Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease

BACKGROUND Growth differentiation factor 15(GDF-15)has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events.This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality,considering traditional risk factors and other biomarkers.METHODS A prospective study was conducted and 3699 patients with stable coronary artery disease(CAD)were enrolled into the research.Baseline GDF-15 levels were measured.Median follow-up was 3.1 years during the study.We analyzed clinical variables and several biomarkers.Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction(MI),heart failure,stroke,cardiovascular death,and non-cardiovascular death.RESULTS Baseline GDF-15 levels for 3699 patients were grouped by quartile(≤1153,1153-1888,1888-3043,>3043 ng/L).Higher GDF-15 levels were associated with older age,male gender,history of hypertension,and elevated levels of N-terminal pro Btype natriuretic peptide(NT-pro BNP),soluble suppression of tumorigenesis-2(sST2),and creatine(each with P<0.001).Adjusting for established risk factors and biomarkers in Cox proportional hazards models,a 1 standard deviation(SD)increase in GDF-15 was associated with elevated risk of clinical events[hazard ratio(HR)=2.18,95%confidence interval(CI):(1.52-3.11)],including:MI[HR=2.8395%CI:(1.03-7.74)],heart failure[HR=2.7195%CI:(1.18-6.23)],cardiovascular and non-cardiovascular death[HR=2.48,95%CI(1.49-4.11)]during the median follow up of 3.1 years.CONCLUSIONS Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death,independent of clinical risk factors and other biomarkers.GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

Dysregulation of mucosal immune response in pathogenesis of inflammatory bowel disease

Inflammatory bowel disease(IBD)includes Crohn’s disease and ulcerative colitis.The exact etiology and pathology of IBD remain unknown.Available evidence suggests that an abnormal immune response against the microorganisms in the intestine is responsible for the disease in genetically susceptible individuals.Dysregulation of immune response in the intestine plays a critical role in the pathogenesis of IBD,involving a wide range of molecules including cytokines.On the other hand,besides T helper(Th)1 and Th2 cell immune responses,other subsets of T cells,namely Th17 and regulatory T cells,are likely associated with disease progression.Studying the interactions between various constituents of the innate and adaptive immune systems will certainly open new horizons of the knowledge about the immunologic mechanisms in IBD.

Clinical value of detecting autoantibodies against β1-, β2-, and α1-adrenergic receptors in carvedilol treatment of patients with heart failure

Objective To determine the possible association of anti-β1-adrenergic receptors(anti-β1-AR), anti-β2-AR and anti-α1-AR with carvedilol treatment in patients with heart failure(HF). Methods A total of 267 HF patients were prospectively enrolled. Blood samples were measured by an enzyme-linked immunosorbent assay. All of the patients received carvedilol for their HF. Each patient was followed up for six months and their cardiac function was measured. Results The final analysis encompassed 137 patients comprising 65 patients with three autoantibodies(positive group) and 72 patients without all three autoantibodies but with one or two autoantibodies(negative group). The frequency and geometric mean titer of anti-β1-AR, anti-β2-AR, and anti-α1-AR were significantly lower in the group without all three autoantibodies after six months of carvedilol treatment(all P < 0.01;from 100% to 57%, 50%, and 49%, respectively;and from 1: 118, 1: 138, and 1: 130 to 1: 72, 1: 61, and 1: 67, respectively). Furthermore, 28 patients in the positive group demonstrated complete ablation of autoantibodies. In addition, left ventricular remodelling and function was significantly improved by the use of carvedilol combined with the standard treatment regime for six months in the positive group(P < 0.01) when compared to the negative group(P < 0.05). Conclusions Carvedilol treatment significantly decreases frequency and geometric mean titer in patients with all three autoantibodies, even up to complete ablation, and significantly improved cardiac function and remodelling. The effect of carvedilol is probably correlated to the presence of all three autoantibodies.

Fifteen-year mortality and prognostic factors in patients with dilated cardiomyopathy:persistent standardized application of drug therapy and strengthened management may bring about encouraging change in an aging society

BACKGROUND There is scarce data on the long-term mortality and associated prognostic factors in patients with dilated car-diomyopathy(DCM).The study aimed to investigate the all-cause mortality up to 15 years(mean 7.9±5.7 years)in such patients,and the independent prognostic factors influencing their long-term mortality.METHODS One hundred and sixty-six consecutive patients with DCM were prospectively enrolled from 2002 to 2003.The mean age of patients was 59.5±10.4 years,and approximately 57%were male.They were followed up by telephone or outpa-tient visit at least every three months until 2019 or all-cause death occurred.Predictors of mortality were identified using mul-tivariate logistic regression analysis.RESULTS During the 15 years of follow-up,five patients were lost to follow-up,and the complete data records of 161 patients were included in the analysis.Patients were treated with angiotensin-converting-enzyme inhibitors(ACEI)or angiotensin-recept-or blocker(ARB),β-blockers,mineralocorticoid receptor antagonist(MRA),diuretics and digitalis from 2002 to 2004,and main-tained at the maximum tolerated doses between 2004 and 2019.Our safety targets to maintain heart rate and blood pressure at 60-80 beats/min and 90-120/60-80 mmHg,respectively.All-cause mortality in the first five years was 55.9%.The independent risk factors for the 5-year mortality were age≥70 years old(OR=5.45,P=0.006),systolic blood pressure(SBP)>120 mmHg(OR=3.63,P=0.004),6-minute walk distance(6MWD)<450 m(OR=3.84,P=0.001).15-year all-cause mortality was 65.8%.The inde-pendent risk factors for 15-year mortality were age≥70 years old(OR=16.07,P=0.009),LVEF≤35%(OR=5.69,P=0.003),and SBP>120 mmHg(OR=9.56,P<0.001).CONCLUSIONS This study was the first to demonstrate the 15-year survival rate of 34%in DCM patients.The DCM patients’first five-year all-cause mortality decreased significantly after continuous standardized treatment and intensive management.The mortality then plateaued in the following 10 years.Age≥70 years,LVEF≤35%,and SBP>120 mmHg were independent predict-ors of 15-year all-cause mortality.