Background: Falls are a leading cause of hospitalization among older adults, strongly affecting quality of life. Fall-Risk-Increasing Drugs (FRIDs) represent a key modifiable risk factor, yet their role in fall-related hospitalizations requires further investigation. This study aimed to assess the risk of falls associated with FRIDs, specifically opioids, dopaminergic agents, antipsychotics, anxiolytics, hypnotics-sedatives, and antidepressants.

Methods: A nested case-control study was conducted using administrative data from two Italian regions (~11% national representativeness). Cases included individuals aged ≥65 hospitalized for fall-injury in 2018, matched 1:1 by sex and age with controls (without fall-related hospitalizations or injuries in the same year). FRIDs exposure was defined as drug classes, duration, and recency. Adjusted odds ratios (aORs) were estimated using logistic regression models, adjusting by polypharmacy and comorbidities.

Results: Among 16,118 cases and 16,118 controls (68.77% females, mean age 79.76 years), cases showed higher prevalence of polypharmacy (5–9drugs: 42.03% vs 37.16%; ≥10drugs: 7.02% vs 5.44%; p<0.0001) and multimorbidity (≥3diseases: 6.42% vs 2.82%; p<0.0001). FRID use was higher in cases (37.7% vs. 26.5%, p<0.0001), with a 50% increased risk of hospitalization (aOR 1.50, 95% CI: 1.42–1.58). Opioids (aOR 1.39, 95% CI: 1.30–1.49) and antidepressants (aOR 1.44, 95% CI: 1.35–1.54) were associated with the highest risks. Prolonged FRID use (>9months; aOR 1.69, 95% CI: 1.55–1.83) and current FRID use (within 30 days before hospitalization; OR 1.78, CI 95%: 1.67-1.90) showed higher risk.

Conclusions: FRID use significantly increased fall-related hospitalisations in older adults. Optimizing prescribing and managing polypharmacy could improve safety.

As population age and the prevalence of non-communicable chronic diseases (NCDs) rises, promoting self-care among older adults has become a key strategy to improve quality of life and reduce the burden on healthcare systems. However, older individuals living with chronic conditions often face not only physical limitations but also psychological barriers that affect their engagement in self-care. Among these, Views on Aging (VoA), that is, how individuals perceive and interpret their own aging, may play a critical role. Evidence shows that negative VoA, such as associating aging with loss or decline, are linked to poorer health outcomes and disengagement from health-promoting behaviors. In contrast, positive VoA, such as viewing aging as a phase of growth and potential, are associated with better health behaviors and outcomes. According to Stereotype Embodiment Theory, age-related stereotypes internalized over time can act as self-fulfilling prophecies, shaping behavior and health trajectories. However, the specific role of VoA in influencing self-care practices among older adults with NCDs remains underexplored, particularly in interaction with Illness Perceptions (IP), which reflect individuals’ beliefs and emotional responses about their illness. This cross-sectional study investigates the associations between VoA (AARC-Gains/Losses), IP (Brief-IPQ), self-care behaviors (SCMI), and quality of life (SF-12) in Italian adults aged ≥60 with chronic conditions. We hypothesize that positive VoA and adaptive IP will predict higher self-care engagement and better quality of life. These findings may inform person-centered interventions that incorporate VoA as psychological resources, in line with the WHO self-care framework, to enhance older adults’ ability to self-care.

Short abstract

Electrocardiography (ECG)-based aging clocks predict mortality, but their application to chronic health conditions remains limited.

We analyzed 24,162 subjects from a prospective Italian population cohort (≥35 y; 51.9% women; ECG assessment 2005-2010). Incident deaths and health conditions through 31/12/2022 were identified through electronic health records. A deep neural network was built to estimate the age of participants, based on sex, heart rate, blood pressure, and 14 ECG abnormalities, then the gap between estimated and chronological age (CA) was regressed on CA. These residuals were used as Heart Aging Acceleration index (HAA, years) and tested for associations with incident events.

