Prevalence and implications of uncontrolled systolic hypertension

Risk of cardiovascular disease (CVD) increases incrementally with blood pressure, even within the high-normal range. In the general population, 27% of CVD in women and 37% in men is attributable to hypertension. A high percentage of these hypertension-related events occur in those with high-normal blood pressure and mild hypertension; about one-fourth of CVD events in elderly women and one-third in elderly men in the Framingham Study occurred in persons who had blood pressures of 140-159 mm Hg systolic and/or 90-95 mm Hg diastolic. The average systolic blood pressure (SBP) at which coronary heart disease occurs is rather modest (141 mm Hg), as is the pulse pressure (59-63 mm Hg). Of the CVD events in elderly participants in the Framingham Study, 24% in men and 36% in women occurred in persons receiving treatment for hypertension. There is a growing recognition of the importance of the systolic component of blood pressure. About 65% of hypertension in the elderly is isolated systolic hypertension (ISH), and CVD risk increases with pulse pressure. Pulse pressure is not simply a marker for stiff diseased arteries; treatment of ISH in trials promptly reduces the CVD risk, indicating that the pulse pressure generated by the stiff artery is the culprit. Analysis of data from clinical trials indicates that greater reliance should be placed on systolic pressure in evaluating the CVD potential of hypertension. Hypertension, including ISH, seldom occurs in isolation from other risk factors and overt CVD. Risk varies widely depending on the burden of accompanying risk factors. This makes global risk assessment mandatory for evaluating risk and the urgency and nature of treatment required. Evidence incriminating systolic pressure as the dominant blood pressure determinant of CVD has not been translated into clinical practice. Most of the uncontrolled hypertension observed in the Framingham Study is concentrated in those with ISH. This also extends to African-Americans, people with diabetes mellitus and the elderly. When should SBP be considered controlled? Substantial evidence supports the value of treating ISH with SBP exceeding 160 mm Hg. Trial data are not yet available to support recommendations to treat lesser elevations of ISH or pulse pressure per se, but since one-half of patients with mild ISH have two or more additional risk factors, most are candidates for treatment. In such patients, ISH should be considered controlled when their global CVD risk is reduced to below the average for their age.     

Open evaluation of amlodipine in the monotherapeutic treatment of systolic hypertension in the elderly

The antihypertensive efficacy and safety of amlodipine (5-10 mg once daily for 10 weeks) was assessed in elderly patients with primary systolic hypertension (average sitting and standing systolic blood pressure > or = 160 mm Hg and diastolic blood pressure < or = 95 mm Hg). Interim analysis of data from 25 patients shows that amlodipine treatment produced significant decreases in sitting blood pressure (-26.8/-11.4 mm Hg; p < 0.05). Efficacy assessments after 8 weeks of therapy showed 15 of 21 (71.4%) evaluable patients were considered therapeutic successes with amlodipine (defined as a fall from baseline in sitting systolic blood pressure of > or = 20 mm Hg or to < or = 150 mm Hg with a fall of > or = 10 mm Hg). Of the six evaluable patients who were not considered therapeutic successes using this definition, three had clinically beneficial falls in systolic blood pressure of 16-18 mm Hg. Fourteen patients were considered therapy successes on the basis of assessments taken 48 h postdose at the end of the study. Investigators' overall impression of efficacy was excellent or good in 21 patients (84%). Amlodipine treatment had no significant effect on heart rate. Amlodipine was generally well tolerated, with no patients being withdrawn due to side effects. Investigators' evaluation of toleration was excellent or good in 22 patients (88%).     

The efficacy and safety of amlodipine in the treatment of mild and moderate essential hypertension in general practice

The antihypertensive efficacy and safety of amlodipine was evaluated in an open, multicenter general practice study. Hypertensive patients with sitting diastolic blood pressure in the range 95-115 mm Hg entered an initial 2-week baseline period during which they received placebo in a single-blind fashion. The dose of any concomitant antihypertensive treatment was kept constant for 4 weeks prior to baseline evaluations and throughout the study. Patients with an average sitting diastolic blood pressure > or = 95 mm Hg and < or = 115 mm Hg at two consecutive visits during the baseline period continued to the 8-week dose adjustment phase of the study. Patients were started on 5 mg of amlodipine once daily adjusted after 4 weeks to 10 mg once daily to achieve a target sitting diastolic blood pressure < or = 90 mm Hg. Amlodipine treatment produced significant falls in blood pressure (-23.7/-17.3 mm Hg; p < 0.05) with no effect on heart rate. Amlodipine was well tolerated, with most adverse events being mild or moderate. Investigators' global evaluation of toleration was excellent or good in 92% of patients. Subgroup analysis showed amlodipine to be equally efficacious and well tolerated in elderly or young patients, and in patients taking amlodipine as monotherapy or combination therapy.     

