Barriers to achieving blood pressure treatment targets in elderly hypertensive individuals.

High blood pressure (BP) is highly prevalent among the elderly, and even with pharmacological therapy BP is difficult to control to guideline recommended levels. Although poor compliance to therapy is associated with less BP control, little is known regarding other barriers to attaining on-treatment target BP. This study examined factors associated with achieving on-treatment target BP in 6010 hypertensive participants aged 65-84 years from the Second Australian National Blood Pressure study. Participants were followed for a median of 4.1 years, with BP monitored every 6 months. 'Target BP' was defined as a reduction of systolic/diastolic BP of at least 20/10 mm Hg and BP <160/90 mm Hg from randomization in two consecutive follow-up visits. Cox regression was used to identify factors associated with achieving target BP from a number of baseline and in-study factors. Mean BP at randomization was 168/91 mm Hg and patients had a median of 9 (range: 2-20) study visits. Target BP was achieved in 50% of patients. Demographic factors associated with achieving target BP were male gender, living in a regional area; and clinical factors included history of antihypertensive therapy, increased plasma creatinine, lower pretreatment pulse pressure and in-study use of multiple BP-lowering drugs. Those aged >80 years and seeking care from multiple doctors (hazard ratio 0.40, 95% confidence interval 0.36-0.45, P<0.001) were less likely to achieve target BP. These findings identify clinical markers that can be targeted for intervention, but also demographic factors related to service delivery, which may provide further opportunity for achieving better BP control in hypertensive elderly.

General practitioner participation in the second Australian National Blood Pressure Study (ANBP2).

1. The second Australian National Blood Pressure Study (ANBP2) is an outcome trial of the treatment of hypertension in the elderly conducted entirely in general practices across Australia. Prior to ANBP2, no study of this size and nature had been undertaken in Australian general practice and the response of General Practitioners (GPs) to becoming involved in long-term cardiovascular research was unknown. 2. Academic departments and Divisions of General Practice were approached to support the project. General Practitioners were approached by letter of invitation and contacted by a regional medical coordinator (RMC) either at a face-to-face meeting or by telephone. 3. At the close of recruitment to ANBP2, 1938 GPs from 950 practices had registered as investigators. Sixty-two Divisions of General Practice were approached to support the study in five mainland Australian states with 39 (63%) participating, although participation by state was highly variable (range: 18-100%). Thirty divisional or promotional dinner meetings were held, with 56% (368/658) of those attending registering as investigators. Of the 8098 GPs sent a letter of invitation to participate in the study, 1357 (17%) expressed interest and eventually enrolled as investigators, ranging from 8% in Queensland to 28% in New South Wales. Ninety-six per cent of GPs who had a personal face-to-face contact (696/724) with the RMC registered in the study. 4. The GP recruitment phase of ANBP2 has been successfully completed. Peer-to-peer recruitment was the most successful strategy; however, success varied between states. General Practitioner recruitment to long-term clinical trials appears to be successful with a multifactorial approach focusing on peer-to-peer recruitment.

Dose response effect of cyclical medroxyprogesterone on blood pressure in postmenopausal women.

OBJECTIVE: This study was designed to compare with placebo the dose-response effect of cyclical doses of the C21 progestogen, medroxyprogesterone acetate (MPA) on blood pressure (BP) when administered to normotensive postmenopausal women receiving a fixed mid-range daily dose of conjugated equine oestrogen (CEE). MATERIALS AND METHODS: Twenty normotensive postmenopausal women (median age 53 years) participated in the study which used a double-blind crossover design. There were four randomised treatment phases, each of 4 weeks duration. The four blinded treatments were MPA 2.5 mg, MPA 5 mg, MPA 10 mg and matching placebo, taken for the last 14 days of each 28 day treatment cycle. CEE 0.625 mg was also administered once daily as open labelled tablets to all subjects throughout the study. Clinic BP was measured weekly with the mean values of weeks 3 and 4 of each phase used for analysis. Ambulatory BP was performed in the final week of each phase. RESULTS: Compared with the placebo phase, end of phase clinic BP was unchanged by any of the progestogen treatments. There was a dose-dependent decrease in ambulatory daytime diastolic and mean arterial BP with the progestogen treatments compared with placebo (P < 0.05). CONCLUSION: In a regimen of postmenopausal hormone replacement therapy with a fixed mid-range daily dose of CEE combined with a cyclical regimen of a C21 progestogen spanning the current clinical dose range, the progestogen has either no effect or a small dose-dependent reduction in clinic and ambulatory BPs over one treatment cycle.

