QJM: An International Journal of Medicine最新文献

Background: The prognosis of idiopathic pulmonary fibrosis (IPF) patients is highly heterogeneous. Abnormalities in lipids and their metabolism play an important role in the development of IPF.

Aim: To investigate the value of lipid parameters, C-reactive protein (CRP) and high-density lipoprotein cholesterol/C-reactive protein (HDL-C/CRP) ratio levels in the prognosis of IPF patients.

Design: An observational cohort study.

Methods: We collected baseline data of non-IPF controls and IPF patients, and IPF patients were followed up for 4 years. All-cause death or lung transplantation and IPF-related death were the outcome events. Receiver operating characteristic curves and Cox proportional hazards models were used to analyze the predictive effect of lipid parameters, CRP and HDL-C/CRP ratio on the prognosis of IPF patients.

Results: IPF patients had lower HDL-C, HDL-C/CRP ratio and higher CRP compared to non-IPF controls. IPF patients who died or underwent lung transplantation were older and had worse pulmonary function, lower HDL-C, HDL-C/CRP ratio and higher CRP compared with surviving patients. HDL-C/CRP ratio was better than HDL-C and CRP in predicting all-cause death or lung transplantation. IPF patients with low HDL-C/CRP ratio had shorter survival times. The HDL-C/CRP ratio and diffusing capacity for carbon monoxide(DLCO)% of predicted were independent protective factors for all-cause death or lung transplantation and IPF-related death in IPF patients, while age and gender-age-physiology (GAP) Stage ≥ 2 (HR = 4.927) were independent risk factors for all-cause death or lung transplantation. Age > 65 years (HR = 3.533) was an independent risk factor for IPF-related death.

Conclusion: HDL-C/CRP ratio was a valid predictor of clinical outcomes in IPF patients, including all-cause death or lung transplantation and IPF-related death.

Background: Ischemic stroke patients are more prone to developing another cardiovascular event.

Aim: This study aims to examine potential biological predispositions to cardiovascular recurrence in patients with ischemic stroke.

Design: Human and preclinical studies.

Methods: Quantitative proteomic analysis, animal stroke, atherosclerosis models and circulating endothelial cells (CECs) were employed to examine candidate biomarkers derived from an ischemic stroke cohort in Singapore.

Results: Proteomic analysis of pooled microvesicles of 'Event' (n = 24) and without 'Event' (n = 24) samples identified NOTCH3 as a candidate marker; plasma NOTCH3 were shown to be elevated in 'Event' patients compared to those without 'Events' and age-matched controls. In a validation cohort comprising 431 prospectively recruited ischemic stroke patients (mean age 59.1 years; median follow-up 3.5 years), men with plasma NOTCH3 (>1600 pg/ml) harbored increased risk of cardiovascular recurrence (adjusted hazards ratio 2.29, 95% CI 1.10-4.77); no significant association was observed in women. Chronic renal failure, peripheral artery disease and NT-pro-brain natriuretic peptide were significant predictors of plasma NOTCH3 in men without ischemic stroke (adjusted r2 = 0.43). Following middle cerebral artery occlusion, NOTCH3 expression in mouse sera increased and peaked at 24 h, persisting thereafter for at least 72 h. In Apoe-/- atherosclerotic mice, NOTCH3 stained the endothelium of defective arterial lining and atherosclerotic plaques. Analysis of CECs isolated from stroke patients revealed increased gene expression of NOTCH3, further supporting endothelial damage underpinning NOTCH3-mediated atherosclerosis.

Conclusion: Findings from this study suggests that NOTCH3 could be important in cardiovascular recurrence following an ischemic stroke.