B-type natriuretic peptide may predict prognosis in older adults admitted with a diagnosis other than heart failure.

BACKGROUND AND AIMS: The diagnosis of heart failure (HF) in elderly patients is often difficult, due to overlap of typical signs and symptoms with those of comorbidities. B-type Natriuretic Peptide (BNP) predicts diagnosis and prognosis of HF, but little is known on its predictive role of short-term prognosis when admission diagnosis is other than HF. METHODS AND RESULTS: We prospectively recruited 404 consecutive patients (aged≥65 years) hospitalized in the Unit of Internal Medicine, University of Catania, Catania, Italy, with an admission diagnosis other than HF. Clinical examination, laboratory data and BNP were evaluated at the admission. The predictive value of BNP and other variables for in-hospital mortality, thirty-day mortality and three month re-hospitalization was assessed. During hospitalization 48 (12%) patients died; by logistic regression analysis, in-hospital mortality was not predicted by BNP>600 pg/ml (OR = 1.36; CI 95% = 0.60-2.80; p = 0.4), while it was by chronic kidney disease (CKD, p < 0.001), WBC count (p < 0.001), immobilization syndrome (p < 0.008) and age (p = 0.012). After discharge, 54 patients (15%) died within 30 days; in these patients thirty-day mortality was significantly predicted by BNP>600 pg/ml (OR = 2.70; CI 95% = 1.40-5.00; p = 0.001), CKD (p < 0.001), malnutrition (p = 0.029) and age (p = 0.033). Re-hospitalized patients were 97 (32%); three month re-hospitalization was predicted by BNP>600 pg/ml (OR = 12.28; CI 95% = 6.00-24.90; p < 0.001) and anamnestic HF (p = 0.002). CONCLUSIONS: Our study shows that BNP>600 pg/ml, CKD, malnutrition and age predict thirty-day mortality after discharge in elderly patients with an admission diagnosis other than HF, while CKD, WBC count, immobilization syndrome and age predict in-hospital mortality. Three-month re-hospitalization was predicted by BNP>600 pg/ml and anamnestic HF.

Neutrophil-to-Lymphocyte Ratio is a strong predictor of atherosclerotic carotid plaques in older adults.

BACKGROUND AND AIMS: The Neutrophil-to-Lymphocyte Ratio (NLR), an index of systemic inflammation, has been reported to be associated with subclinical atherosclerosis, but its predictive role of the presence of carotid atherosclerotic plaques remains undefined. This study aims to assess this association which gives additional value to this biomarker, with respect to the main risk factors, in the prediction of carotid atherosclerosis in older adults. METHODS AND RESULTS: We recruited 324 patients, aged ≥65 years, without hematopoietic disorders, and/or history of malignancies, evidence of acute infections, chronic inflammatory status, and history of glucocorticoid therapy within the past three months, hospitalized in the Unit of Internal Medicine, University of Catania, Catania, Italy from January 2014 to December 2016. All patients underwent blood sampling for white blood cell, neutrophil, lymphocyte and platelet counts, and for measurements of inflammatory markers, NLR was calculated as the ratio of the absolute neutrophil count to the absolute lymphocyte count. Patients also underwent carotid scan by ultrasonography (US) to evaluate abnormalities of carotid wall. NLR resulted a strong predictor of the presence of carotid plaques. NLR > 2.4 predicted with 80% probability carotid plaques (p < 0.01), while NLR > 3.68 gave 97% probability (p = 0.013). Furthermore, NLR > 2.4 was associated with an average presence of 2.86 carotid plaques (p < 0.001). Fibrinogen and CRP performed well, but with lesser significance, as predictors of the presence of carotid plaques (p = 0.002). CONCLUSION: NLR is a strong predictor of the presence and the number of carotid atherosclerotic plaques. Its use could be useful to identify the risk of harboring carotid plaques.

Conceptual basis and methodology of the SOPHIA study.