Dose response effect of conjugated equine oestrogen on blood pressure in postmenopausal women with hypertension.

OBJECTIVE: This study was designed to compare with placebo the dose-response of conjugated equine oestrogen (CEE) on blood pressure in hypertensive postmenopausal women. DESIGN AND METHODS: Fourteen postmenopausal women with grade 1-2 hypertension participated in the study which used a double-blind crossover design. There were four randomised treatment phases, each lasting 4 weeks. The four treatments were CEE 0.3 mg, CEE 0.625 mg, CEE 1.25 mg and placebo. Each subject also received non-blinded medroxyprogesterone acetate (MPA) 10 mg for the final 14 days of each 28-day treatment cycle. Clinic blood pressure was measured weekly with the mean values of weeks 3 and 4 of each phase used for analysis. Ambulatory blood pressure was performed in week 4 of each phase. RESULTS: Compared with placebo, clinic systolic blood pressure was reduced in the CEE 0.3 mg and CEE 0.625 mg phases (p < 0.05) and clinic diastolic blood pressure was reduced in the CEE 0.625 mg phase (p < 0.05). There was no significant effect of CEE on ambulatory blood pressure, although the blood pressure pattern was similar to clinic measurements. CONCLUSION: In hypertensive postmenopausal women, daily CEE together with cyclical MPA has a variable effect on blood pressure depending on CEE dose. The "lower" and "middle" doses of CEE produced a small reduction in blood pressure which reached a nadir and tended to reverse with the "higher" CEE dose.

The effects of different types and doses of oestrogen replacement therapy on clinic and ambulatory blood pressure and the renin-angiotensin system in normotensive postmenopausal women.

OBJECTIVE: The effect on blood pressure of oral replacement' doses of exogenous oestrogen may depend on the type and dose of oestrogen administered. This study was designed to compare with placebo the effect of once daily treatment with a 'natural' oestrogen, piperazine oestrone sulphate, in two different doses and a semisynthetic oestrogen, ethinyloestradiol, on clinic and ambulatory blood pressure and the renin-angiotensin system in postmenopausal women. DESIGN AND METHODS: Twenty-four normotensive postmenopausal women (median age 54 years, range 47-60 years) participated in the study which used a double-blind crossover design. For each subject there were four randomized treatment phases, each lasting 4 weeks. The separate treatments administered once daily were 0.625 mg oestrone sulphate, 2.5 mg oestrone sulphate, 0.02 mg ethinyloestradiol and matching placebo. Clinic blood pressure, heart rate and weight were measured weekly with the mean values of weeks three and four of each phase used for analysis. Ambulatory blood pressure and biochemical measurements were performed in the final week of each phase. RESULTS: Twenty-four subjects entered and 22 completed the randomized phases of the study. Compared with the placebo phase, end-of-phase mean clinic diastolic blood pressure was reduced in subjects taking the semisynthetic oestrogen (P < 0.01) but was unchanged in those taking the 'low' and 'high' dose natural oestrogen. Mean clinic systolic blood pressure was also unchanged by any of the oestrogen treatments. Ambulatory night-time systolic, diastolic and mean arterial blood pressures were reduced with the low-dose natural and semisynthetic oestrogen treatments compared with placebo (P < 0.01), whereas there was no significant effect of the oestrogen treatments on ambulatory daytime blood pressures. A reduction in clinic and ambulatory heart rate was observed with the high-dose oestrone and semisynthetic oestrogen treatments. There was a dose-dependent increase in plasma renin substrate and decrease in plasma renin concentration with all active treatments; however, there was no change in plasma renin activity or plasma aldosterone concentration. CONCLUSION: In normotensive postmenopausal women, replacement doses of natural and semisynthetic oestrogen reduce night-time ambulatory blood pressure with either no change or a small reduction in clinic blood pressure. Reduction in blood pressure is not explained by reduced activity of the renin-angiotensin system but could have a component of reduced central sympathetic drive consistent with the decreased heart rate.

