Isolated Systolic Hypertension: An Update After SPRINT

Isolated systolic hypertension is the most common hemodynamic form of hypertension in the elderly. With a rapidly aging population, the prevalence of hypertension, particularly isolated systolic hypertension, is expected to increase substantially. This phenomenon of increasing systolic pressure in the elderly is believed to be secondary to pathophysiological changes of aging as well as modifiable risk factors. Isolated systolic hypertension is associated with substantial mortality and morbidity, particularly of cerebrovascular disease. It is a rapidly growing public health concern and its management continues to remain a challenge to practicing physicians. Recent studies like the Systolic Blood Pressure Intervention Trial (SPRINT) and Heart Outcomes Prevention Evaluation (HOPE)-3 have implications for antihypertensive therapy in general and for the management of isolated systolic hypertension in particular. In this article we will review: 1) epidemiology and pathophysiologic mechanisms, 2) impact of isolated systolic hypertension on cardiovascular outcomes, 3) optimal management strategies, and 4) systolic blood pressure goals in the light of SPRINT and HOPE 3 trials.     

黄芪陷胸胶囊治疗老年单纯收缩期高血压50例临床观察

目的探讨黄芪陷胸胶囊治疗老年单纯收缩期高血压的疗效及作用机制。方法随机双盲对照法设治疗组50例与对照组50例,治疗组服用黄芪陷胸胶囊及雅施达片模拟药,对照组服用雅施达片及黄芪陷胸胶囊模拟药,运用分子生物学及中西医结合症侯学观察治疗前后疗效的变化。结果治疗5周及10周后两组均能明显改善收缩期血压(P<0.01),治疗组降压总有效率为76%,对照组总有效率为73%,两组差异无显著性。治疗组中医证候改善总有效率为92%,优于对照组(P<0.05)。治疗组血清一氧化氮合酶活力提高,血清丙二醛水平、血浆神经Y肽和同型半胱氨酸浓度降低,与对照组相比差异显著(P<0.05或P<0.01)。结论黄芪陷胸胶囊对老年单纯收缩期高血压有较好的疗效且无明显毒副作用,可调节血清一氧化氮合酶活力、降低血清丙二醛水平及血浆神经Y肽和同型半胱氨酸浓度。     

Systolic Hypertension in the Elderly Program (SHEP): antihypertensive efficacy of chlorthalidone

The Systolic Hypertension in the Elderly Program (SHEP) is a randomized, blinded test of the efficacy of antihypertensive drug treatment. In a large feasibility trial, 551 men and women who had isolated systolic hypertension and were at least 60 years old received chlorthalidone (25 to 50 mg/day) or matching placebo as the step I drug. After 1 year, 83% of the chlorthalidone group and 80% of the placebo group were still taking SHEP medications. Of those still taking chlorthalidone, 88% had reached goal blood pressure (BP) without requiring a step II drug, and most had responded to the lower dose (25 mg/day). The BP response was similar in all age, sex and race subgroups, with an overall mean difference between randomized groups of 17 mm Hg for systolic BP (p less than 0.001) and 6 mm Hg for diastolic BP (p less than 0.001). The only common adverse effects were asymptomatic changes in the serum levels of potassium (0.5 mEq/liter lower in the chlorthalidone group, p less than 0.001), uric acid (0.9 mg/dl higher, p less than 0.001) and creatinine (0.08 mg/dl higher, p = 0.02). This study indicates that chlorthalidone is effective for lowering BP in elderly patients with systolic hypertension and sets the stage for a larger trial of the effects of such treatment on the incidence of cardiovascular disease.     

Treatment of Isolated Systolic Hypertension in the Elderly: The Syst-Eur Trial

The Syst-Eur study investigated whether active antihypertensive treatment could reduce cardiovascular complications in elderly patients with isolated systolic hypertension. Patients ≥ 60 years) were randomly assigned to active treatment (n = 2398), i.e. nitrendipine, with the possible addition of enalapril and hydrochlorothiazide, or matching placebos (n = 2297). In the intention-to-treat analysis, the beween-group difference in blood pressure amounted to 10.1/4.5 mm Hg (P < 0.001). Active treatment reduced the total incidence of stroke (primary endpoint) by 42% (P = 0.003), of all cardiac endpoints by 26% (P = 0.03), and of all cardiovascular endpoints combined by 31% (P < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%; P = 0.07), but all-cause mortality was not influenced (-14%; P = 0.22). For total (P = 0.009) and cardiovascular mortality (P = 0.09), the benefit of antihypertensive treatment weakened with advancing age and for total mortality it decreased with higher systolic blood pressure at entry (P = 0.05). The benefits of active treatment were not independently related to gender or to the presence of cardiovascular complications at entry. Further analyses also suggested benefit in patients who were taking nitrendipine as the sole therapy. The per-protocol analysis largely confirmed the intention-to-treat results. It can be concluded that stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis in elderly patients with isolated systolic hypertension.     