Antihypertensive Effect and Tolerability of Perindopril in Indian Hypertensive and Type 2 Diabetic Patients: 1-Year Randomised, Double-Blind, Parallel Study vs Atenolol

OBJECTIVE: This study compared the antihypertensive effect and acceptability of a perindopril-based group with that of an atenolol-based group in Indian hypertensive type 2 (non-insulin-dependent) diabetic patients. DESIGN AND SETTING: 100 ambulant patients aged between 35 and 69 years were recruited into this monocentric, randomised, double-blind study in two parallel groups for 1 year after a 1-month washout period on placebo. The setting was a tertiary care institution. PATIENTS: All patients had stable, essential hypertension between 95mm Hg and 115mm Hg, type 2 diabetes with glycosylated haemoglobin (HbA(1C)) <12%, and albuminuria between 300mg and 3.5g/24 hours. There were 50 patients per treatment group and two patient population groups were studied, intention-to-treat (ITT) and per-protocol (PP). The former constituted all patients, whilst the latter included those without major protocol deviation and who completed the 12-month study. INTERVENTIONS: The study drugs were perindopril 4 to 8mg once daily or atenolol 50 to 100mg once daily. In each group therapeutic adjustment was planned by doubling the dose and then by the addition of hydrochlorothiazide 25mg daily. Nifedipine 30 to 60mg daily was subsequently added if the desired drop in blood pressure was not obtained. The ITT group was analysed by Student's t-test, and a 2-way analysis of variance was performed for the PP population. MAIN OUTCOME MEASURES: A comparison of the control of hypertension, biochemical abnormalities, blood sugar and adverse effects was performed in the atenolol group versus the perindopril group. RESULTS: On single-dose therapy after 1 month 17 patients (60%) had normal blood pressure [diastolic blood pressure (DBP) 相似文献   

Controlled trial of ketanserin in hypertension.

We have completed a double-blind parallel group comparison of the 5-HT2 receptor antagonist ketanserin with placebo in 22 hypertensive patients. Ketanserin (20-40 mg twice daily) lowered sitting blood pressure more than placebo by 6.9 mm Hg systolic (NS), 13.1 mm Hg diastolic (P less than 0.05) and by 11.4 mm Hg mean arterial pressure (P less than 0.02). The fall in standing blood pressure was similar and we observed no first dose hypotensive effect. Ketanserin lowered the sitting heart rate by 11.1 beats/min (P less than 0.01). The drug was well tolerated.     

Improved outcomes with antihypertensive medication in the elderly with isolated systolic hypertension

Isolated systolic hypertension affects over 15% of all individuals aged >60 years. In the elderly, systolic hypertension is a major modifiable cardiovascular risk factor. Systolic blood pressure (SBP) is associated with higher risk of an adverse outcome, whereas diastolic blood pressure (DBP) is inversely correlated with total mortality, independent of SBP, highlighting the role of pulse pressure as a risk factor. Three placebo-controlled outcome trials on antihypertensive drug treatment in older patients with isolated systolic hypertension have been published: the Systolic Hypertension in the Elderly Program (SHEP), the Systolic Hypertension in Europe (Syst-Eur) Trial and the Systolic Hypertension in China (Syst-China) Trial. These 3 trials demonstrated the benefit of antihypertensive drug treatment. A meta-analysis was performed by pooling the patients from these 3 trials with a subset of patients with isolated systolic hypertension from 5 other trials in the elderly. The pooled results of 15,693 older patients with isolated systolic hypertension prove that antihypertensive drug treatment isjustified if on repeated clinic measurements SBP is 160 mm Hg or higher.     