Comparison of an age adjusted warfarin loading protocol with empirical dosing and Fennerty's protocol.

AIM: A warfarin loading protocol adjusting doses for age was compared to both Fennerty's protocol (Fenn) and empirical dosing (Emp). METHODS: Patients beginning warfarin were randomised to receive doses according to either the age adjusted (Age) protocol or Fenn. Data were retrospectively collected for patients who had begun warfarin in the previous six months to represent empirical dosing. The study was performed on inpatients being commenced on warfarin for the first time at two teaching hospitals. MAIN OUTCOME MEASURES: Endpoints were time to reach a stable, therapeutic International Normalised Ratio (INR) between 2-3, the number of patients experiencing an INR > or =4 in the first week and the number of patients who had a dose held in the first week. RESULTS: Thirty-five patients were assessed in the Age group, 28 in the Fenn group, and 123 patients for the Emp group. Patients using the Age protocol achieved a stable, therapeutic INR more rapidly than either the Fenn (p=0.003, log rank test) or Emp (p<0.001) group. The Age group had a lower proportion of patients experiencing an INR > or =4 in the first week (p<0.05) as well as a lower proportion having doses held in the first week (p<0.01). There were no differences between Emp and Fenn for any of the endpoints. CONCLUSION: Adjustment of warfarin loading doses for age exhibits clear superiority over the use of Fenn or Emp. This becomes increasingly important as the average age of patients being warfarinised increases, with the recognition that atrial fibrillation requires anticoagulation. Fenn consistently overdosed elderly patients, especially those aged 80 years and older.

A placebo-controlled comparison of diltiazem and amlodipine monotherapy in essential hypertension using 24-h ambulatory monitoring.

Thirty patients (17 females, median age 55 years) with mild/moderate hypertension (sitting diastolic blood pressure 95-110 mmHg over 2 consecutive weeks) participated in a study of the efficacy and tolerability of once-daily diltiazem "controlled delivery" 180 mg-360 mg and amlodipine 5-10 mg compared with placebo (using clinic and 24-h ambulatory blood pressure measurement (Accutraker II). The study was conducted in a general practice setting using a randomized double-blind crossover design with Latin square allocation of treatment order within subjects. During each phase, doses were titrated to achieve a predose clinic sitting diastolic blood pressure of 90 mmHg. Three patients withdrew while taking amlodipine and 3 while taking placebo. The numbers of patients receiving the higher dose in each phase were as follows: placebo 22, diltiazem 12 and amlodipine 19. End-of-phase mean clinic sitting blood pressures were as follows: placebo 152/100, diltiazem 146/95 and amlodipine 140/93. End-of-phase mean 24-h ambulatory blood pressures were as follows: placebo 151/93, diltiazem 143/86 and amlodipine 137/84. Both clinic and ambulatory blood pressures were therefore significantly reduced (p < 0.01) in both active phases compared with placebo, and systolic blood pressure was also significantly lower with amlodipine compared with diltiazem. Heart rate was increased with amlodipine. Both drugs were well tolerated, and adverse events were predictable for each agent, with amlodipine causing more vasodilator side effects. Thus both amlodipine and diltiazem once-daily are effective in reducing blood pressure. While amlodipine is more potent than diltiazem in reducing systolic blood pressure, it causes more vasodilator side effects.

Low-dose diuretic and/or dietary sodium restriction when blood pressure is resistant to ACE inhibitor.

