华倚虹

中国医学科学院阜外医院 心血管内科

Efficacy and Safety of 1-Hour Infusion of Recombinant Human Atrial Natriuretic Peptide in Patients With Acute Decompensated Heart Failure: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

The aim of the study was to evaluate the efficacy and safety of 1-h infusion of recombinant human atrial natriuretic peptide (rhANP) in combination with standard therapy in patients with acute decompensated heart failure (ADHF). This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients with ADHF were randomized to receive a 1-h infusion of either rhANP or placebo at a ratio of 3:1 in combination with standard therapy. The primary endpoint was dyspnea improvement (a decrease of at least 2 grades of dyspnea severity at 12 h from baseline). Reduction in pulmonary capillary wedge pressure (PCWP) 1 h after infusion was the co-primary endpoint for catheterized patients. Overall, 477 patients were randomized: 358 (93 catheterized) patients received rhANP and 118 (28 catheterized) received placebo. The percentage of patients with dyspnea improvement at 12 h was higher, although not statistically significant, in the rhANP group than in the placebo group (32.0% vs 25.4%, odds ratio=1.382, 95% confidence interval [CI]: 0.863-2.212, P = 0.17). Reduction in PCWP at 1 h was significantly greater in patients treated with rhANP than in patients treated with placebo (-7.74 ± 5.95 vs -1.82 ± 4.47 mm Hg, P < 0.001). The frequencies of adverse events and renal impairment within 3 days of treatment were similar between the 2 groups. Mortality at 1 month was 3.1% in the rhANP group vs 2.5% in the placebo group (hazard ratio = 1.21, 95% CI: 0.34-4.26; P > 0.99). 1-h rhANP infusion appears to result in prompt, transient hemodynamic improvement with a small, nonsignificant, effect on dyspnea in ADHF patients receiving standard therapy. The safety of 1-h infusion of rhANP seems to be acceptable. (WHO International Clinical Trials Registry Platform [ICTRP] number, ChiCTR-IPR-14005719.).

1.6
4区

Medicine 2016

Profound thrombocytopenia induced by clopidogrel with a prior history of long-term safe administration.

Clopidogrel has shown an excellent safety, tolerability and efficacy ever since its marketing. However, here we report a rare case with profound thrombocytopenia following clopidogrel administration previously safely exposed to this same drug. This reminds us that thrombocytopenia might be induced by clopidogrel even with a prior, safe history of long-term administration.

1.9

World journal of cardiology 2010

Coronary intervention in patients>or=75 years old with ST-elevation myocardial infarction: in-hospital and 6-month clinical outcomes.

BACKGROUND:ST-segment elevation myocardial infarction (STEMI) in elderly patients presents specific clinical characteristics. The study on percutaneous coronary intervention (PCI) in elderly patients (>or=75 years) with STEMI, however, has less been performed.METHODS:In the present study, 522 consecutive STEMI patients undergoing PCI within 12 hours from symptom onset were investigated, and clinical characteristics and in-hospital and 6-month outcomes of 66 elderly patients (>or=75 years, group A) were compared to those of 456 younger patients (<75 years, group B).RESULTS:Compared to younger patients, elderly ones had more females (42.4% vs. 17.8%, P<0.005), a history of cerebral vascular events (7.6% vs. 0.9%, P<0.05), higher serum creatinine level ((96.48+/-31.65) mmol/L vs. (84.87+/-19.81) mmol/L, P<0.005) and fewer smokers (28.8% vs. 45.4%, P<0.05). The elderly ones had worse Killip class (Killip I class: 69.7% vs. 85.7%, P<0.05), less drug-eluting stent implantation and lower rates of TIMI flow 3 following PCI (33.3% vs. 47.1%, and 84.8% vs. 94.7%, P<0.05 respectively). Additionally, both in-hospital mortality and myocardial infarction rate were found to be higher in elderly patients (16.7% vs. 1.5%, and 7.6% vs. 2.6%, P<0.05 respectively), which were also observed until 6-month follow-up (9.1% vs. 0, and 6.1% vs. 0, P<0.05 respectively). In multivariable Cox regression analysis, serum creatinine level, history of hypertension, left anterior descending coronary artery as infarct-related artery and Killip class were independent predictors of 6-month overall death in elderly patients.CONCLUSIONS:The clinical characteristics of elderly patients with STEMI after PCI are different from those of younger patients. Although PCI in this population is with a low rate of PCI failure, it is still associated with a worse outcome.

