Efficacy and safety of sympathetic mapping and ablation of renal nerves for the treatment of hypertension (SMART): 6-month follow-up of a randomised, controlled trial.

Background: Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140 mmHg). Methods: We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) × (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18-65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150 mmHg and ≤180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130 mmHg or daytime SBP ≥135 mmHg or nighttime SBP ≥120 mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45 mL/min/1.73 m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings: Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150 mmHg and ≤180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin -10% (2.69%; 95% CI -4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (-3.25; 95% CI -5.56, -0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p < 0.001 from Baseline; p > 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation: The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP <140 mmHg, with only approximately four targeted ablations per renal main artery, much lower than in previous trials. Funding: SyMap Medical (Suzhou), LTD, Suzhou, China.

Association Between Heart Rate and Major Adverse Cardiovascular Events Among 9,991 Hypertentive Patients: A Multicenter Retrospective Follow-Up Study.

Objective: To assess the effect of heart rate at baseline on major adverse cardiovascular events (MACEs) among hypertensive patients in China. Methods: A multicenter retrospective study was conducted with a 24 month follow-up period. A total of 10,031 hypertensive patients treated with standard antihypertensive drugs were grouped according to their heart rate before treatment: <65 beats per min (bpm), 65-69 bpm, 70-74 bpm, 75-79 bpm, and ≥80 bpm. The occurrence of any of MACEs was as the endpoint event during the 24 month follow-up period. The effect of heart rate at baseline on MACEs was analyzed using univate and multivariable Cox proportional regression analyses, with hazard ratios (HRs) and 95% confidence intervals (CIs). The restricted cubic spline (RCS) model was used to fit the Cox proportional harzard model with 5 knots at the 5th, 25th, 50th, 75th, and 95th percentiles of heart rate. Results: Totally 9,991 patients were finally enrolled with the mean systolic pressure (SBP)/diastolic pressure (DBP) of 130.59 ± 7.13/77.66 ± 5.99 mmHg at 24 month follow-up. The incidence of MACEs was 4.80% (n = 480). After adjustment for age, gender, baseline blood pressure, alcohol drinking, smoking, hyperlipidemia, diabetes, coronary heart disease, cerebrovascular disease and antihypertensive drug use, patients with heart rate <65 bpm (HR = 1.450, 95% CI: 1.098-1.915) and ≥80 bpm (HR = 1.391, 95% CI: 1.056-11.832) showed 0.45 fold and 0.391 fold increases of MACE risks, compared with patients with heart rate of 70-74 bpm. Furthermore, MACE risks were increased by 86.0% and 65.4% in men, and 59.3% and 69.0% in elderly patients aged ≥65 years at heart rate <65 bpm or ≥80 bpm, respectively. We also found a non-liner U-shaped correlation between heart rate and the occurrence of MACEs. Conclusions: Heart rate might be an independent risk factor for MACEs in hypertensive patients. An appropriate range of heart rate control may offer guidance to hypertension treatment.

Endogenous hydrogen sulfide and ERK1/2-STAT3 signaling pathway may participate in the association between homocysteine and hypertension.

BACKGROUND: Homocysteine (Hcy) is a risk factor for hypertension, although the mechanisms are poorly understood. METHODS: We first explored the relationship between Hcy levels and blood pressure (BP) by analyzing the clinical data of primary hypertensive patients admitted to our hospital. Secondly, we explored a rat model to study the effect of Hcy on blood pressure and the role of H2S. An hyperhomocysteinemia (HHcy) rat model was induced to explore the effect of Hcy on blood pressure and the possible mechanism. We carried out tissue histology, extraction and examination of RNA and protein. Finally, we conducted cell experiments to determine a likely mechanism through renin-angiotensin-aldosterone system (RAAS) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. RESULTS: In primary hypertensive inpatients with HHcy, blood pressure was significantly higher as compared with inpatient counterparts lacking HHcy. In the rat model, blood pressure of the Wistar rats was significantly increased with increases in serum Hcy levels and decreased after folate treatment. Angiotensin converting enzyme 1 (ACE1) expression in the Wistar Hcy group was enhanced comparing to controls, but was decreased in the Wistar folate group. Angiotensin II receptor type 1 (AGTR1) levels in the kidney tissue increased in the Wistar folate group. Both serum H2S and kidney cystathionine γ-lyase decreased with elevated levels of serum Hcy. In vitro, increased concentrations and treatment times for Hcy were associated with increased expression of collagen type 1 and AGTR1. This dose and time dependent response was also observed for p-STAT3 and p-ERK1/2 expression. CONCLUSION: Endogenous H2S might mediate the process of altered blood pressure in response to changes in serum Hcy levels, in a process that is partly dependent on activated RAAS and ERK1/2-STAT3 signaling pathway.