AIM: To compare the efficacy of indapamide (1.25 mg daily) and low-salt diet (<100 mmol/day) separately and in combination in essential hypertensive patients with inadequate BP response to perindopril. DESIGN AND METHODS: Randomized double-blind, double-dummy, crossover design. The randomized treatments were indapamide 1.25 mg daily, sodium chloride 80 mmol daily, the combination of indapamide and sodium chloride and placebo. All patients received perindopril 4 mg daily and maintained a low-sodium diet. RESULTS: 19 patients entered and 17 completed the study. Prior to randomization, average clinic sitting blood pressure was 162/101 mm Hg and average 24-h urine sodium excretion was 157 mmol/day. Compared to the phase in which patients received perindopril with sodium repletion, clinic and ambulatory BPs were significantly reduced (p<0.01) in all the other phases. Indapamide had a greater effect on BP than dietary sodium restriction, and in combination their effects were additive. The effect of indapamide on ambulatory BP persisted throughout 24 h, but the effect of the low-salt diet was predominantly observed during waking hours. CONCLUSIONS: In hypertensives with BP resistant to the angiotensin converting enzyme (ACE) inhibitor perindopril, the diuretic indapamide had greater additional efficacy and longer duration of action than dietary sodium restriction. In combination they had additive effects on BP.

Orthostatic blood pressure control and ageing.

Reflex haemodynamic responses to orthostatic stress are attenuated with ageing, the extent of attenuation increasing with advancing age. In 15-20% of individuals aged > 65 years, the attenuation may be so marked that there is an excessive fall of blood pressure (BP) on assumption of the upright posture, sufficient on occasions to cause symptomatic cerebral hypoperfusion--this is known as 'ageing-related' orthostatic hypotension (AOH), a major risk factor for morbidity and mortality. Comparison of the cardiovascular responses to a variety of physiological and pharmacological stresses in healthy young and elderly subjects and in those with AOH suggests that the predominant site of the ageing-related change in cardiovascular reflex function is in the central connections of the arterial baroreflex, affecting particularly the BP buffering response. There is no evidence for ageing-related impairment of the efferent limb of the baroreflex, i.e. there is no significant ageing change in sympathetic vasomotor function or cardiac drive. Ageing-related impairment of baroreflex function also does not appear to result from either attenuation of arterial compliance or the presence of systolic hypertension, despite the epidemiological association between systolic hypertension and AOH. Better understanding of this important problem has the potential to improve the health of all elderly people.

Second Australian National Blood Pressure Study (ANBP2). Australian Comparative Outcome Trial of ACE inhibitor- and diuretic-based treatment of hypertension in the elderly. Management Committee on behalf of the High Blood Pressure Research Council of Australia.

The Second Australian National Blood Pressure Study (ANBP2) is a comparative outcome trial being conducted in general practices throughout Australia of ACE inhibitor- and diuretic-based treatment in 6000 hypertensive patients aged 65-84 years. The study is using a prospective randomised open-label design with blinding of endpoint assessments. The primary objective is to determine whether there is any difference in total cardiovascular events (fatal and non-fatal) over a five year treatment period between the two treatment regimens. Eligible hypertensive patients (average sitting blood pressure at the 2nd and 3rd screening visits > 160 mm Hg systolic and/or > 90 mm Hg diastolic) may be either untreated or previously treated and should have no history of recent cardiovascular morbidity or serious intercurrent illness. Patients are randomised to one of the treatment arms with randomisation stratified for practice and for age. Following randomisation each patient's blood pressure is managed by his/her general practitioner according to guidelines relevant to each treatment arm. Over 700 patients have now been randomised with recruitment intended to be complete by the end of 1997.

Feasibility of conducting cardiovascular outcome research in Australian general practice: results from the ANBP2 pilot study. Australian National Blood Pressure Study.

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was > or = 160 mmHg systolic or > or = 90 mmHg diastolic if systolic BP was > or = 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82,000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP > or = 160/90 mmHg. Forty-seven per cent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.

Lacidipine, hydrochlorothiazide and their combination in systolic hypertension in the elderly.

