Treatment of isolated systolic hypertension in diabetes mellitus type 2

Age-related arterial stiffness is more pronounced in diabetics compared to non-diabetics, which could explain the prevalence of isolated systolic hypertension (ISH, systolic blood pressure > or =140 mmHg and diastolic blood pressure <90 mmHg) being approximately twice that of the general population without diabetes. Large-scale interventional outcome trials have also shown that diabetics usually have higher pulse pressure and higher systolic blood pressure than non-diabetics. Advanced glycation end-product formation has been implicated in vascular and cardiac complications of diabetes including loss of arterial elasticity, suggesting possibilities for new therapeutic options. With increasing age, there is a shift to from diastolic to systolic blood pressure and pulse pressure as predictors of cardiovascular disease. This may affect drug treatment as different antihypertensive drugs may have differential effects on arterial stiffness that can be dissociated from their effects on blood pressure. While thiazide diuretics are associated with little or no change in arterial stiffness despite a robust antihypertensive effect, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and calcium-channel blockers have been shown to reduce arterial stiffness. However, combination therapy is nearly always necessary to obtain adequate blood pressure control in diabetics. There are no randomized controlled trials looking specifically at treatment of ISH in diabetics. Recommendations regarding treatment of ISH in diabetes mellitus type 2 are based on extrapolation from studies in non-diabetics, post-hoc analyses and prespecified subgroup analysis in large-scale studies, and metaanalysis. These analyses have clearly demonstrated that blood pressure lowering in ISH confers improved prognosis and reduced cardiovascular and renal outcomes in both diabetics and non-diabetics.     

A 5-year prospective,observational study of the withdrawal of antihypertensive treatment in elderly people

Abstract. Objectives . To observe blood pressure, cardiovascular events, and total mortality after withdrawing antihypertensive treatment for elderly patients. Design . Multicentre observational study. Setting . Sweden. A 5-year follow-up of 333 elderly hypertensive patients, aged 70–84 years (mean age 75.2 ± sd 3.8 years, 68% females). In all, 74 out of the 333 patients (22%) died during the study period. Method . After withdrawal of the antihypertensive therapy, all patients started in the untreated state and during the 5-year follow-up they could then either remain in the untreated state, or be reverted to blood-pressure-lowering drug treatment because of hypertension or other diseases, e.g. angina pectoris, oedema, congestive heart failure, etc. Results . The probability of remaining without treatment for 5 years was estimated to be 20%. During the state of no treatment the patients had a lower total mortality risk than that of the general Swedish population, matched for age and sex. They also had a lower risk of cardiovascular events than those in the treated states. Markers indicating a successful withdrawal were monotherapy in low doses and relatively low blood pressure before withdrawal. Conclusion . These results suggest that with frequent check-ups, withdrawal of antihypertensive therapy in the elderly can be tried without increased risk of cardiovascular events.     

Antihypertensive efficacy and tolerability of different drug regimens in isolated systolic hypertension in the elderly

The pharmacological treatment, mainly based on diuretics, ofisolated systolic hypertension (ISH) has recently been shownto reduce the risk of stroke and coronary heart disease in theelderly. The purpose of this study was to compare the antithypertensiveeffect and tolerability of different drug regimens in elderlysubjects with ISH (systolic blood pressure—SBP —160mmHg and diastolic blood pressure — DBP — <90mmHg). A multicentre, randomized, controlled open trial wasplanned in the general practice setting. Four widely used treatmentschedules were tested: hydrochlorothiazide 25 mg plus amiloride2·5 mg (H+Am), nifedipine slow release 20 mg (N), atenolol50 mg (At) and atenolol 25mg plus chlorthalidone 6·25mg (At+C). After a baseline evaluation, 308 patients (76·3% female,mean age 75·3 ± 7·1 years) were randomizedand followed up for 6 months. After 3 months the drug dosagewas doubled if the systolic blood pressure goal (SBP<160mmHg and SBP reduction of at least 20 mmHg) had not been reachedNinety-four subjects (30·5%) presented contraindicationsto ß-blockers. At the 3rd- and 6th-month visits alltreatment groups, except At, showed a significant reductionin SBP compared to the control group; DBP showed no significantreduction in any group at any time. At the end of the follow-upthe percentage of hypertensives who had reached the BP goalwas 14·6% in the control group, 52·9% in H+Am,54·8% in N, 28·6% in At and 52·2% in At+C.Over two-thirds of the patients on H+Am or N, and about 50%of those on At or At+ C at 6 months were taking the medicationat low dose. The rate of therapy discontinuation due to side effects duringfollow-up was significantly different among the drug regimenstested: 1·9% in the H+Am group compared to 12·5%,19·2% and 14·8% respectively in N, At and At+Cgroups (P<0·05 for H+Am vs At). The proportion ofsubjects who spontaneously reported, mild adverse effects after3 and 6 months of therapy was not signficantly different inthe study groups, even if an excess was observed in the N groupat 3 months. In conclusion, these data suggest that. diuretics are a firstchoice in the treatment of ISH, because of their hypotensiveefficacy and acceptability; nifedipine, if well tolerated, isan effective alternative to diuretics; a high proportion ofelderly patient with ISH present contraindications to ß-blockers,and atenolol has a poor antihypertensive effect.     