To clarify the role of gene polymorphisms on the effect of losartan and losartan plus hydrochlorothiazide on blood pressure (primary end point) and on cardiac, vascular and metabolic phenotypes (secondary end point) after 4, 8, 12, 16 and 48 weeks treatment, an Italian collaborative study - The Study of the Pharmacogenomics in Italian hypertensive patients treated with the Angiotensin receptor blocker losartan (SOPHIA) - on never-treated essential hypertensives (n = 800) was planned. After an 8 week run-in, losartan 50 mg once daily will be given and doubled to 100 mg at week +4 if blood pressure is more than 140/90 mmHg. Hydroclorothiazide 25 mg once daily at week +8 and amlodipine 5 mg at week +16 will be added if blood pressure is more than 140/90 mmHg. Cardiac mass (echocardiography), carotid intima-media thickness, 24 h ambulatory blood pressure, homeostatic model assessment (HOMA) index, microalbuminuria, plasma renin activity and aldosterone, endogenous lithium clearance, brain natriuretic peptide and losartan metabolites will be evaluated. Genes of the renin-angiotensin-aldosterone system, salt sensitivity, the beta-adrenergic system and losartan metabolism will be studied (Illumina custom arrays). A whole-genome scan will also be performed in half of the study cohort (1M array, Illumina 500 GX beadstation).

Circulating E-selectin as a risk marker in patients with end-stage renal disease.

BACKGROUND: E-selectin is a key adhesion molecule which plays a fundamental role in endothelial progenitor cell-dependent reparative mechanisms in experimental ischaemia and it serves to anchor leucocytes to the endothelium in inflammatory processes. Inflammation is one of the strongest risk factors for death and cardiovascular (CV) events in end-stage renal disease (ESRD). OBJECTIVE: The objective of the current study was to evaluate whether E-selectin is a useful biomarker of clinical outcome in ESRD patients. We tested the prediction power of circulating E-selectin for mortality and CV events in a cohort of 265 ESRD patients. RESULTS: During the follow-up, 59 patients died and 58 had CV events. All-cause mortality was inversely related to serum E-selectin, the risk of death being the lowest in patients in the third E-selectin tertile (HR: 1, reference group), intermediate in those in the second tertile (HR: 1.30) and the highest in patients in the first tertile (HR: 2.02, P = 0.01). Similarly, the risk of fatal and nonfatal CV events followed an inverse pattern being lowest in the third tertile (reference group) and highest in the first tertile (HR: 1.73, P = 0.03). The prediction power of E-selectin for death and CV events was confirmed in a Cox regression analysis where E-selectin emerged as an inverse predictor of these outcomes, particularly so in patients with severe inflammation. CONCLUSIONS: These data are in keeping with the hypothesis that in systemic inflammation altered E-selectin shedding may play a role in arterial damage and implicates this adhesion molecule in atherosclerotic complications in a high-risk condition like ESRD.

Fibrinogen, mortality and incident cardiovascular complications in end-stage renal failure.

OBJECTIVE: Fibrinogen is an established predictor of cardiovascular events in the general population but the relationship between fibrinogen, mortality and incident cardiovascular complications has been very little investigated in patients with end-stage renal disease (ESRD). DESIGN AND SUBJECTS: We investigated the relationship between fibrinogen and all cause mortality and cardiovascular outcomes in a prospective cohort study in 192 patients on chronic haemodialysis treatment (follow-up: 34 +/- 16 months). RESULTS: Fibrinogen was significantly higher in patients who died during the follow-up than in those who survived. Similarly, fibrinogen was higher in patients who had fatal or nonfatal cardiovascular events than in event free patients. On multivariate Cox regression analysis fibrinogen was an independent predictor of survival [hazard ratio (1 g x L(-1) increase in plasma fibrinogen): 1.19, 95% confidence interval (CI): 1.05-1.35, P = 0.006] and a highly significant (P = 0.0008), independent predictor of fatal and nonfatal cardiovascular events [hazard ratio (1 g x L(-1) increase in plasma fibrinogen): 1.25, 95% CI: 1.10-1.43] in a model including traditional risk factors and serum C-reactive protein (CRP) and plasma homocysteine. CONCLUSIONS: Fibrinogen is as an independent risk factor for overall and cardiovascular mortality in patients with ESRD. Intervention studies are required to see whether reducing plasma fibrinogen may help to curb the exceedingly high cardiovascular risk of the uremic population.

Circulating natriuretic peptide concentrations in patients with end-stage renal disease: role of brain natriuretic peptide as a biomarker for ventricular remodeling.