OBJECTIVE: To compare with placebo the efficacies of once-daily administrations of lacidipine and hydrochlorothiazide separately and in combination to elderly patients with systolic hypertension. DESIGN AND METHODS: Nineteen elderly subjects (five men and 14 women, median age 71 years, range 62-79 years) participated in the study, which had a randomized double-blind crossover design. For each subject there were four treatment phases, each of duration 4 weeks. The initial treatments in each phase were 2 mg lacidipine once a day and 25 mg hydrochlorothiazide once a day, separately and in combination, and placebo. Doses of each agent could be doubled after 2 weeks in each phase if the patient's goal systolic blood pressure had not been achieved. The numbers of subjects administered the higher dose of each treatment were 13 for placebo, 14 for lacidipine, 11 for hydrochlorothiazide and eight for lacidipine plus hydrochlorothiazide. RESULTS: End-of-phase mean clinic blood pressures were 164/85 mmHg with placebo, 159/82 mmHg with lacidipine, 157/84 mmHg with hydrochlorothiazide and 152/82 mmHg with lacidipine plus hydrochlorothiazide. Systolic blood pressure was significantly reduced during all active treatment phases compared with placebo and that for the lacidipine plus hydrochlorothiazide phase was also significantly less than those for both of the other active treatment phases. There was no difference between sitting and standing blood pressure for any phase. Factorial analysis of the main effects of treatment indicated that the effects of lacidipine and hydrochlorothiazide on clinic blood pressure were additive and also that heart rate was higher when hydrochlorothiazide had been administered. Ambulatory blood pressure monitoring confirmed the pattern of the responses of blood pressure and showed that administration of hydrochlorothiazide had a significantly greater effect on systolic blood pressure and a longer duration of action than did administration of lacidipine. There was no difference in the frequency of adverse effects among any of the phases. CONCLUSIONS: In treating elderly systolic hypertensives the diuretic hydrochlorothiazide is a more effective antihypertensive agent with a longer duration of action than is the calcium channel antagonist lacidipine. In combination the effects of these two drugs on blood pressure are additive.

Epidemiological study of angioedema and ACE inhibitors.

BACKGROUND: Angioedema is an uncommon and poorly recognised adverse reaction to angiotensin converting enzyme inhibitors (ACE-Is). The epidemiology of this association has not been described. AIMS: To examine the epidemiology of angioedema and its relation to ACE inhibitor prescribing. To examine the characteristics of angioedema occurring in patients taking ACE inhibitors. METHODS: A retrospective case control study and a case note audit were conducted of 40 patients who presented to a teaching hospital Accident and Emergency Department with angioedema on 48 occasions. One hundred and sixty control subjects presenting to the same Accident and Emergency Department but without angioedema were matched to cases by age, sex and presentation date. An ecological study comparing the numbers of angioedema admissions by age cohorts to South Australian (SA) public hospitals with the prescription volumes of ACE-Is in Australia was also undertaken. RESULTS: Case control study: In patients presenting with angioedema compared with controls, the exposure odds ratio for ACE-Is was 5.1 (95% CI 2.03-12.89) and for non-steroidal anti-inflammatory drugs (NSAIDs) was 4.13 (95% CI 1.28-13.39). CASE NOTE AUDIT: 15/40 (38%) patients presenting with angioedema on 19/48 (40%) occasions were taking an ACE-I. These patients were older and less likely to have an atopic history than those not taking an ACE-I. The onset of angioedema after starting an ACE-I was delayed for greater than six months in nine patients. ACE-I therapy was continued after 53% of presentations. ECOLOGICAL STUDY: The number of admissions with angioedema to SA public hospitals increased between 1985-86 and 1994-95, predominantly in older patients, and paralleled the increasing prescription volumes of ACE-Is. CONCLUSIONS: A considerable proportion of patients presenting with angioedema will be taking an ACE-I or a NSAID. The association of ACE-Is and angioedema is not well recognised, partly because the onset of angioedema may be delayed for months or years after commencement of an ACE-I. A persisting risk of angioedema is present in patients who have initially commenced an ACE-I uneventfully. The epidemiology of angioedema is now changing in parallel with the increasing use of ACE-Is.

