Japan's family pharmacist system (FPS) has helped to prevent therapeutic duplication and drug interactions and to improve leftover drug adjustments. However, its association with lower risk of death or hospitalization remains unclear.

To examine the risk of death or hospitalization from any cause among older patients with chronic cardiovascular or endocrine disease among users of an FPS.

This cohort study used administrative claims data in the DeSC Health Insurance Database from April 2015 to March 2024, with a 2-year follow-up period. A prevalent new-user design was adopted to compare patients who initiated FPS use with those receiving standard pharmaceutical care. Patients 75 years of age or older with a history of visiting a pharmacy at least twice for treating hypertension, type 2 diabetes, hyperlipidemia, heart failure, angina, nonvalvular atrial fibrillation, or other arrhythmias were included.

FPS use and nonuse.

The primary outcome was death or hospitalization from any cause, assessed in a time-to-first-event analysis, with each component analyzed individually as a secondary outcome. Cox proportional hazards regression with robust variance estimators was used to estimate hazard ratios (HRs) and the 95% CIs.

FPS users and nonusers each included 22 557 patients (total 45 114; mean [SD] age, 82.8 [5.2] years; 32 254 [71.5%] female) after time-conditional propensity score matching. The risk of death or hospitalization from any cause did not differ significantly between groups (HR, 1.00 [95% CI, 0.97-1.04]). For individual end points, the risk of death from any cause was slightly but significantly lower among users than nonusers (33.9 [95% CI, 32.0-35.9] vs 37.0 [95% CI, 35.0-39.1] deaths per 1000 person-years), with an HR of 0.91 (95% CI, 0.85-0.99). However, no significant difference in risk was observed between FPS users and nonusers for hospitalization from any cause (HR, 1.01 [95% CI, 0.98-1.05]).

This large-scale cohort study found that the use of an FPS was not associated with lower risk of death or hospitalization from any cause. However, the results generated a clinically important hypothesis that FPS use may be associated with slightly lower risk of death among older patients with chronic cardiovascular or endocrine disease.

The high smoking prevalence and growing burden of chronic metabolic diseases have been threatening public health in Northeast China. This study aimed to investigate the association of smoking/quitting status with hypertension, diabetes, and dyslipidemia in residents in Northeast China.

A total of 78,674 adults aged 35-75 years old were enrolled from a cross-sectional study conducted in Northeast China in 2020. Demographic data were collected, and biochemical indices and anthropometric indices were measured. Associations of smoking/quitting status with hypertension, diabetes, and dyslipidemia were investigated using logistic regression. Restricted cubic spline analysis was performed to assess the dose-response relationship between smoking/quitting status and prevalence of dyslipidemia, diabetes, and hypertension.

A total of 16,401 (20.85%) smokers, 25,805 (32.80%) adults with dyslipidemia, 16,812 (21.37%) adults with diabetes, and 33,539 (42.63%) adults with hypertension were identified in this study. The risk of diabetes, dyslipidemia, and hypertension in current heavy smokers and former heavy smokers were higher than that in never-smokers (all P < 0.001). The risk of dyslipidemia, diabetes, and hypertension elevated with the increase of cigarette amounts from "1-5 cigarettes per day" to "≥31 cigarettes per day" and smoking duration from "1-18 years" to "19-31 years". However, excluding quitting smoking for 2-3 years (OR = 1.30, 95% CI: 1.01-1.67, P = 0.041) and 7-20 years (OR = 1.43, 95% CI: 1.12-1.83, P = 0.004) enhancing diabetes risk, quitting duration was not associated with the risk of dyslipidemia, diabetes, and hypertension (all P > 0.05).

Smoking status, smoking amount, and smoking duration, rather than quitting duration, are associated with the risk of dyslipidemia, diabetes, and hypertension among adults in Northeast China.

