贝那普利对高血压并糖尿病肾病抗AT1受体自身抗体阳性患者肾脏的保护作用

目的探讨抗血管紧张素转换酶抑制剂贝那普利对高血压并糖尿病肾病（DN）抗AT1受体自身抗体阳性患者血压及尿蛋白的影响。方法以合成的AT1受体多肽片段为抗原,应用酶联免疫吸附测定技术,检测71例高血压并DN患者和51例糖尿病患者,及正常对照组40例血清抗AT1受体自身抗体。对抗AT1受体自身抗体阳性和阴性的DN患者分别在原胰岛素降糖方案治疗基础给予贝那普利10mg,口服,1次／d;尼群地平10mg,口服,3次／d;双氯噻嗪12．5mg,口服,1次／d;阿司匹林100mg,口服,1次／d。观察贝那普利对AT1受体自身抗体阳性组和阴性组临床降压及尿蛋白的疗效。6个月为一疗程,治疗前后进行24h尿微量白蛋白测定。结果高血压并DN组抗AT1受体自身抗体阳性率（43．7％,31／71）明显高于2型糖尿病组（13．7％,7／51）和对照组（10％,4／40）。临床降压疗效总评定,DN抗AT1受体自身抗体阳性组和阴性组贝那普利治疗总有效率分别为85．6％和45．0％;临床降蛋白尿的疗效总有效率分别为87．1％（27／31）和42．5％（17／40）,两组比较差异具有显著的统计学意义（P〈0．01）。结论贝那普利对高血压合并DN抗AT1受体自身抗体阳性组降压和减少蛋白尿的疗效明显优于阴性组,有针对性的治疗具有重要的临床价值。     

不同类型高血压患者血管紧张素Ⅱ受体1型自身抗体水平的研究

目的探讨抗血管紧张素Ⅱ受体1型(AT1R)第二细胞外环多肽的自身抗体与临床上不同类型高血压的关系。方法采用酶联免疫吸附试验(ELISA)检测170例健康志愿者和五组不同类型高血压患者的血浆中抗AT1R自身抗体。结果对照组、轻度原发性高血压组、顽固性高血压组、肾病不伴高血压组、肾实质高血压组和肾移植后高血压组中检测出抗AT1R的自身抗体分别为15%,16.7%,40%,20%,30%,50%。顽固性高血压组与对照组、轻度原发性高血压组比较、肾移植后高血压组与肾病不伴高血压组比较,差异均有显著性(P<0.05)。结论抗AT1R第二细胞外环的自身抗体可能参与了不同类型的高血压恶性阶段的发生和发展。     

Improved Blood Pressure Control with Nifedipine GITS/Valsartan Combination Versus High‐Dose Valsartan Monotherapy in Mild‐to‐Moderate Hypertensive Patients from Asia: Results from the ADVISE Study,a Randomized Trial

Aims : ADVISE was a 12‐week, multicenter, randomized, prospective, open‐label, parallel‐group study comparing combination therapy of nifedipine GITS 30 mg plus valsartan 80 mg (N + V) with high‐dose valsartan (160 mg) monotherapy (V160) in Asian patients with hypertension. Methods : Patients with hypertension inadequately controlled with valsartan 80 mg for at least 4 weeks were randomized. The coprimary endpoints were the mean changes in clinic systolic and diastolic blood pressures (SBP and DBP, respectively) at Week 12. Other endpoints included blood pressure (BP) control rate, response rate, and adverse events. Results : The full analysis set (FAS) comprised 359 patients. Least squares (LS) mean changes in SBP were ?18.3 mmHg (N + V; n = 177) and ?16.5 mmHg (V160; n = 182) (difference: ?1.9 mmHg; P = 0.0998). DBP LS mean changes were ?9.8 mmHg (N + V) and ?7.4 mmHg (V160) (difference: ?2.4 mmHg; P = 0.0011). BP control rates were significantly higher in the N + V group (Week 4: 51.2% vs. 38.4%, P = 0.0138; Week 8: 68.3% vs. 50.3%, P = 0.0004; and Week 12: 71.2% vs. 55.5%, P = 0.0024). Similar findings were observed when patients were stratified according to smoking status, SBP baseline quartiles, and ESC/ESH guideline‐defined added‐risk category. The BP response rate was also higher in the N + V group compared with the V160 group. Rates of adverse drug reactions (all mild‐to‐moderate) were similar: 4.5% (N + V) and 4.4% (V160). Conclusions : Although one of the coprimary endpoints did not reach statistical significance , combination treatment with N + V provided a greater early and more consistent BP‐lowering effect than monotherapy with V160, including superior reduction in DBP and BP control rates.     

