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Additional File 2: Material

Additional File 1: Hardy-Weinberg equilibrium of genotype of NPC1L1 and HMGCR genes

Supplemental Material, sj-docx-1-ang-10.1177_00033197211021195 for Relationship Between High-Sensitivity C-Reactive Protein and Long-Term Outcomes in Elderly Patients With 3-Vessel Disease by Yue Liu, Ce Zhang, Lin Jiang, Lianjun Xu, Jian Tian, Xueyan Zhao, Xinxing Feng, Dong Wang, Yin Zhang, Kai Sun, Jingjing Xu, Ru Liu, Bo Xu, Wei Zhao, Rutai Hui, Runlin Gao, Zhan Gao, Lei Song and Jinqing Yuan in Angiology

Additional file 1: Table S1. Baseline characteristics of the study population before and after inverse probability of treatment weighting.

Additional file 3: Table S3. Inverse probability of treatment weighting (IPTW) regression analysis based on propensity score.

Additional file 2: Table S2. Competing risks regression for cardiac death and other cardiovascular endpoints.

Background: MicroRNAs play a crucial role in the regulation of pathological cardiac remodeling and heart failure. Previously, we found that overexpression of miR-221 induces heart failure in mice. The miR-222 and miR-221 share the same gene cluster, however, the role of miR-222 in the regulation of cardiac function remained ill-defined. Methods and Results: Transgenic mice with cardiac-specific expression of miR-222 (Tg-miR-222) mice were generated. The Tg-miR-222 mice developed significantly enlarged hearts at 4 weeks of age. Transthoracic echocardiograph data indicated that the hearts of Tg-miR-222 mice exhibited an increased left ventricular end-diastolic internal diameter and decreased fractional shortening. We observed that the LC3-II in Tg-miR-222 mice was decreased accompanied with the upregulation of p62, indicating the autophagy inhibition in the hearts of Tg-miR-222 mice. The mTOR pathway, a negative regulator of autophagy, was activated in the hearts of Tg-miR-222 mice. The expression of p27 was downregulated by miR-222 overexpression. Conclusion: Our data indicate that miR-222 overexpression induces heart failure in mice. The downregulation of p27 and the activation of mTOR pathway may be involved in miR-222-induced heart failure and autophagy inhibition. Thus, targeting miR-222 expression may be a therapeutic strategy against pathological cardiac remodeling.

Hypertrophic cardiomyopathy (HCM) is a serious monogenic disease characterized by cardiac hypertrophy, fibrosis, sudden cardiac death, and heart failure. Previously, we identified that miR-139-5p was down-regulated in HCM patients. However, the regulatory effects of miR-139-5p remain unclear. Thus, we investigated the role of miR-139-5p in the regulation of cardiac hypertrophy. The expression of miR-139-5p in left ventricular tissues in HCM patients and mice subjected to transverse aortic constriction (TAC) was significantly down-regulated. Knockdown of miR-139-5p expression in neonatal rat cardiomyocytes (NRCMs) induced cardiomyocyte enlargement and increased atrial natriuretic polypeptide (ANP) expression. Overexpression of miR-139-5p antagonized isoproterenol (ISO)-induced cardiomyocyte enlargement and ANP/brain natriuretic peptide (BNP) up-regulation. More importantly, we found that c-Jun expression was inhibited by miR-139-5p in NRCMs. Knockdown of c-Jun expression significantly attenuated cardiac hypertrophy induced by miR-139-5p deprivation. Our data indicated that miR-139-5p was down-regulated in the hearts of HCM patients and that it inhibited cardiac hypertrophy by targetting c-Jun expression.

