Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Association of BMI, lipid-lowering medication, and age with prevalence of type 2 diabetes in adults with heterozygous familial hypercholesterolaemia: a worldwide cross-sectional study

Background: Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia. Methods: This worldwide cross-sectional study used individual-level data from the EAS FHSC registry and included adults older than 18 years with a clinical or genetic diagnosis of heterozygous familial hypercholesterolaemia who had data available on age, BMI, and diabetes status. Those with known or suspected homozygous familial hypercholesterolaemia and type 1 diabetes were excluded. The main outcome was prevalence of type 2 diabetes overall and by WHO region, and in relation to obesity (BMI ≥30·0 kg/m2) and lipid-lowering medication as predictors. The study population was divided into 12 risk categories based on age (tertiles), obesity, and receiving statins, and the risk of type 2 diabetes was investigated using logistic regression. Findings: Among 46 683 adults with individual-level data in the FHSC registry, 24 784 with heterozygous familial hypercholesterolaemia were included in the analysis from 44 countries. 19 818 (80%) had a genetically confirmed diagnosis of heterozygous familial hypercholesterolaemia. Type 2 diabetes prevalence in the total population was 5·7% (1415 of 24 784), with 4·1% (817 of 19 818) in the genetically diagnosed cohort. Higher prevalence of type 2 diabetes was observed in the Eastern Mediterranean (58 [29·9%] of 194), South-East Asia and Western Pacific (214 [12·0%] of 1785), and the Americas (166 [8·5%] of 1955) than in Europe (excluding the Netherlands; 527 [8·0%] of 6579). Advancing age, a higher BMI category (obesity and overweight), and use of lipid-lowering medication were associated with a higher risk of type 2 diabetes, independent of sex and LDL cholesterol. Among the 12 risk categories, the probability of developing type 2 diabetes was higher in people in the highest risk category (aged 55–98 years, with obesity, and receiving statins; OR 74·42 [95% CI 47·04–117·73]) than in those in the lowest risk category (aged 18–38 years, without obesity, and not receiving statins). Those who did not have obesity, even if they were in the upper age tertile and receiving statins, had lower risk of type 2 diabetes (OR 24·42 [15·57–38·31]). The corresponding results in the genetically diagnosed cohort were OR 65·04 (40·67–104·02) for those with obesity in the highest risk category and OR 20·07 (12·73–31·65) for those without obesity. Interpretation: Adults with heterozygous familial hypercholesterolaemia in most WHO regions have a higher type 2 diabetes prevalence than in Europe. Obesity markedly increases the risk of diabetes associated with age and use of statins in these patients. Our results suggest that heterozygous familial hypercholesterolaemia does not protect against type 2 diabetes, hence managing obesity is essential to reduce type 2 diabetes in this patient population. Funding: Pfizer, Amgen, MSD, Sanofi-Aventis, Daiichi-Sankyo, and Regeneron

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Does weight loss affect the parameters that are metabolically related to cardiovascular diseases?

WOS: 000482650400004PubMed ID: 30957127Objectives: To assess the differences in the parameters that are metabolically related to cardiovascular diseases after weight loss in obese people with coronary artery diseases (CADs). Methods: This study was conducted on 184 patients who were diagnosed with CADs in Istanbul University Cardiology Institute Hospital, Istanbul, Turkey. The levels of leptin, fibrinogen, homocysteine, high-sensitivity C-reactive protein (hs-CRP), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), fasting blood glucose and insulin, glycated hemoglobin, and uric acid of the obese patients who were put on calorie restricted diet were evaluated retrospectively and compared before and after weight loss. For comparison, non-obese control patients were also studied. Student's t-test and Chi-square test were used for the statistical analysis. Results: Levels of homocysteine, glycated hemoglobin, and leptin were significantly higher in the obese patients than in the non-obese patients. Diabetic obese patients with CADs lost (11.1%) and non-diabetic obese patients with CADs lost (10.5%) of their body weight in 6 months. The levels of cholesterol, LDL-C, and fibrinogen were significantly improved in both groups. Conclusion: The obese patients lost weight after being on calorie-restricted diets and showed significant improvement in the levels of cholesterol, LDL-C, fibrinogen. There was no significant difference in the levels of homocysteine, hs-CRP, and leptin before and after weight loss in both diabetic and non-diabetic obese patients

Applying deep learning models to structural MRI for stage prediction of Alzheimer's disease