Homocysteine and all-cause mortality in hypertensive adults without pre-existing cardiovascular conditions: Effect modification by MTHFR C677T polymorphism.

BACKGROUND: Previous studies support an association between elevated total homocysteine (tHcy) levels and increased all-cause mortality. However, few prospective studies have examined this association in hypertensive patients, and/or tested any effect modification by the methylene tetrahydrofolate reductase (MTHFR) C677T genotype. METHODS: This was a post hoc analysis of the China Stroke Primary Prevention Trial. Serum tHcy and folate were measured at baseline. Individual MTHFR C677T genotype (CC, CT, and TT) was determined. Evidence for death included death certificates or home visits. Cumulative hazards of all-cause mortality by tHcy quartiles were estimated using the Kaplan-Meier method, and group differences were compared by log-rank tests. Hazard ratios (HRs) and 95% confidence intervals were estimated by Cox proportional-hazard regression models, adjusting for age, sex, baseline folate, vitamin B12, blood pressure, body mass index, smoking and alcohol drinking status, study center, total cholesterol, triglycerides, high-density lipoprotein cholesterol, fasting glucose, creatinine, and treatment group. Potential effect modification by the MTHFR genotype on the relationship between tHcy and all-cause mortality was tested. RESULTS: The analyses included 20,424 hypertensive patients (41% males) without a history of myocardial infarction or stroke. Baseline mean age (SD) was 60 ±â€Š7.5 years and mean (SD) serum tHcy was 14.5 ±â€Š8.4 µmol/L. After a mean follow-up period of 4.5 years, there were 612 (3%) all-cause deaths. Kaplan-Meier survival curves revealed a graded relationship between tHcy quartiles and all-cause mortality. The HRs, using the lowest quartile as the reference, were 1.2, 1.2, and 1.5 in Q2, Q3, and Q4, respectively. A linear trend test, using natural log-transformed tHcy, resulted in an HR of 1.5 (95% confidence interval 1.2-1.9, P < .001) after adjustment for lifestyle and health-related variables. Whereas the MTHFR genotype alone had little effect on mortality, it significantly modified the tHcy-mortality association, which was much stronger in the CC/CT genotype than in the TT genotype (P for interaction < 0.05). CONCLUSIONS: Among Chinese hypertensive patients without cardiovascular comorbidities, elevated tHcy was a significant risk marker for death from all causes, and the association was subject to effect modification by MTHFR genotypes. If confirmed that tHcy and MTHFR genotypes may serve as useful biomarkers for mortality risk assessment and targeted intervention.

SLCO1B1 Variants and Angiotensin Converting Enzyme Inhibitor (Enalapril)-Induced Cough: a Pharmacogenetic Study.

Clinical observations suggest that incidence of cough in Chinese taking angiotensin converting enzyme inhibitors is much higher than other racial groups. Cough is the most common adverse reaction of enalapril. We investigate whether SLCO1B1 genetic polymorphisms, previously reported to be important determinants of inter-individual variability in enalapril pharmacokinetics, are associated with the enalapril-induced cough. A cohort of 450 patients with essential hypertension taking 10 mg enalapril maleate were genotyped for the functional SLCO1B1 variants, 388A > G (Asn130Asp, rs2306283) and 521T > C (Val174Ala, rs4149056). The primary endpoint was cough, which was recorded when participants were bothered by cough and respiratory symptoms during enalapril treatment without an identifiable cause. SLCO1B1 521C allele conferred a 2-fold relative risk of enalapril-induced cough (95% confidence interval [CI] = 1.34-3.04, P = 6.2 × 10(-4)), and haplotype analysis suggested the relative risk of cough was 6.94-fold (95% CI = 1.30-37.07, P = 0.020) in SLCO1B1*15/*15 carriers. Furthermore, there was strong evidence for a gene-dose effect (percent with cough in those with 0, 1, or 2 copy of the 521C allele: 28.2%, 42.5%, and 71.4%, trend P = 6.6 × 10(-4)). Our study highlights, for the first time, SLCO1B1 variants are strongly associated with an increased risk of enalapril-induced cough. The findings will be useful to provide pharmacogenetic markers for enalapril treatment.

Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: a randomized, double-blind, placebo-controlled study.

LCZ696 (Japanese adopted name: sucabitril valsartan sodium hydrate), a first-in-class angiotensin receptor neprilysin inhibitor, concomitantly inhibits neprilysin and blocks angiotensin type 1 receptor. This randomized, double-blind, placebo-controlled study, the first in Asia for this drug, evaluated the dose-related efficacy and safety of LCZ696 in patients with hypertension using 24-hour ambulatory blood pressure (BP) monitoring. Asian patients aged ≥18 years (n=389) with hypertension were randomized to receive LCZ696 100 mg (n=100), 200 mg (n=101), 400 mg (n=96), or placebo (n=92) for 8 weeks. The primary end point was mean difference across the 3 single-dose pairwise comparisons of LCZ696 versus placebo in clinic diastolic BP after 8-week treatment. Key secondary efficacy variables included changes in clinic systolic BP and pulse pressure and changes in 24-hour, daytime, and nighttime ambulatory BPs and pulse pressure. Safety assessments included recording all adverse events and serious adverse events. A total of 362 patients completed the study. Reductions in clinic systolic BP, diastolic BP (P<0.0001), and pulse pressure (P<0.001) were significantly greater with all doses of LCZ696 than with placebo. There were also significant reductions in 24-hour, daytime, and nighttime ambulatory systolic BP, diastolic BP, and pulse pressure for all doses of LCZ696 compared with placebo (P<0.0001). LCZ696 was well tolerated, and no cases of angioedema were reported. In conclusion, LCZ696 is effective for the treatment of hypertension in Asian population and, in general, is safe and well tolerated. Clinical Trial Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01193101.

Cell cycle regulator geminin is dispensable for the proliferation of vascular smooth muscle cells.

The proliferation of vascular smooth muscle cells (VSMCs) plays a major role in the pathogenesis of many cardiovascular diseases. Geminin regulates DNA replication and cell cycle progression and plays a key role in the proliferation of cancer cells. We therefore hypothesized that geminin regulates the proliferation of VSMCs. The present study demonstrates that the level of geminin expression was low in quiescent VSMCs (approximately 90% and 10% of cells in the G1 and in S/G2/M phases of the cell cycle, respectively), increased as more cells entered in S/G2/M, and then decreased as cells exited S/G2/M. Further, angiotensin II and norepinephrine stimulated expression of geminin in VSMCs. However, the DNA content, nuclear morphology, percentage of cells at different stages of the cell cycle, and rate of proliferation of VSMCs from which geminin was either depleted or overexpressed were all similar. These findings indicate geminin functions differently in VSMCs than it does in cancer cell lines and that it may provide a target for treating cancers without affecting normal cells.

Folic acid supplementation and cancer risk: a meta-analysis of randomized controlled trials.

There are growing data and a continuing controversy over the effect of folic acid supplementation on cancer risk. We conducted a meta-analysis based on up-to-date published relevant randomized trials to further examine this issue. Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of cancer using a random-effects model. Overall, folic acid supplementation had no significant effect on total cancer incidence (13 trials, n = 49,406, RR = 1.05; 95% CI: 0.99-1.11, p = 0.13), colorectal cancer (seven trials, n = 33,824, 1.01; 0.82-1.23, p = 0.95), other gastrointestinal cancer (two trials, n = 20,228, 1.00; 0.75-1.33, p = 0.99), prostate cancer (five trials, n = 27,065, 1.17; 0.84-1.62, p = 0.35), other genitourinary cancer (two trials, n = 20,228, 0.97; 0.75-1.27, p = 0.84), lung cancer (five trials, n = 31,864, 1.00; 0.84-1.21, p = 0.97), breast cancer (four trials, n = 19,800, 0.82; 0.63-1.07, p = 0.15), hematological malignancy (three trials, n = 25,670, 0.87; 0.64-1.17, p = 0.35) and total cancer mortality (six trials, n = 31,930, 1.02; 0.90-1.15, p = 0.81). However, a significantly reduced risk was observed for melanoma (three trials, n = 19,128, 0.47; 0.23-0.94, p = 0.03). Furthermore, higher total cancer incidence risk was observed among those trials with a higher percent use of lipid-lowering drugs (>60%, 1.10; 1.00-1.20, p = 0.04), or with lower percent baseline hypertension (≤70%, 1.08; 1.00-1.16, p = 0.057).Consistently, meta-regression analyses suggested that the similar trend between percent use of lipid-lowering drugs (p = 0.084) or percent baseline hypertension (p = 0.056) and log-RR for total cancer incidence associated with folic acid supplementation. Our findings indicate that folic acid supplementation has no significant effect on total cancer incidence, colorectal cancer, prostate cancer, lung cancer, breast cancer or hematological malignancy, but reduces the risk of melanoma.

