Oxprenolol in the treatment of hypertension in the elderly

Controversy continues to surround the value of drug treatment of hypertension in the elderly. Epidemiologic evidence implicates hypertension as a major risk factor in the precocious development of stroke and coronary heart disease in the elderly subject as clearly as it is implicated in the younger person. The hemodynamic and neuroendocrine profiles of the older patient with essential hypertension are similar to those of younger patients in the stable phase of the disease. However, the arterial ravages induced by many years of sustained hypertension render the circulation of the elderly subject more sensitive to pharmacologic intervention. The benefit-risk ratio of most antihypertensive drugs appears to be inversely related to age. Diuretics reduce the blood pressure at rest but have no influence on the increases in systolic pressure during normal activity; in addition, they carry potentially serious metabolic hazards in the elderly hypertensive patient. Centrally acting drugs likewise lower the blood pressure at rest without influencing the high systolic pressures induced by exercise. They also enhance the tendency to endogenous depression. Adrenergic-neurone blocking drugs and alpha-adrenoceptor antagonists are contraindicated because of the frequency of impaired cardiovascular reflexes in the elderly. The beta-blocking drugs can reduce the risk of coronary and cerebrovascular disease in the older patient with hypertension. They appear to be well tolerated, but because of their impaired metabolic handling in many elderly patients they should probably be used in smaller doses than those prescribed in younger patients. The influence of antihypertensive treatment on cardiovascular morbidity and mortality in the elderly hypertensive patient is not known.     

Factors influencing the systolic blood pressure response to drug therapy

In the early stage of hypertension, diastolic blood pressure has greater prognostic importance, but in the elderly, systolic blood pressure is the most important marker of cardiovascular complications. Therefore, the need for more strict control of this component of blood pressure must be reconsidered. The benefit obtained in different studies in the elderly suggests that the treatment of isolated systolic hypertension is associated with a reduction in overall cardiovascular mortality of 22%, in coronary heart disease mortality of 26%, and in stroke mortality of 33%. However, a higher percentage of patients (73%) attain the diastolic goal of <90 mm Hg, while only 34% have systolic pressure reduced to <140 mm Hg. In a review of randomized trials comparing at least four different antihypertensive drugs, significant differences in systolic blood pressure reduction have not been demonstrated, except in black populations, in whom calcium channel blockers and diuretics seem to be more effective. In patients with isolated systolic hypertension, data are inconclusive, but calcium channel blockers and diuretics appear to lower blood pressure to a greater degree than do other antihypertensive drugs. Two main predictors of difficulty in controlling systolic blood pressure are the baseline blood pressure and the presence of diabetes. Other predictors are the duration of arterial hypertension, older age, the presence of target organ damage and associated clinical conditions (myocardial infarction, stroke, chronic renal failure), and an elevated serum uric acid level. It appears that the profile of patients with a poorer therapeutic response includes a greater severity of hypertension and/or the presence of cardiovascular disease.     

Is there a preferred antihypertensive therapy for isolated systolic hypertension and reduced arterial compliance?

Isolated systolic hypertension (ISH) is the most common type of hypertension and the most difficult type to control with antihypertensive therapy. ISH, by definition, is wide pulse pressure hypertension resulting largely from excessive large artery stiffness and representing an independent risk factor for cardiovascular disease in the older aged population. Two major intervention studies of ISH have shown significant benefit in reducing systolic blood pressure with active drug therapy, including thiazide diuretics and calcium receptor antagonists. The optimal treatment strategy is to maximize reduction in systolic blood pressure and to minimize reduction in diastolic blood pressure, thereby reducing pulse pressure. All classes of antihypertensive drugs reduce pulse pressure by means of lowering peripheral resistance, but certain drugs like nitrates, angiotensin converting enzyme inhibitors, and other drugs affecting the renin-angiotensin system have multiple actions that improve large artery stiffness and early wave reflection and are especially useful in treating ISH in the elderly.     