Prevalence of postural hypotension at baseline in the Systolic Hypertension in the Elderly Program (SHEP) cohort.

OBJECTIVE: The objective of this study was to examine the prevalence and correlates of postural hypotension (defined as a drop in systolic blood pressure of greater than or equal to 20 mm Hg) in a cohort of elderly persons with isolated systolic hypertension (ISH). DESIGN: Baseline cross-sectional analysis of the 4,736 persons randomized in the Systolic Hypertension in the Elderly Program (SHEP). SETTING: A randomized multi-center double-blind outpatient clinical trial of the impact of treating ISH. PARTICIPANTS: Men and women age greater than or equal to 60 years with the systolic blood pressure (SBP) greater than or equal to 160 mm Hg and diastolic blood pressure (DBP) less than 90 mm Hg. MEASURES: Medical histories were obtained using interviewer-administered, standardized clinical history forms. At entry into the study, seated and standing BP was measured by certified BP technicians using a random zero sphygmomanometer. Postural hypotension (PH) was assessed at 1 and 3 minutes after the participant arose from a seated position. MAIN RESULTS: PH was found in 10.4% of participants at 1 minute and in 12.0% of participants at 3 minutes. 5.3% of participants demonstrated PH at both time intervals while 17.3% demonstrated PH at either or both of the time intervals. Factors significantly (P less than 0.05) associated with the presence of PH were higher mean SBP and a lower mean body mass index. CONCLUSIONS: Somewhat different persons were defined as having PH based upon the 1 minute and 3 minute standing measures of BP, and prevalence estimates of PH can vary depending on whether one or more intervals of measurement are used. Cross-sectional data analysis indicated that PH, in healthy community-dwelling older persons with ISH, may not be associated with a history of disorders or problems usually thought to be related to PH. However, prospective data are needed to determine the prognostic significance of PH, and whether one or multiple measurements carry more significance.     

Isolated systolic hypertension in the elderly: implications of Systolic Hypertension in the Elderly Program (SHEP) for clinical practice and for the ongoing trials.

The Systolic Hypertension in the Elderly Program (SHEP) was a double-blind placebo-controlled outcome trial on the treatment of isolated systolic hypertension (systolic pressure: 160-219 mmHg and diastolic pressure less than 90 mmHg). From 447, 921 screenes (age greater than or equal to 60 years) 4,736 patients were randomised. A significant reduction of non-fatal stroke (37%), non-fatal myocardial infarction (33%) and left ventricular failure (54%) was observed in the active treatment group. By contrast, the reduction in transient ischaemic attacks (25%), and in total (13%), cardiovascular (20%), cerebrovascular (29%) and coronary (20%) mortality did not reach a level of statistical significance. SHEP is a landmark trial on the treatment of isolated systolic hypertension (ISH) in the elderly. However, the question to what extent the SHEP results can be extrapolated to clinical practice remains open for debate. Indeed, it is possible that due to selection, the SHEP patients were not entirely representative of the elderly with ISH in the population at large. By contrast with previous intervention studies in elderly patients with combined systolic and diastolic hypertension, the SHEP trail did not demonstrate a significant beneficial effect of antihypertensive treatment on any of the cardiovascular mortality endpoints. Confirmation or rejection of the SHEP results in other trials, including the Syst-Eur study, conducted by the rejection of the SHEP results in other trials, including the Syst-Eur study, conducted by the European Working Party on High Blood Pressure in the Elderly and the Chinese trial in elderly ISH patients, is now awaited.     

老年单纯收缩期高血压与颈动脉粥样硬化的关系

目的 探讨老年单纯收缩期高血压患者血压与颈动脉粥硬化的关系.方法 2007年5月～2008年10月在我院就诊的老年高血压患者120例,其中单纯收缩期高血压患者60例,非收缩期高血压患者60例,均予做颈动脉超声检测,比较两组颈动脉粥样硬化发生的情况.结果 老年单纯收缩期高血压患者颈动脉内膜中膜增厚及粥样斑块的发生率与老年非单纯性高血压患者相比更高,差异有统计学意义(P<0.05),提示前者病变更加严重.结论 收缩压是比舒张压更强的致动脉粥样硬化的预测因子.     