Effect of indomethacin on blood pressure control during treatment with nitrendipine.

This study tested the hypothesis that treatment with a nonsteroidal anti-inflammatory drug will not alter the hypotensive effect of a dihydropyridine calcium channel antagonist. Fifteen essential hypertensives (ages 58-80 years) had a supine diastolic blood pressure (DBP) < 100 mmHg after 4 weeks monotherapy with nitrendipine 5-20 mg twice daily. They entered a double-blind randomised crossover study in which the addition of indomethacin 25 mg three times daily was compared with placebo in treatment phases each of 4 weeks duration. Subjects were seen weekly and measurements in the last 2 weeks of each phase were compared. Supine blood pressure (mean +/- SE) was higher in the indomethacin phase (158 +/- 4/80 +/- 2) than in the placebo phase (154 +/- 4/76 +/- 3) (p < 0.01 for DBP). In 6/15 (40%) of subjects the increase in supine diastolic blood pressure with indomethacin was > 5 mmHg. Plasma urea was also increased in the indomethacin phase: 7.6 +/- 0.6 mmol/l compared with placebo: 6.3 +/- 0.5 mmol/l (p < 0.001). The study has demonstrated that concurrent treatment with the NSAID indomethacin impairs the blood pressure lowering effect of the dihydropyridine calcium channel antagonist nitrendipine. This increase in blood pressure with indomethacin in subjects treated with nitrendipine may represent either an independent pressor effect of indomethacin or a reduced vasodilator prostanoid contribution to the hypotensive effect of nitrendipine. This blood pressure increase may be sufficient to interfere significantly with clinical blood pressure control in some subjects.

Trough:peak ratio of the blood pressure response to beta-blockers.

UNLABELLED: EFFECT OF ELIMINATION HALF-LIFE ON TROUGH:PEAK RATIO IN BETA-BLOCKERS: Maximal beta-adrenoceptor blockade and peak blood pressure reduction are achieved with plasma concentrations that are below the peak postdose concentrations observed when therapeutic doses are given. As a result, any trough:peak variation in the blood pressure response is likely to depend on the proportion of the dose interval during which maximal beta-blockade is maintained, and on the relationship between the elimination half-life of the drug, the dose and the dose interval. Acceptable trough:peak ratios (> 70%) for the blood pressure response to beta-blockade with a single daily dose are usually found with drugs that have an elimination half-life of over 6 h or when slow-release preparations are used for drugs with a shorter half-life. OTHER FACTORS THAT INFLUENCE THE TROUGH:PEAK RATIO: The interpretation of trough:peak ratios when beta-blockers are used may be complicated by circadian variations in the blood pressure response, with low blood pressure levels during sleep and an early morning rise upon waking. The blood pressure response-time relationships for beta-blockers with vasodilator properties appear to be similar to those for 'plain' beta-blockers, although there may be greater attenuation of the rise in blood pressure upon waking when multiple-action agents are used. Furthermore, the blood pressure of elderly patients with systolic hypertension may show an attenuated response to beta-blockers, resulting in a less favourable trough:peak ratio. CONCLUSIONS: It is not clear whether blood pressure 'responders' to beta-blockers have a pattern of response that is different from the mean of a heterogeneous group. Further studies with appropriate designs are required to clarify these issues.

Effects of age and isolated systolic hypertension on cardiovascular reflexes.

