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Isabella Kardys

Publications and source records attributed to Isabella Kardys.

2 recordsLinked to original sources
PubMed2025

Proteome organ aging and cardiometabolic risk in a population at risk for heart failure.

BACKGROUND: Biological aging varies across individuals and tissues, influencing chronic diseases, including heart failure (HF). Emerging proteome techniques enable quantification of organ-specific aging acceleration (OAA), but whether OAA relates to HF severity and differs by sex remains unclear. We aim to assess the sex-related association between OAA of heart, artery and kidneys and HF severity, and to investigate relevant cardiometabolic risk factors of organ aging. METHODS: In 556 participants from the HELPFul cohort, we estimated predicted biological age for heart, artery, and kidneys using plasma proteomics and calculated OAA as the deviation from chronological age. Associations between OAA and HF stage, echocardiographic parameters, and cardiometabolic risk factors were evaluated using regression models. Composite indices, including triglyceride-glucose body mass index (TyG-BMI), c-reactive protein-triglyceride glucose index and triglyceride-to-HDL cholesterol ratio were assessed for associations with advanced OAA. RESULTS: Mean age was 63 ± 9 years; 65% were women. Patients were classified as HF stage A (35%), B (29%) and C/D (36%). Heart OAA was significantly associated with advanced HF (Stage C/D) in both sexes (OR = 1.12, 95% CI 1.03 to 1.23 in women; OR = 1.18, 95% CI 1.05 to 1.32 in men), while artery OAA was linked to HF only in women (OR = 1.10, 95% CI 1.01 to 1.18). Multi-organ aging (≥ 2 organs with advanced OAA) conferred over three-fold higher odds of being in Stage C/D. Heart OAA correlated with impaired cardiac structure and function, particularly reduced ejection fraction in men and increased left ventricular mass index in both sexes. Diabetes emerged as the most relevant factor of artery and kidney OAA. TyG-BMI was significantly associated with advanced kidney OAA, only in women (z-scored OR = 1.88, 95% CI 1.45 to 2.45). CONCLUSIONS: Proteome-derived organ aging correlates with HF severity, with possible sex-related patterns. Diabetes and higher TyG-BMI are associated with faster organ aging, which may reflect shared aging mechanisms between metabolic dysfunction and HF.

Humans↗
PubMed2025

Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes.

Heart failure (HF) is a major contributor to global morbidity and mortality. While distinct clinical subtypes, defined by etiology and left ventricular ejection fraction, are well recognized, their genetic determinants remain inadequately understood. In this study, we report a genome-wide association study of HF and its subtypes in a sample of 1.9 million individuals. A total of 153,174 individuals had HF, of whom 44,012 had a nonischemic etiology (ni-HF). A subset of patients with ni-HF were stratified based on left ventricular systolic function, where data were available, identifying 5,406 individuals with reduced ejection fraction and 3,841 with preserved ejection fraction. We identify 66 genetic loci associated with HF and its subtypes, 37 of which have not previously been reported. Using functionally informed gene prioritization methods, we predict effector genes for each identified locus, and map these to etiologic disease clusters through phenome-wide association analysis, network analysis and colocalization. Through heritability enrichment analysis, we highlight the role of extracardiac tissues in disease etiology. We then examine the differential associations of upstream risk factors with HF subtypes using Mendelian randomization. These findings extend our understanding of the mechanisms underlying HF etiology and may inform future approaches to prevention and treatment.

Humans↗