As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on chromosome 2. NPs are synthesized and secreted through certain mechanisms by cardiomyocytes, fibroblasts, endotheliocytes, immune cells (neutrophils, T-cells and macrophages) and immature cells (embryonic stem cells, muscle satellite cells and cardiac precursor cells). They are mainly produced by cardiovascular, brain and renal tissues in response to wall stretch and other causes. NPs provide natriuresis, diuresis, vasodilation, antiproliferation, antihypertrophy, antifibrosis and other cardiometabolic protection. NPs represent body’s own antihypertensive system, and provide compensatory protection to counterbalance vasoconstrictor-mitogenic-sodium retaining hormones, released by renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS). NPs play central roles in regulation of heart failure (HF), and are inactivated through not only NP receptor-C, but also neutral endopeptidase (NEP), dipeptidyl peptidase-4 and insulin degrading enzyme. Both BNP and N-terminal proBNP are useful biomarkers to not only make the diagnosis and assess the severity of HF, but also guide the therapy and predict the prognosis in patients with HF. Current NP-augmenting strategies include the synthesis of NPs or agonists to increase NP bioactivity and inhibition of NEP to reduce NP breakdown. Nesiritide has been established as an available therapy, and angiotensin receptor blocker NEP inhibitor (ARNI, LCZ696) has obtained extremely encouraging results with decreased morbidity and mortality. Novel pharmacological approaches based on NPs may promote a therapeutic shift from suppressing the RAAS and SNS to re-balancing neuroendocrine dysregulation in patients with HF. The current review discussed the synthesis, secretion, function and metabolism of NPs, and their diagnostic, therapeutic and prognostic values in HF.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a leading cause of hospitalizations and mortality when diagnosed at the age of ≥ 65 years. HFpEF represents multifactorial and multisystemic syndrome and has different pathophysiology and phenotypes. Its diagnosis is difficult to be established based on left ventricular ejection fraction and may benefit from individually tailored approaches, underlying age-related changes and frequent comorbidities. Compared with the rapid development in the treatment of heart failure with reduced ejection fraction, HFpEF presents a great challenge and needs to be addressed considering the failure of HF drugs to improve its outcomes. Further extensive studies on the relationships between HFpEF, aging, and comorbidities in carefully phenotyped HFpEF subgroups may help understand the biology, diagnosis, and treatment of HFpEF. The current review summarized the diagnostic and therapeutic development of HFpEF based on the complex relationships between aging, comorbidities, and HFpEF.

Stress hyperglycemia ratio (SHR) has emerged as a potential prognostic marker in critical illness, but its association with mortality in cardiovascular disease remains incompletely characterized. This study investigated the relationship between SHR and all-cause mortality in critically ill patients with cardiovascular disease, adjusting for a variety of confounding factors using propensity score matching (PSM). A cohort of 3,352 critically ill patients with cardiovascular disease was stratified by SHR quartiles (Q1–Q4). Baseline characteristics, comorbidities (e.g., heart failure, diabetes), and severity scores (OASIS, APSIII, SOFA) were extracted from a large database containing de-identified health data patients admitted to the intensive care units (ICUs) of Beth Israel Deaconess Medical Center. PSM (670 matched pairs) balanced covariates between high (SHR > 1.355) and low SHR groups. The associations between SHR and mortality risk (in-hospital, 28-day, 90-day, 365-day) were evaluated using Cox models, restricted cubic spline (RCS) analysis, and Kaplan-Meier survival curves. Cox proportional hazards models were implemented with three sequential adjustment levels: Model 1 (unadjusted); Model 2 (adjusted for demographic factors and comorbidities); and Model 3 (fully adjusted). Predictive performance of SHR combined with severity scores was assessed via area under the curve (AUC) improvement. Higher SHR quartiles exhibited greater comorbidity burden (e.g., acute kidney injury: 84.6% in Q4 vs. 79.7% in Q1, P < 0.001) and severity scores (P < 0.001). Unadjusted analysis showed a significant association between SHR and mortality, with Q4 having the highest in-hospital (Q4: 16.3% vs. Q1–Q3: 5.1–6.4%, P < 0.001) and 365-day mortality (Q4: 29.2% vs. Q1–Q3: 15.7–16.9%, P < 0.001). The RCS analysis revealed a U-shaped mortality risk, with average optimal SHR cutoffs of 1.355. After PSM, cox proportional hazard models confirmed that high SHR (Q4) remained associated with early mortality (in-hospital HR = 2.117, [95% CI: 1.223–3.665], P = 0.007; 28-day HR = 1.859, [95% CI: 1.100-3.141], P = 0.020) but not long-term outcomes (90-day mortality, P = 0.127; 365-day mortality, P = 0.123) in the Model 1. Similar trends were obtained after adjusting for demographic factors and comorbidities (Model 2) and in the fully adjusted model (Model 3). Adding SHR improved short-term mortality prediction performance (e.g., OASIS AUC: +0.034 for in-hospital, P < 0.001), though benefits diminished post-PSM (e.g., OASIS: +0.012 for in-hospital, P = 0.009). However, incorporating SHR did not enhance the predictive performance of OASIS and SAPSII for 90-day and 365-day mortality prediction after PSM. Elevated SHR contributes to early mortality in patients with cardiovascular disease, even after rigorous confounder adjustment. The incremental predictive value of SHR support its utility for risk stratification, particularly for short-term outcomes, but its prognostic value fades for long-term mortalities. These findings highlight SHR as a favorable biomarker for clinical decision-making in acute cardiovascular care.

