Increased serum nardilysin is associated with worse long-term outcome of ST-elevation myocardial infarction.

OBJECTIVE: Nardilysin (N-arginine dibasic convertase, NRDC) is a kind of metalloendopeptidase associated with several inflammatory diseases. NRDC is reported to be eligible for early detection of acute coronary syndrome. However, the availability and effectiveness of NRDC in predicting the prognosis of patients with ST-elevation myocardial infarction has never been investigated. PATIENTS AND METHODS: From January 2010 to January 2012, the prospective observational cohort study enrolled a total of 396 STEMI patients, who were sampled with blood within 24 hours after admission. A long-term follow-up was conducted to record the primary endpoint of all-cause mortality, as well as secondary endpoint of myocardial infarction, stroke, emergent revascularization and admission due to heart failure. Hazard ratio (HR) related to the serum NRDC level was estimated by Cox regression model. RESULTS: The enrolled patients completed the follow-up with an average of 4.6 ± 0.5 years, of whom 24 patients died (primary endpoint, 6.1%), while 89 episodes of secondary endpoints occurred (22.5%). Patients with highest quartile level of NRDC (Q4 level, > 2041 pg/ml) were subjected to higher risk of all-cause death [HR 3.973, 95% CI (1.648-9.575), p = 0.002] compared to patients with lower three quartiles level of NRDC (Q1 to Q3, < 2041 pg/ml), while there was no difference in adverse events (p = 0.403). CONCLUSIONS: The increased serum NRDC level at admission is associated with a higher risk of all-cause mortality for ST-elevation myocardial infarction patients.

Ang II receptor expression and effect of Ang II receptor blockade in thyrotoxic rat myocardium.

AIM: To investigate the relationship between expression of the angiotensin II (Ang II) receptors and thyroid hormones in the myocardium of rats with thyrotoxicosis. MATERIALS AND METHODS: Forty-four adult male Sprague-Dawley rats were divided into four groups: control group (saline), losartan group (10 mg/kg), thyrotoxicosis group (0.5 mg/kg L-thyroid hormone sodium) and thyrotoxicosis-plus-losartan group (0.5 mg/kg L-thyroid hormone plus 10 mg/kg losartan) and treated intragastrically daily for four weeks. The heart weight (HW), body weight (BW) and HW/BW ratios were determined. The Ang II protein contents in cardiac homogenates and serum were determined by ELISA. The serum concentrations of levothyroxine (T3), trilodothyronine (T4) and thyroid stimulating hormone (TSH) were measured by radioimmunoassay. The expression of angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) were quantified by real-time PCR and Western blotting. RESULTS: The thyrotoxicosis group had an increased BW/HW and higher cardiac AT1R and AT2R expression compared to controls. AT1R and AT2R expressions significantly reduced in the thyrotoxicosis-plus-losartan group, compared to the thyrotoxicosis group. CONCLUSIONS: Thyroid hormone upregulated cardiac AT1R and AT2R, leading to cardiac remodeling, which was reversed by losartan. Cardiac damage in thyrotoxic rats may be related to upregulation of the Ang II receptors.

Fish oil supplementation improves large arterial elasticity in overweight hypertensive patients.

OBJECTIVES: To observe the effect of fish oil supplementation on arterial elasticity and blood pressure (BP) in overweight hypertensive patients. SUBJECTS AND METHODS: This was a double-blind, randomized and placebo-controlled clinical study, in which 52 overweight hypertensive patients from a community were selected and randomly allocated to two groups (26 in the fish oil group (3 g day(-1), fish oil capsules) and 26 in the placebo group (only capsules). All the subjects were follow-up for 8 weeks. The arterial elasticity was determined by CVProfilor DO-2020 and expressed as elasticity indexes (C(1)-large artery and C(2)-small artery). During the follow-up, totally nine cases were dropped out (three cases from the fish oil group and six cases from the placebo group). RESULTS: After 8 weeks follow-up, the large artery elasticity in the fish oil group, compared with its baseline, was significantly improved (C(1): 15.5+/-1.5 vs 12.8+/-3.7 ml mm Hg(-1) x 10), whereas no effects were found in the placebo group (C(1): 13.0+/-3.4 vs 13.4+/-3.8 ml mm Hg(-1) x 10), P=0.027, RM-ANOVA across the two groups. The small artery elasticity (C(2)), BP and pulse pressure were not found any changes, either in the fish oil group or in the placebo group. At same time, the serum soluble vascular cell adhesion molecule-1(sVCAM-1) and leptin levels, the lipid profile and insulin sensitivity index (ISI) as well, did not show significant differences between two groups. CONCLUSIONS: Fish oil supplementation certainly would improve large arterial elasticity but no effect on BP in overweight hypertensive patients. Further study is needed to confirm the benefits of fish oil supplementation on age-related increases in arterial stiffness.

