This study demonstrated that elevated plasma fibrinogen level is related to increased CHD risk. The presence of -455A allele is significantly associated with higher fibrinogen in non-CHD control subjects and SAP patients but not in ACS patients while -455G/A polymorphism is not a risk factor for CHD in the Chinese population.

No abstract

Inflammation plays a key role in pressure overload‐induced cardiac hypertrophy and heart failure, but the mechanisms have not been fully elucidated. High‐mobility group box 1 (HMGB1), which is increased in myocardium under pressure overload, may be involved in pressure overload‐induced cardiac injury. The objectives of this study are to determine the role of HMGB1 in cardiac hypertrophy and cardiac dysfunction under pressure overload. Pressure overload was imposed on the heart of male wild‐type mice by transverse aortic constriction (TAC), while recombinant HMGB1, HMGB1 box A (a competitive antagonist of HMGB1) or PBS was injected into the LV wall. Moreover, cardiac myocytes were cultured and given sustained mechanical stress. Transthoracic echocardiography was performed after the operation and sections for histological analyses were generated from paraffin‐embedded hearts. Relevant proteins and genes were detected. Cardiac HMGB1 expression was increased after TAC, which was accompanied by its translocation from nucleus to both cytoplasm and intercellular space. Exogenous HMGB1 aggravated TAC‐induced cardiac hypertrophy and cardiac dysfunction, as demonstrated by echocardiographic analyses, histological analyses and foetal cardiac genes detection. Nevertheless, the aforementioned pathological change induced by TAC could partially be reversed by HMGB1 inhibition. Consistent with the in vivo observations, mechanical stress evoked the release and synthesis of HMGB1 in cultured cardiac myocytes. This study indicates that the activated and up‐regulated HMGB1 in myocardium, which might partially be derived from cardiac myocytes under pressure overload, may be of crucial importance in pressure overload‐induced cardiac hypertrophy and cardiac dysfunction.

Simvastatin inhibits vascular inflammation and atherosclerosis in ApoE(-/-) mice, which may be mediated through downregulation of the HMGB1-RAGE axis.

ROCK activity is increased in CHF and it might be associated with the mortality in CHF. ROCK activity might be a complementary biomarker to CHF risk stratification.

Low density lipoprotein receptor-related protein 6 (LRP6), a wnt co-receptor, regulates multiple functions in various organs. However, the roles of LRP6 in the adult heart are not well understood.Methods: We observed LRP6 expression in heart with end-stage dilated cardiomyopathy (DCM) by western blot. Tamoxifen-inducible cardiac-specific LRP6 knockout mouse was constructed. Hemodynamic and echocardiographic analyses were performed to these mice.Results: Cardiac LRP6 expression was dramatically decreased in patients with end-stage dilated cardiomyopathy (DCM) compared to control group. Tamoxifen-inducible cardiac-specific LRP6 knockout mice developed acute heart failure and mitochondrial dysfunction with reduced survival. Proteomic analysis suggests the fatty acid metabolism disorder involving peroxisome proliferator-activated receptors (PPARs) signaling in the LRP6 deficient heart. Accumulation of mitochondrial targeting to autophagosomes and lipid droplet were observed in LRP6 deletion hearts. Further analysis revealed cardiac LRP6 deletion suppressed autophagic degradation and fatty acid utilization, coinciding with activation of dynamin-related protein 1 (Drp1) and downregulation of nuclear TFEB (Transcription factor EB). Injection of Mdivi-1, a Drp1 inhibitor, not only promoted nuclear translocation of TFEB, but also partially rescued autophagic degradation, improved PPARs signaling, and attenuated cardiac dysfunction induced by cardiac specific LRP6 deletion.Conclusions: Cardiac LRP6 deficiency greatly suppressed autophagic degradation and fatty acid utilization, and subsequently leads to lethal dilated cardiomyopathy and cardiac dysfunction through activation of Drp1 signaling. It suggests that heart failure progression may be attenuated by therapeutic modulation of LRP6 expression.

Characteristics of heart failure with preserved ejection fraction (HFPEF) have not yet been fully understood. The objectives of this pilot study are to detect protein expression profile in the sera of HFPEF patients, and to identify potential biomarkers for the disease. Five hundred and seven proteins were detected in the sera of healthy volunteers and patients with either HFPEF or hypertension using antibody microarrays (three in each group). The results showed that the serum concentrations of 17 proteins (e.g. angiogenin, activin A and artemin) differed considerably between HFPEF and non-HFPEF patients (hypertensive patients and healthy controls), while a protein expression pattern distinct from that in non-HFPEF patients was associated with HFPEF patients. The up-regulation of angiogenin in both HFPEF patients with LVEF ≥50% (P = 0.004) and a subset of HFPEF patients with LVEF = 41–49% (P < 0.001) was further validated in 16 HFPEF patients and 16 healthy controls. Meanwhile, angiogenin distinguished HFPEF patients from controls with a mean area under the receiver operating characteristic curve of 0.88 (P < 0.001) and a diagnostic cut-off point of 426 ng/ml. Moreover, the angiogenin levels in HFPEF patients were positively correlated with Lg(N-terminal pro-B-type natriuretic peptide, NT-proBNP) (P < 0.001). In addition, high angiogenin level (≥426 ng/ml) was a predictor of all-cause death within a short-term follow-up duration, but not in the longer term of 36 months. This pilot study indicates that the aforementioned 17 potential biomarkers, such as angiogenin, may hold great promise for both diagnosis and prognosis assessment of HFPEF.

Lower urinary tract symptoms (LUTS) are reported to affect over half of all adults, and they are associated with significantly impaired quality of life (QOL). We performed a population-based study to evaluate the overall prevalence and impact of LUTS including overactive bladder (OAB) in adults aged ≥40 years in China.Adults aged ≥40 years were eligible to participate in this internet-based survey, provided that they had the ability to access the internet, to use a computer and to read the local language. The survey contained questions relating to International Continence Society (ICS) symptom definitions, the International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom Score (OABSS). The primary study objective was to determine the prevalence of LUTS using the ICS 2002 symptom definition.Among the 4136 respondents, 2080 (50.3%) were men and 1347 (32.6%) were aged ≥60 years. LUTS prevalence according to ICS criteria was 60.3% in men and 57.7% in women. All 3 ICS symptom groups (voiding, storage, and postmicturition) were present in 22.8% of women and 24.2% of men, making this the most common combination of ICS symptom groups. The most bothersome symptoms were terminal dribble and nocturia. According to IPSS scores, 32.9% of participants had at least moderate symptoms. The prevalence of OAB was 23.9%. The presence of LUTS—particularly all 3 ICS symptom groups—was associated with reduced sexual QOL in women, reduced satisfaction with erectile function in men, higher anxiety and depression scores, and reduced health-related QOL (physical health and mental health domains). The overall percentage of participants with LUTS visiting healthcare professionals for urinary symptoms was 38%.In conclusion, LUTS affect the majority of adults aged ≥40 years in China, and prevalence increases with increasing age. LUTS are associated with impaired QOL and mental health, but fewer than half of individuals in China with LUTS seek healthcare for their symptoms. There is therefore a need to improve awareness and treatment of the condition.ClinicalTrials.gov identifier: NCT02618421