Emma Espinosa

Plasma atrial natriuretic peptide and natriuretic peptide receptor gene expression in adipose tissue of normotensive and hypertensive obese patients

Objective Human and rat adipose tissue contain very high levels of natriuretic peptides clearance receptor messenger (m)RNA, and fasting inhibits its gene expression in adipose tissue. In this study we evaluated plasma atrial natriuretic peptide (ANP) and gene expression of biologically active type A natriuretic peptide receptor (NPr-A) and clearance natriuretic peptide receptor (NPr-C) in adipose tissue of obese hypertensive and obese normotensive patients. Design and methods We studied 27 untreated obese hypertensives, 26 obese normotensives (body mass index ≥ 30 kg/m2), 24 non-obese essential hypertensives and 23 lean healthy subjects (body mass index ≥ 25 kg/m2). Blood samples were withdrawn for ANP, plasma renin activity and aldosterone radio-immunoassays. Subcutaneous peri-umbilical adipose tissue samples were obtained, by needle aspiration, in 13 obese hypertensives and in 12 obese normotensives and used for RNA extraction. Then, complementary synthesis and semiquantitative polymerase chain reaction (PCR) with primers complementary to sequences of different exons of the genes encoding for NPr-A, NPr-C and β-actin, were performed. 32P-labeled PCR products were separated by electrophoresis, blotted onto nylon membranes, and the exposed autoradiographic films were analysed by densitometry. NPr signals were normalized by the β-actin expression level. Results Plasma ANP was lower in obese hypertensives than in obese normotensives (37.5 ± 7 versus 43.2 ± 6 pg/ml, P < 0.05), but was higher in non-obese hypertensives than in non-obese normotensives. In contrast, plasma renin activity and aldosterone were higher in the obese hypertensives. Although NPr-A and NPr-C expression were not statistically different between the two obese groups, the NPr-A: NPr-C mRNA ratios were significantly lower in obese hypertensives (P < 0.03). Conclusions 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.

Low Calorie Diet Enhances Renal, Hemodynamic, and Humoral Effects of Exogenous Atrial Natriuretic Peptide in Obese Hypertensives

The expression of the natriuretic peptide clearance receptor is abundant in human and rat adipose tissue, where it is specifically inhibited by fasting. In obese hypertensives, plasma atrial natriuretic peptide (ANP) levels were found to be lower than in obese normotensives. Therefore, the increased adipose mass might influence ANP levels and/or its biological activity. The aim of the present study was to evaluate whether the humoral, hemodynamic, and renal effects of exogenous ANP in obese hypertensives might be enhanced by a very low calorie diet. Eight obese hypertensives received a bolus injection of ANP (0.6 mg/kg) after 2 weeks of a normal calorie/normal sodium diet, and blood pressure (BP), heart rate, ANP, cGMP, plasma renin activity, and aldosterone were evaluated for 2 hours before and after the injection. Diuresis and natriuresis were measured every 30 minutes. The patients then started a low calorie/normal sodium diet (510 kcal/150 mmol/d) for 4 days, and then the ANP injection protocol was repeated. The low calorie diet induced a slight weight loss (from 90.6+/-1.1 to 87. 7+/-1.2 kg; P<0.01), which was accompanied by increase of cGMP excretion (from 146.0+/-10.1 to 154.5+/-9.5 nmol/24 h; P<0.05) together with a reduction of BP (P<0.01 versus basal levels). ANP injection after diet was followed by an increase of ANP levels similar to that observed before diet, but plasma cGMP, diuresis, and natriuresis increased significantly only after diet. Similarly, the decrease of BP after ANP administration was significantly higher after diet (change in mean arterial pressure, -6.4+/-0.7 versus -4. 0+/-0.6 mm Hg; P<0.05) as well as that of aldosterone (P<0.01). These data show that a low calorie diet enhances the humoral, renal, and hemodynamic effects of ANP in obese hypertensives and confirm the importance of caloric intake in modulating the biological activity of ANP, suggesting that the natriuretic peptide system can play a role in the acute changes of natriuresis and diuresis associated with caloric restriction.

Mini Nutritional Assessment (short form) and functional decline in older patients admitted to an acute medical ward