OBJECTIVES: Given the reported relationship between systolic hypertension and orthostatic hypotension in the elderly, to test the hypothesis that systolic hypertension causes impairment of the cardiovascular reflex function additional to the effects of age alone. DESIGN: Responses were compared in normotensive healthy young (n = 12) and elderly (n = 15) participants and elderly participants with disproportionate supine systolic hypertension (n = 11) using a baroreceptor-mediated stress (head-up tilt) and two non-baroreceptor-mediated stimuli (cold pressor test and isometric exercise). METHODS: Blood pressure and heart rate were measured by oscillometry before and during the three stress tests. Forearm blood flow was measured by venous occlusion plethysmography and pulse wave velocity (PWV) by Doppler ultrasound. RESULTS: Percentage changes in systolic/diastolic (SBP/DBP) blood pressure with head-up tilt were 0/+11, -3/0 and -6/+1 mmHg in the young and elderly normotensives and elderly systolic hypertensives, respectively. Both elderly groups had reduced DBP responses to tilt compared with the young (P < 0.01). All three groups had similar percentage changes in blood pressure responses to non-baroreflex-mediated stresses (cold pressor test: +10/+23, +11/+11, +10/+15; sustained isometric exercise: +18/+33, +22/+24, +13/+17 in the young and elderly normotensives and elderly systolic hypertensives, respectively). Aorto-iliac PWV adjusted for blood pressure was significantly higher in both elderly groups compared with the young (P < 0.01) but there was no difference between elderly normotensives and hypertensives. Unadjusted PWV was higher in elderly hypertensives than in elderly normotensives (P < 0.05). CONCLUSIONS: Compared with healthy young participants, both elderly groups had similarly attenuated blood pressure responses to tilt and reduced arterial compliance. Systolic hypertension is not associated with additional impairment of cardiovascular reflex function over and above the effects of age. The reported association between supine systolic hypertension and orthostatic hypotension does not appear to be a causative one.

Mono- and combination therapy with felodipine or enalapril in elderly patients with systolic hypertension.

Using a randomised double-blind crossover design with Latin square allocation of treatments in 20 subjects (7 male, 13 female-ages: 61-87 years) with systolic hypertension, we investigated the efficacy and tolerability of once daily felodipine (extended release) 5-20 mg, enalapril 5-20 mg and their combination compared with placebo in four treatment phases each of 6 weeks duration. During each phase, doses were titrated to achieve a predose clinic supine systolic blood pressure of 140 mmHg or to a predetermined maximum dose. In both the felodipine and combination phases, predose supine and standing systolic and diastolic pressures were significantly reduced compared with the placebo phase (decrease in supine pressure: -13/-5 and -18/-7, respectively). Only predose supine diastolic pressure was significantly reduced (-3 mmHg) compared to placebo in the enalapril phase. In combination the effects of the two drugs on predose blood pressure were additive. There was a 40-60% increase in reported symptoms in the felodipine and combination phases compared with the placebo and enalapril phases. Thus, in elderly subjects with systolic hypertension, felodipine effectively reduces blood pressure throughout the dose interval but with vasodilator adverse effects. In contrast, enalapril is well tolerated but is less effective in reducing blood pressure throughout the whole dose interval.

Felodipine, metoprolol and their combination compared with placebo in isolated systolic hypertension in the elderly.

This study compared with placebo the efficacy and tolerability of optimised doses of felodipine 5-20 mg daily, metoprolol 50-200 mg daily and their combination in subjects 60 years or over with isolated systolic hypertension. The study employed a randomised double-blind crossover design with allocation of treatment order within subjects by Latin squares. For each subject, after a single-blind run-in placebo phase, there were four randomised treatment phases each of six weeks duration, with a dose titration step at three weeks if necessary. Twenty-eight subjects entered the randomised phases of the study and twenty-one completed all four phases--13 male, 8 female (ages: median 71, range 59-85 years). At the end of both the felodipine and metoprolol phases systolic and diastolic pressure were reduced at 2 hours postdose compared with the placebo phase (p < 0.001), the blood pressure reduction with felodipine (-40/-20 mmHg) being greater than that with metoprolol (-15/-9 mmHg) (p < 0.01). Immediately predose (12 hours postdose) there was a persisting reduction of supine systolic blood pressure (-17 mmHg) with felodipine (p < 0.001), but there was no significant effect of metoprolol. At both measurement times the two drugs when in combination had an additive effect on blood pressure. There was a 20% increase in reported symptoms during each of the active treatment phases. Four subjects withdrew during the randomised phases because of probable drug-related adverse events and six subjects required dosage reductions during the felodipine or combination phases.(ABSTRACT TRUNCATED AT 250 WORDS)