老年单纯性收缩期高血压的诊疗进展

单纯性收缩期高血压常见于老年人,具有较高的致死、致残率,已成为人们研究的热点。现就老年单纯性收缩期高血压的流行病学、发病机制、诊断、临床特点以及治疗进展进行简要综述。     

老年单纯收缩期高血压的治疗进展

单纯收缩期高血压是心血管疾病的重要危险因素。大量研究显示,积极控制单纯收缩期高血压可以显著降低不良心血管事件危险性。我国高血压防治指南建议将老年单纯收缩期高血压患者收缩压降低至150 mm Hg以下。生活方式干预是治疗老年单纯收缩期高血压的基石,但多数患者需要降压药物治疗才能使血压达标。对于没有明确并发症的老年单纯收缩期高血压患者,可首选利尿剂、长效钙通道阻滞剂或血管紧张素受体拮抗剂,但对于已经发生靶器官损害者则应根据药物的强制性适应证确定治疗方案。     

Treatment of hypertension based on both systolic and diastolic pressure could influence the cost of therapy

Summary The decision to start antihypertensive treatment is based on the statistical results of therapeutic trials done in large populations. The application of statistical estimations may extend the indications for antihypertensive therapy to individual subjects who might be marginally improved by antihypertensive treatment. This problem is due to the well-known heterogeneity of the hypertensive population. One of the most common factors reflecting the heterogeneity of this population is the level of systolic pressure versus that of diastolic pressure. Disproportionate increases in systolic pressure in patients over 50 years reflect principally the arterial changes associated with elevated blood pressure. Arterial changes, as evidenced by the decreased compliance of large arteries, may require a specific therapeutic approach, which could influence the choice and consequently the cost of antihypertensive therapy.     

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。     

125例老年高血压病患者临床特点

125例老年高血压病患者中Ⅲ期较对照组（60岁以下）多，单纯收缩期高血压明显多于对照组（P＜0．01），并发症的发生率和死亡率高于混合性／舒张期高血压。提示纯收缩期高血压的危害性大于后者，具有重要临床意义。由于其血压的不稳定性，在诊断和治疗中应以注意。     

The systolic hypertension in the elderly pilot program: Methodological issues

The Systolic Hypertension in the Elderly Program (SHEP) PilotStudy was conducted to determine the feasibility of conductinga long-term placebo-controlled randomized clinical trial inelderly subjects. Enrolled in the study were 551 men and womenbetween the ages of 60 and 90 years with isolated systolic hypertension(SBP 160 mmHg and DBP < 90 mmHg). The study showed thatit is possible to recruit old and very old subjects into a clinicaltrial; the elderly are good compliers (drugs and follow-up visits),with some decline after the age of 80; control of blood pressurewas accomplished in the large majority of patients; evaluationof side effects represents a potential problem as varied complaintsincrease with age thus creating difficulties in distinguishingthose attributed to the study drug; and finally, cause-specificmortality is probably preferable to all-cause mortality as anend-point in prevention trials of antihypertensive regimens.     

