o-brain natriuretic peptide levels; SD, standard deviation; stage I, 12-month follow-up; stage II, 24-month follow-up. doi:10.1371/journal.pone.0031189.g002 significant, being considered of possible prognostic importance. These results are in concordance with an analysis performed on stable heart failure patients. In contrast, results of prior studies found RCVs around 100%. The clinical relevance of these large RCVs are controversial, but the key to understanding these results is the definition of stability of heart failure and also the estimation of CVs. We think there could be a clinical shift in using natriuretic peptides to change management of those with hypertension and LVH over time. The evidence has clearly demonstrated that NT-proBNP is a powerful predictor of mortality and cardiovascular risk in hypertensive patients. This suggests the importance of NT-proBNP in the assessment of these patients to perform a more accurate risk evaluation and in the future to possibly lead to an NT-proBNP guided therapy able to get a more favorable clinical outcome. Up-regulation and production of cytokines represent an intrinsic or an get Kenpaullone innate stress response against myocardial injury and its elevation predicts short- and long-term incidence of cardiovascular adverse events. In a previous report, our group showed that PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/22179927 the levels of different cytokines were increased in hypertensive patients with LVH. Plasma cytokine levels, such as IL-6 and sTNF-R1, were correlated with left ventricular mass index, but when a logistic regression was performed to predict hypertrophy, only sTNF-R1 was independent predictor. Some authors have shown that NT-proBNP serum 
levels are increased in hypertensive patients with LVH. In this sense, the results of the present study are in concordance with these findings. We found a good relationship between immune system activation and natriuretic peptide levels in hypertensive patients with LVH, specifically, a strong correlation between NT-proBNP and sTNFR1 concentrations. However, the molecular mechanisms by which natriuretic peptides and inflammatory mediators are related are uncertain. Ventricular wall stress is the principal factor stimulating brain natriuretic peptide synthesis and release from cardiomyocytes. Furthermore, this stress also produces an increase in cytokine levels, and the cytokines amplify the signal, because they have a pleiotropic effect. An interesting finding is that the elevation in cytokine expression precedes the increase in natriuretic peptides and collagen expression in a rodent model of myocardial infarction. These results could be translated to other pathological conditions involving heart diseases. As inflammatory mediators are elevated in hypertensive patients with LVH, this might explain in part the significant elevation of NT-proBNP levels compared with patients without hypertrophy and therefore, this also implies new therapeutic options to improve hypertension treatment in the future. However, studies on the relationship between inflammatory markers and natriuretic peptides are limited. In fact, to the best of our knowledge, cytokine levels have never been correlated with NT-proBNP concentrations in hypertensive patients. Thus, more work is necessary to fully understand the role of the cytokines studied in the activation of the neurohormonal system. One limitation of this study is that our patients were on medication and it is known that NT-proBNP values could be Long-Term Variation of N
