Identification of a Plasma Microrna Signature as Biomarker of Subaneurysmal Aortic Dilation in Patients with High Cardiovascular Risk.

Patients with subaneurysmal aortic dilation (SAD; 25-29 mm diameter) are likely to progress to true abdominal aortic aneurysm (AAA). Despite these patients having a higher risk of all-cause mortality than subjects with aortic size <24 mm, early diagnostic biomarkers are lacking. MicroRNAs (miRs) are well-recognized potential biomarkers due to their differential expression in different tissues and their stability in blood. We have investigated whether a plasma miRs profile could identify the presence of SAD in high cardiovascular risk patients. Using qRT-PCR arrays in plasma samples, we determined miRs differentially expressed between SAD patients and patients with normal aortic diameter. We then selected 12 miRs to be investigated as biomarkers by construction of ROC curves. A total of 82 significantly differentially expressed miRs were found by qPCR array, and 12 were validated by qRT-PCR. ROC curve analyses showed that seven selected miRs (miR-28-3p, miR-29a-3p, miR-93-3p, miR-150-5p, miR-338-3p, miR-339-3p, and miR-378a-3p) could be valuable biomarkers for distinguishing SAD patients. MiR-339-3p showed the best sensitivity and specificity, even after combination with other miRs. Decreased miR-339-3p expression was associated with increased aortic abdominal diameter. MiR-339-3p, alone or in combination with other miRs, could be used for SAD screening in high cardiovascular risk patients, helping to the early diagnosis of asymptomatic AAA.

Usefulness of compounds with monacolin K in a case of statins intolerance / Utilidad de los compuestos con monacolina K en un caso de intolerancia a estatinas

Many patients with familial hypercholesterolaemia (FH) or in secondary prevention situations and with statin intolerance do not achieve LDL-C targets, and require treatment with PCSK9 inhibitors (iPCSK9) and ezetimibe. The case is presented on a patient with FH and total intolerance to statins. Treatment with iPCSK9 and ezetimibe failed to achieve her LDL-C target. A compound with red yeast rice derivatives containing 3mg of monacolin K was added, with good therapeutic compliance, and a very good control of LDL-C. The addition of red yeast rice derivatives containing low doses of monacolin K, together with IPCSK9 in patients with total intolerance to statins, may open a new path to obtain LDL-C targets in patients with high/very high cardiovascular risk

Muchos pacientes con hipercolesterolemia familiar (HF) o en situaciones de prevención secundaria con intolerancia a estatinas no logran objetivos a pesar del tratamiento con inhibidores de PCSK9 (iPCSK9) y ezetimiba. Presentamos el caso de un paciente con HF e intolerancia total a las estatinas. El tratamiento con iPCSK9 y ezetimiba no logró el objetivo lipídico. Se añadió un compuesto derivado de la levadura roja del arroz, que contenía 3mg de monacolina K con una excelente tolerancia, lográndose un muy buen control de los objetivos de cLDL. La suma al tratamiento de IPCSK9 de un compuesto derivado de la levadura roja del arroz, con bajas dosis de monacolina K, abre una nueva puerta para lograr los objetivos de cLDL en pacientes de muy alto riesgo cardiovascular

Usefulness of compounds with monacolin K in a case of statins intolerance.

Many patients with familial hypercholesterolaemia (FH) or in secondary prevention situations and with statin intolerance do not achieve LDL-C targets, and require treatment with PCSK9 inhibitors (iPCSK9) and ezetimibe. The case is presented on a patient with FH and total intolerance to statins. Treatment with iPCSK9 and ezetimibe failed to achieve her LDL-C target. A compound with red yeast rice derivatives containing 3mg of monacolin K was added, with good therapeutic compliance, and a very good control of LDL-C. The addition of red yeast rice derivatives containing low doses of monacolin K, together with IPCSK9 in patients with total intolerance to statins, may open a new path to obtain LDL-C targets in patients with high/very high cardiovascular risk.

Disappearance of recurrent pancreatitis after splenectomy in familial chylomicronemia syndrome.