血管紧张素Ⅱ1型和α1肾上腺素能受体抗体对预测老年2型糖尿病合并冠心病患者死亡危险性分析

目的 探讨血清抗血管紧张素Ⅱ 1型和α1肾上腺素能受体抗体与老年T2DM合并冠心病（CAD）患者死亡危险性的关系. 方法 选取老年T2DM患者234例,根据是否合并CAD平均分为T2DM合并冠心病（T2DM＋CAD）组和单纯糖尿病（T2DM）组,进行追踪研究3～11年.以合成的α1R和AT1R多肽片段为抗原,应用酶联免疫吸附法检测上述患者血清中抗α1R和AT1R自身抗体. 结果 （1） T2DM＋CAD组AT1R和α1R抗体阳性率高于T2DM组（48.7％ vs 20.5％,36.8％vs21.4％,P＜0.01）；（2）T2DM＋CAD组抗α1R和AT1R抗体受体阳性组死亡率高于受体抗体阴性组（47.4％vs10.0％,P＜0.01）；（3）α1R和AT1R抗体阳性组（指同一个体α1R和AT1R均阳性）死亡率高于单抗体阳性组（指同一个体仅α1R或AT1R阳性）（37.2％ vs 11.6％ vs 12.3％,P＜0.01）. 结论 α1R和AT1R抗体阳性与老年T2DM合并CAD患者死亡的危险性增高有关,双抗体阳性是老年T2DM合并CAD患者死亡的危险因素.     

药物降压治疗预防脑卒中后病人卒中的发生:脑卒中后降压治疗临床试验的初步结果

脑卒中后降压治疗临床试验（PATS）是一项随机、双盲、安慰剂对照的大样本多中心临床试验研究，旨在探讨降压治疗是否降低脑卒中或一过性脑缺血发作（TIA）后的高血压或正常血压患者脑卒中及其他并发症的再发生与死亡率，采用密封信封系统将5665例符合入选条件的病人随机分为吲哒帕胺治疗组（2841例，吲哒帕胺2.5mg，l／d)和安慰剂对照组（2824例，安慰剂每日1片）。平均收缩压为154mmHg(80～280mmHg）；平均舒张压为93mmHg（50～150mmHg）。平均年龄60岁，其中女性占28％，71％为缺血性脑卒中。平均随访时间近2年。3年随访期间，安慰剂组平均收缩压为149mmHg,吲哒帕胺治疗组为144mmHg,两组平均舒张压分别为89和87mmHg。安慰剂组致死性与非致死性脑卒中的3年初次发生率为12.3%，吲哒帕胺组为9.4％，相对危险度为0.71（P=0.0009）。全病因死亡的相对危险度为0.91（NS）。本试验的初步结果显示：给予脑卒中和TIA后病人吲哒帕胺2.5mgl／d，使血压下降5/2mmHg，可使致死性与非致死性脑卒中发生的危险降低29%，3年的绝对受益为减少29/1000脑卒中事件。     

Combined Pioglitazone and Metformin Treatment Maintains the Beneficial Effect of Short-Term Insulin Infusion in Patients with Type 2 Diabetes: Results from a Pilot Study

Background

The aim of our study was to examine the efficacy of short-term intravenous insulin intervention followed by oral pioglitazone/metformin therapy to prevent patients from continuous insulin application.