Hypertension in the elderly: a review of the importance of systolic blood pressure elevation

The elderly, those 65 years of age and older, will account for 20% of the population by the year 2040. Hypertension affects more than one half of the elderly and its prevalence continues to increase with age. The presence of hypertension confers an increased risk of stroke, congestive heart failure, coronary heart disease, end-stage renal disease, and death. Although both diastolic and systolic blood pressure elevations are independently associated with increased cardiovascular risk in the younger individual, as vascular compliance becomes reduced at age 60, an increasing systolic blood pressure and lower diastolic blood pressure (or wider pulse pressure) increase cardiovascular risk in the elderly. Isolated systolic hypertension is the most common form of hypertension seen in the elderly. Lifestyle modification, including weight loss and salt restriction, reduces blood pressure, and may decrease the need for pharmacologic therapy. When the systolic blood pressure is 160 mm Hg or more and the diastolic blood pressure is <90 mm Hg, the initial use of a diureticbased or calcium channel blocker-based regimen improves outcome. Alpha blocker therapy should not be used as initial monotherapy. Most elderly hypertensives will require two to three drugs to achieve the present blood pressure goal of <140 mm Hg. Caution should be exercised when lowering diastolic pressure to <55 mm Hg in those with isolated systolic hypertension. Although side effects of therapy are no more likely to occur in the elderly than in the younger individual with hypertension, blood pressure reduction should be accomplished gradually.     

收缩性高血压的处理

近年来的循证医学实践给收缩性高血压(SH)的处理,带来新的证据和理念。SH患者收缩压的目标值通常定在<140mmHg,对于合并冠心病、糖尿病和肾脏病的老年患者的目标血压还无明确的结论。J型曲线存在于SH患者,应引起警惕。老年人以容量性高血压多见,噻嗪类利尿剂和二氢吡啶类钙拮抗剂是适宜的治疗选择,血管紧张素转换酶抑制剂和血管紧张素受体阻断剂也可用于SH的初始和维持用药。联合用药已成为降压达标的最重要的治疗策略。     

Exercise in patients with hypertension

A progressive increase in arterial stiffness with aging contributes to systolic hypertension that results in left ventricular hypertrophy and concentric remodeling in the elderly. Lowering of blood pressure in older adults reduces cardiovascular risks. Endurance exercise training can lower blood pressure in older adults with mild (grade I) hypertension. However, the blood pressure-lowering effect of exercise training, compared with antihypertensive medications, is generally modest for both systolic and diastolic blood pressure. Exercise training alone is likely to be ineffective in lowering blood pressure sufficiently in older adults with moderate to severe (grade II and higher) hypertension. However, exercise and weight loss may potentiate the effects of antihypertensive medications in these subjects. Low-intensity endurance exercise training appears to be most effective in reducing blood pressure in older hypertensive adults. Metabolic adaptations to exercise training can significantly reduce other risk factors for coronary artery disease and atherosclerosis, in addition to reducing blood pressure. Endurance exercise training improves exercise capacity and quality of life, and can induce a modest but significant regression of left ventricular hypertrophy and remodeling in older adults with hypertension.     

The diastolic blood pressure in systolic hypertension

Because antihypertensive therapy is effective in elderly patients with isolated systolic hypertension, attention has been focused on the systolic blood pressure as a predictor of cardiovascular risk. However, it is a normal diastolic pressure that separates patients with isolated systolic hypertension from those with essential hypertension. The normal diastolic and elevated systolic pressures are largely due to age-related stiffening of the aorta. An indistensible aorta causes the pressure pulse to travel faster than normal, where it is quickly reflected off the peripheral resistance. The reflected wave then returns to the central aorta in systole rather than diastole. This augments the systolic pressure further, increasing cardiac work while reducing the diastolic pressure, on which coronary flow is dependent. The potential harm of further reducing the diastolic pressure with antihypertensive therapy, especially in patients with coronary heart disease, underlies the controversial "J curve." By decreasing the blood pressure, all antihypertensive agents improve aortic distensibility, but no agents do so directly; the nitrates come the closest. Such an agent would be useful because any therapeutic increase in aortic distensibility would decrease systolic pressure without greatly reducing diastolic pressure. The problem is complicated by the suspected inaccuracy of the cuff technique in predicting the aortic diastolic pressure. New noninvasive methods to predict the aortic diastolic pressure may help in the future. At present, the combination of a high systolic and normal diastolic pressure-a widened pulse pressure-seems to be the best predictor of cardiovascular risk in patients with hypertension or heart disease. Patients with isolated systolic hypertension should be treated, but marked diastolic hypotension should be avoided.     