BACKGROUND AND AIMS: Recurrent pancreatitis is a severe complication of familial chylomicronemia syndrome (FCS) mainly secondary to lipoprotein lipase deficiency. The mechanism and interindividual variability of pancreatitis in FCS are not fully understood, but abnormalities in the drainage system of pancreatic veins could be involved. METHODS AND RESULTS: Two cases of typical FCS are described with a past history of recurrent pancreatitis that dramatically improved after splenectomy performed in both cases for reasons non-related to FCS. CONCLUSIONS: These are the first reports of the disappearance of pancreatitis after splenectomy in FCS and they should be considered of anecdotal nature at this time. The disappearance of pancreatitis following splenectomy could be in part due to subsequent improvements in pancreatic drainage. Extrahepatic portal hypertension induced by hypertriglyceridemic splenomegaly leading to pancreatic congestion could also be a contributing factor.

Usefulness of midregional proadrenomedullin to predict poor outcome in patients with community acquired pneumonia.

BACKGROUND: midregional proadrenomedullin (MR-proADM) is a prognostic biomarker in patients with community-acquired pneumonia (CAP). We sought to confirm whether MR-proADM added to Pneumonia Severity Index (PSI) improves the potential prognostic value of PSI alone, and tested to what extent this combination could be useful in predicting poor outcome of patients with CAP in an Emergency Department (ED). METHODS: Consecutive patients diagnosed with CAP were enrolled in this prospective, single-centre, observational study. We analyzed the ability of MR-proADM added to PSI to predict poor outcome using receiver operating characteristic (ROC) curves, logistic regression and risk reclassification and comparing it with the ability of PSI alone. The primary outcome was "poor outcome", defined as the incidence of an adverse event (ICU admission, hospital readmission, or mortality at 30 days after CAP diagnosis). RESULTS: 226 patients were included; 33 patients (14.6%) reached primary outcome. To predict primary outcome the highest area under curve (AUC) was found for PSI (0.74 [0.64-0.85]), which was not significantly higher than for MR-proADM (AUC 0.72 [0.63-0.81, p > 0.05]). The combination of PSI and MR-proADM failed to improve the predictive potential of PSI alone (AUC 0.75 [0.65-0.85, p=0.56]). Ten patients were appropriately reclassified when the combined PSI and MR-proADM model was used as compared with the model of PSI alone. Net reclassification improvement (NRI) index was statistically significant (7.69%, p = 0.03) with an improvement percentage of 3.03% (p = 0.32) for adverse event, and 4.66% (P = 0.02) for no adverse event. CONCLUSION: MR-proADM in combination with PSI may be helpful in individual risk stratification for short-term poor outcome of CAP patients, allowing a better reclassification of patients compared with PSI alone.

The effects of adiponectin and leptin on human endothelial cell proliferation: a live-cell study.

The effect of adiponectin and leptin on the proliferation of the human microvascular endothelial cell line (HMEC-1) was studied in the absence or presence of fetal bovine serum (FBS). The participation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt (PI-3K/Akt) pathways in this effect were evaluated. We studied the effect of both adipokines on the motility, mitosis, proliferation and cell death processes of HMEC-1 cells using live-cell imaging techniques. Adiponectin but not leptin further increased the proliferative effect induced by FBS on HMEC-1. This effect seems to be the consequence of an increase in the mitotic index in adiponectin-treated cells when compared to untreated ones. The presence of either the mitogen-activated protein kinase (MAPK) inhibitor (PD98059), or PI-3K inhibitor (LY294002), reduced the effect of adiponectin in a dose-dependent manner. Neither adipokine was able to affect HMEC-1 proliferation in FBS-free conditions. Duration of mitosis, cell motility and the cell death process were similar in all conditions. These data suggest that adiponectin and leptin exert different effects on endothelial cell function. Adiponectin was able to potentiate proliferation of HMEC-1. This effect involves the activation of both PI3-K/Akt and ERK/MAPK pathways. However, it seems to exert minimal effects on HMEC-1 function in the case of leptin.

Effects of fluvastatin extended-release (80 mg) alone and in combination with ezetimibe (10 mg) on low-density lipoprotein cholesterol and inflammatory parameters in patients with primary hypercholesterolemia: a 12-week, multicenter, randomized, open-label, parallel-group study.

