Different transcriptional profiling between senescent and non-senescent human coronary artery endothelial cells (HCAECs) by Omeprazole and Lansoprazole treatment.

Recent evidence suggests that high dose and/or long term use of proton pump inhibitors (PPIs) may increase the risk of adverse cardiovascular events in older patients, but mechanisms underlying these detrimental effects are not known. Taking into account that the senescent endothelial cells have been implicated in the genesis or promotion of age-related cardiovascular disease, we hypothesized an active role of PPIs in senescent cells. The aim of this study is to investigate the changes in gene expression occurring in senescent and non-senescent human coronary artery endothelial cells (HCAECs) following Omeprazole (OPZ) or Lansoprazole (LPZ) treatment. Here, we show that atherogenic response is among the most regulated processes in PPI-treated HCAECs. PPIs induced down-regulation of anti-atherogenic chemokines (CXCL11, CXCL12 and CX3CL1) in senescent but not in non-senescent cells, while the same chemokines were up-regulated in untreated senescent cells. These findings support the hypothesis that up-regulated anti-atherogenic chemokines may represent a defensive mechanism against atherosclerosis during cellular senescence, and suggest that PPIs could activate pro-atherogenic pathways by changing the secretory phenotype of senescent HCAECs. Moreover, the genes coding for fatty acid binding protein 4 (FABP4) and piezo-type mechanosensitive ion channel component 2 (PIEZO2) were modulated by PPIs treatment with respect to untreated cells. In conclusions, our results show that long-term and high dose use of PPI could change the secretory phenotype of senescent cells, suggesting one of the potential mechanisms by which use of PPI can increase adverse outcomes in older subjects.

Anticholinergic burden and 1-year mortality among older patients discharged from acute care hospital.

AIM: The association between anticholinergic burden and mortality is controversial. We aimed to investigate whether the anticholinergic cognitive burden (ACB) score predicts 1-year mortality in older patients discharged from acute care hospitals. METHODS: Our series consisted of 807 hospitalized patients aged ≥65 years. Patients were followed up for 12 months after discharge. All-cause mortality was the outcome of the study. The ACB score at discharge (0, 1, ≥2) and increasing ACB score from admission to discharge (no increase, +1, +2 or more) were calculated and used as exposure variables. Cox proportional hazards models adjusted for potential confounders were used for the analysis. Interactions between the ACB score and cognitive impairment or history of falls were also investigated. RESULTS: During the follow-up period, 177 out of 807 participants (21.9%) died. After adjusting for potential confounders, a discharge ACB score of ≥2 (HR 1.69, 95% CI 1.09-2.65) was significantly associated with the outcome, whereas the association between increasing ACB score of +2 or more and mortality was weaker (HR 1.30, 95% CI 0.95-1.92). The interaction between the ACB score at discharge or increasing ACB score and cognitive impairment was statistically significant (P = 0.003 and P = 0.004, respectively), whereas that between the ACB score and falls was not. CONCLUSIONS: The ACB score at discharge and, to a lesser extent, an increasing ACB score during hospital stay are associated with an increased risk of 1-year mortality in older patients discharged from hospital. Such an association is stronger among patients with cognitive impairment. Geriatr Gerontol Int 2018; 18: 705-713.