Natural killer cell function in women at high risk for HIV acquisition: insights from a microbicide trial

OBJECTIVE:: To assess the role of natural killer (NK) cells in HIV acquisition. DESIGN:: We conducted a nested case-control substudy to the Center for the AIDS Programme of Research in South Africa (CAPRISA004) tenofovir gel trial. METHODS:: Thirty women who acquired HIV infection (cases) and 30 women with high-risk sexual activity who remained HIV-negative (controls) were selected. Proliferation, degranulation and interferon-γ (IFNγ) secretion were measured by multiparametric flow cytometry after culture of recombinant human interleukin-2 (rhIL-2)-activated peripheral blood mononuclear cells with 721.221 cells or in-vitro HIV-infected, autologous CD4 T-cell blasts. Relationships between pre-acquisition NK cell responses and HIV acquisition were modeled with logistic regression models. RESULTS:: NK cells from cases had lower IFNγ responses to human leukocyte antigen-deficient 721.221 cells than controls (median %IFNγposNK cells: 13.7 vs. 21.6%, P?=?0.03). rhIL-2-activated NK cells from cases had responses to autologous HIV-infected target cells distinct from controls: cases had fewer proliferating and more frequent degranulating NK cells. NK cells from cases had significantly lower IFNγ responses to in-vitro HIV-infected autologous T cells than controls even after adjusting for responses to uninfected blasts (median %IFNγposNK-cells: 0.53 vs. 2.09%, P?=?0.007). Responses to in-vitro HIV-infected autologous T cells were significantly lower in herpes simplex virus 2 (HSV-2)-infected women (P?=?0.003). IFNγ NK cell responses to autologous HIV-infected cells were associated with lower risk of HIV acquisition (odds ratio adjusted for age, gel arm, HSV-2 and immune activation: 0.582, 95% confidence interval 0.347-0.977, P?=?0.04). CONCLUSION:: At the time of exposure to HIV, women with impaired NK cell IFNγ responses were more likely to acquire HIV infection. NK cells, as early responders to viral exposure, were associated with lower risk of HIV acquisition, independent of the intercalated effect of HSV-2 infection suppressing NK cell responses.     

血小板活化因子在高血压伴心血管危险因素患者中的临床意义

目的探讨血小板活化因子(platelet activating factor,PAF)在原发性高血压(高血压)伴心血管危险因素患者中的临床意义。方法选择在心血管内科门诊诊断为高血压的患者332例,男134例,女198例,年龄(61.4±8.7)岁为研究对象。根据2005年中国高血压防治指南按伴危险因素分层分为4组:Ⅰ组无其他危险因素者50例、Ⅱ组伴1～2个危险因素者134例、Ⅲ组≥3个危险因素或靶器官损害或合并糖尿病者103例、Ⅳ组并存的临床情况者45例;采用酶联免疫吸附测定法对血清PAF浓度进行检测,按PAF不同浓度进行分级,PAF1ng/mL,5ng/mLPAF≥1ng/mL,15ng/mLPAF≥5ng/mL,PAF≥15ng/mL共4级并进行比较。结果血清PAF浓度由低到高例数比例Ⅰ组为40%,42%,10%,8%例;Ⅱ组为68%,42%,25%,9%例;Ⅲ组为12%,14%,34%,41%例;Ⅳ组为9%,20%,31%,40%例。经等级资料秩和检验,采用Kruskal-Wallis秩和检验提示4组之间差异有统计学(χ2=68.959,P=0.000)。等级资料两两比较采用Mann-Whitney Test检验:Ⅰ组与Ⅱ组Z=-2.624,P=0.009;Ⅰ组与Ⅲ组Z=-6.442,P=0.000;Ⅰ组与Ⅳ组Z=-4.940,P=0.000;Ⅱ组与Ⅲ组Z=-6.534,P=0.000;Ⅱ组与Ⅳ组Z=-3.924,P=0.000;Ⅲ组与Ⅳ组Z=-0.827,P=0.408。结论检测PAF浓度对高血压伴心血管疾病危险因素患者的病情评估有一定临床指导意义。     

Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial

Men aged 40-64 years with mild to moderate hypertension [diastolic blood pressure (DBP) 100-130 mmHg] were randomized to treatment with a diuretic (n = 3272) or a beta-blocker (n = 3297), with additional drugs if necessary, to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease (CHD) events and death. Patients with previous CHD, stroke or other serious diseases, or with contraindications to diuretics or beta-blockers were excluded. If normotension (DBP less than 95 mmHg) was not achieved by monotherapy, other antihypertensive drugs were added, but the two basic drugs were not crossed over. Patients were assessed at 6-monthly intervals. The mean follow-up for end-points was 45.1 months. Blood pressure (BP) side effects and end-points were recorded in a standardized manner. Entry characteristics and the BP reduction achieved were very similar in both treatment groups. All analyses were made on an intention-to-treat basis. The incidence of CHD did not differ between the two treatment groups. The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group. Total mortality and the total number of end-points were similar in both groups. The percentage of patients withdrawn due to side effects was similar, whereas the number of reported symptoms, according to a questionnaire, was higher for patients on beta-blockers. The incidence of diabetes did not differ between the two groups. Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers, and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD. Beta-blockers and thiazide diuretics were approximately equally well tolerated. The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group. Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications, including CHD, to a different extent.     

Effects of captopril on renal function in hypertensive patients

The effects of captopril (SQ 14225) on renal function were studied in 10 hypertensive patients. After 7 weeks of treatment (75 to 500 mg/day) renal plasma flow was practically unchanged and glomerular filtration rate was only slightly decreased despite a significant decrease in blood pressure. All indexes of glomerular capillary permeability and of tubular anatomic integrity remained normal during the treatment period.     

Carotid stenting with distal protection in high surgical risk patients: the BEACH trial 30 day results.

BACKGROUND: The BEACH trial evaluated the outcomes of carotid artery stent placement with distal emboli protection, using the Carotid Wallstent and the FilterWire EX/EZ(TM), in patients at high surgical risk for carotid endarterectomy (CEA). METHODS: We enrolled 747 patients at high surgical risk for CEA due to prespecified anatomical criteria and/or medical comorbidities. The trial included both symptomatic (>50% carotid artery stenosis) as well as asymptomatic (>80% carotid artery stenosis) high surgical risk patients. Three groups of patients were included in the trial. The Roll-in (R) group (n = 189/747, [25%]) included up to nine patients per site for familiarization of the device and protocol; the Pivotal (P) group (n = 480/747, [65%]) was intended for presentation to the FDA for consideration of device approval; and a Bilateral (B) registry group (n = 78/747, [10%]) was included because of the need to treat patients with bilateral carotid artery disease. In the 480 Pivotal patients, anatomic criteria represented the most frequent high-risk surgical category for enrollment (58.8%), followed by prior CEA (34.2%), multivessel (>or=2) coronary artery disease (21.7%), and contralateral carotid occlusion (18.1%). RESULTS: The technical success rate for stent deployment and FilterWire EX/EZ deployment and retrieval was 98.2%. The mean postprocedure angiographic diameter stenosis in the Pivotal group was reduced to 10.8%, while the overall procedure success rate (<50% residual diameter stenosis) after stent deployment was 98%. The 30 day composite major adverse event (MAE) rate for the entire cohort of 747 patients (i.e. inclusive of all 3 groups) was 5.8% (all death = 1.5%, all stroke = 4.4%, and all myocardial infarction (MI) = 1.0%). In subgroup analysis, there was no significant difference in the MAE rate between the three groups (P = 5.8%, R = 6.9%, B = 2.6%, P = 0.42). CONCLUSION: The similarity in periprocedural event rates for the Pivotal and Roll-in groups suggests a flat learning curve for experienced operators using this carotid stent system. The similarity in event rates for the Bilateral group, when compared with the Roll-in and Pivotal groups, suggests that staged sequential treatment of bilateral stenoses may be performed at the same risk as for unilateral lesions. The 30-day safety of this stent and distal emboli protection system is encouraging and compares favorably with other carotid stent trials in high surgical risk patients.     

