NLRP3 Contributes to Sarcopenia Associated to Dependency Recapitulating Inflammatory-Associated Muscle Degeneration.

Sarcopenia, a complex and debilitating condition characterized by progressive deterioration of skeletal muscle, is the primary cause of age-associated disability and significantly impacts healthspan in elderly patients. Despite its prevalence among the aging population, the underlying molecular mechanisms are still under investigation. The NLRP3 inflammasome is crucial in the innate immune response and has a significant impact on diseases related to inflammation and aging. Here, we investigated the expression of the NLRP3 inflammasome pathway and pro-inflammatory cytokines in skeletal muscle and peripheral blood of dependent and independent patients who underwent hip surgery. Patients were categorized into independent and dependent individuals based on their Barthel Index. The expression of NLRP3 inflammasome components was significantly upregulated in sarcopenic muscle from dependent patients, accompanied by higher levels of Caspase-1, IL-1ß and IL-6. Among older dependent individuals with sarcopenia, there was a significant increase in the MYH3/MYH2 ratio, indicating a transcriptional shift in expression from mature to developmental myosin isoforms. Creatine kinase levels and senescence markers were also higher in dependent patients, altogether resembling dystrophic diseases and indicating muscle degeneration. In summary, we present evidence for the involvement of the NLRP3/ASC/NEK7/Caspase-1 inflammasome pathway with activation of pro-inflammatory SASP in the outcome of sarcopenia in the elderly.

Functional continuum: independent predictor of one-year mortality and key decision-making element in older adults with severe aortic stenosis amenable to aortic valve replacement.

OBJECTIVES: The impact of functional capacity over the entire functional continuum in older adults undergoing aortic valve replacement (AVR) has not been studied to date. This study aims to analyze 1.- the distribution of a cohort of older adults presenting severe aortic stenosis (AS) amenable to AVR in the different categories of the Functional Continuum Scale (FCS); 2.- its association with decision-making regarding valve disease; and 3.- its impact upon the one-year mortality rate of surgical (SAVR), transcatheter (TAVR) aortic valve replacement, or the decision to provide conservative management (OMT). METHODS: This prospective study included patients from the FRESAS (FRailty-Evaluation-in-Severe-Aortic-Stenosis) registry evaluated by the reference Heart-Team of a region in northern Spain. All the patients underwent comprehensive geriatric assessment. RESULTS: The study comprised 257 patients aged 84.0 ± 3.9 years. MANAGEMENT: SAVR: 25.3%, TAVR: 58.0% and OMT: 16.7%. Increased patient functional capacity was associated with an increased tendency to perform more invasive valve disease treatment. The overall one-year survival rate was 81.3%. One-year all-cause mortality: FCS-1 to FCS-2 "robust" 11.5%, FCS-3 to FCS-4 "prefrail" 14.7%, FCS-5 "frail" 19.2% and FCS-6 to FCS-8 "dependent" 45.0%; p < 0.001. Adjusted mortality analysis: FCS with HR = 1.206 [95%CI, 0.999-1.451 (p = 0.051)]; EuroSCORE-II with HR = 1.071 [95%CI, 1.006-1.161 (p = 0.033)]; and OMT with HR = 2.840 [95%CI, 1.409-5.772 (p = 0.004)] were retained in the final multivariable logistic regression model. CONCLUSIONS: In older AS patients amenable to AVR, the FCS is a useful predictive tool that may aid clinical decision-making.

Frailty Assessment in a Cohort of Elderly Patients with Severe Symptomatic Aortic Stenosis: Insights from the FRailty Evaluation in Severe Aortic Stenosis (FRESAS) Registry.

BACKGROUND: Precise evaluation of the degree of frailty is a fundamental part of the global geriatric assessment that helps to avoid therapies that could be futile. Our main objective was to determine the prevalence of frailty in a specific consult of patients undergoing aortic valve replacement. METHODS: From May 2018 to February 2020, all consecutive patients ≥75 years old, with severe symptomatic aortic stenosis, undergoing valve replacement in the Principality of Asturias (Northern Spain) were evaluated. RESULTS: A total of 286 patients were assessed. The mean age was 84 ± 4.01 years old; 175 (61.2%) were female. The short performance physical battery score was 8.5 ± 2.4 and the prevalence of frailty was 19.6% (56 patients). In the multivariable analysis, age, Barthel index and atrial fibrillation were independent predictors of frailty. CONCLUSIONS: The prevalence of frailty in our sample patients undergoing aortic valve replacement, evaluated by a standardized protocol, was 19.6%.