Methods

This prospective, open-label, 4-month pilot study comprised of 14 diabetes patients (5 female, 9 male; age 60 ± 2 years; body mass index 29 ± 3.2 kg/m²; hemoglobin A1c [HbA1c] 7.6 ± 1.1%) with (1) insufficient glycemic control under a dose of metformin ≥1700 mg/day and/or metformin plus additional oral antidiabetes drugs (OADs) and (2) appropriate residual β-cell function. Initially, an inpatient 34 h continuous intravenous insulin infusion was performed, and metformin was given (2x 850 mg/day). Insulin was stopped, and pioglitazone 30 mg/day was added at the second inpatient day. Patients were followed for four months. Efficacy parameters [change of HbA1c, fasting blood glucose [FBG], intact proinsulin, adiponectin, and high-sensitivity C-reactive protein (hsCRP)] were assessed after initial normalization of blood glucose values by intravenous insulin and at the study end point.

Results

During the acute insulin intervention, FBG levels were stabilized in all study subjects. In the following OAD treatment period, five patients showed an improvement of HbA1c > 0.5% [35.7%; seven patients remained stable (50.0%), two patients were nonresponders (14.3%)].Fasting glucose values dropped after insulin infusion (-17.7%; p < .001). This effect was maintained during the consecutive OAD treatment period (glucose +0.3%, not significant (NS); HbA1c -6.0%; p < .05). The initial decrease in fasting intact proinsulin levels was also maintained during the study (end value -41%, p < .05).Improvements in hsCRP values (postinsulin value, -15%, NS; end value -37%; p < .05) and adiponectin values (postinsulin value +15%, NS; end value +128%; p < .001) were demonstrated at end point only after continued glitazone intake.

Conclusions

Our pilot study demonstrated that a beneficial effect of a short-term intravenous insulin application on glycemic control was effectively maintained by pioglitazone/metformin treatment for at least 4 months. In addition, the oral therapy significantly improved cardiovascular risk parameters.     

Long-Term Effects of Xuezhikang on Blood Pressure in Hypertensive Patients with Previous Myocardial Infarction: Data from the Chinese Coronary Secondary Prevention Study (CCSPS)

Several previous trials from Western population studies have showed that statins may help reduce blood pressure (BP). However, randomized clinical data is limited. Xuezhikang, a partially extract of red yeast rice, contains a family of naturally occurring statins, and has a marked impact on lipids, but it is unknown whether Xuezhikang has any effect on BP during long-term follow-up in the Chinese population. This is a post-hoc subgroup analysis of a randomized, double-blinded, placebo-controlled, parallel group clinical trial, Chinese Coronary Secondary Prevention Study (CCSPS). A total of 2704 hypertensive patients with previous myocardial infarction (MI) were assigned either to placebo (n == 1341) or to Xuezhikang (n == 1363) daily for an average of 4.5 years. The primary outcome was the unadjusted changes in mean arterial pressure (MAP) from baseline to 6 months. We also assessed systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure. Analysis of covariance was used to calculate the adjusted effects of treatment on changes in these outcomes at 6, 12, 24, and 48 months post-random- ization, after controlling for potential confounders. This analysis included 2704//4870 (55.5%%) hypertensive patients for whom BP was measured at baseline and at least one follow-up visit after randomization. Median duration of the follow-up was 4.5 years (54 months), and 25 patients (0.92%%) were lost to the last follow-up because of adverse effects. The results showed that the unadjusted and adjusted changes in MAP, SBP, DBP, or pulse pressure from baseline were not significantly different for Xuezhikang or placebo recipients at 6, 12, 24, and 48 months after randomization. In this post-hoc subgroup analysis, we failed to demonstrate any significant reducing effects of Xuezhikang on BP in Chinese hypertensive patients with previous MI, suggesting that further prospective study on the effects of statins on BP would be needed, especially in high-risk patients.     

