Exercise hypertension in the perspective of systemic arterial hypertension. An overview

Systemic arterial hypertension is one of the most wide-spread diseases in the world. It is a chronic disease with a very long asymptomatic phase. At an estimated prevalence in the developed countries of 15 to 20%, it can be assumed that approximately 80% of men and 60% of women with hypertension are either unaware of their condition or are not treated adequately. These figures show that reliable diagnostic measures are needed to provide efficient detection of high blood pressure in a given population. In this regard, exercise testing has proven particularly well-suited. Using standardized ergometry, patients with latent, borderline or manifest hypertension can be identified. Exercise hypertension is defined on the basis of an abnormal blood pressure increase during physical exercise in persons with normal blood pressure at rest. Because of marked interindividual fluctuation in blood pressure, values measured at rest may be of only limited usefulness in the diagnosis of hypertension. In contrast, the blood pressure during dynamic exercise may be particularly informative with respect to probability of future development of manifest hypertension and treatment of high blood pressure. Long-term studies have shown that within five years up to one-third of patients with exercise hypertension develop manifest hypertension at rest. Based on the Canada Fitness Survey data indicating that about 2% of the population demonstrate exercise hypertension, it can be estimated that approximately 200,000 Canadians will develop manifest hypertension within five years. Similar statistics are also applicable for most of the developed countries of the world.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison in young and elderly patients of pharmacodynamics and disposition of labetalol in systemic hypertension

Pharmacodynamics and pharmacokinetics of labetalol, a combined alpha- and beta-adrenoceptor antagonist drug, were studied in elderly and young hypertensive patients. After receiving intravenous labetalol, elderly patients had a greater maximal mean decrease in systolic blood pressure (BP) (39 +/- 8 vs 25 +/- 13 mm Hg, p less than 0.02); however, maximal decrease in diastolic BP was similar in elderly (18 +/- 10 mm Hg) and young (17 +/- 6 mm Hg) patients. After receiving oral labetalol, elderly patients had a greater maximal decrease in standing systolic BP (41 +/- 16 vs 16 +/- 14 mm Hg, p less than 0.001) and similar decreases in standing diastolic BP (21 +/- 7 vs 17 +/- 9 mm Hg). Sitting maximal BP decreases after oral labetalol treatment were similar in elderly and young patients (12 +/- 16 vs 17 +/- 7 mm Hg systolic and 24 +/- 6 vs 12 +/- 7 diastolic). The decrease in heart rate was greater in young patients after intravenous labetalol administration. To evaluate labetalol pharmacodynamics, a linear model was used. Slope of labetalol concentration vs systolic BP for elderly vs young patients was 0.928 +/- 1.05 vs 0.326 +/- 0.490 ng/ml X mm Hg-1 (difference not significant). The slope of labetalol concentration vs heart rate for elderly vs young patients was 0.176 +/- 0.063 vs 0.406 +/- 0.303 ng/ml X beats/min-1 (p less than 0.05), with 2 elderly patients showing no decrease in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combination therapy with amlodipine and captopril for resistant systemic hypertension

This study was conducted to assess the therapeutic utility of combining amlodipine with captopril in patients with moderate-to-severe hypertension. Patients had hypertension of WHO grades I–III, with initial mean sitting and standing diastolic blood pressure of 100–119 mm Hg (phase V) after 2–4 weeks on placebo, and had remained uncontrolled (diastolic blood pressure > 95 mm Hg) despite a further 4 weeks on low-dose captopril. Twenty-nine patients entered the computer-randomized, double-blind, placebocontrolled, 2-way crossover comparison of either amlodipine 10 mg once daily or matching placebo added to continued therapy with captopril 25 mg twice daily for 4 weeks. Patients then acted as their own control and received the alternative amlodipine/placebo treatment plus their continued captopril therapy for another 4 weeks. Once-daily amlodipine was shown to be effective when combined with captopril. Mean baseline supine systolic blood pressure decreased from 167 to 149 mm Hg and standing systolic blood pressure from 167 to 144 mm Hg. Mean supine diastolic blood pressure decreased from 105 to 92 mm Hg, and standing diastolic blood pressure decreased from 110 to 96 mm Hg. The placebo-corrected amlodipine differences in mean changes from captopril baseline were −18/−12.2 mm Hg for supine and −20.1/−11.9 mm Hg for standing systolic and diastolic blood pressures, respectively (p < 0.001 for all 4 measurements). The most common side effects encountered with amlodipine were flushing and pedal edema. The combination of amlodipine and captopril was well tolerated, and no patient discontinued therapy. No significant treatment-related effects on biochemical and hematologic parameters were noted.     

