This study confirmed the validity of the CIRS as an indicator of health status and demonstrated its ability to predict 18-month mortality and rehospitalization in hospitalized elderly patients. The availability of detailed guidelines for scoring the CIRS can improve its usefulness and facilitate more-widespread use for research and clinical aims.

The obesity pandemic is closely related to hypertension and metabolic syndrome. Visceral adipose tissue plays a key role in the metabolic and cardiovascular complications of being overweight. The pathophysiological link between visceral adiposity and cardiometabolic complications focuses on insulin sensitivity, sympathetic nervous system, renin-angiotensin-aldosterone system (RAAS) and, only recently, on cardiac natriuretic peptide system (CNPS). RAAS and CNPS are endogenous antagonistic systems on sodium balance, cardiovascular system, and metabolism. The circulating RAAS is dysregulated in obese patients, and adipose tissue has a full local renin-angiotensin system that is active at local and systemic level. Adipocyte biology and metabolism are influenced by local renin-angiotensin system, with angiotensin II acting as a 'growth factor' for adipocytes. CNPS induces natriuresis and diuresis, reduces blood pressure, and, moreover, has powerful lipolytic and lipomobilizing activity in humans but not in rodents. In obesity, lower plasmatic natriuretic peptides levels with increasing BMI, waist circumference, and metabolic syndrome have been documented. Thus, reduced CNPS effects coupled with increased RAAS activity have a central role in obesity and its deadly complications. We propose herein an integrated view of the dysregulation of these two antagonistic systems in human obesity complicated with hypertension, metabolic syndrome, and increased cardiovascular risk.

To characterize natriuretic peptide receptor (NPr) gene expression in human tissues, we cloned portions of the cDNAs codifying for NPr with guanylyl cyclase activity (NPr-A and NPr-B) and without guanylyl cyclase activity (NPr-C). Total RNA was extracted from samples taken at surgery from normal human tissues. NPr-A and NPr-B cDNAs obtained from lung as well as NPr-C cDNA obtained from renal cortex were cloned, characterized, and used for comparative Northern analysis. NPr-A mRNA (approximately 4 kb) was most abundant in adipose tissue (8 patients) independently on the site of sampling, whereas it was approximately 2.5-fold and 5-fold less abundant, respectively, in kidney (either renal cortex or papilla from 3 patients) and adrenal (4 patients), known target tissues of natriuretic peptides. NPr-C mRNAs (approximately 7.7 and 6.8 kb) had a similar tissue distribution but the highest levels were found in renal tissue and only very low expression levels were found in adrenals (approximately 20-fold lower than renal cortex). The ratio of NPrA versus NPr-C mRNA levels were highest in adrenal and lowest in renal tissue. NPr-B mRNA (approximately 4 kb), which encodes the receptor for the C-type natriuretic peptide, had a different and wide tissue distribution, including expression in ileum and liver, with the highest levels in venous and prostatic tissue. These results indicate that, in humans, different patterns of NPr expression with different NPr-A/NPr-C mRNA level ratios, are present in known target tissues of natriuretic peptides. "Non-classic" target tissues, such as the adipose one, maximally expressed NPr-A and also NPr-C, suggesting that natriuretic peptides may have wider functional activities than those previously demonstrated.

Our data suggest that in obese hypertensives compared to obese normotensives, the lower NPr-A: NPr-C ratio might determine decreased biological activity and/or an increased clearance of natriuretic peptide in adipose tissue, suggesting that the natriuretic peptide and its receptor system may be important in obesity-related hypertension where ANP levels are lower.