OBJECTIVES: To determine levels of natriuretic peptides (NPs) in patients with end-stage renal disease (ESRD) and to examine the relationship of these cardiovascular peptides to left ventricular hypertrophy (LVH) and to cardiac mortality. PATIENTS AND METHODS: One hundred twelve dialysis patients without clinical evidence of congestive heart failure underwent plasma measurement of NP concentrations and echocardiographic investigation for left ventricular mass index (LVMI). RESULTS: Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations correlated positively with LVMI and inversely with left ventricular ejection fraction, whereas C-type NP and Dendroaspis NP levels did not correlate with LVMI. In dialysis patients with LVH (LVMI >125 g/m2), plasma ANP and BNP concentrations were increased compared with those in dialysis patients without LVH (both P<001). In a subset of 15 dialysis patients without LVH or other concomitant diseases, plasma BNP concentrations were not significantly increased compared with those in 35 controls (mean +/- SD, 20.1+/-13.4 vs 13.5+/-9.6 pg/mL; P=.06), demonstrating that the BNP concentration was not increased by renal dysfunction alone. Furthermore, the BNP level was significantly higher in the 16 patients who died from cardiovascular causes compared with survivors (mean +/- SD, 129+/-13 vs 57+/-7 pg/mL; P<.003) and was significantly associated with greater risk of cardiovascular death in Cox regression analysis (P<.001), as was the ANP level (P=.002). CONCLUSIONS: Elevation of the plasma BNP concentration is more specifically related to LVH compared with the other NP levels in patients with ESRD independent of congestive heart failure. Thus, BNP serves as an important plasma biomarker for ventricular hypertrophy in dialysis patients with ESRD.

Urinary adrenomedullin is related to ET-1 and salt intake in patients with mild essential hypertension. Salt Sensitivity Group of Italian Society of Hypertension.

Adrenomedullin (ADM) infusion increases salt excretion in the rat. However, there is no evidence that this substance is related to changes in salt intake in humans. In this study we sought whether the urinary excretion rate of this autacoid is related to salt intake and by the expected changes in arterial pressure in patients with mild essential hypertension. The influence of salt intake on the renal excretion of ADM was investigated in 55 hypertensive patients in a double blind, randomized and crossover study comparing a 2-week 50 mmol/day salt intake period with a 150 mmol/day salt intake period. Twenty-four-hour ADM and endothelin-1 (ET-1) excretion rate were measured by radioimmunoassay on preextracted urinary samples (intraassay confidence variable <8%). The antibodies used in these assays had minimal ADM-ET-1 cross-reactivity (<1%). Twenty-four-hour microalbuminuria was measured by nephelometry. On univariate analysis changes in urinary ADM were significantly related to those in salt excretion (r = 0.33, P = .01) as well as to changes in urinary ET-1 (r = 0.56, P = .0001). Furthermore, changes in urinary albumin excretion were related to those in urinary ET-1 (r = 0.26, P = .05), but were independent of those in urinary ADM (P = .19). In a multiple regression model including age, sex, body mass index, and changes in systolic pressure, plasma renin activity and plasma aldosterone and urine volume, salt excretion resulted as the stronger independent predictor of urinary ADM (r = 0.33, P = .01). However, changes in urinary salt lost prediction power (P = .11) for urinary ADM when urinary ET-1 was introduced into the model. In this model (multiple r = 0.31) urinary ET-1 resulted to be the only independent predictor of urinary ADM (beta = 0.56, P = .0001). This study is the first to show that the renal excretion of ADM is related to changes in salt intake and that it is tightly linked to that of ET-1. The data support the notion that these autacoids play a role in the regulation of sodium metabolism in patients with mild hypertension. The intercorrelations between ET-1, ADM, and microalbuminuria are compatible with the hypothesis that ET-1 is involved in a salt-induced increase in glomerular pressure and suggest that ADM may act as a counterregulatory factor in this situation.

Diagnostic potential of cardiac natriuretic peptides in dialysis patients.

BACKGROUND: In the general population, the plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are useful to predict left ventricular hypertrophy (LVH) and LV systolic dysfunction. Whether these cardiac hormones have a similar diagnostic potential in dialysis patients is unknown. METHODS: We studied the diagnostic value of ANP and BNP for alterations in LV mass and function in a cohort of 246 dialysis patients without clinical evidence of heart failure. RESULTS: Both ANP and BNP were independently related to left ventricular mass (P < 0.0001) as well as to ejection fraction (P < 0.0001). In an analysis based on a prospectively defined threshold (95th percentile of the normal range), BNP had a significantly higher (P < 0.01) sensitivity (88%) than ANP (51%) for the diagnosis of LVH, but the positive predictive value of the two peptides was very similar (92 and 87%, respectively, P = NS). However, the negative predictive value of BNP for excluding LVH was 22% higher than that of ANP (53 vs. 31%, P = 0.05). Both natriuretic peptides had a high sensitivity for the detection of LV dysfunction (87 and 94%), but their positive predictive value was low (25 and 15%). Importantly, both ANP and BNP proved to be very useful for excluding this alteration (negative predictive value 97 and 96%, respectively). An analysis based on the "best cut-offs" of each peptide as identified on the basis of the ROC curves augmented the positive and negative prediction values of BNP for the diagnosis of LVH to 95 and 61%, respectively. This approach also raised the BNP-positive prediction value for the identification of LV dysfunction to 31% but did not modify the diagnostic potential of ANP (either for LVH or for LV dysfunction). CONCLUSIONS: Measuring the plasma concentration of cardiac natriuretic hormones, particularly BNP, may be useful for the identification of dialysis patients with LVH or for excluding systolic dysfunction.

