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Background: Limited large-scale, real-world data exist on the prevalence and clinical impact of discordance between fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs)., Methods: The J-PRIDE registry (Clinical Outcomes of Japanese Patients With Coronary Artery Disease Assessed by Resting Indices and Fractional Flow Reserve: A Prospective Multicenter Registry) prospectively enrolled 4304 lesions in 3200 patients from 20 Japanese centers. The lesions were classified into FFR+/NHPR-, FFR-/NHPR+, FFR+/NHPR+, or FFR-/NHPR groups according to cutoff values of 0.89 for NHPRs and 0.80 for FFR. The primary study end point was the cumulative 1-year incidence of target vessel failure (a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularization) on a lesion basis., Results: An NHPR cutoff value of 0.89, determined using online software, predicted an FFR of 0.80 across various NHPR types. Discordance between FFR and NHPRs was observed in 20% of lesions (FFR+/NHPR-, 11.2%; FFR-/NHPRs+, 8.8%). Revascularization was deferred in 42.9% and 88.4% of the FFR+/NHPR- and FFR-/NHPR+ groups, respectively. In deferred vessels, the FFR+/NHPR- and FFR-/NHPR+ groups showed a higher 1-year incidence of target vessel failure compared with the FFR-/NHPR- group (7.9% versus 5.5% versus 1.7%; for FFR+/NHPR-, adjusted hazard ratio [aHR], 4.89 [95% CI, 2.68-8.91]; P <0.001; for FFR-/NHPR+, aHR, 2.64 [95% CI, 1.49-4.69]; P <0.001). In revascularized vessels, the 1-year target vessel failure rate was numerically higher in the FFR-/NHPR+ group than in the FFR+/NHPR+ group (9.6% versus 3.4%; aHR, 2.27 [95% CI, 0.70-7.34]; P =0.17), although with similar outcomes between the FFR+/NHPR- and FFR+/NHPR+ groups (2.3% versus 3.4%; aHR, 0.96 [95% CI, 0.37-2.38]; P =0.93). The FFR+/NHPR- group benefited from revascularization compared with medical treatment (aHR, 0.26 [95% CI, 0.08-0.86]; P =0.027); the FFR-/NHPR+ group did not (aHR, 2.39 [95% CI, 0.62-9.21]; P =0.20)., Conclusions: Discordance between FFR and NHPRs was noted in 20% of lesions, and discordant deferred lesions resulted in worse outcomes than concordant negative lesions. Although the outcomes after deferring revascularization were comparable between the FFR+/NHPR- and FFR-/NHPR+ lesions, only FFR+/NHPR- lesions showed a benefit from revascularization compared with medical treatment, suggesting that an FFR-guided strategy is superior to an NHPR-guided strategy in discordant lesions., Registration: URL: https://www.umin.ac.jp; Unique identifier: UMIN000038403.

Inhibition of xanthine oxidoreductase (XOR) was shown to ameliorate the stroke susceptibility in the stroke-prone spontaneously hypertensive rat (SHRSP), suggesting hyperuricemia had a pathological role in this rat model. In this study, we thus aimed to explore mechanisms inducing hyperuricemia in SHRSP. XOR is known to have two forms, xanthine dehydrogenase (XDH) as the prototype and xanthine oxidase (XO) as the converted form through cleavage of a peptide bond or through formation of disulfide bonds in the enzyme. XO was shown to have a greater activity to produce UA and oxidative stress. We thus hypothesized that the excess conversion to XO caused the higher UA level in SHRSP. Male SHRSP at 10 weeks of age showed a higher serum level of UA and a higher activity of XO than those in Wistar-Kyoto rat. As the protein level of the total XOR did not differ between the two strains, the conversion to XO seemed responsible for the high UA level in SHRSP. Meanwhile, NAD + level in SHRSP was lower than that in WKY, suggesting that low NAD + promoted the conversion to XO in this strain. ß-nicotinamide mononucleotide (NMN) supplementation for 2 weeks increased NAD + level and reduced the serum UA level as well as the XO activity in SHRSP. These observations supported that a low NAD + accelerated the conversion of XDH to XO in SHRSP, which resulted in high UA. The current study suggested the potential significance of NMN supplementation in the treatment of hyperuricemia in humans., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:K.K. Lecture Fees: Boehringer Ingelheim Japan, Eli Lilly Japan, Astellas, Novo Nordisk Pharma, Mitsubishi Tanabe, Daiichi Sankyo, Sanofi, Sumitomo Pharma, Kowa, Kyowa Kirin, Taisho, AstraZeneca, Bayer, Novartis, OtsukaCollaboration: Boehringer Ingelheim Japan, Boehringer-Ingelheim (Germany), Kowa, Mitsubishi Tanabe, BayerResearch support: Boehringer Ingelheim Japan, Nipro, Life ScanAcknowledgement: The author would represent cordial thanks to Abe Yoando Pharma, CO. Ltd for generously providing NMN., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This review introduces "space prescribing," an innovative healthcare approach that incorporates the physical environment's role in promoting health beyond traditional clinical settings. Recognizing that individuals spend a significant amount of time outside clinical environments, this approach explores the therapeutic potential of natural and built environments in improving well-being and managing diseases, particularly cardiovascular and mental health conditions.Traditional healthcare models focus on treatments in hospital and clinic settings. However, evidence suggests that environmental factors profoundly influence health outcomes. Space prescribing recommends specific environments that encourage healthier lifestyles and enhance wellbeing. This concept includes social prescribing, in which healthcare professionals direct patients to community-based, non-medical activities such as art classes and sports, acknowledging that well-being transcends biological factors.This review also highlights "Cultural Ecosystem Services" (CES) in health through stress reduction, social connections, and physical activity. For cardiovascular health, elements such as green spaces and urban design are vital for managing conditions, such as hypertension and heart disease. Similarly, the configuration of indoor and outdoor spaces plays a crucial role in mental health. Therapeutic landscapes, including community gardens and culturally enriched urban areas, support mental health recovery, foster community engagement and reduce isolation.In conclusion, space prescribing advocates an integrated approach that considers the physical and social environments as fundamental components of health promotion. This strategy aims to mitigate health disparities and enhance the quality of life, while making health-enhancing activities accessible in urban and rural settings. Through this holistic approach, space prescribing has the potential to transform public health by strategically utilizing environmental designs to support health outcomes.