Systolic hypertension in the elderly: addressing an unmet need

Systolic hypertension is a major public health issue in the elderly and is often under-recognized and under-treated. The concept that systolic blood pressure increases with age should be considered a pathophysiologic concept. Aging of the cardiovascular system is accompanied by endothelial dysfunction, activation of the renin-angiotensin system and, consequently, vascular remodeling. This process leads to an increase in large artery stiffness and an increase in arterial wave reflections to the heart. These processes in daily clinical practice translate to an increase in systolic blood pressure, which is associated with increased cardiovascular morbidity and mortality. Evidence-based medicine recommendations to treat systolic hypertension in the elderly are based on landmark and recent clinical trials, which clearly demonstrated that treatment of isolated systolic hypertension is associated with significant decreases in cardiovascular morbidity and mortality. However, treatment of systolic hypertension in older adults remains disappointing because therapeutic goals often are not reached. Therefore, emphasis should be placed on the treatment of systolic hypertension in the elderly, and there is need for more effective, individualized antihypertensive therapy.     

Hypertension in the Elderly

Hypertension as a risk factor for cardiac and cerebrovascular morbidity and mortality poses a major health problem for our increasingly elderly population. Recent trials have shown large reductions in stroke, heart failure, and coronary artery disease when elderly hypertensive patients are treated. These benefits are also seen in elderly patients with isolated systolic hypertension. The elderly patient with hypertension should be investigated and managed in a similar manner to their younger counterpart. Nonpharmacological measures, such as dietary salt and calorie restriction, regular exercise, cessation of smoking, and reduction of excess alcohol intake, should be recommended. If these are insufficient, pharmacological treatment should be tailored to the individual patient. Diuretics have been shown to improve outcome measures in the elderly. Other antihypertensive drugs may be added or substituted depending on the patient's blood pressure response to therapy and their comorbid conditions. If all elderly hypertensive patients were treated, a major reduction in cardiovascular and cerebrovascular mortality and morbidity would result. Consideration also needs to be given to nonpharmacological treatment, particularly salt restriction in older subjects where blood pressure is at the upper limit of normal, as this would also result in a major reduction in cardiovascular morbidity and mortality.     

Arterial hypertension and systolic left ventricular dysfunction: therapeutic approach

Arterial hypertension is a cardinal precursor of congestive heart failure, and diastolic dysfunction is the most frequent mechanism for it. Systolic left ventricular dysfunction, although less frequent, has a worse prognosis. Most cases of systolic dysfunction in patients with hypertension is due to acute myocardial infarction, although other mechanisms can be involved. In some studies, non-ischemic hypertensive systolic dysfunction is the etiology of chronic heart failure in up to 10% of patients with dilated cardiomyopathy. Diastolic dysfunction and left ventricular hypertrophy are also associated with a higher risk of heart failure and systolic dysfunction. Given the poor prognosis of patients with congestive heart failure and dilated cardiomyopathy, it is fundamental to try to prevent the development of left ventricular dysfunction by means of a correct control of blood pressure, regression of left ventricular hypertrophy and prevention of coronary artery disease. When systolic dysfunction is established, angiotensin converting enzyme inhibitors are the treatment of choice; diuretics and digoxin can be added in patients with overt congestive heart failure. Recent studies suggest that other drugs, such as carvedilol and losartan, can be beneficial, but current evidence is still scarce.     