Objective: Malnutrition is prevalent in elderly with hip fracture and higher than in community-dwelling older adults. Scarce studies have examined the association between preoperative malnutrition and postoperative mortality in elderly Chinese individuals with hip fracture. This study was designed to explore the effect of preoperative malnutrition on the postoperative long-term mortality in elderly Chinese individuals undergoing hip surgery. Methods: As a single-center observational study, this study included 263 consecutive patients above 70 years old with hip fracture and elective surgery. Preoperative nutritional status was evaluated by prognostic nutritional index (PNI). Patients were divided into one group with malnutrition (26 patients with PNI ⩽ 38) and the other group without malnutrition (169 patients with PNI > 38), respectively. Results: The overall malnutrition rate was 13.3% (26 patients). The postoperative long-term mortality rates of patients with and without malnutrition had statistically significant difference [10 patients (38.5%) and 32 patients (18.9%), p < 0.05]. Cox regression analysis showed that malnutrition (hazard ratio: 0.269, 95% confidence interval: 0.085–0.859, p < 0.05) and partial pressure of carbon dioxide (hazard ratio: 0.873, 95% confidence interval: 0.790–0.964, p < 0.05) were independent risk factors for the postoperative long-term mortality. Conclusion: This study demonstrated that preoperative malnutrition was an independent risk factor for the postoperative long-term mortality and resulted in a more than 2.5-fold increase of the postoperative long-term mortality in elderly Chinese individuals undergoing hip surgery.

Aims: Cardiac hypertrophy, an adaptive response of the heart to stress overload, is closely associated with heart failure and sudden cardiac death. This study aimed to investigate the therapeutic effects of chlorogenic acid (CGA) on cardiac hypertrophy and elucidate the underlying mechanisms. Methods and results: To simulate cardiac hypertrophy, myocardial cells were exposed to isoproterenol (ISO, 10 μM). A rat model of ISO-induced cardiac hypertrophy was also established. The expression levels of cardiac hypertrophy markers, endoplasmic reticulum stress (ERS) markers, and apoptosis markers were measured using quantitative reverse transcription PCR and western blotting. The apoptosis level, size of myocardial cells, and heart tissue pathological changes were determined by terminal deoxynucleotidyl transferase dUTP nick-end labelling staining, immunofluorescence staining, haematoxylin and eosin staining, and Masson's staining. We found that CGA treatment decreased the size of ISO-treated H9c2 cells. Moreover, CGA inhibited ISO-induced up-regulation of cardiac hypertrophy markers (atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain), ERS markers (C/EBP homologous protein, glucose regulatory protein 78, and protein kinase R-like endoplasmic reticulum kinase), and apoptosis markers (bax and cleaved caspase-12/9/3) but increased the expression of anti-apoptosis marker bcl-2 in a dose-dependent way (0, 10, 50, and 100 μM). Knockdown of sphingosine-1-phosphate receptor 1 (S1pr1) reversed the protective effect of CGA on cardiac hypertrophy, ERS, and apoptosis in vitro (P < 0.05). CGA also restored ISO-induced inhibition on the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signalling in H9c2 cells, while S1pr1 knockdown abolished these CGA-induced effects (P < 0.05). CGA (90 mg/kg/day, for six consecutive days) protected rats against cardiac hypertrophy in vivo (P < 0.05). Conclusions: CGA treatment attenuated ISO-induced ERS and cardiac hypertrophy by activating the AMPK/SIRT1 pathway via modulation of S1pr1.

Background: Age-related cognitive decline (ARCD) is a common condition among older adults, affecting 100 million people worldwide. Traditional Chinese Medicine’s (TCM) constitution is closely related to the occurrence and development of diseases in the elderly population. However, little is known about the relationships between TCM constitution and ARCD in the super-aged population. The present study aimed to investigate the relationships between the TCM constitution and ARCD in Chinese centenarians and to explore the application of the constitution to prevent ARCD in the elderly population.Methods: Each participant underwent a standardized epidemiological investigation and physical examination, based on the China Hainan Centenarian Cohort Study. Data on the demographic characteristics and TCM constitution were collected using structured questionnaires.Results: The present study included 636 centenarians aged 100–116 years. The prevalence of ARCD was 87.7% (n = 558 centenarians). In multiple linear regression analysis, an inverse relationship between Qi depression and Mini-Mental State Examination scales was significant after controlling for a wide range of other factors (P < 0.05). In multiple logistic regression analysis, Qi depression was positively associated with ARCD after full adjustment (P < 0.05).Conclusion: As the first study in the world, the present study provides strong epidemiological evidence that Qi depression has a significant relationship with ARCD in Chinese centenarians, and regulating Qi depression may be a valuable method to prevent and treat ARCD in the elderly population.