This study investigated whether a low estimated glomerular filtration rate (eGFR) leads to a higher risk of stroke recurrence and a poor prognosis in hemorrhagic stroke patients. A total of 2000 stroke patients were recruited during 2000-2001 and prospectively followed up for a median of 4.5 years. The independent association of a low eGFR with stroke recurrence and poor prognosis was evaluated using Kaplan-Meier analysis and Cox regression models. Among the hemorrhagic stroke patients, the incidence rate of a low eGFR for the compound endpoints (stroke recurrence, myocardial infarction, and all-cause mortality) was greater than that of a normal eGFR (P=0.012). A similar result was observed for the incidence rate of recurrence and death caused by cardiovascular disease or stroke (Csdeath) (P=0.013, and P=0.001, respectively). After adjustment for age, sex, and other cardiovascular risk factors, a low eGFR was associated with a 2.93-fold increased risk of the compound endpoints (P=0.001, RR=2.93, 95% CI=1.58-5.43), 3.06-fold increased risk of recurrent stroke (P=0.003, RR=3.06, 95% CI=1.46-6.40), and 3.57-fold increased risk of Csdeath (P=0.005, RR=3.57, 95% CI=1.46-8.70) among hemorrhagic stroke patients. Among the hemorrhagic stroke patients, a low eGFR was a strong predictor of stroke recurrence and a poor prognosis.

Studies have shown inflammation is involved in the development of acute aortic dissection (AAD). The hypothesis that white blood cell count (WBCc) on admission may have an impact on the short- and long-term outcomes of type A AAD was tested in a large-scale, prospective observational cohort study. From 2008 to 2010, a total of 570 consecutive patients with type A AAD in Fuwai hospital were enrolled and were followed up. Baseline characteristics and WBCc on admission were collected. The primary outcomes were 30-day and long-term all-cause mortality. During a median of 1.89 years of follow-up, the 30-day and long-term all-cause mortality were 10.7% and 6.5%, respectively. Univariate Cox regression analysis identified admission WBCc as an independent predictor of 30-day mortality when considered as a continuous variable or as a categorical variable using the cutoff of 11.0 × 109 cells/L (all P 11.0 × 109 cells/L) remained an independent predictor of 30-day mortality of AAD (hazard ratio = 3.31, 95% confidence interval 1.38–7.93, P = 0.007). No impact of admission WBCc was observed on the long-term all-cause mortality. In conclusion, elevated admission WBCc may be valuable as a predictor of 30-day mortality, and may be useful in the risk stratification of type A AAD during hospitalization.

Background Aortic dissection is a life-threatening cardiovascular disease with high mortality. Little is known about comparisons of the clinical characteristics or the factors that influence the long-term prognosis of Chinese patients with aortic dissection with and without Marfan syndrome (MFS). Methods The authors studied the data of 246 patients with aortic dissection. The patients were hospitalised for aortic abnormalities from 2004 to 2008 in Fuwai Hospital. Medical charts were reviewed to obtain clinical data using a standardised data collection sheet. Results Of the 246 patients with acute aortic dissection, 56 had MFS. Compared with the non-MFS patients, those with MFS were considerably younger (mean±SD age 35.27±11.11 vs 54.11±11.96 years, p Conclusions These clinical results could be useful for rapid assessment of the treatment and prognosis of patients with aortic dissection.

The present study aims to test whether Lycium barbarum L. has anti-hypertensive effect through regulating expression of lncRNA sONE in a rat model of salt-sensitive hypertension. Nine weeks old borderline hypertensive rats (BHRs) were divided into 4 groups receiving high (8% NaCl), medium (0.25% NaCl, as control group), and low salt diet (0.015% NaCl) for 16 weeks, respectively, while the fourth group (high salt + L. barbarum group) fed with high salt diet for 12 weeks, then followed by 8% NaCl and L. barbarum treatment for 4 weeks. Body weight and blood pressure were recorded biweekly. Salt-sensitive hypertension was successfully induced by 12-week high salt diet in BHR model. Blood pressure was significantly increased in the model (P < 0.05), and L. barbarum treatment reversed the elevated blood pressure to normal level. Expression of lncRNA sONE was significantly reduced and eNOS expression level was dramatically improved in the hypertension model rats with the L. barbarum compared with that receiving high salt diet. Our results indicated that L. barbarum L. had anti-hypertensive effect and might lower blood pressure by suppressing the expression of lncRNA sONE in BHR model.