阿托伐他汀联合氨氯地平在老年高血压患者中的应用效果观察

目的观察阿托伐他汀联合氨氯地平在老年高血压患者中的应用效果。方法选取2015-02~2016-05治疗的老年原发性高血压患者116例为研究对象,按照随机数字表法分为两组,每组58例。对照组给予氨氯地平治疗。观察组在对照组基础上联合阿托伐他汀治疗。比较两组患者的降血压疗效及降血脂情况。结果观察组患者治疗2个月、4个月、6个月的收缩压及血脂水平均比对照组低,差异有统计学意义(P0.05)。结论阿托伐他汀联合氨氯地平能有效降低老年高血压患者的血压水平,提高降血脂疗效。     

When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly

The age-related changes in the functions and composition of the human body require adjustments of drug selection and dosage for old individuals. Drug excretion via the kidneys declines with age, the elderly should therefore be treated as renally insufficient patients. The metabolic clearance is primarily reduced with drugs that display high hepatic extraction ('blood flow-limited metabolism'), whereas the metabolism of drugs with low hepatic extraction ('capacity-limited metabolism') usually is not diminished. Reduction of metabolic drug elimination is more pronounced in malnourished or frail subjects. The water content of the aging body decreases, the fat content rises, hence the distribution volume of hydrophilic compounds is reduced in the elderly, whereas that of lipophilic drugs is increased. Intestinal absorption of most drugs is not altered in the elderly. Aside of these pharmacokinetic changes, one of the characteristics of old age is a progressive decline in counterregulatory (homeostatic) mechanisms. Therefore drug effects are mitigated less, the reactions are usually stronger than in younger subjects, the rate and intensity of adverse effects are higher. Examples of drug effects augmented is this manner are postural hypotension with agents that lower blood pressure, dehydration, hypovolemia, and electrolyte disturbances in response to diuretics, bleeding complications with oral anticoagulants, hypoglycemia with antidiabetics, and gastrointestinal irritation with non-steroidal anti-inflammatory drugs. The brain is an especially sensitive drug target in old age. Psychotropic drugs but also anticonvulsants and centrally acting antihypertensives may impede intellectual functions and motor coordination. The antimuscarinic effects of some antidepressants and neuroleptic drugs may be responsible for agitation, confusion, and delirium in elderly. Hence drugs should be used very restrictively in geriatric patients. If drug therapy is absolutely necessary, the dosage should be titrated to a clearly defined clinical or biochemical therapeutic goal starting from a low initial dose.     

Salt sensitivity and systemic hypertension in the elderly

Aging in industrialized societies is accompanied by increases in the incidence and prevalence of hypertension, with a disproportionately greater increase occurring among aging blacks than among aging whites. This geriatric hypertension is generally of a salt-sensitive nature with a disproportionate frequency of isolated systolic hypertension. Although salt-taste acuity declines with age, salt sensitivity among the elderly does not appear to result from a compensatory increase in salt intake. Rather, age-related increases in salt sensitivity result, in part, from a reduced ability to appropriately excrete a salt load, which is due to a decline in renal function and to a reduced generation of natriuretic substances such as prostagiandin E₂ and dopamine. Age-associated declines in the activity of membrane sodium/potassium-adenosine triphosphatase (Na/K-ATPase) may also contribute to geriatric hypertension because this results in increased intracellular sodium that may cause reduced sodium-calcium exchange and thereby increase intracellular calcium and vascular resistance. Reductions in cellular calcium efflux due to reduced calcium-ATPase activity may similarly cause an increase in intracellular calcium and vascular resistance. Increasing dietary calcium intake may represent an effective nonpharmacologic treatment for some salt-sensitive persons because it appears to reduce intracellular calcium by (1) suppressing parathyroid hormone-mediated calcium influx, (2) increasing Na/K-ATPase activity, and (3) reducing intravascular volume due to calcium-induced natriuresis.     