Wnt信号途径与心脏发育及病理条件下成体心脏的修复功能

Wnt家族基因高度保守。其编码脂质修饰的糖蛋白能与跨膜受体结合,激活膜内信号途径。当Wnt蛋白缺乏时,APC/Axin/GSK-3β复合体磷酸化细胞质中的β-Catenin,β-Catenin降解;当Wnt蛋白存在时,与跨膜受体Frizzled和共受体LRP-5/6结合,细胞质中的β-Catenin不被降解,转入核内,与TCF/LEF蛋白作用调控下游基因表达。相反,非经典Wnt信号途径不依赖于β-Catenin,非经典Wnt信号途径分为Wnt/Ga2+信号途径和Wnt/JNK信号途径。①Wnt信号途径....     

高血压患者收缩压控制率

目的 了解目前接受药物治疗的高血压患者收缩压达标率，医师对收缩压达标的认识及临床高血压用药情况。方法 采用调查问卷进行横断面调查，内容包括医师(2291人)和患者(8952人)两部分。医师填写患者收缩压达标的比例，干预收缩压最有效的降压药物。患者部分也由医师填写，包括患者的高血压及相关病史，家族史等，检查结果，治疗情况。结果 患者的收缩压达标率57％，而主观认为达标率大于50％的医生约占30％。经过高血压药物治疗，患者的收缩压幅度下降。随年龄、血压水平和危险分层的增加，收缩压降压幅度也相应增加，但是收缩压的达标率相对较低。心肌梗死、心力衰竭和脑卒中患者的收缩压降压幅度较大，控制率也较高。而糖尿病患者，降压幅度较小，控制率也较低。联合用药的患者降压幅度高于单一用药。收缩压下降的同时舒张压也相应下降，血压水平和危险分层高的患者舒张压下降幅度较大。患者平时使用最多的和医师主观上认为的最有效的降压药物都是钙拮抗剂。结论高血压患者经治疗后收缩压下降，高危患者的治疗需要高度重视，且开始治疗即可联合用药。临床高血压用药以钙拮抗剂为主。     

Serum uric acid, diuretic treatment and risk of cardiovascular events in the Systolic Hypertension in the Elderly Program (SHEP)

OBJECTIVE: To assess longitudinally the association of serum uric acid and its change due to diuretic treatment with cardiovascular events in hypertensive patients. DESIGN: Cohort study in a randomized trial. SETTING: Cohort of hypertensive patients. PARTICIPANTS: A total of 4327 men and women, aged > or = 60 years, with isolated systolic hypertension, randomized to placebo or chlorthalidone, with the addition of atenolol or reserpine if needed, were observed for 5 years. MAIN OUTCOME MEASURES: Major cardiovascular events, coronary events, stroke and all-cause mortality. RESULTS: Cardiovascular event rates for quartiles of baseline serum uric acid were: I, 32.7 per 1000 person-years; II, 34.5 per 1000 person-years; III, 38.1 per 1000 person-years; and IV, 41.4 per 1000 person-years (P for trend = 0.02). The adjusted hazard ratio (HR), of cardiovascular events for the highest quartile of serum uric acid versus the lowest quartile was 1.32 (95% CI, 1.03-1.69). The benefit of active treatment was not affected by baseline serum uric acid. After randomization, an increase of serum uric acid < 0.06 mmol/l (median change) in the active treatment group was associated with a HR of 0.58 (0.37-0.92) for coronary events compared with those with a serum uric acid increase > or = 0.06 mmol/l. This difference was not explained by blood pressure effects. Those with a serum uric acid increase > or = 0.06 mmol/l in the active treatment group had a similar risk of coronary events as the placebo group. CONCLUSIONS: Serum uric acid independently predicts cardiovascular events in older persons with isolated systolic hypertension. Monitoring serum uric acid change during diuretic treatment may help to identify patients who will most benefit from treatment.     