A four-generation pedigree of familial primary pulmonary hypertension (FPPH) with 14 alive members was collected. In the family, three of the 14 alive familial members were diagnosed as FPPH. Mutations in bone morphogenetic protein receptor-II (BMPR-II) gene were screened by using sequencing analysis. A C-to-T transition at position 1471 in exon 11 of the BMPR-II gene was identified, resulting in an Arg491Trp mutation. We confirmed segregation of the mutation within the family and excluded the presence of the mutations in a panel of 240 chromosomes from normal individuals. No mutations were found in BMPR-II gene in other 10 patients with sporadic primary pulmonary hypertension. The Arg491Trp mutation is located in the kinase domain and predicted to disturb the kinase activity of BMPR-II. Total 7 familial members died at age 8-45 years with various symptoms, indicating other genetic or environmental modifiers involved in the modification of the clinical phenotype.

Background Hypertrophic cardiomyopathy (HCM) secondary to mutations in genes encoding sarcomere proteins is most commonly inherited as an autosomal dominant trait. Since nearly 50% of HCM cases occur in the absence of a family history, a recessive inheritance pattern may be involved. Methods A pedigree was identified with suspected autosomal recessive transmission of HCM. The proband and his younger brother were diagnosed with HCM, and his older brother incurred sudden cardiac death at 23 years of age. However, other family members were all clinically normal. Twenty-six HCM-related genes were comprehensively screened for mutations in the proband with targeted second generation sequencing, and the identified mutation was confirmed with bi-directional Sanger sequencing in all family members. Results A novel missense mutation (c.1469G > T, p.Gly490Val) in exon 17 of MYBPC3 was identified. Two siblings with HCM were homozygous for this mutation, whereas other family members were either heterozygous or wild type. Clinical evaluation showed that both homozygotes manifested a typical HCM presentation, but none of others, including 5 adult heterozygous mutation carriers up to 71 years of age, had any clinical evidence of HCM. Conclusions These data suggest that the inheritance pattern of HCM may be more complex than previously thought. The absence of a family history of clinical HCM may be due to not only a de novo mutation, but also recessive mutations that failed to produce a clinical phenotype in heterozygous family members. Therefore, consideration of recessive mutations leading to HCM is essential for risk stratification and genetic counselling.

Objective This study was designed to assess the sex effect on clinical presentation and outcomes in patients with hypertrophic cardiomyopathy (HCM). Sex has been proved to play an important role in the clinical expression and prognosis of various cardiovascular diseases. Methods A total of 621 unrelated patients with HCM, without heart failure (460 males) were enrolled from 1999 to 2011. Results At baseline, female patients were older (49.6 ± 17.2 years vs. 46.7 ± 14.4 years, p = 0.033) at diagnosis, had greater frequency of left ventricular outflow tract obstruction (72/161, 44.7% vs. 149/460, 32.4%, p = 0.005) than male patients. During follow-up of 4 (2–7) years, survival analysis showed that the incidences of all-cause mortality, cardiovascular death and progression to chronic heart failure were greater in women than in men ( p = 0.031, 0.040 and 0.014, respectively). After adjustment for multiple factors that may confound survival and cardiac function, female sex remained an independent risk factor for all-cause mortality, cardiovascular death, and chronic heart failure [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.21–3.95, p = 0.010; HR 2.19, 95%CI 1.17–4.09, p = 0.014; HR 1.73, 95%CI 1.12–2.69, p = 0.014, respectively] in HCM patients. Subgroup analysis revealed that female sex as a risk factor was only identified in patients younger than 50 years old ( p = 0.011, 0.011 and 0.020, respectively), but not in more than 50 years old. Conclusions Our results suggest that female sex is an independent predictor of poor survival and heart failure in HCM patients. Further studies were required to determine whether female hormones modify the clinical expression and prognosis of HCM.