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.

Objectives Frail older adults are at an increased risk for adverse outcomes after an Emergency Department (ED) visit. Comprehensive geriatric assessment (CGA) has been proposed to screen for frailty in the ED, but it is difficult to carry out. We tested whether a CGA-based approach using the Identification of Seniors At Risk (ISAR) screening tool was associated with the brief deficit accumulation index (DAI) of frailty. Design Prospective observational study. Setting Two urban EDs in Italy. Participants A cohort of 200 elderly (≥65 years) ED patients. Measurements Identifiers, triage, clinical and social data along with the administration of ISAR. CGA was performed using: Charlson Index, Short Portable Mental Status Questionnaire and Katz’s ADL. Follow-up data at 30 and 180 days included: mortality, ED revisit, hospital admission, and.functional decline. Frailty was defined according to a brief DAI. Logistic regression evaluated the consistency of the frailty definition; ROC curves evaluated ISAR ability in identifying frailty. Results Frailty was present in 117 (58.5%) subjects and predicted ED revisit and frequent ED return, hospitalization and 6-month mortality. ISAR had an AUC of 0.92 (95%CI 0.88–0.96, p<0.0001) in identifying frail elders in the ED and using a cut-off of 2 showed 94% sensitivity and 63% specificity. Conclusion ISAR is a useful screening tool for frailty and identifies elderly patients at risk of adverse outcomes after an ED visit. ISAR can also be used to select high-risk patients more likely to benefit from a geriatric approach or intervention, independently of admission or discharge.

The clearance receptor for natriuretic peptides (NPRC), a candidate gene for essential hypertension, is highly expressed in adipose tissue, where is nutritionally regulated. The objectives of the present study were to sequence the human 5'flanking regulatory region of NPRC, to identify allelic variants and their frequencies, and to study the genotype/phenotype correlation in hypertensive patients. Using polymerase chain reaction (PCR) and direct automated sequencing, a biallelic (A/C) polymorphism was detected at position −55 in a conserved promoter element named P1. The novel C(−55) variant makes the promoter sequence identical to the mouse gene and introduces a second HgaI site in the amplified DNA, allowing the genotyping of a large number of subjects. In a random sample of 232 white Caucasians the C(−55) allele was more commonly found (81.7% of all alleles) with 155 CC (66.8%), 69 AC (29.7%) and only eight AA (3.5%) genotypes. Atrial natriuretic peptide (ANP) levels were determined in 84 patients with essential hypertension. In the presence of obesity (body mass index (BMI) ≥ 30 kg/m2) the homozygous CC hypertensives (n = 21) had significantly lower plasma ANP (33.6 ± 11.1 pg/ml) compared with the AC patients (n = 11; 46.8 ± 15.9 pg/ml; P = 0.01), whereas systolic blood pressure (SBP) and mean blood pressure (MBP) had the opposite association (SBP 163.9 ± 18.7 versus 150.9 ± 12.9 and MBP 123.3 ± 12 versus 114.5 ± 5.9 mmHg; P < 0.05). The difference in ANP levels were also present when overweight patients (BMI ≥ 27 kg/m2) were considered. A common ‘ancestral’ C(−55) variant of the NPRC P1 promoter is associated with lower ANP levels and higher SBP and MBP in obese hypertensives. The C(−55) variant, in the presence of increased adiposity, might reduce plasma ANP through increased NPRC-mediated ANP clearance, contributing to higher blood pressure.