Do we need another heart failure biomarker. focus on soluble suppression of tumorigenicity 2 (sST2)

If sST2 indeed turns into the HbA1c of heart failure, its value should increase exponentially in our management of patients with heart failure. Serial sST2 levels should allow us to titrate therapy and monitor the clinical state of the patient. In addition, since sST2 is such a strong marker of the risk of death, it would not be surprising to see a level be used to make decisions when patients are on the cusp of such therapies as ICD, CRT, CardioMems implantation and even left ventricular assist devices. A discussion about the use of biomarkers would not be complete without mentioning the issue of surrogates for determining the therapy effectiveness of some of the newer heart failure drugs. Novartis’s EntrestoVR , the brand name for its recently CE marked and FDA approved ARNI1 drug (previously known as LCZ696) and Servier’s ivabradine drug CorlanorVR (marketed by Amgen in the USA), also CE marked and FDA approved, while offering exciting potential benefits to heart failure patients—even being hailed ‘game-changer’ drugs by some—raises the thorny issue of cost vs. benefit. These new drugs are several times the cost of the generics that have become the mainstay of heart failure treatment, i.e. ACE inhibitors, angiotensin receptor blocker (ARBs), beta-blockers, etc. Pushback is therefore expected from payers. Because sST2 changes rapidly with the underlying condition of the patient, is not affected by normal confounding factors, and has a single cut point, it may be ideally suited to help clinicians determine if these newer mediations are effective for each patient, are improving quality of life, and whether dosing needs to be titrated or changed. The new reality of heart failure care is that while more treatment options have opened up, which can literally be a lifesaver for millions of patients, the burden on healthcare systems has skyrocketed. Biomarkers, and particularly sST2, could offer physicians and payers a way to bring treatment down to an individual patient level, providing

ST2 and Multimarker Testing in Acute Decompensated Heart Failure

Most data on heart failure biomarkers have been derived from patient cohorts with chronic disease. However, risk prediction in patients admitted with acute decompensated heart failure (ADHF) remains a challenge. ADHF is not a single disease: it presents in various manners, and different causes may underlie ADHF, which may be reflected by different biomarkers. Soluble suppression of tumorigenicity 2 (ST2) has been shown to be a strong independent predictor of short-, mid-, and long-term outcome in ADHF. Furthermore, combining biomarkers may help further improve the prognostic power of ST2. The ProBNP Investigation of Dyspnea in the Emergency Department study showed that elevated plasma levels of ST2 together with elevated levels of 4 other biomarkers have clear incremental values to predict outcome in ADHF. The Multinational Observational Cohort on Acute Heart Failure study is an international collaborative network that recruited 5,306 patients hospitalized for ADHF that demonstrated that ST2 and midregional pro-adrenomedulin had independently strong value to predict 30-day and 1-year outcome in patients with ADHF. The Multinational Observational Cohort on Acute Heart Failure study also showed that C-reactive protein plus ST2 better classified risk in patients with ADHFs than ST2 alone. Combining biomarkers for risk prediction or risk stratification might have clinical and more importantly pathophysiological meaning

Circulating Biologically Active Adrenomedullin Predicts Organ Failure and Mortality in Sepsis

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Biologically active adrenomedullin (bio-ADM) is an emerging biomarker for sepsis. We explored whether bio-ADM concentration could predict severity, organ failure, and 30-day mortality in septic patients. METHODS: In 215 septic patients (109 patients with sepsis; 106 patients with septic shock), bio-ADM concentration was measured at diagnosis of sepsis, using sphingotest bio-ADM (Sphingotec GmbH, Hennigsdorf, Germany) and analyzed in terms of sepsis severity, vasopressor use, and 30-day mortality. The number of organ failures, sequential (sepsis-related) organ failure assessment (SOFA) score, and 30-day mortality were compared according to bio-ADM quartiles. RESULTS: Bio-ADM concentration was significantly higher in patients with septic shock, vasopressor use, and non-survivors than in patients with solitary sepsis, no vasopressor use, and survivors, respectively (all P<0.0001). Bio-ADM quartiles were associated with the number of organ failures (P<0.0001), as well as SOFA cardiovascular, renal, coagulation, and liver subscores (all P<0.05). The 30-day mortality rate showed a stepwise increase in each bio-ADM quartile (all P<0.0001). Bio-ADM concentration and SOFA score equally predicted the 30-day mortality (area under the curve: 0.827 vs 0.830). CONCLUSIONS: Bio-ADM could serve as a useful and objective biomarker to predict severity, organ failure, and 30-day mortality in septic patients

Obesity and sleep disturbance: the chicken or the egg?