氨氯地平对老年轻中度高血压患者靶器官的保护作用

目的探讨氨氯地平降压治疗对老年轻中度高血压患者颈动脉内-中膜厚度(IMT)、肾功能及心脏结构与功能的影响。方法选取40例轻中度老年原发性高血压患者,经氨氯地平(5~10 mg/d)治疗血压达标后,维持治疗。随访半年至一年,观察IMT、肾功能以及心脏结构与功能的变化。结果高血压患者服用氨氯地平半年后,收缩压较服药前无明显下降(P0.05),仅舒张压较治疗前显著下降(P0.05);治疗一年后,收缩压和舒张压较治疗前下降(P均0.05)。24 h动态血压在服药半年及一年后均较治疗前有显著下降(P均0.01)。与服药前相比较,治疗半年及一年后的IMT明显降低(P均0.01);尿β2-微球蛋白(β2M)、微量白蛋白(ALB)及血肌酐明显低于治疗前(P均0.01);左室舒张末内径(LVEDd)较治疗前有所增加,二尖瓣舒张期血流A峰速度(PAV)较治疗前有明显下降,E/A比值较治疗前有显著升高(P均0.01);左心室重量指数(LVMI)、室间隔厚度(IVST)、左室后壁厚度(PWT)、二尖瓣舒张期血流E峰速度(PEA)和左室射血分数(EF)的均值较治疗前均无明显差异。结论服用氨氯地平降压治疗后,对颈动脉IMT、肾功能有明显改善作用,并且能改善心脏舒张功能,但对收缩功能无明显改善。     

Arterial vasodilator effects of the dihydropyridine calcium antagonist amlodipine alone and in combination with verapamil in systemic hypertension

The arterial vasodilator properties of the dihydropyridine calcium antagonist amlodipine were compared with the effects of vascular muscle cyclic guanosine monophosphate production by sodium nitroprusside and with the effects of a combined infusion of amlodipine and the nondihydropyridine calcium antagonist verapamil in 8 untreated patients with primary hypertension. Arterial vasodilation was assessed by measurement of changes of forearm blood flow by mercury in Silastic strain-gauge plethysmography during brachial artery drug infusions. Forearm blood flow increased during amlodipine infusions (0.4 to 45 micrograms/min/100 ml forearm tissue) from 2.9 +/- 1.7 to a maximum of 23.6 +/- 7.6 ml/min/100 ml (687%), while sodium nitroprusside caused an increase from 3.0 +/- 1.8 to 16.2 +/- 5.4 ml/min/100 ml (449%), attesting to the importance of transmembrane calcium influx for the maintenance of vascular tone. The addition of verapamil 40 micrograms/min/100 ml to an infusion of amlodipine 44.5 micrograms/min/100 ml resulted in a further increase of forearm blood flow, from 23.6 +/- 7.6 to 34.4 +/- 9.8 ml/min/100 ml (p less than 0.05). The precise mechanisms of this finding have yet to be elucidated but may be due to interactions of the effects of the binding of these 2 chemically and pharmacologically different calcium antagonists to distinct binding sites at calcium channels. The clinical relevance of this observation for the treatment of coronary artery disease and systemic hypertension needs further study.     

Nebivolol vs amlodipine as first-line treatment of essential arterial hypertension in the elderly

The antihypertensive efficacy of nebivolol and amlodipine and their tolerability were compared in a multicentre, randomized, active-controlled, double-blind parallel-group trial in elderly patients with mild to moderate essential arterial hypertension. One hundred and eighty-four subjects aged > or = 65 years were screened. After a run-in phase of 4 weeks, only 168 of these were randomized with either nebivolol 2.5-5 mg daily (n = 81) or amlodipine 5-10 mg daily (n = 87) over a period of 12 weeks. The response rate to treatment and the changes of sitting diastolic blood pressure (BP) at week 12 were similar between the two groups. A lower sitting systolic BP (SBP) was detected with amlodipine at week 4 (p < 0.05) and at week 8 (p < 0.05). Standing BP showed no changes between the two groups; only SBP was lower with amlodipine at week 8 (p < 0.05). Heart rate was lower at all treatment visits with nebivolol (p < 0.001). The incidence of adverse events was no different between the two groups; however the incidence of headache and ankle oedema was significantly higher with amlodipine (p < 0.05). In elderly subjects with essential hypertension, the antihypertensive efficacy of nebivolol and amlodipine was similar. Both drugs were well tolerated, although amlodipine was accompanied by higher incidence of drug-related adverse events.     