Efficacy and tolerability of valsartan in combination with hydrochlorothiazide in essential hypertension

OBJECTIVE: This study compared the efficacy and tolerability of two combination regimens of valsartan and hydrochlorothiazide (HCTZ) with valsartan monotherapy in patients with essential hypertension inadequately controlled with valsartan 80mg once daily. PATIENTS AND METHODS: A total of 708 patients with inadequately controlled blood pressure after 4 weeks' treatment with valsartan 80mg once daily participated in this double-blind comparative trial. Patients were randomly allocated once-daily treatment with valsartan 80mg, valsartan 160mg, valsartan 80mg + HCTZ 12.5mg or valsartan 80mg + HCTZ 25mg for 8 weeks. RESULTS: Statistically significant decreases in mean sitting diastolic blood pressure (SDBP) and mean sitting systolic blood pressure (SSBP) from baseline were seen in all treatment groups (least squares mean change from baseline SDBP: -5.1mm Hg, -6.2mm Hg, -8.2mm Hg, -10.8mm Hg; SSBP: -3.9mm Hg, -6.5mm Hg, -9.8mm Hg, -16.0mm Hg for valsartan 80mg, valsartan 160mg, HCTZ 12.5mg combination, HCTZ 25mg combination, respectively). A significant difference for mean SDBP, SSBP and responder rates in favour of the combination regimens was observed compared with either valsartan monotherapy. All treatments were well tolerated with the percentage of patients reporting treatment-related adverse experiences at any time ranging from 9.9% (valsartan 160mg) to 21.0% (HCTZ 25mg combination). CONCLUSION: The study demonstrated that a combination of valsartan 80mg and HCTZ 12.5mg or 25mg provides an effective and well tolerated treatment in patients who need additional blood pressure control beyond valsartan monotherapy.     

First-step treatment of mild to moderate uncomplicated essential hypertension by a new calcium antagonist: nicardipine

Nicardipine, a new calcium antagonist, was tested in a 14-week double-blind trial including 15 outpatients with uncomplicated essential hypertension. They were randomly assigned to nicardipine (20-30 mg three times daily) or placebo as first-step treatment. When necessary but always after a minimum of 4 weeks, pindolol (15 mg/day) was combined with nicardipine or placebo. At the end of step 1 (85 +/- 6 days with nicardipine vs. 58 +/- 6 days with placebo, p less than 0.01), nicardipine induced larger drops in supine systolic and diastolic blood pressure (SBP and DBP) than the placebo (21 +/- 2.5 vs 1.4 +/- 3 mm Hg, p less than 0.001, and 13 +/- 2 vs. 3.5 +/- 1.5 mm Hg, p less than 0.001, respectively). In the nicardipine group (n = 57), 53% of patients had controlled blood pressure (SBP less than 160 mm Hg and DBP less than 95 mm Hg) versus 17% in the placebo group (n = 47), p less than 0.001. There was no significant correlation between the decrease in blood pressure and the age of patients. The most common side effects in the nicardipine group were flushes (12%), headache (8%), ankle edema (5%), and asthenia (4%). When blood pressure was not brought under control and pindolol was prescribed as the second-step treatment, the nicardipine group (n = 52) displayed larger drops in SBP and DBP than the placebo group (n = 40) (27 +/- 5 vs. 15 +/- 3 mm Hg, p less than 0.01, and 18 +/- 1 vs. 9 +/- 2 mm Hg, p less than 0.001, respectively). These results show that a calcium antagonist is useful for first-step treatment of hypertension.     

Comparison of once daily endralazine with placebo in the treatment of hypertension uncontrolled by a beta-blocker and diuretic

Summary We report the first placebo controlled parallel group study of once daily endralazine (5–20 mg) in hypertension uncontrolled by a beta-blocker plus a diuretic.Following a 4-week run-in period 22 patients with a sitting mean arterial pressure (MAP) greater than 110 mm Hg were entered into the study and received either endralazine 5 mg or placebo. Blood pressure was measured 2 h and 24 h after dosing and the drug dose doubled at 2 and 4 weeks if the 24-h MAP remained >110 mg Hg. The final blood pressure assessment was made after 6 weeks treatment in the 19 patients who completed the study. Three patients withdrew from the study because of side effects. The hypotensive effect (sitting) was in excess of placebo at 2 h by 15.8 mm Hg systolic (NS), 15.4 mm Hg diastolic (p<0.01), 15.5 mm Hg MAP (p<0.02) and at 24 hours by 7.7 mm Hg systolic (NS), 8.9 mm Hg diastolic (p<0.02) and 11.1 mm Hg MAP (p<0.02). This study suggests that endralazine should be prescribed twice daily.     

