Identification of six cardiovascular risk biomarkers in the young population: A promising tool for early prevention.

BACKGROUND AND AIMS: The predictive value of traditional CV risk calculators is limited. Novel indicators of CVD progression are needed particularly in the young population. The main aim of this study was the identification of a molecular profile with added value to classical CV risk estimation. METHODS: Eighty-one subjects (30-50 years) were classified in 3 groups according to their CV risk: healthy subjects; individuals with CV risk factors; and those who had suffered a previous CV event. The urine proteome was quantitatively analyzed and significantly altered proteins were identified between patients' groups, either related to CV risk or established organ damage. Target-MS and ELISA were used for confirmation in independent patients' cohorts. Systems Biology Analysis (SBA) was carried out to identify functional categories behind CVD. RESULTS: 4309 proteins were identified, 75 of them differentially expressed. ADX, ECP, FETUB, GDF15, GUAD and NOTCH1 compose a fingerprint positively correlating with lifetime risk estimate (LTR QRISK). Best performance ROC curve was obtained when ECP, GDF15 and GUAD were combined (AUC = 0.96). SBA revealed oxidative stress response, dilated cardiomyopathy, signaling by Wnt and proteasome, as main functional processes related to CV risk. CONCLUSIONS: A novel urinary protein signature is shown, which correlates with CV risk estimation in young individuals. Pending further confirmation, this six-protein-panel could help in CV risk assessment.

Immunochemical assays for an early diagnosis of endemic nephropathy.

Comparative studies aiming at the detection of certain tubular protein elements by means of Ouchterlony's immunodiffusion, in parallel with lysozyme and guanase assays, were carried out in the unconcentrated urines of 746 subjects, of whom 655 apparently healthy inhabitants (mostly children) from a region with endemic nephropathy (EN) and from Bucharest, as well as 91 adults with EN or various other diseases with renal involvement. The presence of light chains, of lysozymuria exceeding 2 microgram/ml, of beta2 microglobulin and of guanase in the urines of children and adults from the endemic area was significantly more frequent than in the control groups. These immunochemical changes are hence considered as valuable criteria for the detection of EN prior to the uremic stage. They should be looked for, first and foremost, in the young relatives of patients with this disease. In the stage of nitrogen retention the diagnostic value of these tests is reduced, since the same changes can also be found in the urines of patients suffering from other diseases with renal involvement, which show nitrogen retention as well.