Beneficial Impact of Pork Dry-Cured Ham Consumption on Blood Pressure and Cardiometabolic Markers in Individuals with Cardiovascular Risk.

BACKGROUND: Evidence suggests that bioactive peptides reduce hypertension and affect certain metabolic pathways. METHODS: Fifty-four volunteers with stage 1 prehypertension and/or hypercholesterolemia and/or basal glucose >100 mg/dL were recruited and randomized to pork dry-cured ham (n = 35) or cooked ham (placebo group; n = 19) for 28 days. After a wash-out period, meat products were changed for 28 additional days. Bioactive peptides composition and enzyme inhibitory activities of both products were characterized. Treatment comparisons for the main effects were made using a two (treatment) × two (times) repeated measures minus the effect of cooked ham (placebo). RESULTS: 24 h mean systolic and diastolic pressures decreased up to 2.4 mmHg in the dry-cured ham period (treatment effect, p = 0.0382 y p = 0.0233, respectively) as well as the number of systolic pressure measures > 135 mmHg (treatment effect, p = 0.0070). Total cholesterol levels also decreased significantly after dry-cured ham intake (p = 0.049). No significant differences were observed between the two treatments for basal glucose, HOMA-IR index and insulin levels (p > 0.05). However, a significant rise of ghrelin levels was observed (treatment effect, p = 0.0350), while leptin plasma values slightly decreased (treatment effect, p = 0.0628). CONCLUSIONS: This study suggested the beneficial effects of regular dry-cured ham consumption on the improvement of systolic/diastolic blood pressures and facilitated the maintenance of metabolic pathways, which may be beneficial in the primary prevention of cardiovascular disease.

Impact of pre-hospital renal function on the detection of acute kidney injury in acute decompensated heart failure.

BACKGROUND: Acute kidney injury (AKI) is a serious complication in patients hospitalized for decompensated heart failure (HF). Currently, AKI definitions consider creatinine levels at admission as reference of baseline renal function (RF). However, renal impairment may already be present at admission. We aimed to study the impact on AKI detection of considering outpatient RF as reference. METHODS: In a cohort of 458 patients hospitalized for decompensated HF, we studied the occurrence of AKI using the standardized KDIGO criteria and grading (stages: 1, 2, 3), and considering two different definitions according to the RF used as reference or baseline: the latest outpatient measurement prior to admission vs. the first measurement at admission. We compared the prevalence, timing and prognostic value for both AKI definitions. RESULTS: The definition based on outpatient RF was associated with an increase in overall AKI detection from 20.1% to 33.8% (p < 0.001), and from 3.1% to 5.0% for advanced stages (2-3) (p < 0.001); additionally, 12.5% of patients already had criteria of AKI at admission (36.8% of AKI cases). Both definitions were associated with longer hospital stay. However, only AKI already present at admission, as based on pre-hospital creatinine, was independently associated with all-cause death, in-hospital and after discharge, and death or HF readmission in the follow-up: 1 stage (HR 2.72, 95%CI 1.83-4.06, p < 0.001) and 2-3 stage (HR 7.29, 95%CI, 3.02-17.64, p < 0.001). CONCLUSIONS: Evaluation of AKI in patients admitted with HF should consider pre-hospital RF, since it improves early identification of AKI and has implications for risk assessment.

Urinary oxylipin signature as biomarkers to monitor the allograft function during the first six months post-renal transplantation.