Effects and cost-effectiveness of a guideline-oriented primary healthcare hypertension management program in Beijing, China: results from a 1-year controlled trial.

Hypertension control rates are unacceptably low in China. The present study demonstrates if a customized, guideline-oriented training program can cost-effectively improve hypertension management in primary healthcare. Four typical community health centers in Beijing were selected and randomized to intervention or control (one urban and one rural each). A sample of 140 patients with hypertension and blood pressure uncontrolled was recruited from each center. Primary healthcare providers in intervention centers provided management to the recruited patients for 1 year after receiving training with customized hypertension management guidelines, and primary healthcare providers in control provided with usual care. Intention-to-treat analysis showed that hypertension control (systolic blood pressure (SBP) <140 mm Hg and diastolic blood pressure (DBP) <90 mm Hg)) rate was significantly higher in interventions than controls at month 3 (42.1% vs. 34.3% in urban and 30.7% vs. 10.0% in rural centers) and the trend increased to month 12 (70.7% vs. 40.0% in urban and 72.9% vs. 27.9% in rural); P-values by logistic mixed model were all <0.001 for both urban and rural after adjustment for baseline multiple variables including blood pressure. Mean reductions of SBP and DBP were significantly larger in interventions. The intervention was cost-saving, with an average incremental cost-saving of US$ 20.3 per patient in urban sites and $ 7.0 per patient in rural sites. Corresponding results from per-protocol analysis were very similar. The customized, guideline-oriented hypertension management program in primary healthcare in China effectively improved blood pressure control and was cost-saving.

Prevalence of hyperhomocysteinaemia and its major determinants in rural Chinese hypertensive patients aged 45-75 years.

We aimed to investigate the prevalence of hyperhomocysteinaemia (total plasma homocysteine (tHcy) ≥ 10 µmol/l) and its major determinants in rural Chinese hypertensive patients. A cross-sectional investigation was carried out in Lianyungang of Jiangsu province, China. This analysis included 13 946 hypertensive adults. The prevalence of hyperhomocysteinaemia was 51.6 % (42.7 % in women and 65.6 % in men). The OR of hyperhomocysteinaemia were 1.52 (95 % CI 1.39, 1.67) and 2.32 (95 % CI 2.07, 2.61) for participants aged 55-65 and 65-75 v. 45-55 years; 1.27 (95 % CI 1.18, 1.37) for participants with a BMI ≥ 25 v. < 25 kg/m²; 1.14 (95 % CI 1.06, 1.23) for participants with v. without antihypertensive treatment; 1.09 (95 % CI 1.00, 1.18) for residents inland v. coastal; 0.89 (95 % CI 0.82, 0.97) and 0.83 (95 % CI 0.74, 0.92) for participants with moderate and high v. low physical activity levels; 1.54 (95 % CI 1.41, 1.68) and 2.47 (95 % CI 2.17, 2.81) for participants with a glomerular filtration rate 60-90 and < 60 v. ≥ 90 ml/min per 1.73 m²; and 1.20 (95 % CI 1.07, 1.35) and 3.81 (95 % CI 3.33, 4.36) for participants with CT and TT v. CC genotype at methylenetetrahydrofolate reductase 677C>T polymorphism, respectively. Furthermore, higher tHcy concentrations were observed in smokers of both sexes (men: geometric mean 12.1 (interquartile range (IQR) 9.2-14.5) v. 11.9 (IQR 9.-14.) µmol/l, P= 0.005; women: geometric mean 10·3 (IQR 8.3-13.0) v. 9.6 (IQR 7.8-11.6) µmol/l, P= 0.010), and only in males with hypertension grade 3 (v. grade 1 or controlled blood pressure) (geometric mean 12.1 (IQR 9.2-14.4) v. 11.7 (IQR 9.2-14.0), P= 0.016) and in male non-drinkers (yes v. no) (geometric mean 12.3 (IQR 9.4-14.8) v. 11.7 (IQR 9.1-13.9), P= 0.014). In conclusion, there was a high prevalence of hyperhomocysteinaemia in Chinese hypertensive adults, particularly in the inlanders, who may benefit greatly from tHcy-lowering strategies, such as folic acid supplementation and lifestyle change.

