Reversal of pathophysiologic changes with long-term lisinopril treatment in isolated systolic hypertension.

The purpose of this study was to evaluate in a prospective, double-blind, placebo-controlled study the effect of long-term (2-year) lisinopril treatment on cardiovascular end-organ damage in patients with previously untreated isolated systolic hypertension (ISH). All patients with ISH were derived from a population screening program. End-organ damage measurements, done initially and after 6 and 24 months of treatment, included measurements of aortic distensibility and echocardiographic left ventricular mass index (LVMI) and diastolic function. Blood pressure was measured by office and ambulatory measurements. Of the 97 subjects with ISH selected from the screening, 62 (30 lisinopril) completed the study according to protocol. Office blood pressure decreased in both groups, but ambulatory results significantly decreased with lisinopril-treatment only. Aortic distensibility increased significantly with lisinopril, as opposed to a decrease in placebo-treated subjects. The main effect of increased distensibility occurred between 6 and 24 months, whereas ambulatory blood pressure changed mainly in the first 6 months of treatment. LVMI decreased in both treatment groups, with a significantly higher reduction in lisinopril-treated subjects. Left ventricular diastolic function showed no significant changes in either group. The vascular pathophysiologic alterations of ISH-a decreased aortic distensibility-can be improved with long-term lisinopril treatment, whereas values deteriorate further in placebo-treated subjects. These results, in one of the first studies including subjects with previously untreated ISH only, indicate that lisinopril treatment might favorably influence the cardiovascular risk of ISH.

Two-year follow-up study to evaluate the reduction of left ventricular mass and diastolic function in mild to moderate diastolic hypertensive patients.

OBJECTIVE: To compare the effects of two antihypertensive agents, amlodipine and lisinopril, on left ventricular mass and diastolic filling in patients from primary care centers with mild to moderate diastolic hypertension. STUDY DESIGN: A second-year, open follow-up of a prospective, double-blind, randomized, parallel group, comparative study. METHODS: Male and female patients between 25 and 75 years-of-age with elevated diastolic blood pressure (four measurements > or = 95 mmHg from multiple measurements taken on three occasions and average diastolic blood pressure < 115 mmHg) were recruited from a population survey. After 4 weeks' placebo run-in, 71 patients were included of whom 60 finished the first study year and 51 finished the second study year. Patients were randomly assigned to receive doses of 5-10 mg amlodipine or 10-20 mg lisinopril, which were titrated on the basis of the effects on blood pressure. Primary endpoints were left ventricular mass index (LVMI) and early to atrial peak filling velocity. Office and ambulatory blood pressure were considered secondary endpoints. RESULTS: The decrease in blood pressure was equal for both treatment regimens in the first year. A statistically significant (P< 0.001) decrease in LVMI in both treatment groups was observed in the first year [-11.0 g/m2 (95% Cl -6.0 to -16.1) in the amlodipine group and -12.6 g/m2 (95% Cl -8.2 to -17.0) in the lisinopril group]. Early to atrial peak filling velocity did not change significantly within the treatment groups in the first year [+0.07 (95% CI -0.01 to +0.15) in the amlodipine group and +0.01 (95%9 Cl -0.06 to +0.08) in the lisinopril group. Blood pressure, LVMI and early to atrial peak filling velocity did not change in the second year of treatment. No significant differences in primary and secondary endpoints between treatment groups were found in the first or second year. CONCLUSION: The effects of amlodipine and lisinopril on left ventricular mass and early to atrial filling peak velocity after 2 years of treatment were similar and these effects were already observed after 1 year of treatment. Additional studies of longer duration (> or = 4 years) and with a larger sample size are recommended.

Effects of amlodipine and lisinopril on left ventricular mass and diastolic function in previously untreated patients with mild to moderate diastolic hypertension.