Oxylipins such as isoprostanes (IsoPs), prostaglandins (PGs) and thromboxanes (TXs) are lipid mediators derived from the oxidation of polyunsaturated fatty acids, which regulate the magnitude of oxidative stress and inflammation processes and play an important role in pathophysiological processes in the kidney. A total of 36 oxylipins were analyzed by UHPLC-QqQ-MS/MS in the urine of 41 renal recipients from cadaveric donors of the Nephrology Unit of the University Hospital Virgen de la Arrixaca during the first six months after renal transplantation, in order to investigate several candidate oxylipins as more accurate and predictive biomarkers in renal transplantation than classical biological variables. A decrease in nine PGs, mostly from the AA-D pathway (p < 0.05) and one IsoP: 15-keto-15-F2t-IsoP (p < 0.001) was observed. Moreover, two PGs (2,3-dinor-11ß-PGF2α and 17-trans-PGF3α) increased between five days and six months after renal transplantation (p < 0.05). In addition, when kidney function improved, a positive correlation between oxylipin levels and the excretion of urine proteins was observed. These results suggest that oxylipins could be useful markers for monitoring renal function in the post-renal transplantation period. These findings could be of utility not only for the development of strategies for long-term preservation of graft function, but also for innovative and alternative therapies -using oxylipins as predictive markers-to avoid organ rejection.

Snapshot situation of oxidative degradation of the nervous system, kidney, and adrenal glands biomarkers-neuroprostane and dihomo-isoprostanes-urinary biomarkers from infancy to elderly adults.

We analyzed biomarkers of lipid peroxidation of the nervous system -F2-dihomo-isoprostanes, F3-neuroprostanes, and F4-neuroprostanes- in urine samples from 158 healthy volunteers ranging from 4 to 88 years old with the aim of analyzing possible associations between their excretion values and age (years). Ten biomarkers were screened in the urine samples by UHPLC-QqQ-MS/MS. Four F2-dihomo-isoprostanes (ent-7-(R)-7-F2t-dihomo-isoprostane, ent-7-epi-7-F2t-dihomo-isoprostane, 17-F2t-dihomo-isoprostane, 17-epi-17-F2t-dihomo-isoprostane), and one DPA-neuroprostane (4-F3t-neuroprostane) were detected in the samples. On the one hand, we found a significant, positive correlation (Rho: 0.197, P=0.015) between the age increase and the amount of total F2-dihomo-IsoPs. On the other hand, the values were significantly higher in the childhood group (4-12 years old), when compared to the adolescence group (13-17 years old) and the young adult group (18-35 years old). Surprisingly, no significant differences were found between the middle-aged adults (36-64 years old) and the elderly adults (65-88 years old). We display a snapshot situation of excretory values of oxidative stress biomarkers of the nervous system, using healthy volunteers representative of the different stages of human growth and development. The values reported in this study could be used as a basal or starting point in clinical interventions related to aging processes and/or pathologies associated with the nervous system.

Potential applications of lipid peroxidation products - F4-neuroprostanes, F3-neuroprostanesn-6 DPA, F2-dihomo-isoprostanes and F2-isoprostanes - in the evaluation of the allograft function in renal transplantation.

F4-neuroprostanes, F3-neuroprostanesn-6 DPA, and F2-dihomo-isoprostanes, metabolites of non-enzymatic lipid peroxidation of polyunsaturated fatty acids [docosahexaenoic acid, n-6 docosapentanoic acid, and adrenic acid respectively], have become important biomarkers for oxidative stress in several diseases like epilepsy and alzheimer. These biomarkers and the 15-F2t-isoprostane (also known as 8-iso-PGF2α), a F2-isoprostane isomer measured as reference oxidative marker at systemic level, were analyzed by UHPLC-QqQ-MS/MS in the urine of 60 renal recipients from cadaveric donors of the Nephrology Unit of the University Hospital Virgen de la Arrixaca, at six different times during the first six months after renal transplantation, and were compared with a control group of 60 healthy subjects from the same hospital. A total of 11 metabolites were analyzed and different patterns were observed. A tendency to decrease was observed in three metabolites (4-epi-4-F3t- NeuroPn-6 DPA, ent-7(RS)-7-F2t-dihomo-IsoP, and ent-7(S)-7-F2t-dihomo-IsoP) and in our reference oxidative marker (15-F2t-IsoP) when kidney function improved and the excretion of urine proteins decreased. These results suggest that these three biomarkers of oxidative stress could be useful to assess renal function in the postransplant phase. Unfortunately, little is known about this kind of biomarker in this cohort of patients, so further investigation would be required in the clinical field to clarify the relationship between oxidative stress and the graft function, as well as the usefulness of these biomarkers as rejection markers.

