Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis.

BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of heart failure and carries a high mortality rate. Myocardial recovery in DCM-related heart failure patients is highly variable, with some patients having little or no response to standard drug therapy. A genome-wide association study may agnostically identify biomarkers and provide novel insight into the biology of myocardial recovery in DCM. METHODS: A genome-wide association study for change in left ventricular ejection fraction was performed in 686 White subjects with recent-onset DCM who received standard pharmacotherapy. Genome-wide association study signals were subsequently functionally validated and studied in relevant cellular models to understand molecular mechanisms that may have contributed to the change in left ventricular ejection fraction. RESULTS: The genome-wide association study identified a highly suggestive locus that mapped to the 5'-flanking region of the CDCP1 (CUB [complement C1r/C1s, Uegf, and Bmp1] domain containing protein 1) gene (rs6773435; P=7.12×10-7). The variant allele was associated with improved cardiac function and decreased CDCP1 transcription. CDCP1 expression was significantly upregulated in human cardiac fibroblasts (HCFs) in response to the PDGF (platelet-derived growth factor) signaling, and knockdown of CDCP1 significantly repressed HCF proliferation and decreased AKT (protein kinase B) phosphorylation. Transcriptomic profiling after CDCP1 knockdown in HCFs supported the conclusion that CDCP1 regulates HCF proliferation and mitosis. In addition, CDCP1 knockdown in HCFs resulted in significantly decreased expression of soluble ST2 (suppression of tumorigenicity-2), a prognostic biomarker for heart failure and inductor of cardiac fibrosis. CONCLUSIONS: CDCP1 may play an important role in myocardial recovery in recent-onset DCM and mediates its effect primarily by attenuating cardiac fibrosis.

Vascular age, cardiovascular disease risk factors, and hematological parameters in patients with Schizophrenia: An exploratory study.

Objectives: Patients with schizophrenia have shortened life expectancy due to greater cardiovascular disease (CVD) risk. Due to sparse data, index study was planned to assess the CVD risk factors, vascular age (VA), and hematological parameters in patients with schizophrenia and the concordance between Framingham Risk Score (FRS) for lipids and body mass index (BMI) (FRSLIPIDS and FRSBMI). Materials and Methods: Patients with schizophrenia (n = 53) were evaluated for the presence of metabolic syndrome (MS) using the modified NCEP ATP III criteria, along with their functionality, illness severity, physical activity and nutritional score, FRSLIPIDS and FRSBMI, and hematological parameters. Results: Prevalence of MS was 39.6%; in addition, 47% of patients were at risk for developing MS as they fulfilled one or two components of MS criteria and 56% of patients were obese. BMI, obesity, and RBC count were found as significant correlates for MS. CVD risk (FRS) median score (3.10) was comparable for BMI and lipid criteria along with significant correlation for FRSLIPIDS and FRSBMI (r = 0.555, P < 0.001). Conclusion: VA and 10-year CVD risk (FRS for BMI and lipid criteria) represent easier way to communicate with the patients and caregivers and also to guide for comprehensive treatment plan, appropriate nutrition, physical activity, and cardiometabolic screening.