BACKGROUND: Combining lipid-lowering agents with complementary mechanisms of action can provide greater cholesterol reductions than using either agent alone, improving achievement of target low-density lipoprotein cholesterol (LDL-C) levels. OBJECTIVES: The aim of this study was to assess the effects of fluvastatin extended-release (XL) 80 mg/d administered alone or combined with ezetimibe 10 mg/d on plasma lipid levels and inflammatory parameters in patients with primary hypercholesterolemia. The tolerability of both regimens was also evaluated. METHODS: In this multicenter, randomized, open-label, parallel-group study, patients with hypercholesterolemia were randomized in a 1:1 ratio to receive fluvastatin XL 80 mg/d alone or in combination with ezetimibe 10 mg/d for 12 weeks. The primary end point was the percentage change from baseline to week 12 in LDL-C level with fluvastatin XL + ezetimibe combination therapy compared with fluvastatin XL alone. Plasma concentrations of inflammatory biomarkers were measured at baseline and week 12. Proportions of patients who achieved National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C goals were calculated. Tolerability was assessed by the monitoring and recording of all adverse events (AEs) and laboratory values. RESULTS: A total of 82 patients were enrolled (mean [SD] age, 50.0 [12.0] years; 44% male; 100% white; mean [SD] weight, 73.5 [14.9] kg; combination group, 38 patients; monotherapy group, 44). Fluvastatin XL + ezetimibe and fluvastatin XL monotherapy were associated with significant decreases from baseline in mean LDL-C level (by 49.9% and 35.2%, respectively; between-group difference, P < 0.001). Fluvastatin XL + ezetimibe was associated with significantly greater reductions from baseline than fluvastatin XL monotherapy in total cholesterol (38.2% vs 27.5% P < 0.001), triglycerides (21% vs 3.8% P = 0.02) and apolipoprotein B (34.8% vs 22.5% P < 0.001). NCEP ATP III LDL-C goals were achieved by 87% of patients receiving fluvastatin XL + ezetimibe and 67% of patients receiving fluvastatin XL monotherapy (between-group difference, P = 0.042). The combination was associated with significantly lowered high-sensitivity C-reactive protein (hs-CRP) levels in patients with high baseline hs-CRP (>2 mg/L; P < 0.02), >1 cardiovascular risk factor (P < 0.05), or hypertension (P = 0.015); both regimens were associated with significantly reduced plasma levels of interleukin-1B. No significant between-group differences in the incidences of AEs were found. Most AEs were mild or moderate in intensity. Headache was the most common AE, occurring in 5/44 (11.4%) patients in the fluvastatin XL group and 2/38 (5.3%) patients in the fluvastatin XL + ezetimibe group. One serious AE (convulsive crisis) occurred in a patient receiving fluvastatin XL + ezetimibe, but was not suspected to be related to study medication. CONCLUSION: Fluvastatin XL in combination with ezetimibe was found to be well-tolerated and effective, allowing the majority (87%) of these patients with primary hypercholesterolemia to achieve current treatment goals, and reduced hs-CRP levels in patients at higher cardiovascular risk.

[PREVENCAT study: control of cardiovascular risk in primary care]. / Estudio PREVENCAT: control del riesgo cardiovascular en atención primaria.