Compliance to treatment for hypertension in elderly patients: the SHEP pilot study. Systolic Hypertension in the Elderly Program

Assessing the compliance of people over 60 years of age and older with an antihypertensive treatment regimen was a major objective of the Systolic Hypertension in the Elderly Program (SHEP) pilot study. The study randomized 551 men and women over the age of 60 (mean age = 72 years) to a stepped care treatment that included chlorthalidone or placebo in a double-blind trial. Three measures of compliance to treatment protocol--pill count, self-report, and a urine chlorthalidone assay--all indicated high levels of compliance in 80 to 90% of participants at 3 months and 1 year after randomization. Pill-taking compliance was similar in the active and placebo groups, although the rate of discontinuance from study medications at 1 year was higher in the placebo than in the active group. Compliance was high in all age categories, including those over age 80. These data suggest that elderly patients can achieve high levels of compliance with antihypertensive medications.     

Cost-Effectiveness Analysis in the Treatment of Hypertension: A Medical View

The clinical benefits of anti-hypertensive treatment include reductions in stroke and myocardial infarction, heart failure, renal and ocular damage and possibly cognitive impairment. The cost-effectiveness of treatment generally falls within a range considered acceptable to funders of health care in developed countries, and has been shown to vary with age, gender and pre-treatment blood pressure. In a largely asymptomatic condition, small quality of life impairments resulting from treatment could offset these clinical and economic benefits, but evidence suggests that treatment is associated with slight improvements in quality of life. A limitation of these analyses is that the needs of developing countries are not met. The ccst-effectiveness of anti-hypertensive treatment may be unattractive to developing countries when compared with interventions that achieve greater health gains per dollar spent.     

辽宁省农村地区单纯收缩期高血压的患病率及危险因素调查

目的了解辽宁省农村地区单纯收缩期高血压的患病率及危险因素,为辽宁省农村地区高血压的防治提供科学依据。方法采用分层整群随机抽样方法对辽宁省阜新地区7个乡镇年龄≥35岁的30 214名农村常住(≥5年)成年人进行调查。由培训过的医师对调查对象进行血压测量和资料收集。结果辽宁省农村居民单纯收缩期高血压患病率为11.92%,标化患病率为12.00%;男性患病率为11.42%,标化患病率为11.29%;女性患病率为12.42%,标化患病率为12.80%,男女间差异有显著性(P<0.01)。不同乡镇间高血压患病率差异较大,范围为7.81%~15.04%。随着年龄的增高,单纯收缩期高血压患病率呈明显的增高趋势。多元Logistic逐步回归分析发现,年龄、性别、民族、体质指数、饮酒、食盐量等因素是单纯收缩期高血压患病的危险因素。结论辽宁省农村居民单纯收缩期高血压患病率高,且存在多种危险因素,应采取全面的预防控制措施。     

单纯收缩期高血压患者血浆B型钠尿肽水平与左心室肥厚、舒张功能变化的关系

目的观察非高血压病者和单纯收缩期高血压病(ISH)伴或不伴左心室肥厚(LVH)者血浆B型钠尿肽(BNP)水平,及血管紧张素受体阻滞剂(ARB)治疗前后BNP、左心室肥厚及舒张功能变化情况,探讨BNP变化与左心室肥厚、舒张功能改变的关系。方法筛选非高血压病者(正常对照组)33例,ISH患者38例,ISH+LVH患者42例,予高血压病患者口服缬沙坦片80~120 mg/d,治疗前后采用超声心动图测定左心室质量指数(LVMI),E/A比值;放射免疫分析法测定血浆BNP水平。结果高血病各组血浆BNP水平明显高于正常对照组(P0.01或P0.05);与ISH组相比,ISH+LVH组LVMI增高(P0.05),而E/A值降低(P0.01);经ARB治疗后,血浆BNP水平在高血压病各组中均表现降低(P0.05或P0.01),LVMI值在ISH+LVH组表现为下降(P0.01),而E/A值表现为增高(P0.01);治疗前,血浆BNP水平与LVMI呈显著正相关(r2=0.61,P0.01),与E/A值呈显著负相关(r2=0.26,P0.01)。结论血浆BNP水平可作为判断ISH左心室肥厚、舒张功能改善的敏感指标。     

Antihypertensive Therapy in Elderly Patients with Isolated Systolic Hypertension: Third Progress Report of the Syst-Eur Trial