Treatment of hypertension in the elderly

Summary Treatment of hypertension in the elderly is beneficial, and benefit exceeds risk, but in some individuals it may be difficult to decrease blood pressure to goal or normotensive levels. Recent data suggest that the use of diuretics and, in some instances, beta-adrenergic inhibitors will reduce morbidity and mortality in elderly hypertensives and will probably not alter metabolic parameters to a clinically significant degree in most individuals.     

5-单硝异山梨酯缓释剂治疗老年单纯收缩期高血压疗效观察

目的 观察5-单硝异山梨酯缓释剂（ISMN）对老年单纯收缩期高血压（ISH）患者降压治疗的疗效。方法 80例ISH患者随机分为对照组39例和治疗组41例，对照组给予氨氯地平5mg，吲达帕安2．5mg每日1次口服，治疗组在上述治疗的基础上给予5-单硝异山梨酯缓释剂40mg每日1次口服，疗程4周。结果 （1）治疗组从第一周开始收缩压（SBP）下降幅度即大于对照组，先于对照组于第二周降至正常，差异有显著性（P〈0．05）；（2）从第一周开始治疗组舒张压（DBP）下降幅度即小于对照组（P〈0．05），第三周开始差距加大，差异有非常显著性（P〈0．01），整个观察期内治疗组DBP下降幅度始终小于对照组，且从第二周开始处于相对稳定状态；（3）第一周开始治疗组脉压（PP）下降幅度即大于对照组（P〈0．05），第二周开始差距进一步加大，差异有非常显著性（P〈0．01）。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患者降压治疗有益。     

Controversies in hypertension: mild hypertension, isolated systolic hypertension, and the choice of a step one drug

The realization that cardiovascular morbidity and mortality increases in patients with mild elevation of either systolic or diastolic blood pressure has led to a consideration to treat millions of patients with mild diastolic or isolated systolic hypertension. The cost of administering a successful antihypertensive treatment program and the potential adverse effects of pharmacologic agents is of great concern. It has been emphasized that the risk of premature mortality differs in individual patients according to the number of associated cardiovascular risk factors at any level of blood pressure. This has led to a suggestion that only high risk patients be treated. However, a significant number of low risk patients with mild hypertension develop a more severe or complicated form of their disease even over a follow-up period of five to ten years. There is no good way to identify these patients. Trials of antihypertensive therapy suggest a beneficial effect of blood pressure lowering in mild hypertension. No trials of antihypertensive therapy in elderly patients with isolated systolic hypertension have been reported, but the elevation in systolic blood pressure appears to be an independent risk factor for cardiovascular mortality. Even the choice of the first step agent in treatment is debatable. Diuretics or beta blockers effectively lower blood pressure in the majority of hypertensive patients, particularly if modest dietary sodium restriction is achieved. The incidence of side effects, either symptomatic or biochemical, is similar but diuretics are unquestionably cheaper and probably more effective. Successful application of an antihypertensive treatment program may continue to reduce our unacceptably great incidence of cardiovascular disease.     

老年收缩期高血压与无症状性腔隙脑梗塞发病的研究

对老年单纯收缩期高血压腔隙性脑梗塞发病情况进行研究，61例老年收缩期高血压（ISH组）和59例老年对照组（NT组）进行脑CT扫描。两组年龄分别为67.85±5．55和66.85±6.03岁。两组病例均无有相关临床症状和神经定位体征。结果表明腔隙性脑梗塞（LCI）者ISH组占31．11％，NT组占15．25％，两组对比有显著性差异（P＜0.05）。LCI部位两组均以基底节为多见，说明无症状LCI多见于高血压。     

Conclusions and Implications of the Systolic Hypertension in the Elderly Program

Isolated systolic hypertension has a higher prevalence with age and an associated excess cardiovascular risk. The Systolic Hypertension in the Elderly Program (SHEP) was a randomized, prospective, double blind clinical trial to assess the efficacy and safety of a antihypertensive regimen based on low dose diuretic therapy in reducing the five year combined incidence of fatal and nonfatal stroke. SHEP demonstrated a significant 36% reduction in stroke incidence. Also, 27% reduction in coronaryheart disease incidence and a 32% reduction in major cardiovascular disease incidencewere achieved. Thebenefits accrued to all subgroups identifiedbased onbaseline age, race, sex, blood pressure, serum cholesterol levels, and ECG abnormalities. A low-dose diuretic regimen should be the initial treatment of choice for most hypertensive patients, based on demonstrated reduction in risk for major cardiovascular events, its safety, acceptanceby patients, and low cost.     