Assessment of oxidative stress biomarkers - neuroprostanes and dihomo-isoprostanes - in the urine of elite triathletes after two weeks of moderate-altitude training.

This randomized and controlled trial investigated whether the increase in elite training at different altitudes altered the oxidative stress biomarkers of the nervous system. This is the first study to investigate four F4-neuroprostanes (F4-NeuroPs) and four F2-dihomo-isoprostanes (F2-dihomo-IsoPs) quantified in 24-h urine. The quantification was carried out by ultra high pressure liquid chromatography-triple quadrupole-tandem mass spectrometry (UHPLC-QqQ-MS/MS). Sixteen elite triathletes agreed to participate in the project. They were randomized in two groups, a group submitted to altitude training (AT, n = 8) and a group submitted to sea level training (SLT) (n = 8), with a control group (Cg) of non-athletes (n = 8). After the experimental period, the AT group triathletes gave significant data: 17-epi-17-F2t-dihomo-IsoP (from 5.2 ± 1.4 µg/mL 24 h(-1) to 6.6 ± 0.6 µg/mL 24 h(-1)), ent-7(RS)-7-F2t-dihomo-IsoP (from 6.6 ± 1.7 µg/mL 24 h(-1) to 8.6 ± 0.9 µg/mL 24 h(-1)), and ent-7-epi-7-F2t-dihomo-IsoP (from 8.4 ± 2.2 µg/mL 24 h(-1) to 11.3 ± 1.8 µg/mL 24 h(-1)) increased, while, of the neuronal degeneration-related compounds, only 10-epi-10-F4t-NeuroP (8.4 ± 1.7 µg/mL 24 h(-1)) and 10-F4t-NeuroP (5.2 ± 2.9 µg/mL 24 h(-1)) were detected in this group. For the Cg and SLT groups, no significant changes had occurred at the end of the two-week experimental period. Therefore, and as the main conclusion, the training at moderate altitude increased the F4-NeuroPs- and F2-dihomo-isoPs-related oxidative damage of the central nervous system compared to similar training at sea level.

[Usefulness of NTproBNP in the emergency management of patients with severe dyspnea and an uncertain heart failure diagnosis]. / Utilidad del NTproBNP en el manejo urgente del paciente con disnea severa y diagnóstico dudoso de insuficiencia cardíaca.

INTRODUCTION AND OBJECTIVES: Measurement of N-terminal pro-B-type natriuretic peptide (NTproBNP) helps in diagnosing heart failure (HF). The test's usefulness may be greatest in patients with severe dyspnea of uncertain origin. However, NTproBNP has not been evaluated specifically in this setting. PATIENTS AND METHOD: This prospective emergency department study included 70 patients with shortness of breath at rest as their chief complaint. In the attending physician's opinion, both HF and a non-cardiac cause were equally probable. Blinded NTproBNP measurement was carried out in blood samples collected on admission. Patients were monitored and their final diagnoses were based on clinical findings, therapeutic responses, and cardiac and noncardiac tests performed during hospitalization. RESULTS: The NTproBNP level was higher in the 49 patients (70%) with a final diagnosis of HF (P = .006); the area under the ROC curve was 0.72 (0.60-0.82). The optimum diagnostic cut-off value was 900 pg/mL, which had an accuracy of 87%, a sensitivity of 98%, and a negative predictive value of 92%. The NTproBNP level was significantly higher in the 6 patients (9%) who died during hospitalization (P = .009); the area under the ROC curve was 0.87 (0.76-0.93) and the optimum cut-off value for predicting death was 5500 pg/mL, which had an accuracy of 77%, a sensitivity of 100%, and a positive likelihood ratio of 4.2. CONCLUSIONS: In patients with severe dyspnea and an uncertain diagnosis of HF, an NTproBNP level < 900 pg/mL helps exclude the presence of HF, whereas a NTproBNP level > 5500 pg/mL identifies patients at an increased risk of death.