High altitude has a considerable impact on the pathophysiology of the human cardiovascular system and disease occurrence. We aim to use an integrated approach of metabolomics and proteomics to reveal key pathways and biomarkers of hypertension at high altitude. Thirty Tibetan patients with hypertension and 30 healthy individuals residing on the Tibetan Plateau at a very high altitude (> 4500 m) were included in the study. Metabolomic analysis was conducted using Vanquish ultra-high performance liquid chromatography, while proteomic analysis utilized the timsTOF Pro2 mass spectrometer. Correlation analysis revealed key signaling pathways and biomarkers associated with hypertension in Tibetan patients. The results showed 87 differentially expressed metabolites and 61 differentially expressed proteins in individuals with hypertension at high altitude. The results of metabolomic differential metabolite pathway analysis indicated that Caffeine metabolism had the most significant impact. Specific metabolites like PI(16:0/16:0), Caffeine, and Plastoquinone 3 were found to be significantly up-regulated in hypertensive patients. The combination of five metabolites achieved an area under the curve (AUC) of 0.871 for hypertension prediction. Proteomic analysis revealed that the identified differential proteins primarily functioned in signaling receptor binding. It was confirmed that Creatine kinase B (CKB) and Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) could serve as a protein biomarker combination for hypertension in plateau regions, showing an AUC of 0.764 (0.585-0.944). Upon conducting an integrated analysis of metabolomics and proteomics, the combined AUC improved to 0.982 (0.949-1.000). A comprehensive analysis utilizing metabolomics and proteomics revealed that alterations in signal transduction-related pathways and lipid metabolism pathways were implicated in hypertension among plateau populations. Additionally, YWHAZ was observed as a potential biomarker for this condition.

Obesity is an independent driver of cardiovascular disease (CVD), mediated through adverse haemodynamic loading, insulin resistance, systemic inflammation, endothelial dysfunction and prothrombotic pathways. Contemporary obesity therapies show cardiovascular (CV) benefits beyond improvements in traditional risk factors. Across large CV outcome trials, glucagon-like peptide 1 receptor agonists consistently reduce three-point major adverse CV events (MACE) in patients with overweight, obesity and established CVD with and without diabetes. In obesity-related heart failure of preserved ejection fraction, semaglutide and tirzepatide improve symptoms and functional capacity and reduce worsening heart failure events, while effects on CV mortality remain uncertain. In contrast, evidence for metabolic bariatric surgery is dominated by large observational cohorts and meta-analyses, which are associated with durable weight loss and lower observed rates of MACE, heart failure and all-cause mortality compared with non-surgical care, though causal inference is constrained by residual confounding. Data support that sustained weight loss of at least 10% is more likely to translate into CVD event reduction, alongside other organ specific mechanisms that impact CV health independent from weight reduction. Obesity treatments offer a safe and effective method to lose weight with varying CV benefits, with current evidence still in early stages to establish robust clinical recommendations.

Justicia pectoralis Jacq. (Acanthaceae), known as chambá, is traditionally used in Latin America for respiratory ailments as an expectorant with bronchodilatory and anti-inflammatory properties. However, scientific validation of its efficacy and safety is limited.

To develop a standardised extract (TI-138) and evaluate its stability, pharmacokinetics, efficacy, safety, and molecular mechanism of action.

The extract was standardised and characterised by LC-MS/MS. Pharmacokinetics and CYP3A4 interaction were studied in rats. Efficacy was assessed in three respiratory models. Mechanistic insights were obtained via PCR array, RT-qPCR, and ELISA. Safety was assessed through genotoxicity assays, acute and long-term toxicity studies, and CNS, cardiovascular, and respiratory safety pharmacology conducted under GLP conditions.

TI-138 showed a stable phytochemical profile for over two years and four months and good oral absorption. In rats, pharmacokinetics showed rapid absorption (0.25 h) with peak plasma levels of ∼1.5 μg/mL (coumarin) and 2.0 μg/mL (o-coumaric acid). Orally administered TI-138 had expectorant and antitussive effects, reduced airway inflammation and remodelling in asthma, and modulated inflammatory and immune-related gene expression. Safety studies showed no genotoxicity and acceptable toxicity at therapeutic doses. Notably, TI-138 suppressed the expression of several important genes involved in pro-inflammatory and immune-regulatory pathways, including Cd19, Ctla4, Cyp7a1, H2-Eb1, Il2, Il4, Il10, Il13, Il17a, and Tnf, and reduced the expression of Ccl19, Ccl5, Ccr4, Cd28, and Cd4 to levels below those observed in animals challenged with saline alone (saline + vehicle). Also of relevance, TI-138 significantly reduced pulmonary levels of pro-inflammatory cytokines-including IL-5, IL-13, and TNF-α-as well as IgE production.

