Background Data comparing outcomes in heart failure ( HF ) across Asia are limited. We examined regional variation in mortality among patients with HF enrolled in the ASIAN ‐HF (Asian Sudden Cardiac Death in Heart Failure) registry with separate analyses for those with reduced ejection fraction ( EF ; <40%) versus preserved EF (≥50%). Methods and Results The ASIAN ‐ HF registry is a prospective longitudinal study. Participants with symptomatic HF were recruited from 46 secondary care centers in 3 Asian regions: South Asia (India), Southeast Asia (Thailand, Malaysia, Philippines, Indonesia, Singapore), and Northeast Asia (South Korea, Japan, Taiwan, Hong Kong, China). Overall, 6480 patients aged >18 years with symptomatic HF were recruited (mean age: 61.6±13.3 years; 27% women; 81% with HF and reduced r EF ). The primary outcome was 1‐year all‐cause mortality. Striking regional variations in baseline characteristics and outcomes were observed. Regardless of HF type, Southeast Asians had the highest burden of comorbidities, particularly diabetes mellitus and chronic kidney disease, despite being younger than Northeast Asian participants. One‐year, crude, all‐cause mortality for the whole population was 9.6%, higher in patients with HF and reduced EF (10.6%) than in those with HF and preserved EF (5.4%). One‐year, all‐cause mortality was significantly higher in Southeast Asian patients (13.0%), compared with South Asian (7.5%) and Northeast Asian patients (7.4%; P <0.001). Well‐known predictors of death accounted for only 44.2% of the variation in risk of mortality. Conclusions This first multinational prospective study shows that the outcomes in Asian patients with both HF and reduced or preserved EF are poor overall and worst in Southeast Asian patients. Region‐specific risk factors and gaps in guideline‐directed therapy should be addressed to potentially improve outcomes. Clinical Trial Registration URL : https://www.clinicaltrials.gov/ . Unique identifier: NCT 01633398.

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The clinical features and microbiological characteristics of 315 patients with definite or possible infective endocarditis (IE) from January 1995 to December 2003 were evaluated. There were 187 males and 128 females with a mean age of 51 years (range, 1 month to 92 years). Ninety-three patients (30%) had a diagnosis of valvular heart disease and 24 (8%) had received prosthetic valve replacement. Blood culture was negative in 62 patients (20%). Staphylococci (91 patients, 32%), including methicillin-susceptible Staphylococcus aureus (15%), methicillin-resistant S. aureus (11%), and coagulase-negative staphylococci (6%), were the most commonly encountered pathogens followed by viridans group streptococci (77 patients, 24%). Eight patients (25%) had various neurological, renal, embolic, and cardiac complications. Patients with neurological complications [odds ratio (OR) 8.175, P<0.001], nosocomial IE (OR 6.661, P<0.001), underlying malignancy (OR 4.993, P<0.001), elevated serum creatinine level (OR 3.132, P=0.001), or elevated WBC count (>15000/mm3) (OR 2.537, P=0.007) were at significantly increased risk of mortality. This study found mortality from IE was associated with several factors, among which neurological complications were the most hazardous. Patients with more than one risk factor had poorer prognosis. These results suggest the need for more aggressive management in patients with IE when multiple risk factors for mortality are identified.

Background Renin-guided therapeutics using plasma renin activity (PRA) values may lead to clinically significant blood pressure (BP) reductions. We were to compare the effect of renin-guided therapy versus (not renin-based) routine practice on short-term BP reductions in young untreated hypertensive patients who mostly have high renin activity would benefit from renintargeted antihypertensive drugs.

BackgroundKnown associations between diabetes and cancer could logically be attributed to hyperglycemia, hypersecretion of insulin, and/or insulin resistance. This study examined the relationship between initial glycemic biomarkers among men and women with impaired fasting glucose or undiagnosed diabetes and cancer mortality during follow up.MethodsThe cohort included subjects aged 40 years and above from the Third National Health and Nutrition Examination Survey (NHANES III) with fasted serum glucose >100 mg/dl without the aid of pharmaceutical intervention (insulin or oral hypoglycemics). Cancer mortality was obtained from the NHANES III-linked follow-up database (up to December 31, 2006). A Cox regression model was applied to test for the associations between cancer mortality and fasting serum glucose, insulin, glycosylated hemoglobin (HbA1c), C-peptide, insulin like growth factor (IGF-1), IGF binding protein 3 (IGFBP3) and estimated insulin resistance.ResultsA total of 158 and 100 cancer deaths were recorded respectively from 1,348 men and 1,161 women during the mean 134-month follow-up. After adjusting for the effect of age and smoking in women, all-cause cancer deaths (HR: 1.96 per pmol/ml, 95% CI: 1.02–3.77) and lung cancer deaths (HR: 2.65 per pmol/ml, 95% CI: 1.31–5.36) were specifically associated with serum C-peptide concentrations. Similar associations in men were not statistically significant. Serum glucose, HbA1c, IGF-1, IGFBP3 and HOMA were not independently related to long-term cancer mortality.ConclusionC-peptide analyses suggest a modest association with both all-cause and lung cancer mortality in women but not in men. Further studies will be required to explore the mechanisms.