氨氯地平和西拉普利逆转高血压左室肥厚的效应对比

目的　评价并比较氨氯地平（ＡＭ） 和西拉普利（ ＣＩ） 对老年高血压左室肥厚（ ＬＶＨ） 的逆转作用和左室舒张功能的影响。　方法　５０ 例合并ＬＶＨ 的高血压患者,随机分为ＡＭ 和ＣＩ 治疗组,分别于治疗前及治疗２４周后进行血压测量和超声心动图检查。　结果　ＡＭ 和ＣＩ 治疗后均能显著降低血压（ Ｐ 均＜ ０－０１） ;左室质量指数（ＬＶＭＩ） 均显著下降［ 由（１６４－７ ±３８－２）ｇ·ｍ － ２和（１６３－３ ±３９－２）ｇ·ｍ －２ 分别降至（１３１－０ ±２５－４）ｇ·ｍ －２ 和（１３０－７ ±２６－７）ｇ·ｍ －２,Ｐ 均＜ ０－０１）］ ;左室舒张功能改善（ Ｐ 均＜ ０－０１） ,２ 组间降压幅度、ＬＶＭＩ、Ｅ／ Ａ 变化无显著差异（ Ｐ＞０－０５） 。　结论　ＡＭ 和ＣＩ 每日１ 次给药均可作为治疗高血压伴ＬＶＨ 的有效药物     

Nutrition in the elderly: An overview

Older people develop special nutritional requirements and acquire dietary habits that put them at increased risk of various nutritional deficits. Aging and nutritional decays act in conjunction with diseases, medications, and economic constraints to diminish overall health in elderly patients.     

缬沙坦联合氨氯地平或氢氯噻嗪对老年高血压患者血压变异性的影响

目的 观察比较缬沙坦分别联合氨氯地平或氢氯噻嗪对老年高血压患者血压及其变异性的影响.方法 选取138例老年高血压患者,随机分为两组,A组70例给予口服缬沙坦80 mg联合氨氯地平5mg qd;B组68例给予口服缬沙坦80 mg联合氢氯噻嗪12.5 mg qd.分别在治疗前、治疗8w时进行24 h动态血压监测,观察24 h、白天与夜间收缩压变异性(systolic blood pressure variability,SBPV)和舒张压变异性(diastolic blood pressure variability,DBPV);24h、白天与夜间平均收缩压(systolic blood pressure,SBP)和平均舒张压(diastolic blood pressure,DBP).结果 与治疗前比较治疗后第8周A组与B组24 h、白天、夜间SBP、DBP、SBPV均下降(P＜0.05),A组下降幅度均大于B组(P＜0.05).A组治疗8w后,DBPV均有下降(分别地,P＜0.05),而B组无变化,组间比较差异有统计学意义(P＜0.05).结论 缬沙坦联合氨氯地平或氢氯噻嗪治疗均能有效控制老年高血压患者的血压,但缬沙坦联合氨氯地平具有更佳的血压达标率和更低的血压变异性.     

Beneficial cardiometabolic actions of telmisartan plus amlodipine therapy in elderly patients with poorly controlled hypertension

Background

There is a growing body of evidence that blood pressure (BP) level is one of the major determinants of cardiovascular morbidity and mortality in individuals, including elderly people. However, to achieve a target BP level in the elderly is more difficult compared with patients aged <65 years. Current guidelines recommend combination drug therapy with different modes of action for the treatment of elderly patients with moderate hypertension (HT). However, the optimal combination regimen is not well established in elderly HT.

Hypothesis

We hypothesized that combination therapy of telmisartan plus amlodipine would exert favorable cardiometabolic actions in elderly HT.

Methods

Seventeen elderly patients with essential HT who failed to achieve a target home BP level with treatment of 5 mg amlodipine plus 80 mg valsartan or 8 mg candesartan for at least 2 months were enrolled. Then the patients were assigned to replace their valsartan or candesartan with 40 mg telmisartan. The subjects were instructed to measure their own BP at home every day during the study periods.

Results

Replacement of valsartan or candesartan by telmisartan in amlodipine‐treated elderly hypertensive patients showed a significant reduction in morning home systolic BP and evening home systolic and diastolic BP at 12 weeks. Switching to telmisartan significantly increased serum adiponectin level.

Conclusions

Our present study suggests that combination therapy with telmisartan plus amlodipine may exert more beneficial cardiometabolic effects in elderly patients with HT compared with valsartan or candesartan plus amlodipine treatment. © 2011 Wiley Periodicals, Inc. This work was supported in part by Grants of Collaboration with Venture Companies Project from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to S.Y.). The authors have no other funding, financial relationships, or conflicts of interest to disclose.     