BACKGROUND AND OBJECTIVE: Most studies of cardiovascular risk factors (CVRF) conducted in our environment concentrate in a single CVRF. The PREVENCAT study was designed to estimate the control of CVRF in the population attended in primary care presenting arterial hypertension (HT), type 2 diabetes mellitus (DM2) and/or hypercholesterolemia (HC) as well as to assess the prevalence of Metabolic Syndrome in these patients. PATIENTS AND METHOD: Multicenter, cross-sectional study, in patients with HT, DM2 and/or HC, consecutively recruited by primary care physicians in Spain. The blood pressure, cholesterol, basal glycaemia, obesity, smoking and physical activity were assessed. The degree of control of these CVRF and the prevalence of MS were estimated. RESULTS: 2,649 patients were recruited, aged 64 (11.3) years, with a 51.6% of women. The most frequent diagnosis was HT (78.9%), followed by HC (58.4%) and DM2 (37.4%). In the whole sample, the percentages of patients who had a control or had initially normal values of blood pressure, cholesterol and basal glycemia were 40.0% (confidence interval [CI], 95% 38.2-41.9), 42.6% (95% CI, 40.5-44.7) and 62.7% (95% CI, 60.8-64.5), respectively. 15.6% of cases (95% CI, 14.3-17.0) had body mass index < or = 25 kg/m2; 87.5% were non-current smokers (95% CI, 86.2-88.8); and 46.2% practiced regular physical activity (95% CI, 44.3-48.1). 40% of patients had < or = 2 CVRF in good control. The prevalence of metabolic syndrome was 50.6% (95% CI, 48.7-52.5). CONCLUSIONS: The control of the CVRF considered in primary care attended population is insufficient. Hardly one of each 2 patients with HT, DM2 and HC is under control. The overweight and sedentarism control is still poorer.

Estudio PREVENCAT: control del riesgo cardiovascular en atención primaria / PREVENCAT study: control of cardiovascular risk in primary care

Fundamento y objetivo: Muchos estudios de factores de riesgo cardiovascular (FRCV) realizados en nuestro medio se centran en sólo uno. El estudio PREVENCAT se diseñó para estimar el control de los principales FRCV en población asistida en atención primaria que presenta hipertensión arterial (HTA), diabetes mellitus tipo 2 (DM-2) y/o hipercolesterolemia (HC) y para conocer la prevalencia de síndrome metabólico en estos pacientes. Pacientes y método: Estudio multicéntrico, transversal, en pacientes con HTA, DM-2 y/o HC, reclutados de forma consecutiva por médicos de atención primaria en España. Se evaluaron la presión arterial, el colesterol, la glucemia basal, la obesidad, el tabaquismo y el ejercicio físico, y se estimaron el grado de control de estos FRCV y la prevalencia del síndrome metabólico. Resultados: Se incluyó en el estudio a 2.649 pacientes (un 51,6% mujeres) con una media (desviación estándar) de edad de 64 (11,3) años de edad. El diagnóstico más frecuente fue la HTA (78,9%), seguido de HC (58,4%) y de DM-2 (37,4%). En toda la muestra, el porcentaje de pacientes que tenía bien controlada o basalmente normal la presión arterial, el colesterol y la glucemia basal fue del 40,0% (intervalo de confianza [IC] del 95%, 38,2-41,9), del 42,6% (IC del 95%, 40,5-44,7) y del 62,7% (IC del 95%, 60,8-64,5), respectivamente. El 15,6% de los casos (IC del 95%, 14,3-17,0) tenía un índice de masa corporal menor o igual a 25 kg/m2, el 87,5% no fumaba en la actualidad (IC del 95%, 86,2-88,8) y el 46,2% practicaba ejercicio físico regular (IC del 95%, 44,3-48,1). El 40% de los pacientes presentaba 2 o menos FRCV bien controlados. La prevalencia del síndrome metabólico fue del 50,6% (IC del 95%, 48,7-52,5). Conclusiones: El control de los FRCV considerados en población atendida en atención primaria es insuficiente. Apenas uno de cada 2 pacientes con HTA, DM-2 o HC está controlado. El control del sobrepeso y el sedentarismo es aún peor

