Association of SDF1 and MMP12 with Atherosclerosis and Inflammation: Clinical and Experimental Study.

BACKGROUND: Atherosclerosis is the main etiology of cardiovascular diseases (CVD), associated to systemic inflammation. Matrix metalloproteinases (MMPs) are related to atherosclerosis progression through the SDF1/CXCR4 axis promoting macrophages recruitment within the vascular wall. The goal was to assess new circulatory inflammatory markers in relation to atherosclerosis. METHODS: Measurement of SDF1, MMP12 and CRP in blood samples of 298 prospective patients with cardiovascular risk. To explore atherosclerosis progression, CXCR4/SDF1 axis and MMP12 expression were determined by RT-qPCR and by immunohistochemistry in the aorta of accelerated and delayed atherosclerosis mice models (Apoe-/- and Apoe-/-Mmp10-/-). RESULTS: SDF1, MMP12 and CRP were elevated in patients with clinical atherosclerosis, but after controlling by confounding factors, only SDF1 and CRP remained increased. Having high levels of both biomarkers showed 2.8-fold increased risk of presenting clinical atherosclerosis (p = 0.022). Patients with elevated SDF1, MMP12 and CRP showed increased risk of death in follow-up (HR = 3.2, 95%CI: 1.5-7.0, p = 0.004). Gene and protein expression of CXCR4 and MMP12 were increased in aortas from Apoe-/- mice. CONCLUSIONS: The combination of high circulating SDF1, MMP12 and CRP identified patients with particular inflammatory cardiovascular risk and increased mortality. SDF1/CXCR4 axis and MMP12 involvement in atherosclerosis development suggests that they could be possible atherosclerotic targets.

Análisis de subpoblaciones monocitarias en relación con los factores de riesgo cardiovascular / Analysis of monocitary subpopulations in relation to cardiovascular risk factors

Introducción: La participación monocitaria en la progresión aterosclerótica y sus efectos pro- o antiinflamatorios dependen de las subpoblaciones circulantes. El objetivo de este estudio es la caracterización de dichas subpoblaciones y su asociación con los factores de riesgo cardiovascular. Métodos: Estudio transversal que incluye 102 pacientes seleccionados; edad media: 65 años (rango 41-86 años), 69% varones. Se utilizó un panel de anticuerpos específicos frente a monocitos clásicos (Mon1, CD14+CD16− CD300e+HLADR+), intermedios (Mon2, CD14+CD16+CD300e+HLADR+) y no clásicos (Mon3, CD14-k-CD16+CD300e+HLADR+). Se establecieron tres grupos de estudio; grupo 1: sujetos asintomáticos con más de un factor de riesgo cardiovascular (n = 17); grupo 2: sujetos asintomáticos, pero con patología vascular por ecografía o microalbuminuria (n = 56); y grupo 3: pacientes con algún evento vascular aterotrombótico previo (n = 19). Asimismo, se calculó el riesgo cardiovascular mediante las escalas Framingham y REGICOR. Resultados: Se observó una asociación entre las subpoblaciones Mon1 y Mon2 y los grupos del estudio (ANOVA, p < 0,05), independiente de la edad y el sexo para los Mon2. Asimismo, las subpoblaciones Mon1 y Mon 2 se asociaron con eventos vasculares adversos (ß = 0,86, p = 0,02 y ß = 0,1 p = 0,002, respectivamente), siendo la asociación de Mon2 independiente de la edad y el sexo. Además, el porcentaje de Mon3 se asoció con la presencia de más de 2 factores de riesgo cardiovascular (ß=0,21, p=0,04) en el análisis univariante. Finalmente, se halló una correlación entre los niveles de Mon1 y Mon2 con el número de leucocitos (r = 0,7, p < 0,001 y r = 0,26 p < 0,01, respectivamente). Conclusiones: El análisis de subpoblaciones monocitarias es de gran interés clínico, ya que permite establecer un diferente perfil inflamatorio según los grupos de riesgo cardiovascular establecidos

Introduction: Monocytes play an important role in atherosclerotic progression having both pro and anti-inflammatory effects depending on different circulating monocyte subpopulations. The objective of this study is to characterize these subpopulations and their association with cardiovascular risk factors. Methods: Transversal study including 102 selected patients, mean age: 65 years-old (range 41-86), 69% males. A set of specific antibodies against classical monocytes (Mon1, CD14+CD16- CD300e+HLADR+), intermediate (Mon2, CD14+CD16+CD300e+HLADR+) and non-classical (Mon3, CD14-CD16+CD300e+HLADR+) was assayed. Three groups of patients were included: 17 asymptomatic with more than one cardiovascular risk factor (group 1), 56 subjects asymptomatic but with vascular pathology assessed by ultrasound or microalbuminuria (group 2) and 19 patients with a previous atherothrombotic event (group 3). The cardiovascular risk was determined by Framingham and REGICOR scores. Results: An association between study groups and the percentage of Mon1 and Mon2 was observed (ANOVA, p < .05), being independent of age and sex for Mon2. Likewise Mon1 and Mon2 subpopulations were associated with cardiovascular adverse events (ß = 0.86, p =.02 y ß = 0.1 p =.002, respectively), independently of age and sex in the case of Mon2. Moreover the percentage of Mon3 was associated with the presence of several cardiovascular risk factors (ß = 0.21, p = .04) in the univariate analysis. In addition, there was a correlation between the levels of Mon1 and Mon2 and leukocytes (r = 0.7, p < .001 and r = 0.26, p = .01, respectively). Conclusions: The analysis of monocyte subpopulations may be clinically useful to stratify the inflammatory profile related to the different cardiovascular risk groups

Analysis of monocitary subpopulations in relation to cardiovascular risk factors. / Análisis de subpoblaciones monocitarias en relación con los factores de riesgo cardiovascular.

