibility for Primary Prevention Statin Therapy in US Adults
The 2026 dyslipidemia guideline substantially expands primary prevention statin eligibility in US adults, with an estimated 87.5 million adults (56.6% of the target population) eligible for therapy, including 21.5 million newly eligible individuals. The expansion primarily affects younger, lower-risk adults compared with prior recommendations.
KEY FINDINGS: The 2026 dyslipidemia guideline substantially increases the number of US adults recommended for primary prevention statin therapy. This expansion includes a large group of individuals who were not previously considered candidates for statins and who generally have lower estimated 10-year ASCVD risk. The findings highlight the potential impact of updated risk assessment strategies on preventive cardiovascular care and clinical decision-making regarding statin initiation.
BACKGROUND: The 2026 American Heart Association/American College of Cardiology/multisociety guideline on dyslipidemia introduced updated recommendations for estimating atherosclerotic cardiovascular disease (ASCVD) risk and determining eligibility for primary prevention statin therapy. This study evaluated the projected population-level impact of these updated recommendations compared with the 2018 lipid guidelines.
DETAILS: This nationally representative cross-sectional study analyzed data from nonpregnant adults aged 30 to 79 years without known ASCVD who participated in the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2023. The analysis included 4366 participants representing 154.5 million US adults. Data were analyzed from March to May 2026.
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The study compared statin eligibility under the 2026 dyslipidemia guideline with recommendations from the 2018 lipid guidelines. The investigators assessed the proportion of adults eligible for primary prevention statin therapy, including individuals qualifying based on low-density lipoprotein cholesterol (LDL-C) levels, diabetes, chronic kidney disease, or ASCVD risk estimation.
The study estimated that the 2026 guideline would expand primary prevention statin eligibility to 21.5 million US adults who were not previously recommended statin therapy. Overall, 87.5 million US adults (56.6% of the target population) were estimated to be eligible for statins under the new guideline.
Among the weighted sample, 5.5% (95% CI, 4.7%-6.6%) had untreated LDL-C below 70 mg/dL, 17.8% (95% CI, 16.3%-19.5%) reported current statin use, and 8.6% (95% CI, 7.6%-9.8%) met criteria for statin therapy independent of ASCVD risk estimation based on LDL-C of 190 mg/dL or greater, diabetes, or chronic kidney disease.
Eligibility increased substantially among older adults, with more than 93% of adults aged 70 to 79 years and 85% of adults aged 60 to 69 years meeting criteria for primary prevention statin therapy, compared with 11% of adults aged 30 to 39 years.
The newly eligible population generally represented younger and lower-risk adults compared with those previously recommended statins. The mean estimated 10-year ASCVD risk was 3.1% (95% CI, 2.7%-3.5%) among newly eligible individuals compared with 6.1% (95% CI, 5.8%-6.4%) among those previously eligible.
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Source: Anderson, T. S., Wilson, L. M., and Sussman, J. B. Implications of the 2026 Dyslipidemia Guideline for Primary Prevention Statin Therapy. JAMA. 2026; Published: July 20, 2026. DOI: 10.1001/jama.2026.11246
Accuracy of Fetal Echocardiography for Detecting Associated Lesions and Predicting Surgical Management in Dextro-Transposition of the Great Arteries and Double Outlet Right Ventricle with Subpulmonary Ventricular Septal Defect
In a cohort of 99 fetuses with D-TGA or DORV-SPV, fetal echocardiography showed high diagnostic accuracy for simple D-TGA but lower accuracy for complex lesions. Serial assessment frequently altered VSD characterization, while fetal aortic measurements and aortic-to-pulmonary artery ratios (AUC above 0.9) accurately predicted postnatal CoA repair.
KEY FINDINGS: Fetal echocardiography demonstrated excellent diagnostic performance for simple D-TGA but substantially lower accuracy in complex D-TGA and DORV-SPV with associated lesions. Serial fetal assessment frequently altered qualitative VSD size estimation, while many small postnatally confirmed VSDs did not require surgical repair. Quantitative fetal aortic measurements and aortic-to-pulmonary artery ratios showed strong discriminatory ability (AUC >0.9) for identifying fetuses requiring postnatal CoA repair, supporting their role in improving prenatal risk stratification and surgical planning.
BACKGROUND: Associated cardiac lesions, including ventricular septal defect (VSD), coarctation of the aorta (CoA), and pulmonary stenosis (PS), substantially influence prenatal counseling and postnatal surgical management in fetuses with dextro-transposition of the great arteries (D-TGA) and double outlet right ventricle with subpulmonary ventricular septal defect (DORV-SPV). This study assessed the diagnostic accuracy of fetal echocardiography (FE) for identifying associated lesions and predicting the postnatal surgical approach.
DETAILS: This single-center retrospective cohort study included 99 fetuses with D-TGA or DORV-SPV managed at Lucile Packard Children's Hospital (Palo Alto, California, USA) between January 2013 and January 2024. Eligible fetuses were liveborn, had a documented prenatal surgical plan, and underwent postnatal management at the study center. In 65% of cases, serial fetal echocardiograms were available. Prenatal diagnoses and predicted surgical plans were compared with postnatal echocardiographic findings and the surgical procedures ultimately performed. Receiver-operating characteristic (ROC) analysis evaluated the predictive performance of fetal aortic and pulmonary artery measurements for postnatal CoA repair. Among the 99 fetuses, postnatal diagnoses included 45 with simple D-TGA, 38 with complex D-TGA, 15 with DORV, and 1 case reclassified from prenatal DORV-SPV to truncus arteriosus. Diagnostic concordance between fetal and postnatal echocardiography was highest for simple D-TGA (95% (42/44)) and D-TGA with VSD and PS (100% (3/3)), followed by D-TGA with VSD (93% (25/27)). Lower concordance was observed for DORV-SPV (60% (3/5)), DORV-SPV with CoA (40% (4/10)), D-TGA with VSD and CoA (29% (2/7)), D-TGA with isolated CoA (0% (0/2)), and DORV-SPV with PS (0% (0/1)). Surgical-plan prediction showed a similar pattern, with the greatest accuracy in simple D-TGA and D-TGA with VSD and PS. Qualitative assessment of VSD size frequently changed across serial fetal examinations, with defects generally appearing larger prenatally but often smaller on postnatal echocardiography. Only 50% of small VSDs identified postnatally required repair. All infants undergoing postnatal CoA repair had an associated VSD. ROC analysis demonstrated that fetal aortic measurements and aortic-to-pulmonary artery dimension ratios achieved area under the curve values greater than 0.9 for predicting the need for postnatal CoA repair.
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Source: Chandrasekar, H., Kaplinski, M., Maskatia, S. A., et al. Accuracy of Fetal Echocardiography in Detecting Lesions Associated With, and Predicting Surgical Plan for, Dextro-Transposition of the Great Arteries and Double Outlet Right Ventricle With Subpulmonary Ventricular Septal Defect and Predicted Transposition Physiology. Ultrasound in Obstetrics & Gynecology. 2026; 68(1):v79-87. Published: January 30, 2026. DOI: 10.1002/uog.70169
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