Background The influence of sleep duration on vulnerable coronary plaques, as evaluated via optical coherence tomography (OCT), has not been clearly defined in coronary artery disease (CAD). Here, the relationships between habitual sleep duration and thin-cap fibroatheroma (TCFA) detected by OCT were investigated in individuals with CAD. We further investigated whether systemic inflammation, represented by the neutrophil-to-lymphocyte ratio (NLR), represents a mediator of this association. Methods Overall, 1,178 patients with angiographically confirmed CAD who underwent OCT imaging and completed standardized sleep questionnaires were enrolled. Participants were categorized according to reported sleep duration. Multivariable logistic regression modeling was employed to assess the link between sleep duration and TCFA. Linear regression analyses assessed the association between sleep duration and NLR. Restricted cubic spline (RCS) modeling was applied as a means of detecting possible nonlinear associations between NLR and TCFA. Mediation analyses were then conducted to determine whether NLR functioned as an intermediate variable linking sleep duration and plaque vulnerability. Results These results offer the first clinical evidence of the link between sleep duration and TCFA presence in individuals with CAD, with the TCFA risk in the abnormal sleep duration group being 2.16 times that of the normal group (95% CI: 1.63-2.88, P < 0.001). Sleep duration was also independently correlated with NLR, and RCS analysis highlighted a nonlinear relationship between NLR levels and TCFA risk (P < 0.001). Importantly, mediation analysis demonstrated that NLR partially mediated the effect of sleep duration on TCFA, supporting the existence of a sleep-inflammation-plaque vulnerability axis. Conclusion The sleep duration has been shown to be significantly associated with the risk of developing TCFA. In addition, a partial mediating effect of NLR on this relationship has been found.
Background Guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (HFrEF) relies on quadruple therapy, including beta-blockers (BB), angiotensin receptor-neprilysin inhibitors (ARNi), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter 2 inhibitors (SGLT2i). Elderly patients with HF represent a high-risk population and often face therapeutic inertia but also more adverse events. We aimed to assess the efficacy and safety of an intensive titration program (ITP) for elderly HFrEF patients. Methods We conducted a prospective, single-center, observational study including HFrEF patients aged >= 75 years managed with an ITP between January 2024 and February 2025. The primary outcome was the prescription rate of quadruple GDMT at 3 months, irrespective of dose. Secondary outcomes included prescription of quadruple therapy at >= 50% of GDMT target doses and identification of predictors of limited implementation. Safety outcomes included adverse events occurring during titration and within 3 months after completion. Results Sixty-four patients were included (Median age 80 years, 70% male, 28% diabetes, median eGFR 50 mL/min). The mean titration period was 100 days (14 weeks). At 3 months, 33% of patients were prescribed quadruple therapy, with 5% achieving >= 50% of the recommended target dose in each drug class. Target dose achievement improved across all drug classes between baseline and 3 months: ARNi (1% vs. 31%), MRA (1% vs. 14%), and BB (3% vs. 5%) (all P < 0.05). These improvements were associated with short-term clinical and biological benefits (NT-proBNP reduction, improved left ventricular ejection fraction). Reported adverse events included symptomatic hypotension (8% with treatment discontinuation) and acute kidney injury (8 % requiring hospitalization). Older age and chronic kidney disease were associated with limited initiation of quadruple therapy. Conclusion An intensive titration program for HFrEF therapy appears feasible and relatively safe in elderly patients.
Background Sarcopenia is a progressive age-related skeletal muscle disorder characterized by the loss of muscle mass, strength, and physical performance. Increasing evidence suggests that activation of the renin-angiotensin system (RAS) contributes to muscle wasting through promotion of protein degradation and impairment of anabolic signaling. Azilsartan (AZL), a highly selective angiotensin II type 1 receptor (AT1R) blocker, has demonstrated pleiotropic effects beyond blood pressure control. However, its effects on skeletal muscle atrophy and the underlying mechanisms remain incompletely understood. Methods We combined a prospective observational study with mechanistic investigations in animal and cellular models. Older adults with hypertension and sarcopenia received AZL (40 mg/day) or other antihypertensive therapies for 6 months, and muscle strength, gait speed, and appendicular skeletal muscle mass were assessed. Moreover, Ang II-induced skeletal muscle atrophy models were established in mice and C2C12 myotubes to evaluate the effects of AZL on muscle morphology and signaling pathways. Results AZL treatment was associated with significant improvements in handgrip strength, gait speed, and appendicular skeletal muscle mass in older hypertensive patients. In experimental models, Ang II induced skeletal muscle dysfunction and atrophy, characterized by reduced exercise capacity, decreased grip strength, and muscle fiber loss, were attenuated by AZL treatment. Mechanistically, AZL restored PI3K/Akt/FOXO3a signaling and suppressed the expression of the muscle-specific ubiquitin ligases Atrogin-1 and MuRF1. The protective effects of AZL were abolished by the AT1R agonist TRV120027 in both in vivo and in vitro models and were further attenuated by the PI3K inhibitor LY294002 in C2C12 myotubes. Conclusions AZL attenuates Ang II-induced skeletal muscle atrophy through AT1R blockade and subsequent activation of PI3K/Akt/FOXO3a signaling, thereby suppressing ubiquitin-proteasome system-mediated muscle protein degradation. These findings provide mechanistic and translational evidence supporting the potential of AZL as a therapeutic strategy for preserving skeletal muscle health in older adults with hypertension.
Background Diabetes is an established risk factor for atrial fibrillation (AF). However, whether prediabetes is also a risk factor for AF is unclear. This meta-analysis examined the relationship between prediabetes and AF risk. Methods EMBASE, MEDLINE, and Publicly Available Contents (from Jan. 1, 1950 to Jan. 29, 2025) were used to comprehensively search for observational studies of the incidence or prevalence of AF among those with prediabetes or normoglycemia. Each relative risk (RR) for prediabetes vs. normoglycemia and the population attributable fraction (PAF) of prediabetes to AF incidence in longitudinal studies and the odds ratio (OR) for prediabetes vs. normoglycemia in cross-sectional studies were pooled with a random-effects model. Results Identified were 46 eligible studies. Pooled RR and PAF (95% confidence interval [CI]) were 1.12 (1.06-1.18) and 2.7% (1.4%-4.0%), respectively. Pooled crude RR and crude OR (95% CI) were 1.49 (1.37-1.62) and 1.42 (1.23-1.64), respectively. Higher RR was revealed in populations >= 65 years old vs. < 65 years old (P = 0.02) and in Asian vs. non-Asian countries (P = 0.047). Higher PAF was revealed in studies with a population >= 65 years old vs. < 65 years old (P < 0.001) and in male-dominant vs. female-dominant studies (P < 0.001). Only by examining the RR for both diabetes and prediabetes vs. normoglycemia, the pooled RR/PAF (95% CI) was 1.12 (1.15-1.20)/1.6% (0.9%-2.3%) for prediabetes and 1.15 (1.10-1.20)/1.0% (0.7%-13%) for diabetes. Conclusions Prediabetes is a modest but significant risk factor for AF, comparable to that of diabetes. The impact of prediabetes was strong among the elderly, males, and Asian people.