Efficacy and tolerability of a single-pill combination of amlodipine/valsartan in Asian hypertensive patients not adequately controlled with valsartan monotherapy.

This randomized, double-blind study evaluated efficacy of a single-pill combination of amlodipine/valsartan (Aml/Val) in Asian patients with hypertension not responding to Val 80 mg. Patients with mean sitting diastolic blood pressure (DBP) ≥90-≤110 mmHg were randomized to Aml/Val 5/80, Val 80, or Val 160 mg for 8 weeks. At week-8 endpoint, significantly greater reductions in BP were seen with Aml/Val 5/80 mg than valsartan monotherapies (p < 0.0001). The BP control was greater with Aml/Val 5/80 (70.5%) than Val (44.1-58.6%) monotherapies. The combination was well tolerated. In conclusion, single-pill combination with Aml/Val provided significant additional BP reduction and control in hypertensive patients not responding to Val 80 mg.

Protective effects of dehydrocavidine on carbon tetrachloride-induced acute hepatotoxicity in rats.

AIM OF THE STUDY: To investigate the protective effects of dehydrocavidine (DC), a main active ingredient of Corydalis saxicola Bunting (Yanhuanglian), on carbon tetrachloride (CCl4)-induced hepatotoxicity and the possible mechanisms involved in male Sprague-Dawley rats. MATERIALS AND METHODS: Acute hepatotoxicity was induced by CCl4 intoxication in rats. Serum biological analysis, lipid peroxides and antioxidants estimation, histopathological studies were carried out. RESULTS: Both pre-treatment with DC prior to CCl4 administration and post-treatment with DC after CCl4 administration significantly prevented increases in serum enzymatic activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and total bilirubin (TBIL). In addition, pre- and post-treatment with DC also significantly prevented formation of hepatic malondialdehyde (MDA), depletion of glutathione peroxidase (GPx) and depression of superoxide dismutase (SOD) in the liver of CCl4-intoxicated rats. ALT, AST, LDH, ALP and TBILL levels, as well as MDA, SOD and GPx activities were unaffected in normal rats by treatment with DC alone. GST, a phase II enzyme, had no significant changes during our experiments. Histopathological changes induced by CCl4 were also significantly attenuated by DC treatment in both preventive and curative experiments. CONCLUSIONS: DC has a potent hepatoprotective effect on CCl4-induced liver injury in rats through its antioxidant activity.

[Effects of intracoronary autologous bone marrow mononuclear cells transplantation in patients with anterior myocardial infarction].

OBJECTIVES: To investigate the efficacy of intracoronary transfer of autologous bone marrow mononuclear cells (ABMMNCs) to patients with myocardial infarction (MI) on left ventricular function and myocardial perfusion. METHODS: Thirty-five patients with MI (> 4 weeks) were enrolled in this prospective, open-labeled study (20 patients in cell transplantation group; 15 patients in control group). All patients were treated by standard drug therapy and percutaneous coronary intervention (PCI). Baseline and 3 months follow-up evaluations included complete clinical and laboratory examinations, six minutes walk test, echocardiography, Dual-isotope simultaneous acquisition single photon emission computed tomography (DISA-SPECT) and cardiac magnetic resonance imaging (MRI). RESULTS: Baseline parameters were similar between the two groups. NYHA classification and six minutes walk test at 3 months follow-up were also similar between the two groups. However, left ventricular ejection fraction (LVEF) determined by echocardiography and DISA-SPECT was significantly higher; regional wall motion measured by echocardiography and cardiac MRI, myocardial viability and myocardial perfusion in the infarct zone assessed by DISA-SPECT were all significantly improved than before transplantation and than that in control group at 3 months follow-up. CONCLUSIONS: Our results indicate that intracoronary transplantation of ABMMNCs could improve the left ventricular systolic function and beneficially affect myocardial perfusion up to 3 months post transplantation in patients with myocardial infarction.