Background and aims: Protein and/or energy malnutrition is common in hospitalized older patients and is associated with poor outcomes. Among recommended nutritional screening tools, contrasting data exist about the usefulness of the Mini Nutritional Assessment Short-Form (MNA-SF). We evaluated whether the MNA-SF, alone or integrated with serum albumin levels, is a reliable predictor of functional decline in older patients. Methods: We studied 275 elderly patients (mean age 76.5, 60.7% males) admitted to an acute medical ward of a tertiary-care teaching hospital over a 12-month period. In this observational study, we evaluated nutritional status, with the MNA-SF alone or integrated with albumin. Data were collected at admission and related to laboratory and geriatric assessment features, and length of stay (LOS). Functional decline (defined as a loss ≥10% in terms of Barthel Index score at discharge compared with 2 weeks before admission) was considered as outcome. Results: The MNA-SF estimated 46% patients at risk of malnutrition. These subjects had worse clinical features (lower total cholesterol and albumin levels), longer LOS (13.3 vs 11.2 days, p=0.014) and considerable functional decline (OR 4.25, 95% CI 1.83–9.9, p=0.001). Integrating the MNA-SF with albumin values, we obtained an effective instrument to detect older inpatients with protein-energy malnutrition, at higher risk of undergoing functional decline (OR 16.19, 95% CI 4.68–56.03, p<0.0001). Conclusions: The MNA-SF is a useful screening tool for hospitalized elders at risk of malnutrition. It is associated with poor clinical outcomes and is able to predict functional decline. Together with hypoalbuminemia, it better identifies patients with true protein-energy malnutrition.

Summer does not always mean lower: seasonality of 24 h, daytime, and night-time blood pressure.

Objective: Evaluation of seasonal influences on ambulatory blood pressure monitoring (ABPM) values in a very large population living in a mild-climate geographic area. Methods: Among patients referred to our Hypertension Center between September 2002 and January 2011 with a reliable ABPM, we considered those in the two hottest (July and August) vs. those in the two coldest (January and February) months. Results: Seven hundred and forty-two men (53.2%) and 653 women (46.8%) were studied; 1245 (89.3%) were hypertensive patients of which 795 (63.9%) were drug-treated. In winter, mean daytime SBP and DBP were higher (P = 0.001 and P < 0.001, respectively), but only 24-h DBP was significantly higher (P = 0.012). On the contrary, higher night-time SBP and pulse pressure were recorded in summer (P = 0.005 and P = 0.023, respectively). Uncontrolled hypertensive patients had the highest mean difference between winter and summer night-time SBP (127.1 ± 13.4 vs. 131.0 ± 12.6 mmHg; P = 0.001). In winter a dipping pattern was prevalent (58.2%), whereas in summer a nondipping pattern prevailed (61.9%; P < 0.001). Isolated nocturnal hypertension (INH) was present in 9.8% in winter vs. 15.2% in summer (P = 0.003). Conclusion: Our data on a very large ABPM sample confirmed that hottest summer months are associated with lower daytime BP and also lower 24-h DBP. However, we found an inverse relationship regarding night-time BP, dipping pattern, and INH that were higher or more common in summer. These findings were even more evident in treated patients, especially when not at target. Different sleeping behaviors or improper dose reduction of drug therapy in summer may explain the findings.

NT-proBNP and Its Correlation with In-Hospital Mortality in the Very Elderly without an Admission Diagnosis of Heart Failure

Background The diagnosis of heart failure (HF) is often difficult and underestimated in very elderly comorbid patients, especially when an echocardiographic evaluation is not available or feasible. Aim: to evaluate NT-proBNP values and their correlation with in-hospital mortality in a population of very elderly hospitalized for medical conditions other than HF. Methods We performed a prospective observational study on 403 very elderly admitted to an Internal Medicine and Geriatrics Department. Exclusion criterion was an admission diagnosis of HF. Patients with at least one symptom or sign compatible with HF were tested for NT-proBNP. NT-proBNP values < 300 pg/ml were considered as an age-independent exclusion criterion for HF (high negative predictive value), while NT-proBNP values ≥ 1800 pg/ml were considered as a diagnostic criterion. Main comorbidities and laboratory parameters were considered to adjust regression analyses between NT-proBNP and in-hospital mortality. Results NT-proBNP values ≥ 1800 pg/ml were present in 61.0% of patients and 32.8% of patients laid between 300 ≤ NT-proBNP < 1800 pg/ml values. NT-proBNP values were associated with the main indices of disease severity/organ failure considered such as reduced eGFR, reduced albumin and elevated CRP. NT-proBNP values ≥ 1800 pg/ml and ln(NT-proBNP) values were significantly associated with in-hospital mortality independently from the main comorbidities and lab parameters considered. The patients, who were already taking ACE inhibitors/Angiotensin Receptor Blockers before admission, showed lower in-hospital mortality. Conclusions Testing for NT-proBNP should be strongly recommended in the hospitalized very elderly, because of the very high prevalence of underlying HF and its impact on in-hospital mortality, to identify an underlying cardiac involvement that requires appropriate treatment.

Interarm blood pressure differences predict target organ damage in type 2 diabetes.