Effect of a new calcium antagonist, tiapamil, in hypertension of the elderly.

The antihypertensive effect of a single oral dose of tiapamil (450 mg) and placebo were compared in a single blind randomized cross-over study in 10 71-86 year old hypertensive patients. Blood pressure (BP) and heart rate (HR) were recorded every 15 min for 12 h by an automatic device. Tiapamil led to a decrease in mean daytime systolic (SBP) and diastolic (DBP) BP from 171 +/- 12/98 +/- 10 mm Hg to 159 +/- 11/90 +/- 9 mm Hg (P less than 0.001) without significant variation in HR. Thereafter patients received tiapamil 450 twice daily; by the seventh day of treatment mean daytime SBP and DBP were 155 +/- 13/85 +/- 14 mm Hg (P less than 0.001 vs placebo). The hourly mean values of SBP recorded for 8/12 h (first tiapamil day) and 10/12 h (seventh tiapamil day) were significantly lower than the corresponding values after placebo. We conclude that tiapamil in the elderly exerts a sustained antihypertensive effect lasting 12 h or more, with only minor variations in HR. This effect predominates on systolic pressure and is significant from the first dose.     

The effect of intravenous enalaprilat (MK-422) administration in patients with mild to moderate essential hypertension

The antihypertensive effect of enalaprilat (MK-422), an intravenous (IV), nonsulfhydryl converting-enzyme inhibitor, was evaluated in a double-blind study of 14 patients with mild to moderate hypertension. The seven patients in the treatment group initially received IV enalaprilat 1.25 mg q6h for 24 hours. Thereafter, responding patients (diastolic blood pressure [BP] less than or equal to 95 mm Hg) continued receiving this dose q6h for an additional 24 hours, whereas nonresponding patients were increased to IV enalaprilat 5 mg q6h for another 24 hours. Baseline BP for enalaprilat was 161 +/- 5/107 +/- 2 mm Hg (+/- SEM), and for placebo it was 150 +/- 5/103 +/- 2 mm Hg. Within the first 60 minutes, a significant reduction in both systolic and diastolic BP was noted in the enalaprilat group (P less than .05), without significant changes occurring in the placebo group. Although there was a gradual decline in both systolic and diastolic BP throughout the 48-hour study period in the placebo group, systolic and diastolic BP reduction was greater in the enalaprilat group, reaching a maximal decrease of 133 +/- 3/87 +/- 3 mm Hg. Adverse side effects did not occur in any patient.     

A comparison of dilevalol and placebo in the management of isolated systolic hypertension using ambulatory monitoring.

1. The antihypertensive effect of dilevalol, a compound which combines beta-adrenoceptor blocking and vasodilating properties due to beta 2-adrenoceptor agonism, was studied in nineteen patients with isolated systolic hypertension (ISH). A randomized, double-blind, placebo-controlled, cross-over trial with two 4 week treatment periods was used to compare the efficacy of once daily dosing with dilevalol (in the range of 100-400 mg daily) against placebo. Assessment of response involved both casual blood pressure readings (amongst all patients) and 24 h ambulatory blood pressure monitoring (in ten of the nineteen patients). 2. A mean fall of 12/5 mm Hg (s.e. mean 3/2, P less than 0.05) and 9/3 mm Hg (s.e. mean 3/2, P less than 0.05) in supine and standing blood pressure respectively was observed with dilevalol. Mean heart rate was unchanged. The ambulatory monitoring profile demonstrated a smaller reduction in mean blood pressure (7/8 mm Hg) over the 24 h period and a reduction of 10/11 mm Hg over the daytime period. A blunting of the early morning increase in systolic pressure was observed with dilevalol. 3. The drug was well tolerated with light headedness and lethargy being reported more commonly than with placebo. Biochemical parameters were unaffected. 4. It is concluded that dilevalol in the doses used has a small but measurable antihypertensive effect as monotherapy in the treatment of ISH.     