Smoking, blood pressure and serum albumin are major determinants of carotid atherosclerosis in dialysis patients. CREED Investigators. Cardiovascular Risk Extended Evaluation in Dialysis patients.

AIM: To investigate the relationship between carotid atherosclerosis and some major cardiovascular risk factors in uremic patients on chronic dialysis. METHODS: A cross-sectional study was carried out in 119 unselected dialysis patients (89 on hemodialysis and 30 on chronic ambulatory peritoneal dialysis, CAPD). Fasting blood sampling for serum lipids, albumin, hemoglobin, and echo-colour-Doppler evaluation of common carotid arteries were performed in all patients (during the non-dialysis day in hemodialysis patients). In hemodialysis patients BP was measured before and after dialysis; in CAPD patients home BP values were recorded during the month before the study day. RESULTS: Ninety-five patients had at least one plaque and 57 had at least four plaques. Thirty-eight had mild and eleven severe carotid stenosis. In multiple regression models, the mean internal diameter of carotid arteries was explained (R=0.52, P=0.0001) by systolic pressure (r=0.39), serum cholesterol (r=-0.28), age (r=0.27) and smoking (r=0.24) while the degree of carotid stenosis was predicted (R=0.39, P=0.0001) by age (r=0.36) and smoking (r=0.25). The number of atherosclerotic plaques was explained (R=0.51, P=0.0001) by age (r=0.36), smoking (r=0.25) and pulse pressure (r=0.20), serum albumin just failing to reach statistical significance (P = 0.06). However, serum albumin was a significant and independent predictor of the number of atherosclerotic plaques (r=-0.26) in hemodialysis patients (n=89). Sex, diabetes, Kt/V, duration of dialysis treatment, hemoglobin, serum calcium and phosphate did not add any predictive power to the models. CONCLUSIONS: In dialysis patients arterial pressure and smoking are associated with carotid atherosclerosis. Serum albumin appears to serve as an independent predictor of carotid atherosclerosis.

Atrial natriuretic peptide response to postural changes and upright exercise in patients with venous valvular insufficiency.

To investigate the effects of postural changes and upright exercise on atrial natriuretic peptide release and renin-angiotensin-aldosterone system behavior in patients with venous valvular insufficiency, plasma ANP, plasma renin activity and aldosterone were measured in 11 patients with venous disease and in 11 age-matched controls. In patients with large varicose veins and venous valvular dysfunction, standing was associated with a greater fall in circulating ANP levels (p < 0.05) and upright exercise was accompanied by a smaller rise in ANP concentrations (p < 0.05) as compared with controls. A significant (p < 0.001) inverse relationship was found between the number of venous segments with reflux and both upright and exercise plasma ANP concentrations (r = -0.91; r = -0.84, respectively). In the two groups the response of the renin-angiotensin-aldosterone system to upright position and physical stress was similar. These results suggest that a decreased atrial stretch, due to a reduced venous return, could account for the blunted ANP response to erect posture and exercise in patients with venous valvular incompetency.

Transient myocardial ischemia stimulates atrial natriuretic factor release.