Utilidad del NTproBNP en el manejo urgente del paciente con disnea severa y diagnóstico dudoso de insuficiencia cardíaca / Usefulness of NTproBNP in the emergency management of patients with severe dyspnea and an uncertain heart failure diagnosis

Introducción y objetivos. El NTproBNP ayuda a identificar a los pacientes con insuficiencia cardíaca. Su utilidad podría ser máxima en pacientes con disnea severa de origen incierto; sin embargo, esta población no ha sido específicamente evaluada. Pacientes y método. Estudio prospectivo de 70 pacientes que acudieron a urgencias refiriendo disnea de reposo, cuyo diagnóstico clínico inicial fue establecido como dudoso, con probabilidad intermedia de insuficiencia cardíaca. A la llegada a urgencias se extrajeron las muestras analíticas y se determinó el valor de NTproBNP de forma ciega. Los pacientes fueron controlados y el diagnóstico final se estableció sobre la base de los hallazgos clínicos, la respuesta al tratamiento y las pruebas practicadas durante el curso hospitalario. Resultados. El NTproBNP fue mayor en los 49 pacientes (70%) con un diagnóstico final de insuficiencia cardíaca (p = 0,006), obteniendo un área bajo la curva ROC de 0,72 (0,60-0,82). El valor de corte diagnóstico óptimo fue 900 pg/ml, con una precisión del 87%, una sensibilidad del 98% y un valor predictivo negativo del 92%. En los 6 pacientes (9%) fallecidos durante la hospitalización, el NTproBNP fue significativamente mayor (p = 0,009), con un área bajo la curva ROC de 0,87 (0,76-0,93) y un valor de corte pronóstico óptimo de 5.500 pg/ml, con una precisión del 77%, una sensibilidad del 100% y una razón de probabilidad positiva de 4,2. Conclusiones. En una población con disnea severa que acude a urgencias con diagnóstico dudoso de insuficiencia cardíaca, un valor de NTproBNP 5.500 pg/ml identifica a los pacientes con un mayor riesgo de muerte hospitalaria

Introduction and objectives. Measurement of N-terminal pro-B-type natriuretic peptide (NTproBNP) helps in diagnosing heart failure (HF). The test's usefulness may be greatest in patients with severe dyspnea of uncertain origin. However, NTproBNP has not been evaluated specifically in this setting. Patients and method. This prospective emergency department study included 70 patients with shortness of breath at rest as their chief complaint. In the attending physician's opinion, both HF and a non-cardiac cause were equally probable. Blinded NTproBNP measurement was carried out in blood samples collected on admission. Patients were monitored and their final diagnoses were based on clinical findings, therapeutic responses, and cardiac and noncardiac tests performed during hospitalization. Results. The NTproBNP level was higher in the 49 patients (70%) with a final diagnosis of HF (P=.006); the area under the ROC curve was 0.72 (0.60-0.82). The optimum diagnostic cut-off value was 900 pg/mL, which had an accuracy of 87%, a sensitivity of 98%, and a negative predictive value of 92%. The NTproBNP level was significantly higher in the 6 patients (9%) who died during hospitalization (P=.009); the area under the ROC curve was 0.87 (0.76-0.93) and the optimum cut-off value for predicting death was 5500 pg/mL, which had an accuracy of 77%, a sensitivity of 100%, and a positive likelihood ratio of 4.2. Conclusions. In patients with severe dyspnea and an uncertain diagnosis of HF, an NTproBNP level 5500 pg/mL identifies patients at an increased risk of death