Over 21,514 cardiovascular disease (CVD) free subjects with non-missing data, we observed positive association of HAA with incident fatal/non-fatal CVD (HR: 1.03 [1.03-1.04] per year), coronary heart disease (1.04 [1.03-1.05]) and type 2 diabetes (1.03 [1.02-1.05]), but not with fatal/non-fatal cancer and brain disorders. HAA was also associated with mortality for all (HR: 1.03 [1.02-1.03]) and CVD causes (HR: 1.03 [1.02-1.04]), but not with cancer deaths. C-index in multivariable models was 0.79 for fatal/non-fatal CVD and 0.90 for CVD deaths, vs 0.78 and 0.83 for the best performing CVD risk prediction score. Time-dependent Area Under the Curve (AUC) increased over the years of follow-up for CVD mortality (from 0.78 to 0.92) but was quite stable for fatal/non-fatal CVD events (0.81-0.82).

These findings highlight the potential of the ECG-based Heart Aging as a non-invasive, cost-effective marker to stratify the risk of incident morbidity and mortality from cardiovascular and non-cardiovascular causes in populations.

Extended abstract

Background: Electrocardiography (ECG)-based aging clocks predict mortality, but their application to chronic health conditions remains limited, restricting their use as potential markers for risk stratification.

Methods: We analyzed 24,162 subjects from the Moli-sani study, a prospective Italian population cohort (≥35 y; 51.9% women), with standard 12-lead resting ECG data available at baseline recruitment (2005-2010). Incident deaths and health conditions through Dec 31, 2022 were identified through linkage with the Italian death, the regional drug prescription and the hospital discharge registers. A tuned 2 hidden-layers perceptron network was built to estimate the age of participants, based on sex, heart rate, blood pressure, and 14 ECG (MINNESOTA) abnormalities. The gap between estimated and chronological age (CA) was regressed on CA, and the residuals were used as Heart Aging acceleration index (years) and tested for associations with incident events, in multivariable models adjusted for CA, sex, education, lifestyles, prevalent chronic conditions, wellbeing and other blood-based aging clocks (BloodAge and PhenoAge accelerations).

Results: Over 21,514 cardiovascular disease (CVD) free subjects with non-missing data, Cox PH models revealed a positive association of Heart Aging acceleration index with incident fatal/non-fatal CVD (HR: 1.03 [1.03-1.04] per year), coronary heart disease (1.04 [1.03-1.05]) and type 2 diabetes (1.03 [1.02-1.05]), but not with fatal/non-fatal cancer and brain disorders. Heart Aging was also associated with mortality for all (HR: 1.03 [1.02-1.03]) and CVD causes (HR: 1.03 [1.02-1.04]), but not with cancer deaths. C-index in multivariable models was 0.786 for fatal/non-fatal CVD and 0.900 for CVD deaths, vs 0.777 and 0.825 for the best performing CVD risk prediction score. When other clocks were added to the models, the performance further increased (C-index 0.972 and 0.908, respectively) and all the clocks tested showed positive associations with incident CVD and related death risk. Time-dependent Area Under the Curve (AUC) increased over the years of follow-up for CVD mortality (from 0.78 at year 1 to 0.92 at year 17) but was quite stable for fatal/non-fatal CVD events (0.81-0.82 in the whole period).

Conclusions: These findings highlight the potential of the ECG-based Heart Aging as a non-invasive, cost-effective marker to stratify the risk of incident morbidity and mortality from cardiovascular and non-cardiovascular causes in population settings, also in conjunction with other systemic aging clocks.

Abstract

Background:
Epicardial Adipose Tissue (EAT) is a metabolically active visceral fat depot surrounding the myocardium. Under physiological conditions, it provides thermogenic and mechanical protection to the heart and releases anti-inflammatory cytokines. However, in pathological conditions, EAT becomes a source of pro-inflammatory and pro-atherogenic cytokines, contributing to cardiovascular and cerebrovascular dysfunction. Previous studies suggest a link between increased EAT and poorer cognitive performance in older adults, though the underlying mechanisms remain unclear. Heart Rate Variability (HRV), a marker of autonomic nervous system function, has also been associated with both EAT thickness and cognitive decline.

Objective:
This study aimed to investigate the relationship between EAT thickness, cognitive performance, and HRV parameters in elderly individuals with varying degrees of cognitive function.

Methods:
Ninety-nine patients aged >65 years were enrolled at the Federico II University Hospital outpatient clinics. All underwent transthoracic echocardiography, 24-hour ECG Holter monitoring, and cognitive evaluation using the Mini Mental State Examination (MMSE). Subjects were classified as cognitively normal, with mild cognitive impairment (MCI), or mild/moderate dementia based on DSM-V criteria and MMSE scores. HRV parameters were derived from time and frequency domains. Multivariate linear regression models were used to identify independent predictors of cognitive performance.