Atrial natriuretic factor release during transient myocardial ischemia was investigated in 29 patients with coronary artery disease and symptoms of angina (Canadian Cardiovascular Association classes II-III). Eleven patients (group I) underwent single-vessel percutaneous transluminal coronary angioplasty. Repeat determinations of mean pulmonary artery wedge pressure and blood sampling from pulmonary artery for atrial natriuretic factor measurements were performed at baseline, and at 2, 5, and 15 minutes after percutaneous transluminal coronary angioplasty was begun. Baseline atrial natriuretic factor levels (34.6 +/- 4.5 pg/ml) rose to 56.3 +/- 7.3 pg/ml (p = 0.02) and decreased at 5 minutes (43.7 +/- 5.7 pg/ml, not significant) and 15 minutes (35.3 +/- 4.4 pg/ml, not significant). Changes in atrial natriuretic factor concentrations were significantly correlated with those in mean pulmonary artery wedge pressure (2 minutes: r = 0.69, p = 0.02; 5 minutes: r = 0.90, p less than 0.001). In group II (n = 10) the increase in atrial natriuretic factor after dye load occurred later (baseline: 25.8 +/- 2.1; 60 minutes: 40.6 +/- 2.6 pg/ml; p = 0.005) than that observed in group I after percutaneous transluminal coronary angioplasty. In group III, atrial natriuretic factor during angina rose as early (baseline 11.3 +/- 1.3; 5 minutes: 20 +/- 2.3 pg/ml; p = 0.006) as after percutaneous transluminal coronary angioplasty. Results indicate that transient myocardial ischemia stimulates atrial natriuretic factor release, probably through changes in cardiac function.

Comparison of ketanserin and enalapril in the treatment of mild-to-moderate essential hypertension.

In a double-blind 3-month study in mild-to-moderate essential hypertensive patients over 50 years of age, ketanserin, a selective S2-serotoninergic antagonist with additional alpha 1-adrenergic blocking properties, has been compared with enalapril, an angiotensin-converting enzyme inhibitor. Supine and upright blood pressures and heart rates were recorded for placebo and during active treatment (-4, -2, 0, 2, 4, 6, 8, 10, and 12 weeks). Metabolic profile (plasma glucose, creatinine, sodium, potassium, total and HDL-cholesterol, triglycerides, uric acid) was monitored during treatment with placebo and at the end of the study. Mean blood pressure was equally and significantly (p less than 0.001) lowered by both drugs from 2 weeks of treatment, whereas no changes occurred in mean heart rate or in biochemical variables. Dizziness was observed in three patients on ketanserin and in one patient on enalapril, whereas headache occurred in only one patient on enalapril. These data indicate that ketanserin is as effective and well tolerated as enalapril in hypertensive patients over 50 years of age.

Baseline and post-atrial pacing release of atrial natriuretic factor in mitral stenosis.

To investigate the release of atrial natriuretic factor (ANF) in mitral stenosis and the influence of the increase on the frequency of atrial contraction or atrial distention on ANF secretion, we studied 10 patients with symptoms of congestive heart failure (New York Heart Association classes II and III) in sinus rhythm, who were undergoing cardiac catheterization as part of an evaluation workup for mitral stenosis. Echocardiographic tracings, repeat determinations of mean pulmonary artery wedge pressure (MPAWP) and mean right atrial pressure, and blood sampling from the pulmonary artery for measurements of ANF were performed at baseline, during atrial pacing (pacing rate of 125 beats/min for 5 minutes), and 5 minutes after the pacing protocol was completed. Baseline ANF levels were closely related to right atrial pressure (r = 0.89; p less than 0.001) and increased markedly after atrial pacing from 205.6 +/- 39.8 (SEM) to 343.9 +/- 57.9 (SEM) pg/ml. A similar pacing-induced increase was shown for MPAWP and left atrial size. Our data indicate that pacing-induced increases in atrial distention and intracavitary pressure further stimulate release of ANF. However, an independent effect of frequency of atrial pacing on plasma ANF in humans could not be identified.

Evidence for a further stimulation of atrial natriuretic factor release by atrial pacing in patients with mitral stenosis.

To investigate the release of atrial natriuretic factor (ANF) in mitral stenosis and the effect of an increased atrial contraction frequency on atrial distension and ANF secretion, we studied 14 patients [New York Heart Association (NYHA) grades II-III] in sinus rhythm, undergoing cardiac catheterization for mitral stenosis. Echocardiographic tracings, repeat determinations of mean pulmonary artery wedge pressure and blood samples from the pulmonary artery for ANF measurements were taken at baseline, during atrial pacing (125 beats/min for 5 min) and 5 min after pacing. After pacing, ANF levels rose markedly with a parallel increase in mean pulmonary artery wedge pressure and left atrial size. These data indicate that atrial pacing is capable of further stimulating ANF release, even in patients with elevated baseline ANF and left atrial pressure and an increased left atrial dimension.

Coarctation of the abdominal aorta and multiple renal artery stenosis. Case report.

A case of coarctation of the abdominal aorta associated with multiple stenotic renal arteries is reported. The patient was operated upon with successful thoraco-abdominal aortic bypass and direct reimplantation of 3 renal arteries on the graft. Surgical techniques for treatment of coarctation are discussed.