Patients with type 2 diabetes mellitus are at high risk for atherosclerotic disease, and proper blood pressure measurement is mandatory. The authors examined the prevalence of an interarm difference (IAD) in blood pressure and its association with cardiovascular risk factors and organ damage (nephropathy, retinopathy, left ventricular hypertrophy, and vascular damage) in a large diabetic population. A total of 800 consecutive patients with type 2 diabetes mellitus were evaluated with an automated simultaneous bilateral device (men: 422 [52.8%]; mean age: 68.1±12.2 years). Diabetic patients with systolic IAD ≥5 and systolic IAD ≥10 mm Hg showed an increased risk of having vascular damage (adjusted odds ratios: 1.73 and 2.49, respectively) and higher pulse pressure. IAD is highly prevalent in patients with diabetes, is associated with vascular damage, even for IAD ≥5 mm Hg, and should be accurately obtained to avoid underdiagnosis and undertreatment of hypertension.

Urinary kallikrein excretion and blood pressure response to angiotensin converting enzyme inhibitors and calcium antagonists in hypertensive patients.

Objective: To investigate whether the hypotensive effects of angiotensin converting enzyme (ACE) inhibitors in comparison with those of calcium antagonists might be predicted by urinary kallikrein activity, a marker of the activity of the renal kallikrein—kinin system. Design: Seventy-five essential hypertensive patients were randomly assigned to treatment with ACE inhibitors (enalapril or lisinopril 20 mg once a day) or with calcium antagonists (nifedipine 20 mg twice a day or lacidipine 4 mg once a day). Fifty-four had normal (NK) and 21 low (LK) kallikrein activity. Blood pressure was measured after 2 weeks, and 3 and 6 months. Patients whose diagnostic blood pressure, 2 weeks after the first dose, decreased by at least 15mmHg or was ≤90mmHg were defined as responders. The others were defined as non-responders. In non-responders a second drug was added and the patients were not considered for further analysis. Methods: Urinary kallikrein activity was determined by a spectrophotometric assay using a synthetic chromogenic substrate. Results: After 2 weeks therapy with ACE inhibitors 88% of NK patients were responders, whereas in the LK subgroup 40% were responders, a significant difference between subgroups. For the patients treated with calcium antagonists, conversely, 59% of NK patients were responders in comparison with 82% of the LK subgroup, a significant difference between drug groups. After 3 and 6 months of treatment blood pressure was significantly lower in NK patients treated with ACE inhibitors and in LK patients treated with calcium antagonists. In the NK group on ACE inhibitors the mean arterial pressure after the first dose was significantly related to that observed after 6 months (n=0.71, P<0.01). Conclusions: Our data indicate that urinary kallikrein activity may represent an index to predict the chronic antihypertensive effect not only of ACE inhibition but also of calcium antagonism, and support the concept that the renal kallikrein—kinin system might play some contributory role in modulating the hypotensive action of ACE inhibitors.

OS 31-03 CLINICAL EFFECTIVENESS OF ANTI-HYPERTENSIVE THERAPY WITH ACEI OR ARB ASSESSED BY PLASMA RENIN ACTIVITY/PLASMA ALDOSTERONE CONCENTRATION RATIO.

Objective: ACE inhibitors and angiotensin receptor blockers (ARB) modulate the renin-angiotensin system (RAS) leading to an increase in plasma renin activity (PRA) together with a reduction of plasma aldosterone concentration (PAC), likely proportional to the pharmacological effect. Aim: to evaluate the efficacy of therapy based on ACEI or ARB, using PRA/PAC ratio values in real-life clinical-practice. Design and Method: We studied 184 essential hypertensives (59.2 ± 11.9 years, 63% males) in stable treatment for at least three months with an ACEI or ARB as part of the treatment. PRA was expressed as ng/ml and PAC as ng/dl, and then the ratio was multiplied by 100. Tertiles of PRA/PAC ratio were considered for the analysis. ABPM was performed to evaluate the BP control. Results: Tertiles of PRA/PAC: 1st 0.2 to 5.7; 2nd 5.9 to 28.4; 3rd 29.4 to 509.8. There was no difference by age, sex, BMI and eGFR between PRA/PAC tertiles. A significant reduction in 24hour, daytime and night-time BP values was associated with increasing PRA/PAC tertiles (all p < 0.05). An increase of PRA/PAC tertiles was associated with a higher prevalence of controlled patients during the night-time period (1st: 14.5%; 2nd: 43.3%; 3rd: 45.9%; p < 0.001). PRA/PAC ratio was also a predictor of night-time BP control, as shown by ROC curve (AUC: 0.664, 95% CI: 0.582–0.745; p < 0.001). Conclusions: An increasing PRA/PAC ratio reflects reduced values of PAC despite higher values of PRA as expression of a more effective RAS blockade by ACEIs or ARBs. These findings are associated with lower BP values and better BP control, especially in night-time period, highlighting the effectiveness and compliance to the anti-hypertensive therapy with ACEI or ARB. Therefore, PRA/PAC ratio may be not only a useful biomarker of effective treatment based on ACEI or ARB, but also can be used an indirect index of drug intake and therapy compliance.