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A fluorescence antibody microarray has been developed for the determination of relevant cardiovascular disease biomarkers for the analysis of human plasma samples. Recording characteristic protein molecular fingerprints to assess individual's states of health could allow diagnosis to go beyond the simple identification of the disease, providing information on its stage or prognosis. Precisely, cardiovascular diseases (CVDs) are complex disorders which involve different degenerative processes encompassing a collection of biomarkers related to disease progression or stage. The novel approach that we propose is a fluorescent microarray chip has been developed accomplishing simultaneous determination of the most significant cardiac biomarkers in plasma aiming to determine the CVD status stage of the patient. As proof of concept, we have chosen five relevant biomarkers, C-reactive protein (CRP) as biomarker of inflammation, cystatin C (CysC) as biomarker of renal failure that is directly related with heart failure, cardiac troponin I (cTnI) as already established biomarker for cardiac damage, heart fatty acid binding protein as biomarker of ischemia (H-FABP), and finally, NT-proBNP (N-terminal pro-brain natriuretic peptide), a well-established heart failure biomarker. After the optimization of the multiplexed microarray, the assay allowed the simultaneous determination of 5 biomarkers in a buffer solution reaching LODs of 15 ± 5, 3 ± 1, 24 ± 3, 25 ± 3, and 3 ± 1 ng mL−1, for CRP, CysC, H-FABP, cTnI, and NT-proBNP, respectively. After solving the matrix effect, and demonstrating the accuracy for each biomarker, the chip was able to determine 24 samples per microarray chip. Then, the microarray has been used on a small pilot clinical study with 29 plasma samples from clinical patients which suffered different CVD and other related disorders. Results show the superior capability of the chip to provide clinical information related to the disease in terms of turnaround time (1 h 30 min total assay and measurement) and amount of information delivered in respect to reference technologies used in hospital laboratories (clinical analyzers). Despite the failure to detect c-TnI at the reported threshold, the microarray technology could be a powerful approach to diagnose the cardiovascular disease at early stage, monitor its progress, and eventually providing information about an eminent potential risk of suffering a myocardial infarction. The microarray chip here reported could be the starting point for achieving powerful multiplexed diagnostic technologies for the diagnosis of CVDs or any other pathology for which biomarkers have been identified at different stages of the disease. [ABSTRACT FROM AUTHOR]

A higher neprilysin activity has been suggested in women. In this retrospective analysis, we evaluated the association of sex and body mass index (BMI) with soluble neprilysin (sNEP) and recurrent admissions among 1021 consecutive HF outpatients. The primary and secondary endpoints were the number of HF hospitalizations and all-cause mortality, respectively. The association between sNEP with either endpoint was evaluated across sex and BMI categories (≥ 25 kg/m2 vs. < 25 kg/m2). Bivariate count regression (Poisson) was used, and risk estimates were expressed as incidence rates ratio (IRR). During a median follow-up of 6.65 years (percentile 25%-percentile 75%:2.83–10.25), 702 (68.76%) patients died, and 406 (40%) had at least 1 HF hospitalization. Median values of sNEP and BMI were 0.64 ng/mL (0.39–1.22), and 26.9 kg/m2 (24.3–30.4), respectively. Left ventricle ejection fraction was < 40% in 78.9% of patients, and 28% were women. In multivariable analysis, sNEP (main effect) was positively associated with HF hospitalizations (p = 0.001) but not with mortality (p = 0.241). The predictive value of sNEP for HF hospitalizations varied non-linearly across sex and BMI categories (p-value for interaction = 0.003), with significant and positive effect only on women with BMI ≥ 25 kg/m2 (p = 0.039). For instance, compared to men, women with sNEP of 1.22 ng/mL (percentile 75%) showed a significantly increased risk (IRRs: 1.26; 95% CI: 1.05–1.53). The interaction analysis for mortality did not support a differential prognostic effect for sNEP (p = 0.072). In conclusion, higher sNEP levels in overweight women better predicted an increased risk of HF hospitalization. [ABSTRACT FROM AUTHOR]