The standardised Justicia pectoralis extract (TI-138) demonstrated efficacy in preclinical models of respiratory inflammation and cough, with no genotoxicity and a favourable safety profile. Its activity appears to involve the modulation of relevant genes associated with airway inflammation, supporting further clinical studies to develop a new, approved phytomedicine for clinical use.

Acute myocarditis can lead to chronic inflammatory cardiomyopathy (Infl-CMP), a condition characterized by increased risk of ventricular arrhythmias (VA), left ventricular (LV) systolic dysfunction (LVSD), and heart failure (HF). Immunosuppressive therapy is generally not recommended for Infl-CMP when diagnosed non-invasively by cardiac magnetic resonance imaging (CMRI) or fluorodeoxyglucose-positron emission tomography (FDG-PET). We are assessing, in the CMP-MYTHiC trial, whether colchicine (0.5 mg in patients <70 kg or 1 mg in patients ≥70 kg), an immunomodulatory drug with a good safety profile, can reduce myocardial inflammation in patients with Infl-CMP.

The CMP-MYTHiC, a multicenter investigator-initiated single-blinded randomized controlled trial, screens adult patients diagnosed with infl-CMP by CMRI or FDG-PET within the prior 3 months at 12 Italian centers. Eligibility is further defined by the presence of VA or LVSD/HF phenotype. VA phenotype is determined by a high burden of premature ventricular complexes (PVCs) on baseline 24-hour ECG ambulatory monitoring, non-sustained ventricular tachycardia (NSVT), or sustained ventricular tachycardia (SVT). The LVSD/HF phenotype is characterized by reduced LV ejection fraction (LVEF<50% on echocardiogram or <60% on CMRI) or elevated natriuretic peptide levels. Key exclusion criteria include a history of myocardial infarction, cardiomyopathy attributed to other specific causes, and systemic autoimmune disorders.

The efficacy of colchicine compared to placebo will be assessed when CMRI or FDG-PET scans and 24-h ambulatory ECG monitoring are repeated at 6 months after randomization. The primary endpoint of the trial analyzed according to the intention-to-treat population is the proportion of patients who are alive and free from any clinical (cardiac death or hospitalization due to HF or VA episodes), arrhythmic (PVC burden increase ≥50%, NSVT increase ≥30%, or any SVT), or imaging (LVEF reduction >10% or new areas of edema plus increased inflammation) worsening, and who demonstrate improvement in either imaging (reduction in edema on CMRI or FDG uptake) or arrhythmic (PVC burden reduction ≥70% with no NSVT/SVT) outcomes at 6 months. Assuming 80% power with an overall type I error of 0.025 using one-sided Fisher's Exact test, 40 patients per group are required to demonstrate that the primary endpoint will be reached in 66% of patients in the colchicine group compared to 33% in the placebo. Twenty-nine patients were randomized since December 2023, and the conclusion is expected in 2029.

The results can define the role of colchicine in treating patients with Infl-CMP noninvasively diagnosed by CMRI or FDG-PET.

NCT06158698.

No significant coronary artery lesion is seen on an emergent coronary angiogram in 5 to 10% of patients with myocardial infarction. These patients are most often female, younger and with less risk factors for atherosclerotic disease. Causes of myocardial infarction with no significant coronary artery stenosis (MINOCA) include plaque rupture, coronary artery spasm and coronary microvascular lesions. MINOCA is diagnosed using clinical (prolonged chest pain) ECG and biological (rise in troponin) data. A coronary angiogram is mandatory to confirm the absence of significant coronary artery lesion. Endovascular imaging is often performed. Cardiac MRI confirms the diagnosis of myocardial infarction and rules out other causes of prolonged chest pain and rise of troponin such as myocarditis and Takotsubo syndrome. Long term follow-up by a cardiologist is necessary.