Comparative effectiveness of an angiotensin receptor blocker,olmesartan medoxomil,in older hypertensive patients

The efficacy and safety of olmesartan medoxomil (OM) vs active control (AC) monotherapy among elderly patients aged 60‐79 years (N = 4487) was evaluated by meta‐analysis (25 studies). In all patients, change from baseline to end point in blood pressure (BP) was significantly greater with OM vs AC (−19.5/−11.9 vs −16.8/−10.7 mm Hg). Greater proportions of OM‐ vs AC‐treated patients achieved BP goals. In patients with impaired renal function (estimated glomerular filtration rate <60 mL/min/1.73 m²), OM treatment resulted in a greater mean change from baseline in systolic BP vs AC (−21.2 vs −18.7 mm Hg, respectively) and a greater proportion of patients achieving BP goals. These parameters were similar in both groups for elderly patients with diabetes. OM was well tolerated with few adverse events. OM monotherapy can be used as an initial treatment for hypertension in elderly patients, including those with renal impairment or diabetes.     

北京市城乡老年人抗高血压药物7年变化趋势

目的: 了解北京市城乡老年人抗高血压药物使用7年变化情况。 方法: 采用分层、随机、整群等距的抽样原则,于2000、2004和2007年3次选取北京地区≥60岁的2 832、1 828和2 277例老年人进行血压测量及相关资料的收集,应用χ2检验对不同性别、年龄、居住地区与高血压用药7年变化趋势进行单因素分析。结果: 钙通道阻滞剂（CCB）、血管紧张素转换酶抑制剂（ACEI）、利尿剂和β-受体阻滞剂的使用逐年增多,而降压片的使用明显减少。结论: 老年高血压病的治疗已不仅仅局限于降压,还要考虑防治并发症,提高高血压病患者的生命质量。     

Treatment of hypertension in the elderly—What have we learned from the recent trials?

Summary Treatment of hypertension in the elderly has so far mainly been based on clinical judgment and very few large controlled trials. During the last year several large new trials have been published, the so-called STOP-Hypertension, SHEP, and MRC trials. All have shown that drug treatment of hypertension in the elderly (65–85 years) with permanent diastolic hypertension or isolated systolic hypertension reduces stroke incidence. Most patients have needed combined drug treatment with diuretics and beta-blockers. When thiazide diuretics are used, serum postassium should be followed very closely and most likely amiloride should be added to the thiazide therapy, since this was done both in the STOP and the MRC trials. Since many elderly patients with hypertension suffer from other diseases that might represent contraindications to thiazide diuretics or beta-blockers, the choice of drug must be made after careful clinical evaluation. With the newer classes of antihypertensive agents (calcium antagonists, ACE inhibitors and alpha-blockers) side effects are probably seen less often, but long-term data on morbidity and mortality are still lacking.     

The case for antihypertensive drug treatment in subjects over the age of 60

Summary The already strong case for drug treatment of hypertensive patients aged over 60 has been reinforced by the reports on the SHEP, STOP, and, to a lesser extent, MRC trials. SHEP showed benefit in isolated systolic hypertension, mainly in relation to stroke, but with a strong trend towards also reducing myocardial infarction. SHEP demonstrated advantages from low-dose chlorthalidone, especially if hypokalemia was prevented. STOP in patients aged 70–84 at entry demonstrated a reduction in stroke and all-cause mortality but not in myocardial infarction; benefit was apparent in women as well as men. The MRC trial, in subjects over 65, many of whom had isolated systoli hypertension, found a reduction in stroke but not in coronary events or all-cause mortality. Extensive cross-contamination of allocated treatment groups restricted worthwhile evaluation of different drug regimens in MRC. Potential benefits from antihypertensive drug treatment in old people are substantial but are in danger of being discredited because of intemperate and inaccurate claims.