Characteristics of 15,314 hypertensive patients at high coronary risk. The VALUE trial. The Valsartan Antihypertensive Long-term Use Evaluation

Valsartan is an orally active, selective antagonist of the angiotensin II-1 (AT1) receptor developed for the treatment of hypertension. The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) Trial of Cardiovascular Events in Hypertension is a double-blind, randomized prospective, parallel group study designed to compare the effects of valsartan with those of the calcium-antagonist amlodipine on the reduction of cardiac morbidity and mortality. Patients with essential hypertension, aged 50 years and older, and at particularly high risk of coronary events were enrolled. 18,119 patients were screened and 15,314 patients in 31 countries were randomized mainly between January 1998 and December 1999. These hypertensives had a mean blood pressure of 154.7/87.5 mmHg at the time of their randomization to blinded medication. The population comprises both genders (men 57.6%), Caucasians (89.1%), mean age 67.2 years, mean body mass index 28.6 kg/m2, coronary heart disease (45.8%), high cholesterol (33.0%), type 2 diabetes mellitus (31.7%) and smokers (24.0%). More than 92% of the randomized participants had been treated for high blood pressure for at least 6 months when screened for the study. The randomized population is now being treated (goal blood pressure < 140/90 mmHg) in adherence with the protocol until at least 1450 patients experience primary cardiac endpoint defined as clinically evident or aborted myocardial infarction, hospitalization for heart failure or death caused by coronary heart disease.     

Clinical significance of cognitive performance by hypertensive patients

Fifty-four subjects with uncomplicated essential hypertension and 54 normotensive subjects were compared with regard to a widely employed clinical index of cognitive dysfunction (the Average Impairment Rating) calculated from neuropsychological tests that discriminate between brain-damaged and neurologically normal persons. Hypertensive subjects exhibited lower mean scores on this index when education was ignored, but results were not the same for highly educated and less well educated groups. There were no differences between exceptionally well educated hypertensive and normotensive subjects, but in the less well educated group, hypertensive subjects performed more poorly than normotensive subjects. The percentages of hypertensive and normotensive subjects scoring in a cognitively impaired range on the Average Impairment Rating were low and did not differ for either education group. These data indicate the important role of subtle differences in education level with respect to positive or negative findings for studies comparing hypertensive and normotensive subjects and illustrate the important role of clinical neuropsychological indices of cognitive dysfunction when one wishes to make meaningful inferences regarding cerebral cortical function in hypertensive subjects.     

Orlistat in hypertensive overweight/obese patients: results of a randomized clinical trial

OBJECTIVE: To assess the effect of orlistat plus diet compared with diet alone in promoting weight loss and blood pressure reduction in hypertensive, overweight/obese patients. DESIGN: A pragmatic randomized, controlled trial. SETTING: Hypertension clinic of a university hospital. PATIENTS: Hypertensive patients aged 18-75 years with a body mass index greater than 25 kg/m(2). INTERVENTIONS: Orlistat 360 mg/day combined with a hypocaloric diet (treatment group), or a calorie-restricted diet alone (control group). MAIN OUTCOME MEASURES: Primary outcomes were reductions in weight and blood pressure. Secondary outcomes were decreases in lipid and glucose concentrations. A subgroup analysis of the main outcomes among diabetic and non-diabetic patients was also performed. RESULTS: A total of 204 patients were included in the intention-to-treat analysis. After 12 weeks the orlistat group lost, on average, 3.7 kg and the control group lost 2.0 kg in weight (P < 0.001). Systolic (SBP) and diastolic (DBP) blood pressures decreased by 15.3 and 11.4 mmHg, respectively, in the group given orlistat plus a hypocaloric diet and by 11.6 and 5.2 mmHg, respectively, in the control group given the calorie-restricted diet alone (P = 0.25 and P = 0.0004, respectively). Fasting glucose (0.82 and 0.17 mmol/l, P = 0.01) and total cholesterol (0.85 and 0.56 mmol/l, P = 0.05) were reduced to a greater extent with orlistat than with diet alone. The mean reduction in triglycerides with orlistat plus the hypocaloric diet was 0.75 mmol/l and that in the control group was 0.30 mmol/l (P = 0.28); the increases in high-density lipoprotein cholesterol were 0.05 and 0.00 mmol/l, respectively, in the two groups (P = 0.17). Treatment improved blood pressure and glucose control in the individuals with diabetes, but not in those without diabetes. CONCLUSION: In both groups there was a reduction in weight, blood pressure and metabolic parameters. The orlistat group performed better in reducing weight, DBP, glucose and cholesterol. Results show that even a small reduction in weight helps to control blood pressure and glucose. The cost-benefit of the use of orlistat should be evaluated for hypertensive obese patients.     