Alzheimer's disease is a brain disease that causes impaired cognitive abilities in memory, concentration, planning, and speaking. Alzheimer's disease is defined as the most common cause of dementia and changes different parts of the brain. Neuroimaging, cerebrospinal fluid, and some protein abnormalities are commonly used as clinical diagnostic biomarkers. In this study, neuroimaging biomarkers were applied for the diagnosis of Alzheimer's disease and dementia as a noninvasive method. Structural magnetic resonance (MR) brain images were used as input of the predictive model. T1 weighted volumetric MR images were reduced to two-dimensional space by several preprocessing methods for three different projections. Convolutional neural network (CNN) models took preprocessed brain images, and the training and testing of the CNN models were carried out with two different data sets. The CNN models achieved accuracy values around 0.8 for diagnosis of both Alzheimer's disease and mild cognitive impairment. The experimental results revealed that the diagnosis of patients with mild cognitive impairment was more difficult than that of patients with Alzheimer's disease. The proposed deep learning-based model might serve as an efficient and practical diagnostic tool when MRI data are integrated with other clinical tests

Application of Artificial Neural Networks in Dementia and Alzheimer's Diagnosis

Diagnosis in the early phases of many diseases makes it possible to treat the disease and affects the treatment process positively. This is especially important for diseases like Alzheimer in the field of neurology. The use of a computerized support system, which can autonomously perform the diagnostic process by the expert in this process, saves time and helps to reduce the most human errors. In this study, machine learning models with the ability to diagnose dementia and Alzheimer's disease were developed by predicting the Clinical Dementia Rating (CDR) value. Artificial Neural Networks (ANN), Logistic Regression (LR), k-nearest neighbors (KNN), and Decision Tree (DT) classifiers were applied to compare the classification performances. The Open Access Series of Imaging Studies (OASIS) longitudinal and cross-sectional datasets have been used to train models. As a result of the tests, best performance of the detection and identification of Alzheimer's disease has been shown by LR and YSA models

Differences Between Morbid Obesity With Metabolic Syndrome and Overweight Turkish Adult Participants in Multiple Atherosclerotic Cardiovascular Disease Risk Factors

Obesity and metabolic syndrome (MetS) are public health problems and are increasing globally. We assessed the differences in lipid profiles through lipid testing, thrombotic and inflammatory parameters, and oxidative stress indexes between overweight and obese patients with MetS in a Turkish adult population. We included 100 obese (body mass index [BMI] &gt;30 kg/m2) patients with MetS (66 women, 34 men, mean age 54.0 ± 10.1 years) and 15 overweight (BMI 25-30 kg/m2) individuals (11 women, 4 men, mean age 50.2 ± 14.5 years) as controls. The group with MetS had significantly higher levels of glycaemia, uric acid, high-sensitivity C-reactive protein, homocysteine, fibrinogen, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, small dense LDL, oxidized LDL, apolipoprotein B (Apo B), lipoprotein (a), small and intermediate high-density lipoprotein (HDL) particles, oxidative stress index, and significantly lower levels of HDL-cholesterol (HDL-C), Apo A, and large HDL particles. In conclusion, obesity with MetS increase atherogenic dyslipidemia and thrombotic, inflammatory and oxidative stress biomarkers. Furthermore, obesity with MetS decreases protective mechanisms of atherosclerosis. We should at least try to prevent overweight individuals from becoming obese with MetS. </jats:p

Differences Between Morbid Obesity With Metabolic Syndrome and Overweight Turkish Adult Participants in Multiple Atherosclerotic Cardiovascular Disease Risk Factors

Obesity and metabolic syndrome (MetS) are public health problems and are increasing globally. We assessed the differences in lipid profiles through lipid testing, thrombotic and inflammatory parameters, and oxidative stress indexes between overweight and obese patients with MetS in a Turkish adult population. We included 100 obese (body mass index [BMI] >30 kg/m(2)) patients with MetS (66 women, 34 men, mean age 54.0 +/- 10.1 years) and 15 overweight (BMI 25-30 kg/m(2)) individuals (11 women, 4 men, mean age 50.2 +/- 14.5 years) as controls. The group with MetS had significantly higher levels of glycaemia, uric acid, high-sensitivity C-reactive protein, homocysteine, fibrinogen, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, small dense LDL, oxidized LDL, apolipoprotein B (Apo B), lipoprotein (a), small and intermediate high-density lipoprotein (HDL) particles, oxidative stress index, and significantly lower levels of HDL-cholesterol (HDL-C), Apo A, and large HDL particles. In conclusion, obesity with MetS increase atherogenic dyslipidemia and thrombotic, inflammatory and oxidative stress biomarkers. Furthermore, obesity with MetS decreases protective mechanisms of atherosclerosis. We should at least try to prevent overweight individuals from becoming obese with MetS