Renal and cardiovascular protection associated to antihypertensive treatment in the elderly

The incidence of arterial hypertension increases with age in such a way that by the age of 60 the incidence is greater than 50% in men and women. This increase is particularly relevant if we consider the changes in systolic blood pressure (increase) and diastolic blood pressure (decrease) in relation to age and as a consequence in the reduction of vascular compliance which is common in men and women over the age of 60. These disorders are associated to artheriosclerosis and the corresponding increase in pulse pressure. It is for these reasons that the most common form of hypertension is isolated systolic hypertension (SBP > 140 mmHg and SBP < 90 mmHg), which represents 50% of hypertensive patients in the elderly population. Isolated systolic hypertension is also associated to an increase in cardiovascular disease (MI, stroke), increasing the risk of mortality four times. In elderly people, hypertension and isolated systolic hypertension are risk factors that can be managed. Today there is sufficient evidence from clinical trials that show a clear benefit in the reduction of the cardiovascular and renal risk associated to the antihypertensive treatment in the elderly, at least when the blood pressure is greater than 160/90 mmHg. The target blood pressure figures to control in the elderly person, probably below 160/90 mmHg, still need to be determined.     

Hypertension in older people: part 2

There is overwhelming evidence that pharmacologic treatment of isolated systolic hypertension (ISH) (systolic blood pressure >or=140 mm Hg and diastolic blood pressure <90 mm Hg) reduces cardiovascular events and extends longevity in the elderly; in the very old (80 years or older), the evidence supports decreased incident stroke and heart failure, but is less convincing in terms of longevity. Thus, the inherent increased risk for ISH vascular events highlights the importance of its control. Importantly, ISH in the elderly, primarily related to large artery stiffness, remains more difficult to control than diastolic hypertension in the young, which is primarily related to increased peripheral vascular resistance. Appropriate lifestyle and pharmacologic intervention is indicated in individuals with systolic blood pressure >or=140 mm Hg in general and >or=130 mm Hg in persons with diabetes or chronic kidney disease. Lifestyle intervention may reduce the need for extensive antihypertensive therapy and minimize associated cardiovascular risk factors. To date, only a small percentage of older ISH patients are being treated to goal. Reaching target systolic blood pressure levels most often requires the use of polypharmacy that includes a diuretic and perhaps specific agents that target arterial stiffness and early wave reflection.     

Epidemiologic appraisal of hypertension as a coronary risk factor in the elderly

Five decades of epidemiologic research has established elevated blood pressure as a major contributor to atherosclerotic cardiovascular diseases in the elderly, including coronary heart disease. Clinicians formerly favored the diagnosis and treatment of hypertension in terms of the diastolic blood pressure and categorical "hypertension." Epidemiologic data now emphasize the essential role of systolic blood pressure, pulse pressure, and a graded influence of blood pressure, even within the high-normal range. The risk of coronary heart disease, the most common lethal sequela of hypertension, increases with the extent of risk factor clustering. Among hypertensive persons, about 39% of coronary events in men and 68% in women are attributable to the presence of two or more additional risk factors. When risk factor clustering is associated with glucose intolerance, obesity, and dyslipidemia, it may be attributed to insulin resistance promoted by abdominal obesity. Other hazardous influences often accompanying hypertension in the elderly are the presence of an elevated heart rate, elevated levels of fibrinogen, and left ventricular hypertrophy. Because clustering with other risk factors is characteristic of hypertension in the elderly, it is essential to screen for them and for the presence of comorbid cardiovascular diseases, target organ disease, and subclinical vascular disease likely to be present. Multivariate risk assessment profiles enable global estimation of hypertensive risk of developing coronary heart disease. Hypertensive elderly patients are more appropriately targeted for antihypertensive therapy by such risk stratification than by relying solely on the severity of the blood pressure elevation. The goal of therapy should be to improve the multivariate risk profile as well as the level of the blood pressure.     

Systolic hypertension: occurrence and treatment in a defined community.

Systolic hypertension, a disorder occurring predominantly in the elderly, is associated with an increased incidence of stroke and coronary artery disease. Based on the supposition that it is a risk factor, many authorities have urged that it be treated. This report concerns an experience in treating systolic hypertension in a defined ambulatory population of 898 hypertensive subjects in a work-site program. The systolic hypertension group (N = 39) was compared with a matched diastolic hypertension group and with a matched systolic/diastolic hypertension group (N = 39 each). The patients with systolic hypertension responded to standard treatment (chiefly with diuretics), but less satisfactorily than did the patients with diastolic hypertension. Side effects or toxicity were uncommon and did not interfere with the therapeutic regimen. However, the ultimate value of such therapy in the prevention of vascular complications remains to be determined.     