The Effects of Antihypertensive Treatment on the Doppler-Derived Myocardial Performance Index in Patients with Hypertensive Left Ventricular Hypertrophy: Results from the Swedish Irbesartan in Left Ventricular Hypertrophy Investigation Versus Atenolol (SILVHIA)

Objectives: To investigate the effects of antihypertensive treatment on the Doppler-derived myocardial performance index (MPI) in patients with hypertensive left ventricular hypertrophy. Methods: The MPI was measured at baseline and after 48 weeks of antihypertensive treatment in 93 participants of the SILVHIA trial, where individuals with primary hypertension and left ventricular hypertrophy were randomized to double blind treatment with either irbesartan or atenolol. Results: Antihypertensive treatment lowered MPI (mean difference −0.03 ± 0.01, P = 0.04). Changes in MPI by treatment were associated with changes in left ventricular ejection fraction (β-coefficient −0.35 P = 0.005), stroke volume/pulse pressure (reflecting arterial compliance, β-coefficient −0.39 P < 0.001) and peripheral vascular resistance (β-coefficient 0.28 P < 0.04). Furthermore, there was a borderline significant association between changes in MPI and changes in E-wave deceleration time (reflecting diastolic function, β-coefficient 0.23, P = 0.06). No associations were found between changes in MPI and changes in blood pressure, E/A-ratio, left ventricular mass index, relative wall thickness or heart rate. A stepwise multivariable regression model confirmed the association between changes in MPI and changes in ejection fraction and stroke volume/pulse pressure (all P < 0.05), as well as the trend for E-wave deceleration time (P = 0.08), but not in the case of peripheral vascular resistance. Conclusion: The MPI exhibited a modest decrease after 48 weeks of antihypertensive treatment in patients with hypertensive left ventricular hypertrophy. Changes in MPI were associated with changes in left ventricular function and vascular compliance, rather than with changes in left ventricular remodeling or blood pressure.     

Effect of Intravascular Cooling on Microvascular Obstruction (MVO) in Conscious Patients with ST-Elevation Myocardial Infarction Undergoing Primary PCI: Results from the COOL AMI EU Pilot Study

ObjectiveCOOL AMI EU pilot was a multi-center, randomized controlled trial to assess feasibility and safety of rapid intravascular therapeutic hypothermia (TH) in conscious patients with anterior ST-elevation myocardial infarction (STEMI) undergoing primary PCI (PPCI). We report the effect of hypothermia upon microvascular obstruction (MVO).MethodsConscious patients with anterior STEMI and symptom duration <6 h were recruited and randomized to PPCI + TH or PPCI alone. TH was induced using the ZOLL® Proteus™ intravascular temperature management system and rapid infusion of 1 L of cold normal saline, with a target temperature of 32 °C. MVO was measured by cardiac magnetic resonance (CMR) at 4 to 6 days post-MI. MVO larger than 3.9% of LV was considered as extensive MVO.Results50 patients were randomized; mean age was 58 years, and 86% were men. At reperfusion, mean intravascular temperature for the TH group was 33.6 ± 1 °C. The presence of MVO was high and not different in both groups (74% vs. 77%, p = 0.79). The proportion of patients with extensive MVO was 11% in the TH group and 23% in the control group (OR 0.4 95%CI 0.07–2.35, p = 0.30). Patients with extensive MVO showed reduced EF at 4–6 days (34% versus 43%, p = 0.01). The percentage of patients with EF <35% at 30 days was 6% in the TH group versus 24% in the control group (p = 0.19).ConclusionIn the COOL-AMI Pilot Trial, the presence of MVO in both test groups was high and extensive MVO was related with reduced LVEF. The efficacy of therapeutic hypothermia (TH) in MVO reduction should be tested in a pivotal trial.     

