Background and Objectives: There is consensus on the negative effects of obesity on the development of heart failure. However, several studies have suggested that obesity may have paradoxical survival benefits in heart failure patients. Therefore, the aim of this study is to investigate whether the obesity paradox exists in heart failure with reduced ejection fraction (HFrEF) patients in Jordan. Materials and Methods: In this retrospective cohort study, data were retrieved from electronic hospital records of heart failure patients admitted to King Abdullah University Hospital between January 2010 and January 2020. Patients were divided into five BMI (kg/m²) subgroups: (1) Less than 25.0, (2) Overweight 25.0–29.9, (3) Obese Class I 30.0–34.9, (4) Obese Class II 35.0–39.9, and (5) Obese Class III ≥40.0. Changes in patients’ clinical and echocardiographic parameters over one year were analyzed. Results: Data of a total of 297 patients were analyzed to determine the effect of obesity on heart failure. The mean age was 64.6 ± 12.4 years, and most patients (65.7%) were male. Among several co-morbidities, diabetes mellitus and hypertension were the most common and were present in 81.8% and 81.1% of patients, respectively. Over all patients, there was no significant change in EF after 1 year compared to baseline. However, only patients in the Obese Class I group had a statistically significant improvement in EF of 38.0 ± 9.81% vs. 34.8 ± 6.35% (p = 0.004) after 1 year. Importantly, among non-diabetic individuals, only Obese Class I patients had a significant (p < 0.001) increase in EF after 1 year compared to other BMI subgroups, a feature that was not observed among patients with diabetes. On the other hand, only Obese Class I patients with hypertension had a significant improvement (p < 0.05) in EF after 1 year compared to other BMI subgroups, a feature that was not observed among patients without hypertension. Conclusions: Our study demonstrates an inverted U-shaped relationship between BMI and EF such that patients with mild obesity (i.e., Obese Class I) had significant improvement in EF compared to those having a lower and higher BMI. We, therefore, suggest the existence of the obesity paradox among HFrEF patients in Jordan.

Achillea santolina is traditionally utilized in herbal therapy; nonetheless, its xanthine oxidase inhibitory and cellular antioxidant properties are not extensively investigated. This work aimed to identify the phytochemical composition of the methanolic extract of A. santolina aerial parts via LC–MS and to assess its xanthine oxidase (XO) inhibitory activity and its modulatory effects on intracellular reactive oxygen species (ROS) in HepG2 cells. The methanolic extract underwent LC–MS analysis for phytochemical identification, and XO inhibitory activity was assessed spectrophotometrically using allopurinol as the reference medication. Intracellular ROS levels were determined using the DCFH-DA fluorescent assay following xanthine-induced oxidative stress. LC–MS profiling identified ten compounds representing 95.1% of the extract, with flavonoid glycosides (44.1%) as the predominant class. Rutin (18.6%) and luteolin-7-O-glucoside (15.2%) were the major constituents. The extract demonstrated concentration-dependent inhibition of XO, with an IC₅₀ value of 29.3 ± 0.4 µg/mL, compared to 2.1 ± 0.3 µg/mL for allopurinol. In HepG2 cells, xanthine significantly increased ROS production, while pre-treatment with the extract greatly diminished ROS levels in a dose-dependent manner, reaching approximately 75% inhibition at 50 µg/mL. The results demonstrate that the methanolic extract of A. santolina exhibits significant xanthine oxidase inhibitory and antioxidant properties, possibly due to its elevated flavonoid concentration, indicating its potential utility in addressing oxidative stress-related disorders. To the best of our knowledge, this study provides the first report on the combined xanthine oxidase inhibitory and intracellular ROS-modulating activities of A. santolina methanolic extract.