Smooth blood pressure control obtained with extended-release felodipine in elderly patients with hypertension: evaluation by 24-hour ambulatory blood pressure monitoring

OBJECTIVE: To assess, by smoothness index (SI), distribution of the antihypertensive effect of extended-release (ER) felodipine over 24 hours in elderly patients with hypertension. METHODS: After a 4-week washout phase, 35 elderly patients (mean age 69 +/- 4 years) with mild-to-moderate hypertension received 2 weeks' treatment with ER felodipine 5mg once daily. The dosage of ER felodipine was doubled to 10 mg/day and given for a further 2 weeks in non-responders (sitting clinic blood pressure > 140/90mm Hg). The study had an open-label design with no placebo control. After each period, clinic and ambulatory blood pressures were measured. Trough-to-peak (T/P) ratio was computed by dividing the blood pressure (BP) change at trough (22 to 24 hours after drug intake) by the change at peak (2 adjacent hours with a maximal BP reduction between the second and eighth hour after drug intake). SI was calculated as the ratio between the average of the 24, hourly, treatment-induced BP changes and its standard deviation. RESULTS: After the initial 2-week treatment period, clinic and 24-hour ambulatory BP values were higher in non-responders (145 +/- 11/87 +/- 8 and 135 +/- 17/80 +/- 6mm Hg, respectively) than in responders (133 +/- 6/81 +/- 3 and 130 +/- 9/77 +/- 7mm Hg). In non-responders, clinic and 24-hour BP values were lowered after a further 2 weeks of treatment with ER felodipine 10 mg/day (128 +/- 11/78 +/- 6 and 128 +/- 12/75 +/- 5mm Hg). SI was high in responders (0.8 +/- 0.8/0.7 +/- 0.7 for systolic/diastolic BP) and low in non-responders (0.5 +/- 0.6/0.3 +/- 0.6) during the first 2-week treatment period. It increased in non-responders after an additional 2 weeks of treatment with ER felodipine 10 mg/day (1.0 +/- 0.8/0.7 +/- 0.6). Median T/P ratios were 0.73 and 0.61 (systolic BP and diastolic BP) in responders and 0.41 and 0.61 in non-responders after 2 weeks of treatment. At variance with SI, T/P ratios did not increase in non-responders after doubling the dosage of ER felodipine (0.34 and 0.18). ER felodipine did not increase 24-hour heart rate. A total of nine adverse events were recorded in six patients (17%), but no patients withdrew from the study. CONCLUSION: ER felodipine 5 to 10 mg/day smoothly and safely reduces 24-hour ambulatory BP in elderly patients with hypertension.     

Enalapril and nifedipine in the treatment of mild to moderate essential hypertension: a 6 month comparison.

1. In a double-blind, randomised, parallel group study, 128 patients with sitting diastolic blood pressure between 95 and 125 mm Hg (Phase V) after 2-4 weeks run-in on placebo, received enalapril 10-40 mg once daily (65 patients) or nifedipine retard 10-40 mg twice daily (63 patients), utilising a double dummy technique. Dual target blood pressures were less than 150 mm Hg systolic and less than 90 mm Hg sitting diastolic. Inadequate responders had hydrochlorothiazide 12.5-50 mg once daily added. 2. The 3 h post-dose sitting blood pressures were lowered by 18/14 mm Hg (enalapril) and 20/14 mm Hg (nifedipine), but nifedipine gave greater standing reductions (16/13 mm Hg enalapril, 22/17 mm Hg nifedipine). The dual target blood pressures were achieved by 45% of those taking enalapril monotherapy and 43% of those taking nifedipine monotherapy. At the end of the hydrochlorothiazide phase the dual target pressures were achieved by 63% of the enalapril group and 56% of the nifedipine group. 3. Overall, 17 patients reported adverse events during the placebo run-in. During the active treatment-periods, 42 patients in the enalapril group experienced adverse events, as did 49 of those on nifedipine. Orthostatic effects were confined to those taking enalapril, whereas flushing/erythema, oedema and palpitations were more common in the nifedipine group. 4. Five patients in the enalapril and 14 in the nifedipine groups were withdrawn because of adverse events. One of those withdrawn on enalapril had angioneurotic oedema.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serotonergic blockade compared with beta-adrenergic blockade in systemic hypertension: a double-blind comparison of ketanserin with propranolol