Housing Characteristics and their Influence on Health-Related Quality of Life in Persons Living with HIV in Ontario, Canada: Results from the Positive Spaces, Healthy Places Study

Although lack of housing is linked with adverse health outcomes, little is known about the impacts of the qualitative aspects of housing on health. This study examined the association between structural elements of housing, housing affordability, housing satisfaction and health-related quality of life over a 1-year period. Participants were 509 individuals living with HIV in Ontario, Canada. Regression analyses were conducted to examine relationships between housing variables and physical and mental health-related quality of life. We found significant cross-sectional associations between housing and neighborhood variables—including place of residence, housing affordability, housing stability, and satisfaction with material, meaningful and spatial dimensions of housing—and both physical and mental health-related quality of life. Our analyses also revealed longitudinal associations between housing and neighborhood variables and health-related quality of life. Interventions that enhance housing affordability and housing satisfaction may help improve health-related quality of life of people living with HIV.     

Effects of lifestyle intervention on weight and metabolic parameters in patients with impaired glucose tolerance related to beta‐3 adrenergic receptor gene polymorphism Trp64Arg(C/T): Results from the Japan Diabetes Prevention Program

The beta‐3 adrenergic receptor (ADRB3), primarily expressed in adipose tissue, is involved in the regulation of energy metabolism. The present study hypothesized that ADRB3 (Trp64Arg, rs4994) polymorphisms modulate the effects of lifestyle intervention on weight and metabolic parameters in patients with impaired glucose tolerance. Data were analyzed from 112 patients with impaired glucose tolerance in the Japan Diabetes Prevention Program, a lifestyle intervention trial, randomized to either an intensive lifestyle intervention group or usual care group. Changes in weight and metabolic parameters were measured after the 6‐month intervention. The ADRB3 polymorphisms were determined using the polymerase chain reaction restriction fragment length polymorphism method. Non‐carriers showed a greater weight reduction compared with the carriers in both the lifestyle intervention group and usual care group, and a greater increase of high‐density lipoprotein cholesterol levels than the carriers only in the lifestyle intervention group. ADRB3 polymorphisms could influence the effects of lifestyle interventions on weight and lipid parameters in impaired glucose tolerance patients.     

Impact of ABCB1 Gene (C3435T/A2677G) Polymorphic Sequence Variations on the Outcome of Patients with Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia in Kashmiri Population: A Case–Control Study

Inherited polymorphic sequence variations in drug transport genes like ABCB1 impact a portion of patients with hematologic malignancies that show intrinsic or acquire resistance to treatment. Keeping in view inter-individual sensitivities for such drugs, we through this case–control study tested whether ABCB1 C3435T and G2677T polymorphisms have any influence on the risk and treatment response in patients with chronic myeloid leukemia (CML) and B-acute lymphoblastic leukemia (B-ALL). Genotyping for ABCB1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism in 100 CML and 80 B-ALL patients along with 100 age and gender matched healthy controls. ABCB1 C3435T and G2677T polymorphism showed no association with CML. Genotype distribution revealed significant higher frequency of TT genotype for both SNPs in B-ALL cases and associated with increased B-ALL risk (OR 2.5, p = 0.04 for 3435TT; OR 2.4, p = 0.04 for 2677TT). There was no significant difference in genotype frequency of 3435C > T and 2677G > T among resistant and responsive groups for the two leukemia types. Kaplan–Meier survival plots revealed significantly lower event free survival in CML and B-ALL patients that were carriers of 3435TT genotype (p < 0.05). Multivariate analysis considered 3435TT genotype as independent risk factor for imatinib resistance in CML cases (HR 6.24, p = 0.002) and increased relapse risk in B-ALL patients (HR 4.51, p = 0.03). The current study provides preliminary evidence of a significant association between variant TT genotype and increased B-ALL risk. Also, results suggest that ABCB1 3435TT genotype increases imatinib resistance in CML and influence therapeutic outcome in B-ALL.