A malignant phenotype of hypertrophic cardiomyopathy caused by Arg719Gln cardiac beta-myosin heavy-chain mutation in a Chinese family.

Mutations of the cardiac beta-myosin heavy-chain (beta-MHC) gene cause hypertrophic cardiomyopathy (HCM). Recent genotype-phenotype correlation studies have shown that mutations carry prognostic significance. We studied five unrelated Chinese families with hypertrophic cardiomyopathy. Exons 3-27 and 40 of the beta-MHC gene were screened with both the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method and the cycle sequencing of the PCR products. A previously reported heterozygous mutation Arg719Gln (arginine-->glutamine in codon 719) in exon 19 was found in one family. The proband is a 30-year-old female diagnosed at age of 25 years when she presented with symptoms of chest pain, palpitations, and frequent incidents of dizziness and syncope. A two-dimensional echocardiogram showed moderate asymmetrical septal hypertrophy with left atrial enlargement. There was no obstruction of the left ventricular outflow tract (LVOT). The patient also developed atrial fibrillation. The proband's mother and one of her sisters had similar clinical manifestations and both died suddenly at the age of 38 years. In addition, two silent nucleotide substitutions (ACT63ACC, TTT244TTC) in the cardiac beta-MHC gene were identified in the other four families. These synonymous mutations did not cosegregate with the disease in the families and they were also present in the 60 healthy and age-matched control subjects. Of the five families studied, we did not find any missense mutation in the remaining four families. The missense mutation Arg719Gln found in the Chinese family is associated with a malignant phenotype of severe clinical symptoms and poor survival prognosis. This mutation also causes atrial enlargement and atrial fibrillation. Our study provides further evidence that the mutation, which alters the charge of the myosin heavy chain, is associated with a serious clinical outcome.

Study of autoantibodies against the adenine nucleotide translocator in idiopathic dilated cardiomyopathy.

The frequency, dynamical change and effects of autoantibodies against the adenine nucleotide translocator (ANT) in idiopathic dilated cardiomyopathy (IDC) were studied. Sera of 16 patients with IDC showed significant binding capacity to the ANT protein (33.3%). Anti-ANT antibody titre was gradually tapered in approx. 2-3 months duration. However, anti-ANT antibody can inhibit the ADP/ATP exchange of heart mitochondria and be organ-specific. Short-term (6 weeks) treatment of 15 anti-ANT antibody-positive IDC patients with prednisone was of beneficial effect. Our results show that autoimmunity to the ANT can contribute to the pathogenesis and/or progression of IDC to a certain extent. But we must pay more attention to the fact that anti-ANT antibody characteristically exists short-term. Therefore, a short-term immunosuppressive treatment should be given to those IDC patients whose anti-ANT antibody is positive.

Intra-cellular electrolyte changes and levels of endogenous digoxin-like substance within the plasma in patients with congestive heart failure.

In this study, the lymphocytes and erythrocytes from peripheral venous blood were used as the study model from which were measured the cellular contents of potassium, sodium, calcium and magnesium in 50 patients with chronic congestive heart failure and 39 control patients. Levels of endogenous digoxin-like substance in the plasma and activities of Na/K ATPase in red cell membrane wer monitored simultaneously. In the patients with heart failure, the intracellular contents of potassium and magnesium were decreased while those of sodium and calcium were increased significantly. The levels of endogenous digoxin-like substance were much higher in the plasma than those either in healthy controls or in patients with heart disease but without congestive failure (273.7 +/- 35.5 vs 23.3 +/- 2.2 and vs 32.9 +/- 3.6 pg/ml, respectively, P less than 0.001 for both). The activities of Na/K-ATPase were much lower in the patients with heart failure than in the controls. Values for intracellular electrolytes were significantly correlated with the rising levels of digoxin-like substance in the plasma. Non-digitalis inotropic therapy was associated with the recovery of these alterations of heart function, with the levels of the digoxin-like substance decreasing and activity of Na/K-ATPase going up. We conclude that endogenous digoxin-like substance might play a role in the imbalance of intra-cellular electrolytes seen in patients with congestive heart failure. Digoxin may exacerbate the loss of intracellular potassium.