6.1
3区

Chinese medical journal 2010

Polymorphisms of MMP-2 gene are associated with systolic heart failure prognosis.

BACKGROUND:MMP-2 is a proteolytic enzyme involved in myocardial remodeling that occurs in congestive heart failure (HF). We hypothesized MMP-2 genetic variations could influence the prognosis of systolic HF.METHODS:To test our hypothesis, we performed a follow-up study of 605 patients with systolic HF. Three single nucleotide polymorphisms (SNPs) of MMP-2 (rs243864, rs243866, rs17859821) were analyzed by restriction fragment length polymorphism (RFLP) methods.RESULTS:Totally 526 patients (86.9%) were followed up. At follow up (median 24 months), 116 patients (22.1%) died, 102 patients (19.4%) were readmitted because of HF. One, two, three and four year survival rate was 86.9%, 81%, 77.9% and 77.9%. MMP-2 rs17859821 A allele carriers had lower all cause death rate, cardiac death rate and MACE rate than did GG genotype carriers (OR = 0.655, 0.580, 0.705; P = 0.030, 0.008, 0.011). After adjustment for age, bundle branch block, LVEF and NYHA grade by using cox regression analysis, MMP-2 A allele carriers had lower cardiac death rate and MACE rate than did GG genotype carriers (OR = 0.643 and 0.746; P < 0.05). However, the genotypes had no association with plasma levels of proMMP-2. Haplotype analysis had confirmed the above results. MMP-2 rs243866, rs243864 had no association with systolic HF prognosis.CONCLUSION:The findings of the present study suggest that MMP-2 rs17859821 A allele was associated with better prognosis of systolic HF in the northern Han Chinese population.

5.0
3区
第一作者

Clinica chimica acta; international journal of clinical chemistry 2009

Polymorphisms of MMP-2 gene are associated with systolic heart failure risk in Han Chinese.

BACKGROUND:Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes responsible for protein degradation. MMP-2 has been demonstrated to play a pivotal role in myocardial remodeling process that occurs in congestive heart failure (HF). We hypothesized that MMP-2 genetic variations could be associated with systolic HF risk.METHODS:To test the association of single nucleotide polymorphisms of MMP-2 with systolic HF risk, we performed a hospital-based, case-control study of 605 patients with systolic HF and 689 controls without HF. Three single nucleotide polymorphisms of MMP-2 (rs243864, rs243866, and rs17859821) were genotyped by restriction fragment length polymorphism methods.RESULTS:The genotype frequencies of MMP-2 rs243866 AA and AG in the control group were significantly higher than that in the case group (24.7% versus 17.9%, P < 0.01). Compared with the GG homozygotes, MMP-2 rs243866 A allele carriers had a significantly lower risk of systolic HF (adjusted OR 0.69, 95% CI 0.49-0.98; P = 0.035). Haplotype analysis indicated the haplotype GGG (rs243864-rs17859821-rs243866) was associated with higher risk of systolic HF (adjusted OR 2.05, 95% CI 1.08-3.89; P = 0.028).CONCLUSION:The findings of the current study suggest that MMP-2 rs243866 A allele was associated with lower risk of systolic HF in Han Chinese.

3.1
4区
第一作者

The American journal of the medical sciences 2009

Haplotype analysis of the stromelysin-1 (MMP3) and gelatinase B (MMP9) genes in relation to coronary heart disease.

The functional genetic polymorphisms present in the promoters of stromelysin-1 (MMP3) and gelatinase B (MMP9) have been shown to be associated with angiographically measured atherosclerosis; however, haplotype analysis of the genetic polymorphisms occurring in the promoters and coding regions of MMP3 and MMP9 has been infrequently performed in the past. The aim of this study was to analyze the occurrence of the -1612 5A/6A, -376C/G, and Glu45Lys polymorphisms of MMP3 and the -1562C/T and R279Q polymorphisms of MMP9 and their relation to the risk of coronary heart disease (CHD; stenosis >/=50% of the diameter in at least one major coronary artery) in a Chinese Han population. The present study involved 1373 patients with CHD and 695 healthy controls. The Glu45Lys polymorphism of MMP3 was significantly associated with an increased risk of CHD. Compared with the 45Glu homozygotes, 45Lys allele carriers had a significantly elevated risk of CHD (adjusted OR = 1.50; 95%CI 1.11-2.03; p= 0.008). Moreover, haplotype analysis identified both the 6A-C-Lys (-1612 6A, -376C, 45Lys) haplotype and the 6A-G-Lys (-1612 6A,-376G, 45Lys) haplotype of MMP3 as associated with an increased risk of CHD. Our study suggests that common genetic variations in the MMP3 gene may affect the risk of CHD in the Chinese population.