Background and objective: Most studies of cardiovascular risk factors (CVRF) conducted in our environment concentrate in a single CVRF. The PREVENCAT study was designed to estimate the control of CVRF in the population attended in primary care presenting arterial hypertension (HT), type 2 diabetes mellitus (DM2) and/or hypercholesterolemia (HC) as well as to assess the prevalence of Metabolic Syndrome in these patients. Patients and method: Multicenter, cross-sectional study, in patients with HT, DM2 and/or HC, consecutively recruited by primary care physicians in Spain. The blood pressure, cholesterol, basal glycaemia, obesity, smoking and physical activity were assessed. The degree of control of these CVRF and the prevalence of MS were estimated. Results: 2,649 patients were recruited, aged 64 (11.3) years, with a 51.6% of women. The most frequent diagnosis was HT (78.9%), followed by HC (58.4%) and DM2 (37.4%). In the whole sample, the percentages of patients who had a control or had initially normal values of blood pressure, cholesterol and basal glycemia were 40.0% (confidence interval [CI], 95% 38.2-41.9), 42.6% (95% CI, 40.5-44.7) and 62.7% (95% CI, 60.8-64.5), respectively. 15.6% of cases (95% CI, 14.3-17.0) had body mass index 25 kg/m2; 87.5% were non-current smokers (95% CI, 86.2-88.8); and 46.2% practiced regular physical activity (95% CI, 44.3-48.1). 40% of patients had 2 CVRF in good control. The prevalence of metabolic syndrome was 50.6% (95% CI, 48.7-52.5). Conclusions: The control of the CVRF considered in primary care attended population is insufficient. Hardly one of each 2 patients with HT, DM2 and HC is under control. The overweight and sedentarism control is still poorer

A six-month, multicenter, open-label, noncomparative, prospective, observational study of the efficacy and tolerability of atorvastatin in the primary care setting(estudio del control de las hiperlipidemiasen atención primaria): the cheap study.

BACKGROUND: A close relationship exists between high levels of total cholesterol (TC) (particularly low-density lipoprotein cholesterol [LDL-C]) and low levels of high-density lipoprotein cholesterol (HDL-C), which is associated with an increased risk for arteriosclerosis and cardiovascular disease (CVD). Evidence shows that atorvastatin produces significantly greater reductions in LDL-C and TC than other hydroxymethylglutaryl-coenzyme A reductase inhibitors. However, the results achieved in clinical studies could be different from those found in general clinical practice, where patient follow-up is less thorough and poorer compliance may reduce the effectiveness of the lipid-lowering therapy. OBJECTIVE: The aim of this study was to assess the effectiveness of atorvastatin in achieving the LDL-C levels recommended by several Spanish scientific societies, as well as its tolerability in standard clinical use. METHODS: This 6-month, open-label, noncomparative, prospective, observational study was conducted in 1351 primary care centers in Spain. All patients were aged 18 to 80 years and had primary hypercholesterolemia (TC >200 mg/dL and triglycerides [TG] 200 mg/dL and fasting TG 200-400 mg/dL). All patients also had LDL-C levels higher than those established by the Spanish Society of Arteriosclerosis (Sociedad Española de Arteriosclerosis [SEA]) according to baseline cardiovascular risk and previous use of lipid-lowering therapy (for patients with low, moderate, or high cardiovascular risk, the recommended LDL-C goals are ≤175 mg/dL, ≤155 mg/dL, and ≤135 mg/dL, respectively; for patients with CVD, the LDL-C goal is ≤100 mg/dL). None of the patients had creatine kinase activity ≥540 U/L or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥60 U/L. Study visits occurred at months 0, 2, and 6 of treatment. Patients received atorvastatin calcium 10 mg/d for 2 months. The dosage was then doubled to 20 mg/d in patients who did not achieve the SEA LDL-C goal and also in those patients whose primary care physicians (PCPs) deemed this higher dosage necessary; this dosage was continued for at least 4 additional months, to complete at least a 6-month course of treatment. The percentage of patients who achieved their goals was used to measure atorvastatin effectiveness. Percentages of change in LDL-C, TC, TG, and HDL-C from baseline to the final study visit also were used as measures of effectiveness. The incidence of adverse events (AEs) per 10,000 patient-months was used for the primary tolerability analysis. A secondary tolerability analysis was performed in all patients treated with atorvastatin who had some recorded follow-up, regardless of whether the patient met inclusion criteria. Information was obtained from data recorded in the case-report forms. RESULTS: A total of 5317 outpatients (2715 women, 2598 men, 4 sex unknown; mean [SD] age, 58.7 [10.5] years) were enrolled. Among patients receiving known dosages of atorvastatin, 1580 of 4033 (39.2%) and 2378 of 3585 (66.3%) patients met the SEA LDL-C goal after 2 and 6 months of therapy, respectively (P