An overview of PCI in the very elderly

Cardiovascular disease, and in particular ischemic heart disease (IHD), is a major cause of morbidity and mortality in the very elderly (> 80 years) worldwide. These patients represent a rapidly growing cohort presenting for percutaneous coronary intervention (PCI), now constituting more than one in five patients treated with PCI in real-world practice. Furthermore, they often have greater ischemic burden than their younger counterparts, suggesting that they have greater scope of benefit from coronary revascularization therapy. Despite this, the very elderly are frequently under-represented in clinical revascularization trials and historically there has been a degree of physician reluctance in referring them for PCI procedures, with perceptions of disappointing outcomes, low success and high complication rates. Several issues have contributed to this, including the tendency for older patients with IHD to present late, with atypical symptoms or non-diagnostic ECGs, and reservations regarding their procedural risk-to-benefit ratio, due to shorter life expectancy, presence of comorbidities and increased bleeding risk from antiplatelet and anticoagulation medications. However, advances in PCI technology and techniques over the past decade have led to better outcomes and lower risk of complications and the existing body of evidence now indi-cates that the very elderly actually derive more relative benefit from PCI than younger populations. Importantly, this applies to all PCI set-tings: elective, urgent and emergency. This review discusses the role of PCI in the very elderly presenting with chronic stable IHD, non ST-elevation acute coronary syndrome, and ST-elevation myocardial infarction. It also addresses the clinical challenges met when considering PCI in this cohort and the ongoing need for research and development to further improve outcomes in these challenging patients.     

Comparison of effects of nisoldipine-extended release and amlodipine in patients with systemic hypertension and chronic stable angina pectoris

The efficacy and safety of nisoldipine-extended release (ER) and amlodipine were compared in a 6-week multicenter, randomized, double-blind, double-dummy, parallel group, titration-to-effect trial in patients with stage 1 to 2 systemic hypertension (90 to 109 mm Hg diastolic blood pressure [BP]) and chronic stable angina pectoris. After a 3-week placebo run-in period, patients (n = 120) were randomly assigned to active treatment with either nisoldipine-ER (20 to 40 mg) or amlodipine (5 to 10 mg) once daily, titrated as necessary after 2 weeks to achieve diastolic BP <90 mm Hg. After 6 weeks, the mean reduction in systolic/diastolic BP from baseline was 15/13 mm Hg with nisoldipine-ER and 13/11 mm Hg with amlodipine (p = NS/p = NS). Both drugs resulted in similar BP responder rates (diastolic BP <90 mm Hg in 87% of patients who received nisoldipine-ER and 78% of patients on amlodipine, p = NS) and anti-ischemic responder rates (increasing exercise time >20% in 20% and 27%, respectively [p = NS], and increasing exercise time >60 seconds in 32% and 29% of patients, respectively [p = NS]. Also, after 6 weeks of active therapy, there was a similar mean increase in total exercise duration (23 seconds in the nisoldipine-ER group and 21 seconds in the amlodipine group, p = NS). Neither drug increased heart rate and both decreased frequency of anginal episodes. Adverse events were infrequent, and typically were vasodilator-related effects (including headache and peripheral edema) that occurred with somewhat higher incidence in the nisoldipine-ER group. Thus, nisoldipine-ER and amlodipine provided comparable antihypertensive and anti-ischemic efficacy, and both were generally well tolerated.     

An overview of diabetes mellitus in older persons.

Diabetes mellitus is very common in older persons. Changes in exercise habits, body habitus, leptin, amylin, tumor necrosis factor alpha, and nitric oxide all play a role in the pathogenesis of age-related insulin resistance. In older persons elevated glucose levels not only produce retinopathy, neuropathy, and nephropathy but also decrease quality of life, pain tolerance, cognition, and functional status and increase injurious falls, nocturia, incontinence, pressure ulcers, and orthostatic hypotension. The availability of multiple new therapies has enhanced the ability of physicians to improve glycemic control in older persons without unacceptable levels of hypoglycemia. Caregivers play an important role in the management of older diabetics. Depression increases mortality rate and hospital admissions in older diabetics. In many nursing homes the quality of diabetic care is marginal. A new causative theory of the metabolic syndrome involving cytokines and nitric oxide-the NO cytokine theory-is proposed.