The safety and efficacy of ketanserin, a competitive serotonin blocking agent, and propranolol were compared in 33 patients with mild to moderate hypertension (sitting diastolic blood pressure [DBP] 95-115 mm Hg) using a placebo run-in, randomized, double-blind parallel study design. All patients received placebo for 4 weeks, then were randomized to receive increasing doses of either ketanserin (20, 40 mg twice daily) or propranolol (40, 80 mg twice daily) to achieve a goal sitting DBP less than 90 mm Hg. Patients not achieving the goal blood pressure with either drug as monotherapy, received the other drug in combination. At the end of the active monotherapy phase (week 10 of the study), propranolol demonstrated a greater decrease in DBP from baseline, as compared to ketanserin (-7.9 +/- 10.9 mm Hg with propranolol, P less than 0.05; -1.0 +/- 7.2 mm Hg with ketanserin, P = NS). Four out of 16 patients achieved goal response on propranolol, compared to 3/17 for ketanserin. With combination treatment, 9/18 patients reached the goal response; the addition of propranolol to ketanserin in non-responders resulted in further reduction of sitting DBP of -10.3 +/- 6.3 compared to monotherapy (P less than 0.001), while the addition of ketanserin to non-responders produced no significant response in sitting DBP. Propranolol showed a consistent effect in slowing heart rate. Ketanserin displayed less frequent side effects than propranolol. Propranolol used twice daily appears to be more effective than twice daily ketanserin use in patients with mild to moderate hypertension.     

Labetalol in the treatment of hypertension in elderly and younger patients

The efficacy and safety of labetalol therapy were evaluated in 20 patients 60 years and older with isolated systolic or diastolic hypertension and 19 patients aged younger than 60 years with diastolic hypertension. After a two-week placebo washout period, labetalol was titrated for up to four weeks (100-400 mg bid) until blood pressure control was achieved (standing systolic less than 160 mm Hg or greater than or equal to 10% reduction from baseline, and standing diastolic less than 90 mm Hg or a decrease of 10 mm Hg from baseline). Mean decreases in standing systolic and diastolic blood pressure from baseline were statistically significant for both age groups (greater than or equal to 60 years, -23/-13; less than 60 years, -18/-12, P less than .01). Control criteria were met in 18 (90%) older and 15 (79%) younger patients who then entered a four-week maintenance period. Sixteen (80%) of the older patients and six (32%) of the younger patients maintained blood pressure control on 200 mg or less of labetalol bid (P less than .05). Three patients, two of whom withdrew from the study, were judged to have experienced adverse events that were drug related. It was concluded that labetalol was effective and well-tolerated antihypertensive therapy in both elderly and younger patients. In addition, significantly less medication was required to achieve blood pressure control in the elderly.     

Antihypertensive response to ketanserin: influence of race and weight

The antihypertensive effects of the 5-HT2 receptor antagonist ketanserin were evaluated in 16 patients with uncomplicated essential hypertension. Following a three week single-blind placebo treatment period, patients were randomized to receive in a double-blind manner oral ketanserin 20 mg or 40 mg twice a day for 10 weeks. In the racially mixed patient population, mean (+/- SD) seated blood pressure 12 hours after the last dose of placebo was 161 +/- 11/99 +/- 9 mm Hg and 155 +/- 19/98 +/- 10 mm Hg after ketanserin (P greater than .05). Ketanserin 20 mg twice a day did not lower blood pressure significantly. In contrast, 40 mg twice a day significantly decreased systolic blood pressure (P less than .02), and lowered diastolic blood pressure (P = .06). White patients (N = 7) showed a significant decrease in blood pressure (BP) with ketanserin treatment (158 +/- 5/98 +/- 8 vs. 147 +/- 13/92 +/- 6 mm Hg, P less than .05) while black patients (N = 9) did not (165 +/- 13/100 +/- 9 vs. 161 +/- 21/102 +/- 10 mm Hg, P greater than .05). For black patients only, significant correlations were observed between body weight and the change in diastolic BP (r = -.86, P less than .005). The racial difference in response to ketanserin could not be attributed to differences between the two groups in age, sex, body weight, pretreatment blood pressure or ketanserin dose. The nature of the racial difference in the chronic antihypertensive response to ketanserin warrants further evaluation.     

Effect of temazepam on blood pressure regulation in healthy elderly subjects.