[Relationship of CTLA-4 exon 1 A49-->G polymorphism with sCTLA-4 and Th1/Th2 bias in idiopathic dilated cardiomyopathy].

OBJECTIVE: To investigate the association of cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene exon 1 A49-->G polymorphism with the genetic susceptibility to idiopathic dilated cardiomyopathy (IDC) in Chinese Han nationality. METHODS: Peripheral blood samples were collected from 48 patients with IDC, 31 males and 17 females, and 50 sex- and age-matched normal controls. ELISA was used to examine the cytokines: sCTLA-4, gamma-interferon (IFN-gamma), and interleukin-4 (IL-4)with the ratio of IFN-gamma/IL-4 as an indicator for Th1/Th2 bias. PCR-RFLP was used to analyze the A/G polymorphism of CTLA-4 exon 1 A49-->G. The relationship of CTLA-4 genotype and alleles frequencies with sCTLA-4, IFN-gamma and IFN-gamma/IL-4 was evaluated by linear regression analysis. RESULTS: Compared with the normal controls, the frequencies of GG genotype (0.6042 and 0.7396, P = 0.012) and the G allele (0.36 and 0.56, P = 0.008) were significantly increased in the patients with IDC. Increased serum sCTLA-4 was found in the IDC group compared with the controls (1.87 microg/L +/- 1.06 microg/L vs. 0.54 microg/L +/- 0.19 microg/L, P < 0.05). IFN-gamma was significantly lower in the IDC group than in the control group (16 ng/L +/- 6 ng/L vs. 30 ng/L +/- 10 ng/L, P < 0.05). The ratio of IFN-gamma/IL-4 was significantly in the IDC group than in the control group (1.63 +/- 0.50 vs. 3.01 +/- 0.89, P < 0.05). No statistically difference was found in the IL-4 level between the two groups. Linear regression analysis manifested significant interrelationship between the GG genotype, G allele frequencies and serum sCTLA-4 (r = 0.57, P = 0.021), IFN-gamma/IL-4 ratio (r = 0.42, P = 0.028) in the IDC group. While no correlation was found for AA, AG genotype and the A allele frequency. CONCLUSION: CTLA-4 gene exon 1 A49-->G substitution is associated with an increased IDC genetic susceptibility, which implicates that the CTLA-4 gene may have a significant role in IDC, possibly via a Thr-->Ala change in CTLA-4 signal peptide, with a result of functional change of sCTLA-4. The bias of Th1/Th2 paradigm is associated with the increased sCTLA-4 level under certain background of immunogenicity.

[Case control study on the association of coronary artery disease and cigarette smoking].

OBJECTIVE: To determine the association of cigarette smoking and coronary artery diseases (CAD). METHODS: A case-control study involving 355 people classified as CAD or without CAD was performed. But people treated with diuretic, aspirin, lipid-lowering agents, heparin or those with renal, hepatic diseases were excluded. Gender, age, body mass index, plasma glucose under fasting, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fibrinogen, cigarette smoking consumption grade (0: no smoking, 1: less or equal 100 cigarette year, 2: one hundred cigarette year < cigarette index

[Prevalence and relevant factors on echocardiographic left ventricular hypertrophy among community-based hypertensive patients in Shanghai].

OBJECTIVE: To investigate the prevalence and relevant factors on the echocardiographic left ventricular hypertrophy (LVH). METHOD: A cross-sectional study was conducted among the hypertensive patients in an urban community. RESULTS: The prevalence of LVH was 29.2% in 1 686 hypertensive patients, with 25.4% in males and 34.5% in females, respectively. The prevalence was significantly higher in females than in males (chi(2) = 16.17, P < 0.01). The rate was increasing with age and significantly higher prevalence was observed in 45-, 55-, 65- age groups of females (P < 0.05). Moreover, elevated systolic blood pressure and higher BMI were related to the LVH in hypertensive patients, while higher education level seemed a protective factor. CONCLUSION: These results implied that a comprehensive intervention should be taken in the prevention of LVH.