Prevention of cardiovascular events by treating hypertension in older adults: an evidence-based approach

Hypertension in older adults is not well controlled in clinical practice. Isolated systolic hypertension is often more difficult to manage. A systematic PubMed search was conducted to look for evidence showing benefits of lowering blood pressure (BP) in older hypertensive adults. Lowering BP in these individuals significantly reduces the risk of coronary artery disease, stroke, and cardiovascular and all-cause mortality. Based on trial evidence, a low-dose diuretic should be considered the most appropriate first-step treatment for preventing cardiovascular morbidity and mortality. Therapy with >1 medication is often necessary to reduce BP in these patients. There is unequivocal evidence that cardiovascular events can be prevented in older adults, even those older than 80 years, by treating hypertension.     

Systolische Hypertonie—Treat or Not to Treat?

HEMODYNAMICS: Elevated diastolic as well as elevated systolic blood pressure substantially contribute to the increase of cardiovascular risk. Conclusive results have proven that lowering diastolic and/or systolic blood pressure can reduce cardiovascular risk. There is evidence that not only the absolute values for diastolic and systolic blood pressure alone but also the pulse pressure as an additional indicator of cardiovascular risk have to be considered. The prevalence of isolated systolic hypertension increases with age. Remodeling of the arterial wall with increase of collagen and decrease of elastic fibers are leading to an impaired arterial compliance. Decreased compliance and acceleration of the pulse wave velocity can elevate systolic and lower diastolic blood pressure. In consequence cardiac stress and pulse pressure will rise. CONCLUSION: There is a strong correlation in elderly patients between cardiovascular mortality and morbidity and systolic blood pressure. Antihypertensive therapy is able to lower cardiovascular event rate in elderly patients with isolated systolic hypertension with a predominant risk reduction for stroke.     

社区老年人群踝间血压差异的检出率调查

目的探讨佛山市顺德区容桂街道老年人踝间血压差异(IAND)情况。方法选择老年人1032例,被调查且资料完整人数929例。调查的项目有年龄、性别、吸烟史、高血压家族史、高血压史及服用降压药物史、糖尿病史、身高和体重;检测空腹血糖、TC、TG、HDL-C和LDL-C。结果容桂街道老年人群的踝间收缩压差异检出率为28.6%,踝间舒张压差异检出率为16.9%。总体上右踝收缩压明显高于左踝,左踝舒张压明显高于右踝(P<0.05)。男性右踝收缩压和舒张压高于左踝,但差异无统计学意义;女性左踝舒张压明显高于右踝。踝高收缩压和踝高舒张压人群踝间收缩压差异检出率和踝间舒张压差异检出率均明显高于无踝高血压人群。左右踝部收缩压的绝对差值和左右踝部收缩压的绝对差值/踝收缩压与冠心病危险因素积分呈正相关。结论容桂街道老年人群踝高收缩压和踝高舒张压是影响IAND检出率的主要因素。     

Benefits and risks of antihypertensive medications in the elderly

Hypertension is highly prevalent in older age and accounts for a large proportion of cardiovascular (CV) morbidity and mortality worldwide. Isolated systolic hypertension is more common in the elderly than younger adults and associated with poor outcomes such as cerebrovascular disease and acute coronary events. International guidelines are inconsistent in providing recommendations on optimal blood pressure targets in hypertensive elderly patients as a result of the limited evidence in this population. Evidence from clinical trials supports the use of antihypertensive drugs in hypertensive elderly patients due to benefits in reducing CV disease and mortality. However, elderly participants in these trials may not be typical of elderly patients seen in routine clinical practice, and the potential risks associated with use of antihypertensive drugs in the elderly are not as well studied as younger participants. Therefore, the purpose of this review was to provide a comprehensive summary of the benefits and risks of the use of antihypertensive drugs in elderly patients (aged ≥65 years), highlighting landmark clinical trials and observational studies. We will focus on specific outcomes relating to the benefits and risks of these medications in hypertensive elderly patients, such as CV disease, cognitive decline, dementia, orthostatic hypotension, falls, fractures, cancer and diabetes, in order to provide an update of the most relevant and current evidence to help inform clinical decision‐making.     