The Syst-Eur trial is a randomised, double-blind, placebo-controlled trial that examines the hypothesis that antihyper-tensive treatment can prevent or delay cardiovascular complications in elderly patients (> 60 years) with isolated systolic hypertension. On March, 1st 1993 a total of 1395 patients with a sitting systolic blood pressure on placebo averaging 160–219 mmHg and a diastolic blood pressure < 95 mmHg were randomised into this trial. The placebo and active treatment groups were similar at randomisation with respect to age (7 2 ±7 years, mean ± SD), percentage of women (68%), percentage of patients with cardiovascular complications (30%) and sitting blood pressures (175±12/85±6 mmHg). The fall in sitting systolic and diastolic blood pressures from baseline to 2 years was significantly more pronounced (p<0.001) in the actively treated (-22±18/-6±9 mmHg) as compared with the placebo treated Syst-Eur patients (-10±20/- 1±9 mmHg). Active treatment consists of nitrendipine if necessary associated with a converting-enzyme inhibitor and a thiazide. Whether treatment with these antihypertensive agents results in a clinically meaningful reduction of cardiovascular morbidity and mortality is the subject of investigation in this trial.     

硝酸酯类药物对老年单纯收缩期高血压的有益作用

目的　观察硝酸酯类药物对老年单纯收缩期高血压 (ISH)患者降压治疗的有益作用。方法　 87例ISH患者随机分为对照组 4 6例和治疗组 4 1例 ,对照组给予非洛地平缓释片 5mg ,每日一次口服 ,治疗组在上述治疗的基础上给予加用单硝酸异山梨酯 (ISMN) 2 0mg ,每日二次口服 ,疗程8周。结果　 (1)治疗组从第 2周开始收缩压 (SBP)下降幅度即大于对照组 ,且先于对照组于第 4周降至正常 ,差别有显著性 (P <0 0 5 ) ;(2 )从第 2周开始治疗组舒张压 (DBP)下降幅度即小于对照组(P <0 0 5 ) ,第 6周开始差距进一步加大 ,差别有显著性 (P <0 0 1) ,整个观察期内治疗组DBP下降幅度始终小于对照组 ,且从第 4周开始处于相对稳定状态 ;(3)第 2周开始治疗组PP下降幅度即大于对照组 (P <0 0 5 ) ,第 4周开始差距进一步加大 ,差别有显著性 (P <0 0 1)。结论　硝酸酯类药物能降低ISH患者的SBP ,而对DBP影响不大 ,使PP减小 ,对ISH患者降压治疗的有益。     

长期尼群地平治疗对老年收缩期高血压患者血压及左心功能的影响

４７例老年收缩期高血压患者经随机分组、尼群地平及安慰剂双盲对照治疗后，两组相比。治疗组血压控制满意、心血管并发症发生明显降低，且治疗组左室收缩功能及舒张功能均明显优于安慰剂组，表明尼群地平是适于老年收缩期高血压长期治疗的首选药物。     

氨氯地平和依那普利对老年纯收缩期高血压患者动态血压的影响

目的　比较氨氯地平和依那普利对老年纯收缩期高血压患者的 2 4h动态血压的影响。方法　将 6 0例轻中度纯收缩期高血压老年患者随机分为两组 ,每组 30例。分别选用氨氯地平片 5mg和依那普利片 10mg ,每日一次 ,共 4周。用药前后进行 2 4h动态血压监测。结果　两组药物治疗第 4周末 2 4h动态血压发现 ,2 4h平均收缩压、脉压、舒张压、平均动脉压均较服药前明显降低 ,统计学上有显著性差异。氨氯地平组治疗后总体收缩压和舒张压分别下降 17.0 3± 8.5 5mmHg和 4 .83± 4 .82mmHg ;平均动脉压下降了 8.86± 4 .76mmHg ,依那普利组治疗后总体收缩压和舒张压分别下降 14 .30± 7.2 6mmHg和 5 .97± 2 .87mmHg ,平均动脉压下降了 8.74± 3.0 7mmHg ,组间比较收缩压下降幅度无差异 (P =0 .187) ,脉压下降幅度有统计学意义 (P =0 .0 0 5 )。氨氯地平组脉压差下降幅度大于依那普利组 (16 .97± 14 .0 6mmHg比 8.33± 7.84mmHg ,P =0 .0 0 5 ) ,两药对舒张压的影响组间比较无统计学差异。两组有效率相似 (76 .7%比 73.3% ,P =0 .76 6 ) ,达标率的差异无统计学意义 (6 6 .7%比 5 6 .7% ,P =0 .4 2 6 )。氨氯地平组发生胫前水肿 2例 ,依那普利组咳嗽 5例。结论　氨氯地平与依那普利对老年纯收缩期高血压均有效 ,尤其