Fibroblast growth factors (FGFs) 21 and 23 are recently identified hormones regulating metabolism of glucose, lipid, phosphate and vitamin D. Here we conducted a genome-wide association study (GWAS) for circulating FGF21 and FGF23 concentrations to identify their genetic determinants. We enrolled 5,000 participants from Taiwan Biobank for this GWAS. After excluding participants with diabetes mellitus and quality control, association of single nucleotide polymorphisms (SNPs) with log-transformed FGF21 and FGF23 serum concentrations adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for body mass index (BMI) and a third model additionally adjusted for BMI and estimated glomerular filtration rate (eGFR) were used. A total of 4,201 participants underwent GWAS analysis. rs67327215, located within RGS6 (a gene involved in fatty acid synthesis), and two other SNPs (rs12565114 and rs9520257, located between PHC2-ZSCAN20 and ARGLU1-FAM155A respectively) showed suggestive associations with serum FGF21 level (P = 6.66 × 10-7 , 6.00 × 10-7 and 6.11 × 10-7 respectively). The SNPs rs17111495 and rs17843626 were significantly associated with FGF23 level, with the former near PCSK9 gene and the latter near HLA-DQA1 gene (P = 1.04 × 10-10 and 1.80 × 10-8 respectively). SNP rs2798631, located within the TGFB2 gene, was suggestively associated with serum FGF23 level (P = 4.97 × 10-7). Additional adjustment for BMI yielded similar results. For FGF23, further adjustment for eGFR had similar results. We conducted the first GWAS of circulating FGF21 levels to date. Novel candidate genetic loci associated with circulating FGF21 or FGF23 levels were found. Further replication and functional studies are needed to support our findings. Fibroblast growth factor (FGF) superfamily includes 22 family members. Except for the endocrine FGF19, FGF21, and FGF23, other family members act as autocrine or paracrine factors 1. Recent evidence showed that FGF21 exerts metabolic effects by acting both centrally and peripherally, mostly in the liver, adipose tissue and pancreas. In prolonged starvation, FGF21 is secreted by the liver to promote gluconeogenesis, increases hepatic

Diabetes mellitus has reached epidemic proportion worldwide. One of the diabetic complications is cardiomyopathy, characterized by early left ventricular (LV) diastolic dysfunction, followed by development of systolic dysfunction and ventricular dilation at a late stage. The pathogenesis is multifactorial, and there is no effective treatment yet. In recent years, 4-hydroxy-2-nonenal (4-HNE), a toxic aldehyde generated from lipid peroxidation, is implicated in the pathogenesis of cardiovascular diseases. Its high bioreactivity toward proteins results in cellular damage. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is the major enzyme that detoxifies 4-HNE. The development of small-molecule ALDH2 activator provides an opportunity for treating diabetic cardiomyopathy. This study found that AD-9308, a water-soluble andhighly selective ALDH2 activator, can improve LV diastolic and systolic functions, and wall remodeling in streptozotocin-induced diabetic mice. AD-9308 treatment dose-dependently lowered serum 4-HNE levels and 4-HNE protein adducts in cardiac tissue from diabetic mice, accompanied with ameliorated myocardial fibrosis, inflammation, and apoptosis. Improvements of mitochondrial functions, sarco/endoplasmic reticulumcalcium handling and autophagy regulation were also observed in diabetic mice with AD-9308 treatment. In conclusion, ADLH2 activation effectively ameliorated diabetic cardiomyopathy, which may be mediated through detoxification of 4-HNE. Our findings highlighted the therapeutic potential of ALDH2 activation for treating diabetic cardiomyopathy.