Comparison of sirolimus- and paclitaxel-eluting stents in patients with moderate renal insufficiency: results from the J-DESsERT trial

BackgroundIt is unclear whether there are differences in clinical outcomes between sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in patients with moderate renal insufficiency (RI).MethodsThe Japan-Drug Eluting Stents Evaluation; a Randomized Trial (J-DESsERT) was a prospective, randomized multicenter trial which compared 1:1 coronary stenting between SES and PES patients. Patient with serious RI (serum creatinine value 2 mg/dL or higher) were excluded. Patients were classified into 2 arms according to renal function: a non-RI arm of 2220 patients (SES 1094 and PES 1126 patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL min^− 1 1.73 m^− 2) and an RI arm of 1206 patients (SES 613, PES 593 with 30 ≤ eGFR < 60 mL min^− 1 1.73 m^− 2).ResultsAt 12 months, the primary endpoint of target vessel failure in the non-RI arm occurred in 6.0% in the SES group and 8.7% in the PES group (p = 0.02). In the RI arm, this occurred in 5.7% and 8.1% (p = 0.10). Mortality rates were 0.8% vs 0.7% (p = 0.78) in the non-RI arm, and 2.2% vs 2.1% (p = 0.90) in the RI arm. Cardiac death was 0.4% vs 0.1% (p = 0.17) in the non-RI arm, and 1.0% vs 1.0% (p = 0.96) in the RI arm. Mortality was higher in patients with RI than those without RI (2.1% vs 0.8%; p < 0.01). Cardiac death rates increased in the RI arm compared with those in the non-RI arm (1.0% vs 0.2%; p < 0.01).ConclusionsRegardless of the presence or absence of moderate RI, differences in outcomes between SES and PES change little except mortality and cardiac death.     

SCORE model underestimates cardiovascular risk in hypertensive patients: results of the Polish Hypertension Registry

OBJECTIVE. The aim of the present study was to compare the effectiveness of Systemic COronary Risk Evaluation (SCORE) charts and European Society of Hypertension/European Society of Cardiology (ESH/ESC) hypertension guidelines for identifying high-risk hypertensive patients. METHODS. The data on hypertensive patients was collected using the Polish Hypertension Registry. We enrolled 636 patients (357 females and 279 males, mean age 54.4 (+/-) 7.9 years) from hypertension centres in Poland. RESULTS. Only 3.5% of the subjects had no additional risk factors. Thirty-six per cent of the patients had three or more risk factors. Metabolic syndrome was found in 40.1% of the patients. According to the SCORE charts, 9.0% of females and 27.2% of males had high to very high cardiovascular risk (p < 0.001). Taking into account risk factors and the metabolic syndrome, 55.7% of females and 56.3% of males (p = NS) had high or very high additional cardiovascular risk according to the 2007 ESH/ESC guidelines. For both females and males, the prevalence of high to very high risk was greater (p < 0.001) from the calculation based on the 2007 ESH/ESC guidelines than from the SCORE charts. Fifty-two per cent of patients classified as low to moderate risk according to the SCORE system, had high or very high risk according to the 2007 ESH/ESC guidelines. CONCLUSIONS. The SCORE charts seem to underestimate the burden of the cardiovascular risk among hypertensive patients. The cardiovascular risk, especially in the hypertensive female population, seems to be much higher when estimated according to the 2007 ESH/ESC guidelines.     

Relationship between renal function and heart failure in hypertensive patients

The HICAP (Hypertension and Heart Failure in Primary Care) study is a cross-sectional, multicentre, epidemiological study conduced in primary care centres in Spain. The results indicate that among hypertensive patients without heart failure (HF), diagnosed renal dysfunction is associated with the risk for developing HF and that the renal function evaluation using the Modification of Diet in Renal Disease Study Group formula could be useful to detect hypertensive patients at high risk of developing HF.     

依那普利治疗老年肾实质性高血压的临床观察

应用依那普利治疗３０例老年性肾实质性高血压，治疗前后随访观察表明，治疗后血压下降，头晕、头痛症状明显减轻，心功能不全、心绞痛得到不同程度纠正及缓解，２４ｈ尿蛋白排出量减少，但心率、眼底改变、血尿变化不明显。观察结果显示，有效控制老年肾实质性高血压，能延缓肾功能不全的进展，以及减少心脑血管并发症的发生。