血压与冠状动脉造影病变的关系

目的研究血压与冠状动脉病变的关系。方法选择可疑冠心病患者540例,根据冠状动脉有无病变分为病变组和无病变组;根据冠状动脉病变的范围分为单支血管病变组、双支血管病变组和三支血管病变组。所有患者入院后测量血压,并对每一个患者进行高血压、吸烟和糖尿病病史的调查,测定血脂水平。采用Judkins法进行冠状动脉造影。结果病变组高血压病程(5.85±8.87年)、收缩压(133±29 mm Hg)、舒张压(83±13 mm Hg)、脉压(51±17 mm Hg)及平均压(100±14 mm Hg)均明显高于无病变组(分别为1.78±4.27年、125±21 mm Hg、80±13mm Hg4、8±15 mm Hg和97±15 mm Hg)(P<0.05)。三支血管病变组高血压病程、收缩压和脉压水平(分别为7.42±10.10年、137±21 mm Hg和54±17 mm Hg)均高于单支血管病变组(分别为4.51±7.21年、132±19 mm Hg和49±16 mm Hg)和双支血管病变组(分别为5.76±8.79年1、34±23 mm Hg和52±17 mm Hg)(P<0.05)。随着高血压病程增加、收缩压、脉压及平均压水平的增高,冠状动脉病变狭窄程度逐渐增大;经多因素回归分析高血压病程(OR值=0.139,P<0.05)、年龄(OR值=1.045,P<0.05)等因素是冠心病发生独立的危险因素。结论随着年龄增大和高血压病程增加,患冠心病的机会增加,并且收缩压和脉压的升高对冠状动脉的危害性较大。     

Pulse pressure as a risk factor for cardiovascular events in the MRC Mild Hypertension Trial.

OBJECTIVES: The aim of this study was to determine whether pulse pressure is a risk factor for coronary artery disease using data from the MRC trial of treatment of mild hypertension, and whether the effect of anti-hypertensive drug therapy on pulse pressure may be a determinant of outcome in treated patients. METHODS: Logistic regression and Cox regression analyses were used to compare systolic and diastolic blood pressure, pulse pressure and mean blood pressure as predictors of coronary events and stroke in the MRC Mild Hypertension Trial. The effects of anti-hypertensive drug treatment with bendrofluazide and propranolol on pulse pressure were assessed using 1-year follow-up data. Event rates in the placebo-treated group and responses to anti-hypertensive treatment were measured in quartiles of age-adjusted entry pulse pressure. A 'four-corners' analysis was performed, with subjects divided into the upper and lower halves of the distributions of systolic and diastolic blood pressure at entry. RESULTS: Pulse pressure was a stronger predictor of coronary events than systolic, diastolic or mean blood pressure in males by logistic regression. Pulse pressure was similar to systolic pressure as a coronary event predictor on Cox regression. Stroke was predicted most strongly by mean blood pressure. Fatal and non-fatal coronary event rates increased progressively in ascending quartiles of age-adjusted pulse pressure, but there was also a strong correlation with systolic blood pressure. The values of partial logistic regression coefficients in models containing both systolic and diastolic blood pressure also supported a role for pulse pressure in predicting coronary events and for mean blood pressure in predicting stroke. Coronary risk, but not stroke, was inversely related to diastolic blood pressure in the four-corners analysis. In a Cox model, regressions of coronary event probability on systolic blood pressure at entry were significantly and inversely related to diastolic blood pressure categorized in quartiles. Bendrofluazide but not propranolol decreased pulse pressure significantly and was associated with a reduction in cardiovascular events overall, but no definite relationship between the effect of drugs on pulse pressure and specific responses to treatment was seen. CONCLUSION: Pulse pressure is a strong risk factor for coronary events in untreated hypertensive male subjects in the MRC Mild Hypertension Trial, whereas stroke is best predicted by mean blood pressure. Bendrofluazide and propranolol have different effects on pulse pressure which may be related to their relative efficacy in the treatment of hypertension, but this possibility requires further study in more suitable populations.