RESUMO
Objective: Vascular calcification (VC) is an important predictor of cardiovascular morbidity and mortality in patients with chronic renal failure (CRF). It is well-known that obesity and metabolic syndrome (OB/MS) predicts poor prognosis of CRF patients. However, the influence of OB/MS on VC in CRF patients isn't clear. IL-18 mediates OB/MS-related inflammation, but whether IL-18 is involved in OB/MS -mediated VC in CRF patients hasn't been studied. In this study, it was explored that whether OB/MS caused by high-fat diet (HFD) can affect the level of serum IL-18 and aggravate the degree of VC in CRF rats. Furthermore, it was studied that whether IL-18 induces rat vascular smooth muscle cells (VSMCs) calcification by activating the MAPK pathways. Approach: The rats were randomly assigned to the sham-operated, CRF and CRF + HFD groups. CRF was induced by 5/6 nephrectomy. Serum IL-18 levels and aortic calcification indicators were compared in each group. Primary rat VSMCs calcification were induced by ß-glycerophosphate and exposed to IL-18. VSMCs were also treated with MAPK inhibitors. Results: The weight, serum levels of hsCRP, TG and LDL-C in CRF + HFD group were significantly higher than those in sham-operated and CRF groups (p < 0.05). Compared with the sham-operated group, the calcium content and the expression of BMP-2 of aorta in CRF and CRF + HFD groups were significantly increased (p < 0.05). Moreover, the calcium content and the expression of BMP-2 of aorta in CRF + HFD group was significantly higher than those in CRF group (p < 0.05). And the serum IL-18 level was positively correlated with aortic calcium content. It was also found that p38 inhibitor SB203580 can suppress the VSMCs calcification and osteoblast phenotype differentiation induced by IL-18. But the JNK inhibitor SP600125 can't suppress the VSMCs calcification and osteoblast phenotype differentiation induced by IL-18. Conclusions: These findings suggest that obesity-related inflammation induced by high-fat diet could exacerbate VC in CRF rats. Furthermore, serum IL-18 level had a positive correlation with the degree of VC. It is also found that IL-18 promoted osteogenic differentiation and calcification of rat VSMCs via p38 pathway activation.
RESUMO
BACKGROUND: Low minimum heart rate (MHR) is common in critically ill myocardial infarction (MI) patients. However, the association between MHR and the mortality of critically ill MI patients remains unclear. METHODS: In this retrospective cohort study, a total of 2,031 critically ill MI patients were enrolled from the Medical Information Mart for Intensive Care (MIMIC)-III database. Patients were divided into a low MHR group [MHR <60 beats per minute (bpm)] and a high MHR group (MHR ≥60 bpm). A Cox proportional hazard model was used to elucidate the association between these two groups and the mortality of MI patients. The association between mortality and MHR as a continuous variable was analyzed non-parametrically using restricted cubic splines. Sensitivity analyses were conducted to determine the impact of different admission heart rate, hypertension, atrial fibrillation, and vasopressor use on our results. RESULTS: MI patients in the low MHR group had higher 30-day and 1-year mortality than those in the high MHR group (20.59% vs. 10.91%, P<0.001 and 29.76% vs. 19.31%, P<0.001, respectively). After adjustment, the low MHR group was significantly correlated with 30-day mortality [hazard ratio, 1.779, 95% confidence interval (CI), 1.400-2.261, P<0.001] and 1-year mortality (hazard ratio, 1.537, 95% CI, 1.272-1.859, P<0.001). This correlation remained remarkable in patients with low or high admission heart rate, with or without hypertension, and with or without atrial fibrillation. An apparent L-curve relationship was observed between the 30-day mortality or 1-year mortality and MHR as a continuous variable. CONCLUSIONS: MHR under 60 bpm may be associated with a higher risk for both 30-day and 1-year mortality in critically ill MI patients. These findings highlight the possibility of MHR as an early risk indicator and potential therapeutic target for mortality in critically ill MI patients, which warrants further investigation.