Results:
EAT thickness was inversely correlated with MMSE scores (ρ = -0.341, p = 0.001) and directly correlated with the SDNN index of HRV (ρ = 0.212, p = 0.036). No significant associations were found between MMSE scores and other HRV indices. EAT thickness was significantly higher in the dementia group compared to cognitively normal individuals, while the LF/HF ratio was significantly lower in dementia compared to MCI. In multivariate analysis, EAT thickness independently predicted MMSE scores even after adjusting for age, gender, BMI, comorbidities, and HRV parameters.

Conclusions:
EAT thickness is inversely associated with cognitive function in the elderly and may serve as an indirect marker of visceral adiposity and neuroinflammatory risk. The study also identifies a possible link between increased EAT and parasympathetic hyperactivity, as indicated by HRV alterations. These findings highlight EAT as a potential imaging biomarker for early detection of cognitive decline. Further studies with larger cohorts are warranted to validate these associations and clarify the role of autonomic dysfunction in the EAT-cognition axis.

Background:
Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome commonly associated with comorbidities such as hypertension, obesity, type 2 diabetes, and aging¹. Epicardial adipose tissue (EAT) has been increasingly recognized as a contributor to cardiovascular dysfunction, with its volume and thickness linked to metabolic syndrome, insulin resistance, and coronary artery disease. Recent studies suggest that elevated EAT thickness may reflect an inflammatory-metabolic phenotype in HFpEF². This study investigates the role of EAT in modulating cardiac mitochondrial function in a novel preclinical HFpEF model using Gottingen minipigs. It further explores the cardioprotective actions of GLP-1 receptor agonists and SGLT2 inhibitors, and the potential of L-arginine to enhance glucose and lipid oxidation, offering insights into novel therapeutic approaches for HFpEF and metabolic syndrome.

Methods:
A new preclinical HFpEF model was developed and validated in Gottingen minipigs using a "Multihit" approach. Animals were subjected to a 20-week regimen combining a Western-style high-calorie, high-sodium diet with subcutaneous implantation of slow-release deoxycorticosterone acetate (DOCA).

Results:
Cardiac structure and function were assessed via M-mode and Doppler echocardiography. Compared to control (CTRL) animals, HFpEF minipigs exhibited structural changes typical of human HFpEF, including thickening of the interventricular septum (IVSd, IVSs) and left ventricular posterior wall (LVPWd, LVPWs), along with reductions in ventricular diameters (LVIDd, LVIDs) and volumes (EDV, ESV), all while maintaining a preserved ejection fraction (EF). Cardiac mass was significantly increased, and concentric remodeling was confirmed by a relative wall thickness (RWT) exceeding 0.42. These findings confirm the model's ability to recapitulate key features of the human HFpEF phenotype.Mitochondrial function was evaluated using high-resolution respirometry (Oroboros O2k) on left ventricular tissue samples. HFpEF animals demonstrated enhanced complex II-linked respiration, indicating increased succinate-driven oxidative phosphorylation. However, maximal oxygen consumption following FCCP-induced uncoupling was significantly higher in the CTRL group, suggesting impaired mitochondrial reserve capacity in HFpEF. Additionally, reduced respiratory control ratios (RCR) in the HFpEF group indicated a decline in the efficiency of mitochondrial oxidative phosphorylation.

Main implication of the research

This study establishes a large-animal model that successfully mimics the structural, functional, and metabolic alterations characteristic of HFpEF. It highlights mitochondrial dysfunction as an early event in disease progression and underscores the therapeutic potential of targeting EAT, metabolic pathways, and mitochondrial energetics to improve outcomes in HFpEF.

Reference

1. Shah SJ, Katz DH, Selvaraj S, Burke MA, Yancy CW, Gheorghiade M, Bonow RO, Huang CC, Deo RC. Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation. 2015 Jan 20;131(3):269-79. https://doi:10.1161/CIRCULATIONAHA.114.010637
2. Goldman, S, Requena-Ibanez, J, Devesa, A. et al. Uncovering the Role of Epicardial Adipose Tissue in Heart Failure With Preserved Ejection Fraction. JACC Adv. 2023 Nov, 2 (9). https://doi.org/10.1016/j.jacadv.2023.100657