Epidemiological studies suggested an association between obesity and sleep disturbances. Obstructive sleep apnea is the most prevalent type of obesity-related sleep disorder that lead to an increased risk for numerous chronic health conditions. In addition the increased visceral adipose tissue might be responsible for the secretion of inflammatory cytokines that could contribute to alter the sleep-wake rhythm. Unhealthy food characterized by high consumption of fat and carbohydrate seems to negatively influence the quality of sleep while diet rich of fiber is associated to more restorative and deeper sleep. Although obesity could cause through several pathogenetic mechanisms an alteration of sleep, it has been reported that subjects suffering from sleep disorders are more prone to develop obesity. Experimental laboratory studies have demonstrated that decreasing either the amount or quality of sleep increase the risk of developing obesity. Experimental sleep restriction also causes physiological, hormonal and food behavioral changes that promote a positive energy balance and a compensatory disproportionate increase in food intake, decrease in physical activity, and weight gain. Thus, the aim of this review is to provide observational evidence on the association of obesity with sleep disturbances and viceversa with emphasis on possible pathophysiological mechanisms (hormonal and metabolic) that link these two pathological conditions

Importance of spinal deformity index in risk evaluation of VCF (vertebral compression fractures) in obese subjects: prospective study.

Introduction Obesity and osteoporosis share many features and recent studies have identified many similarities suggesting common pathophysiological mechanisms. Obesity is associated with a higher risk of non-traumatic fractures despite bone mineral density (BMD) being normal or even increased. Materials and methods 54 obese subjects were analyzed (51 ± 16 years, 10 males, 44 females). Spinal deformity index (SDI) is a semi-quantitative method that may be a surrogate index of bone microarchitecture. SDI index was higher in patients than in controls. In 87.5 % of patients and 10 % of controls we found morphometric vertebral fractures, despite a DEXA Tscore not diagnostic of osteoporosis. Conclusion The objective of this study was to assess in obese patients levels of 25OH vitamin D, parathyroid hormone, serum and urinary calcium (Ca) and phosphorus (P), BMD, and SDI. 87.5 % of the obese subjects present nontraumatic vertebral fractures and reduced bone quality as measured by SDI

Somatotropic Axis and Obesity: Is There Any Role for the Mediterranean Diet?

Obesity is associated with reduced spontaneous and stimulated growth hormone (GH) secretion and basal insulin-like growth factor I (IGF-1) levels-which in turn is associated with increased prevalence of cardiovascular risk factors. The aim of this study was to investigate: (1) the association of somatotropic axis with cardiometabolic status; (2) the association of somatotropic axis with the Mediterranean diet and nutritional pattern in people with obesity. Cross-sectional observational study was carried out in 200 adult women, aged 36.98 ± 11.10 years with severe obesity (body mass index-BMI of 45.19 ± 6.30 kg/m2). The adherence to the Mediterranean diet and the total calorie intake was assessed. Anthropometric measurements, body composition and biochemical profile were determined along with Growth Hormone (GH)/Insulin like Growth Factor 1 (IGF-1) axis and insulin resistance (homeostatic model assessment for insulin resistance-HoMA-IR). The enrolled subjects were compared after being divided according to GH peak response and according to IGF-1 standard deviation scores (SDS). Derangements of GH peak were detected in 61.5% of studied patients while IGF-1 deficiency was detected in 71% of the population. Both blunted GH peak response and IGF-1 SDS were indicators of derangements of somatotropic axis and were associated with comparable results in terms of cardiometabolic sequelae. Both GH peak and IGF-1 levels were inversely associated with anthropometric and metabolic parameters. The adherence to the Mediterranean diet predicts GH peak response. Fatty liver index (FLI), fat mass (FM) and phase angle (PhA) were predictive factors of GH peak response as well. In conclusion derangements of somatotropic axis is associated with a worse cardiometabolic profile in people with obesity. A high adherence to the Mediterranean diet-and in particular protein intake-was associated with a better GH status

BEYOND WAIST CIRCUMFERENCE IN AN ADULT MALE POPULATION OF SOUTHERN ITALY: IS THERE ANY ROLE FOR SUBSCAPULAR SKINFOLD THICKNESS IN THE RELATIONSHIP BETWEEN INSULIN-LIKE GROWTH FACTOR-1 SYSTEM AND METABOLIC PARAMETERS ?

ABSTRACT Background: Apart from waist circumference, other adiposity measures, such as subscapular skin fold (SST), arouse growing interest due to their relationship to metabolic complications and cardiovascular risk. The Insulin-like Growth Factor (IGF)-1 system is deregulated in obese subjects in proportion to their degree of visceral adiposity. Aim : To examine the association among IGF-1, IGF-Binding Protein (BP)1 and 3 levels and different measures of adiposity in a sample of adult male population in Southern Italy. Materials and Methods: A complete database for this analysis was available for 229 (age range 50–82 years) participating at 2002-2004 Olivetti Heart Study follow-up. Results: After adjustment for age, IGF-1 was inversely associated with BMI and waist circumference (p<0.05). IGFBP1 was inversely associated with BMI, waist circumference, SST, Homeostasis Model Assessment (HOMA) index, Fat Mass (FM). HOMA index, age and SST significantly predicted the IGFBP1 plasma levels, with 24% of IGFPB-1 variability explained at a linear regression analysis. Conclusions: IGFBP1 inversely correlated to adiposity and HOMA index. Among adiposity indexes, SST was the best predictor of IGFPB-1 levels. The evaluation of some components of the IGFs system, and simple measures of body adiposity, such as SST, may represent a further tool to better evidence phenotype profiles associated to the pathogenetic mechanism of cardiovascular risk factor clustering in male adults

