Journal of Clinical Medicine

Background: Vitamin D metabolic disorders are a critical prognostic factor in patients with chronic kidney disease (CKD). However, the dose–response association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and all-cause mortality in the CKD population remains controversial. This study aimed to quantify this association and explore a preliminary reference serum 25(OH)D range for CKD patients. Methods: We systematically searched PubMed, EMBASE, Web of Science, and Cochrane Library databases up to 10 March 2026, for prospective cohort studies investigating the association between serum 25(OH)D and all-cause mortality in CKD patients. Summary hazard ratios (HRs) were pooled using a random-effects model. Generalized least squares regression models were applied to assess the quantitative dose–response association of serum 25(OH)D with all-cause mortality. Results: A total of 17 prospective cohort studies involving 33,550 CKD patients were included. Higher serum 25(OH)D levels are significantly associated with a lower risk of all-cause mortality (pooled HR = 0.58, 95% CI: 0.53–0.64, p < 0.001; I² = 52.7%). Dialysis status (p = 0.005) and follow-up duration (p = 0.006) were significant effect modifiers of this association. Dose–response analysis revealed a significant non-linear association with a potential U-shaped pattern (p for non-linearity < 0.001). Conclusions: Serum 25(OH)D suggests a U-shaped association with mortality in CKD; the upward risk at higher concentrations may reflect confounding, with 25(OH)D likely a marker of health status rather than a modifiable risk factor. Findings are constrained by the observational design and moderate between-study heterogeneity; future trials are warranted to validate these results and elucidate relevant mechanisms.

Background/Objectives: Malnutrition, inflammation, muscle loss, and frailty often coexist in older patients with acute coronary syndrome (ACS); we assessed their prognostic value. Methods: Following PRISMA 2020 (PROSPERO CRD420261512821), PubMed, Scopus, and Web of Science were searched on 20 September 2026 and supplemented on 1 November 2026. Observational studies of older patients with ACS (mean, median, or minimum age ≥65 years) relating nutritional, inflammatory, muscle-related, or frailty measures to mortality or major adverse cardiovascular events (MACE) were included. Risk of bias and certainty were assessed with the Newcastle–Ottawa Scale and GRADE. Results: We included 162 reports from 121 cohorts. Clinical Frailty Scale-defined frailty was associated with all-cause mortality (8 cohorts; HR 2.69, 95% CI 2.14–3.39; moderate certainty). Administrative frailty scores showed consistent but heterogeneous associations. Low Geriatric Nutritional Risk Index (HR 2.81, 95% CI 1.40–5.61) and higher CONUT scores (HR 1.29 per point, 95% CI 1.11–1.51) were associated with mortality and MACE, respectively, but not after Hartung–Knapp adjustment (very low certainty). Inflammatory indices were mostly associated with mortality but heterogeneous; muscle-related data were sparse; no study assessed ventricular remodeling. Conclusions: Frailty, and to a lesser extent malnutrition, are associated with adverse outcomes; their added value for risk stratification remains unproven.

Obesity and pulmonary hypertension (PH) frequently coexist, but obesity is not a distinct PH group. This narrative review of the literature published through 27 September 2026 appraises the evidence by PH group. Obesity is most clearly linked to PH through intermediate conditions, particularly heart failure with preserved ejection fraction, obstructive sleep apnea, and obesity hypoventilation syndrome, and it can complicate hemodynamic classification because elevated intrathoracic pressure may raise the measured pulmonary arterial wedge pressure. Experimental studies suggest direct pulmonary vascular effects through adipokine imbalance, inflammation, altered estrogen metabolism, oxidative stress, and insulin resistance; however, an independent causal role of obesity in human pulmonary arterial hypertension has not been established. Small, mostly observational studies report lower estimated pulmonary pressures after bariatric surgery, but a benefit of intentional weight loss on invasive hemodynamics or clinical PH outcomes is unproven. Incretin-based therapies produce substantial weight loss and improve symptoms in obesity-related heart failure with preserved ejection fraction; acute human hemodynamic data are emerging, but long-term efficacy in PH has not been tested. Higher body mass index has been associated with lower observed mortality in several PH cohorts, possibly reflecting confounding and reverse causation. We distinguish established findings from hypotheses and highlight research priorities.