INTRODUCTION: Monocytes play an important role in atherosclerotic progression having both pro and anti-inflammatory effects depending on different circulating monocyte subpopulations. The objective of this study is to characterize these subpopulations and their association with cardiovascular risk factors. METHODS: Transversal study including 102 selected patients, mean age: 65 years-old (range 41-86), 69% males. A set of specific antibodies against classical monocytes (Mon1, CD14+CD16- CD300e+HLADR+), intermediate (Mon2, CD14+CD16+CD300e+HLADR+) and non-classical (Mon3, CD14-CD16+CD300e+HLADR+) was assayed. Three groups of patients were included: 17 asymptomatic with more than one cardiovascular risk factor (group 1), 56 subjects asymptomatic but with vascular pathology assessed by ultrasound or microalbuminuria (group 2) and 19 patients with a previous atherothrombotic event (group 3). The cardiovascular risk was determined by Framingham and REGICOR scores. RESULTS: An association between study groups and the percentage of Mon1 and Mon2 was observed (ANOVA, p<.05), being independent of age and sex for Mon2. Likewise Mon1 and Mon2 subpopulations were associated with cardiovascular adverse events (ß=0.86, p=.02 y ß=0.1 p=.002, respectively), independently of age and sex in the case of Mon2. Moreover the percentage of Mon3 was associated with the presence of several cardiovascular risk factors (ß=0.21, p=.04) in the univariate analysis. In addition, there was a correlation between the levels of Mon1 and Mon2 and leukocytes (r=0.7, p<.001 and r=0.26, p=.01, respectively). CONCLUSIONS: The analysis of monocyte subpopulations may be clinically useful to stratify the inflammatory profile related to the different cardiovascular risk groups.

Critical appraisal of bilastine for the treatment of allergic rhinoconjunctivitis and urticaria.

Bilastine is a second generation antihistamine indicated for the treatment of seasonal or perennial allergic rhinoconjunctivitis and chronic urticaria with a daily dose of 20 mg, in adults and children over 12 years of age. The efficacy of bilastine has been shown to be similar to that of the comparator drugs for the control of the nasal and nonnasal symptoms of allergic rhinoconjunctivitis, while also showing a subjective improvement in the quality of life and in overall clinical impression. For chronic urticaria the symptoms (itching and the development of papules) lessens from the second day of treatment onwards, in a similar way to other antihistamines used as comparators. Bilastine should not be administered at meal times to avoid interference with the absorption process. It is not distributed to the central nervous system, is scarcely metabolized, and elimination is through the kidneys and feces, with a 14-hour elimination half-life. It has no effect on cytochrome P450. During clinical development, bilastine was shown to be a drug that is adequately tolerated, with a similar effect to placebo with regard to drowsiness and changes in heart rate. In relation to its use, headaches were the most frequent adverse effect to be reported. No cardiotoxic effects have been observed, and the therapeutic dose does not alter the state of alertness.

Results of a retrospective observational study of intermediate care staffed by hospitalists: impact on mortality, co-management, and teaching.

BACKGROUND: Hospitalized patients are complex and institutions have to face the high cost of critical care and the limited resources of the ward. Intermediate care appears as an attractive strategy to provide rational care according to patient needs. It is an interesting scenario to expand co-management and teaching. STUDY DESIGN: Retrospective observational study. SETTING: Intermediate care unit (ImCU) of a single academic hospital. PATIENTS AND METHODS: 456 patients admitted from April 2006 to April 2010 were included in the study. Demographics, admission physiologic parameters and in-hospital mortality were recorded. We used the Simplified Acute Physiology Score II (SAPS II) as prognostic score system. Co-management with medical and surgical teams, and the number of training residents were evaluated. RESULTS: In-hospital mortality was 20.6%, whereas the expected mortality was 23.2% based on SAPS II score. The correlation between SAPS II predicted and observed death rates was accurate and statistically significant (Rho = 1.0, p < 0.001). Co-management was performed with several medical and surgical teams, with an increase in perioperative comanagement of 22.7% (p = 0.014). The number of training residents in ImCU increased from 4.3% to 30.4% (p = 0.002) CONCLUSIONS: An ImCU led by hospitalists showed encouraging results regarding patient survival and SAPS II is an useful tool for prognostic evaluation in this population. Intermediate care serves as an expansion of role for hospitalists; and clinicians, trainees and patients may benefit from co-management and teaching opportunities at this unique level of care.