The role of the emergency department in the management of acute heart failure: an international perspective on education and research

Emergency departments are a major entry point for the initial management of acute heart failure (AHF) patients throughout the world. The initial diagnosis, management and disposition - the decision to admit or discharge - of AHF patients in the emergency department has significant downstream implications. Misdiagnosis, under or overtreatment, or inappropriate admission may place patients at increased risk for adverse events, and add costs to the healthcare system. Despite the critical importance of initial management, data are sparse regarding the impact of early AHF treatment delivered in the emergency department compared to inpatient or chronic heart failure management. Unfortunately, outcomes remain poor, with nearly a third of patients dying or re-hospitalised within 3 months post-discharge. In the absence of robust research evidence, consensus is an important source of guidance for AHF care. Thus, we convened an international group of practising emergency physicians, cardiologists and advanced practice nurses with the following goals to improve outcomes for AHF patients who present to the emergency department or other acute care setting through: (a) a better understanding of the pathophysiology, presentation and management of the initial phase of AHF care; (b) improving initial management by addressing knowledge gaps between best practices and current practice through education and research; and (c) to establish a framework for future emergency department-based international education and research

Patient empowerment and the Mediterranean diet as a possible tool to tackle prediabetes associated with overweight or obesity: a pilot study

AIM: The objective of this study was to investigate the effect of implementation of short-term patient empowerment as applied to Mediterranean diet (MD) adherence on metabolic and anthropometric parameters in prediabetic overweight or obese subjects. METHODS: The sample included 42 subjects with prediabetes, aged 18-75 years and with body mass index (BMI) > 25 kg/m2, who received dietary advice on MD by nutritionists during session groups every 2 weeks for 4 months. Data on energy caloric intake and macronutrient consumption were collected using a 7-day food diary record. Adherence to MD was investigated through the PREvención con DIeta MEDiterránea (PREDIMED) questionnaire. No advice was given regarding caloric restriction and physical activity. At baseline and at the end of the study, each subject underwent anthropometric, metabolic, and nutritional assessments. RESULTS: Approximately 40.5% of subjects had achieved restoration of normal glucose tolerance by the end of the study. Fasting plasma glucose, glycated hemoglobin (HbA1C), BMI, waist circumference, blood pressure, visceral adiposity index, triglycerides, and total and LDL cholesterol levels were significantly decreased, while HDL cholesterol had significantly increased by the end of the study. The subjects significantly increased adherence to MD, as assessed by the PREDIMED questionnaire at follow-up. A reduction of prevalence of the metabolic syndrome was also reported. Interestingly, the PREDIMED score correlated with HbA1C values at follow-up, after adjusting for BMI and total caloric intake. CONCLUSIONS: Implementation of short-term patient empowerment as applied to MD adherence was shown to improve anthropometric and metabolic parameters in prediabetic overweight or obese subjects. This is of considerable importance, given that diet must be the cornerstone of treatment in patients at high risk of developing type 2 diabetes

Alteration of the growth hormone axis, visceral fat dysfunction, and early cardiometabolic risk in adults: the role of the visceral adiposity index

The aim of the study is to clarify the relationship between adipose tissue dysfunction, metabolic profile and growth hormone (GH)/insulin-like growth factor (IGF)-I secretion in healthy adult subjects. We investigated the metabolic profile in a cohort of 231 consecutive healthy subjects in relation to GH, IGF-I levels, and visceral adiposity index (VAI). Anthropometric measures, lipid profile, and glucose and insulin levels during oral glucose tolerance test, Homa-IR and ISI Matsuda, IGF-I and GH peak after GHRH plus Arginine test were analyzed. The subjects with high VAI showed lower GH peak (22.8 ± 11.1 vs. 42.2 ± 21.3 µg/L; p = 0.049) and lower IGF-I (presented as IGF-I under normal range, UNR) (0.54 ± 0.14 vs. 0.64 ± 0.12; p = 0.005) than group with normal VAI. ROC curve analysis identified the cut-off, able to detect subjects with high VAI, i.e., 31.8 µg/L for GH peak and 0.63 for IGF-1 UNR. The subjects with GH peak and IGF-I UNR under the cut-off showed significantly higher levels of VAI, systolic and diastolic blood pressure, glucose and insulin levels, Homa-IR, and lower ISI Matsuda, with a concomitant worse lipid profile (all p < 0.001). A strong relationship between GH axis, VAI and metabolic risk has been demonstrated. A percentage of apparently healthy subjects show a degree of visceral adipose dysfunction associated with GH and IGF-I levels that do not meet the criteria of overt GH deficiency (GHD). Long-term prospective studies could help to clarify and confirm whether a hypothetical condition of subclinical GHD could be taken into account as a new clinical entity