1. Blood pressure regulation was studied in 12 healthy elderly subjects after double-blind randomised administration of placebo, 15 mg and 30 mg temazepam at 10.00 h and 22.00 h. 2. Supine and standing heart rate and blood pressure were measured after daytime administration and supine measurements were obtained during sleep. 3. Temazepam caused a fall in systolic blood pressure and an increase in heart rate after morning administration. These changes were greater in the standing position and were dose-dependent; for standing blood pressure and heart rate 1 h after administration there was a 7 mm Hg fall and 6 beats min-1 increase after 15 mg temazepam and a 10 mm Hg fall and 8 beats min-1 increase after 30 mg temazepam. Temazepam magnified the fall in systolic blood pressure and increase in heart rate that occurred with standing. Temazepam enhanced the fall in systolic blood pressure that occurred during sleep (mean +/- s.d.; placebo: -23 +/- 10 mm Hg, 15 mg temazepam: -31 +/- 13 mm Hg, 30 mg temazepam: -36 +/- 14 mm Hg). 4. These changes in blood pressure regulation caused by temazepam may have clinical importance in some elderly individuals.     

Epidemiology of hypertension in the elderly.

Epidemiological studies confirm that hypertension, particularly systolic hypertension, is a major cardiovascular and cerebrovascular risk factor in the elderly. Clinical trials convincingly demonstrate the benefits of treating both diastolic hypertension in persons up to age 80 years, and isolated systolic hypertension in persons over age 60. The European Working Party on Hypertension in the Elderly (EWPHE) trial showed that reducing elevated blood pressure resulted in a 27% reduction in overall cardiovascular mortality, as well as significant reductions in severe congestive heart failure, strokes and deaths from myocardial infarction. The Systolic Hypertension in the Elderly Program (SHEP) also reported a 36% reduction in the incidence of stroke and decreases in cardiovascular events, including myocardial infarctions, when hypertension was treated. Additional EWPHE data suggest that the optimal level of systolic blood pressure control is between 146 and 158mm Hg, while patients in the SHEP trial with isolated systolic hypertension derived benefits at an average treated systolic blood pressure of 143mm Hg. Elderly study populations comply well with antihypertensive treatment, and blood pressure can be safely lowered with simple drug regimens. Nonpharmacological treatment is recommended for initial treatment of mild diastolic hypertension and isolated systolic hypertension, and as adjuvant treatment with medication. Since all antihypertensive agents can lower blood pressure in the elderly, therapy should be chosen based on its potential for side effects, drug interactions and effects on concomitant disease states.     

Effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on blood pressure in nondiabetic patients with mild to moderate hypertension

The effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on ambulatory blood pressure was assessed in nondiabetic patients with mild to moderate hypertension in a randomized, double-blind, placebo-controlled, 3-period crossover study. Nineteen patients on stable treatment with antihypertensive agent(s) received sitagliptin 100 mg b.i.d., 50 mg b.i.d., or placebo for 5 days, with at least a 7-day washout interval between periods. Twenty-four-hour ambulatory blood pressure, including systolic blood pressure, diastolic blood pressure, and mean arterial pressure, were monitored on days 1 and 5. Relative to placebo on day 1, the mean difference in 24-hour systolic blood pressure was -0.9 mm Hg (90% confidence interval: -2.9 to 1.1; P = .46) with sitagliptin 50 mg b.i.d. and -2.8 mm Hg (90% confidence interval: -4.9 to -0.8; P < .05) with 100 mg b.i.d. On day 5, the mean difference in 24-hour systolic blood pressure was -2.0 mm Hg (90% confidence interval: -3.5 to -0.4; P < .05) with 50 mg b.i.d. and -2.2 mm Hg (90% confidence interval: -3.7 to -0.6; P < .05) with 100 mg b.i.d. relative to placebo. For 24-hour diastolic blood pressure, there were no between-group differences in mean 24-hour diastolic blood pressure on day 1. On day 5, sitagliptin 50 mg and 100 mg b.i.d significantly (P < .05) lowered mean 24-hour diastolic blood pressure by -1.8 mm Hg (90% confidence interval: -2.8 to -0.8) and -1.6 mm Hg (90% confidence interval: -2.6 to -0.7), respectively, relative to placebo. Sitagliptin produced small but statistically significant reductions of 2 mm Hg to 3 mm Hg in 24-hour ambulatory blood pressure measurements acutely (day 1) and at steady state (day 5), and was generally well tolerated in nondiabetic patients with mild to moderate hypertension.