1.9
4区

Annals of human genetics 2009

[Body mass index and prognosis in patients with systolic heart failure].

OBJECTIVE:In individuals without cardiovascular disease, elevated body mass index (BMI) is associated with an increased risk of death. However, in patients with certain chronic diseases, including heart failure, low BMI has been associated with increased mortality. We investigated the association between BMI and prognosis in patients with systolic HF.METHOD:Follow-up was made on 540 patients (mean age 58.53 years, 84.2% men) with systolic HF (LVEF < or = 45%) and association between BMI and adverse cardiac events was analyzed.RESULTS:During a median follow-up of 24 months, 92 patients died including 87 cases of cardiac death and 92 patients were rehospitalized. Compared with patients with BMI higher than 28.0 kg/m(2), patients in lower BMI categories (BMI < or = 18.5 kg/m(2) and > or = 18.5 kg/m(2) < 24.0 kg/m(2)) had a graded increase in the all cause death rate [5.44 (1.78 - 16.66), 4.30 (1.71 - 10.82)], cardiac death rate [OR(95%CI): 5.42 (1.77 - 16.59), 4.00 (1.59 - 10.10)], HF death rate [8.94 (2.37 - 33.74), 4.97 (1.52 - 16.20)] and MACE rate [2.10 (1.09 - 4.07), 1.79 (1.14 - 2.82)]. After adjustment for age, gender, LVEF and NYHA grade using cox regression analysis, BMI categories still significantly associated with all cause death rate (OR = 0.77, P < 0.05), cardiac death rate (OR = 0.78, P < 0.05) and HF death rate (OR = 0.79, P < 0.05).CONCLUSION:In patients with systolic heart failure, lower BMI was an independent predictor of increased all cause death rate, cardiac death rate and HF death rate.

第一作者

Zhonghua xin xue guan bing za zhi 2009

[Association between single nucleotide polymorphisms of matrix metalloproteinase-3 gene and the severity of coronary atherosclerosis in patients with coronary artery disease].

OBJECTIVE:To investigate the association between the severity of coronary arteries in patients with coronary artery disease and the single nucleotide polymorphisms of MMP-3 gene.METHODS:One thousand and three hundred seventy-one patients with coronary artery disease (CAD) diagnosed by coronary angiography and six hundred and ninety-five healthy controls without CAD were enrolled in this study. The SNPs of -1612 5A/6A, -376C/G, Glu45Lys of MMP-3 were genotyped by restriction fragment length polymorphism analysis (RFLP) in all subjects. Univariate analysis was applied to measure the association of the single nucleotide polymorphisms with the severity of coronary arteries.RESULTS:The minor allele frequency of -1612 5A/6A was 0.189, 0.185, 0.183 and 0.152 (P < 0.05 vs. non-CAD control and single stenosis), the minor allele frequency of -376C/G was 0.311, 0.329, 0.326 and 0.325, and the minor allele frequency of Glu45Lys was 0.367, 0.423, 0.417 and 0.405 in non-CAD control, CAD patients with single, two and three vessels stenosis, respectively. 5A allele frequency is significant lower in the group with three vessels stenosis than in non-CAD control and CAD patients with single vessel stenosis (OR = 0.74, P = 0.04). The 5A/5A and 5A/6A genotypes frequency is significant lower in the group with three vessels stenosis than in the non-CAD group and CAD patients with single vessel stenosis (OR = 0.74, P = 0.04).CONCLUSIONS:The single nucleotide polymorphism of -1612 5A/6A of MMP-3 gene may be associated with the severity of coronary atherosclerosis in the Chinese Han patients with coronary artery disease, and the 5A allele might therefore, play a protective role on the progression of coronary atherosclerosis.

Zhonghua xin xue guan bing za zhi 2008