Summary: Patients with chronic kidney disease (CKD) are characterized by a state of inflammation and oxidative stress that seems to improve after kidney transplantation (KT). Nevertheless, there is controversy regarding what is the best marker that better define inflammation and specially oxidative stress. Objective: To evaluate the biomarkers which are associated with improvements in inflammation and lipid peroxidation in patients who have undergone KT. To evaluate the relationship between inflammation, lipid peroxidation and mortality in KT. Patients: 196 KT (between 2003 and 2008). 67.9% men; median age: 51.9 years. Inflammation markers analyzed previous KT and 3 months after KT: c-reactive protein(CRP), interleukin 6(IL-6), tumor necrosis factor alpha(TNFα), soluble tumor necrosis factor receptor alpha(sTNFRα), soluble interleukin-2 receptor (sIL-2R). Lipid peroxidation markers analyzed: oxidized low-density lipoprotein (oxLDL) and anti-oxLDL antibodies. Calculation of glomerular filtration rate after KT: MDRD equation. Results: Following KT, there is a significant decrease in CRP ( p = 0.006), IL-6 ( p = 0.0037), TNFα ( p < 0.0001), sTNFRα ( p < 0.0001) and sIL-2R ( p < 0.0001), while levels of oxLDL increase after KT ( p < 0.0001) and there is not a significantly difference in anti-oxLDL. 12.8% of the patients had died in 2012. These patients had higher levels of IL-6 ( p = 0.011) and sTNFRα ( p < 0.006) after KT and a lower MDRD ( p < 0.0001), hemoglobin ( p = 0.012) and albumin ( p = 0.007). We observed no statistically differences in the levels of markers previous KT. Of the patients who died, the 43.5% of them had anti-oxLDL antibody levels greater than 75th percentile (P: 3781 UI/ml, p = 0.028). In the multivariate analysis, age (OR:1.12; p = 0.0129), MDRD (OR:0.92; p = 0.013) and P of anti-oxLDL(OR: 5.19; p = 0.026) were independent risk factors for mortality. Independent risk factors for survival were: P of IL-6 (HR: 2.45; p = 0.027), oxLDL (HR:19.85; p = 0.002) and anti-oxLDL (HR: 9.55; p = 0.003). Conclusions: KT improved inflammation but not lipid oxidative state. KT patients who died had a higher inflammatory state (with higher levels of IL-6 and sTNFRα), a worse lipid oxidative state and a worse renal function 3 months after KT. Age, anti-oxLDL and renal function at 3 months after KT were independent risk factors for mortality. [ABSTRACT FROM AUTHOR]

The number of recreational/non-elite athletes participating in marathons is increasing, but data regarding impact of endurance exercise on cardiovascular health are conflicting. This study evaluated 79 recreational athletes of the 2016 Barcelona Marathon (72% men; mean age 39 ± 6 years; 71% ≥35 years). Blood samples were collected at baseline (24-48 h before the race), immediately after the race (1-2 h after the race), and 48-h post-race. Amino-terminal pro-B type natriuretic peptide (NT-proBNP, a marker of myocardial strain), ST2 (a marker of extracellular matrix remodeling and fibrosis, inflammation, and myocardial strain), and high-sensitivity troponin T (hs-TnT, a marker of myocyte stress/injury) were assayed. The median (interquartile range, IQR) years of training was 7 (5-11) years and median (IQR) weekly training hours was 6 (5-8) h/week, respectively. The median (IQR) race time (h:min:s) was 3:32:44 (3:18:50-3:51:46). Echocardiographic indices were within normal ranges. Immediately after the race, blood concentration of the three cardiac biomarkers increased significantly, with 1.3-, 1.6-, and 16-fold increases in NT-proBNP, ST2, and hs-TnT, respectively. We found an inverse relationship between weekly training hours and increased ST2 (p = 0.007), and a direct relationship between race time and increased hs-TnT (p < 0.001) and ST2 (p = 0.05). Our findings indicate that preparation for and participation in marathon running may affect multiple pathways affecting the cardiovascular system. More data and long-term follow-up studies in non-elite and elite athletes are needed. [ABSTRACT FROM AUTHOR]