The aim of the study was to compare the effects of two long-acting antihypertensive agents, the calcium-antagonist amlodipine and the ACE inhibitor lisinopril, on left ventricular mass and diastolic filling in patients with mild to moderate diastolic hypertension from primary care centres. It is a 1-year prospective, double-blind, randomized, parallel group, comparative study. Patients between 25 and 75 years of age with untreated hypertension with elevated diastolic blood pressure (> or = 95 mmHg) on three occasions (twice on the first visit and once only on the second and third visits) were recruited from a population survey. After 4 weeks placebo run-in 71 patients were randomized to dosages of amlodipine 5-10 mg or lisinopril 10-20 mg, which were titrated on the basis of the effects on blood pressure. Fifty-nine patients completed the study period. Primary endpoints were left ventricular mass index and early to atrial peak filling velocity. Office and ambulatory blood pressure and other echocardiographic measurements were considered secondary. Decrease in blood pressure was equal for both treatment regimens. A statistically significant decrease in left ventricular mass index in both treatment groups was observed: -11.0 g/m2 (95% CI: -6.0, -16.1) in the amlodipine group and -12.6 g/m2 (95% CI: -8.2, -17.0) in the lisinopril group. The higher the baseline value of left ventricular mass before treatment, the more the decrease after treatment. Early to atrial peak filling velocity did not change significantly within the treatment groups: +0.07 (95% CI: -0.01, +0.15) in the amlodipine group and +0.01 (95% CI: -0.06, +0.08) in the lisinopril group. However, analysis of time measurements of the early peak showed significant changes for both treatment groups. No significant differences in primary and secondary endpoints between treatment groups were found. Twelve patients did not complete the study, seven in amlodipine and five in lisinopril, basically due to adverse events. The effects of amlodipine and lisinopril on left ventricular mass and early to atrial filling peak velocity after 1 year of treatment in patients with previously untreated mild to moderate hypertension are similar. Further studies are recommended, particularly with a larger sample size and a follow-up of longer duration.

Effect of quinapril and triamterene/hydrochlorothiazide on cardiac and vascular end-organ damage in isolated systolic hypertension.

We compared, in a prospective double-blind randomized study, the effect of the angiotensin-converting enzyme inhibitor quinapril (QUI) with that of triamterene/hydrochlorothiazide (THCT) treatment on cardiovascular end-organ damage in subjects with untreated isolated systolic hypertension (ISH). End-organ damage measurements, performed initially and after 6 and 26 weeks of treatment, included echocardiographic determination of left ventricular mass index (LVMI) and of diastolic function and measurement of aortic distensibility and peripheral vascular resistance. Blood pressure was significantly reduced in the 44 subjects (21 QUI, 23 THCT) completing the study. Both LVMI and aortic distensibility had changed at 6 weeks, with comparable improvements in both groups. LV diastolic function showed overall no significant changes, although patterns of early filling did differ between the two drug groups. Peripheral vascular resistance appeared to increase between 6 and 26 weeks in THCT subjects only, along with a decreased aortic distensibility. Blood pressure and LV mass were rapidly and markedly reduced in both treatment groups of ISH subjects, paralleled by an improvement of aortic distensibility. In interpreting these results, the pathophysiologic alterations in ISH need to be taken into account, because these differ strongly from those in diastolic hypertension. Results of LV diastolic function and peripheral vascular resistance were less clear but appear to show less favorable changes in the THCT subjects treatment group.

High prevalence of concentric remodeling in elderly individuals with isolated systolic hypertension from a population survey.

Echocardiographic determination of left ventricular mass index (LVMI) is shown to be valuable in the assessment of cardiovascular risk. Determination of left ventricular geometry, including concentric remodeling, provides additional prognostic information. In isolated systolic hypertension (ISH), the few echocardiographic studies available show an increased LVMI, but criteria and patient populations differ. No comparison with diastolic hypertension (DH) has been made, nor has left ventricular geometry (with concentric remodeling) been evaluated. We compared both LVMI and left ventricular geometry of newly diagnosed ISH subjects with normotensive and DH subjects, all previously untreated and from the same population. The echocardiographic LVMI of 97 previously untreated ISH subjects (4 x systolic pressure > or = 160 mm Hg, diastolic pressure < 95 mm Hg) was clearly elevated compared with values in age- and sex-matched normotensive subjects (98 and 71 g/m2, respectively; P < .001). The geometric pattern was abnormal in most ISH subjects, with a high prevalence (43%) of concentric remodeling. Both LVMI and left ventricular geometry of ISH subjects did not differ significantly from values in DH subjects (LVMI, 92 g/m2; concentric remodeling, 56%). Sex differences in LV geometry in ISH were present only with the Framingham criteria, not with the Koren criteria. This study shows a high prevalence of concentric remodeling in elderly individuals with previously untreated ISH. The increase of LVMI and abnormality in left ventricular geometry are comparable with those in DH subjects, further defining the place of ISH as a cardiovascular risk factor in the elderly. Whether there are sex differences in cardiac adaptation in ISH and whether the geometric classification can be used to adjust treatment remain to be investigated.

Predictive value of ambulatory blood pressure shortly after withdrawal of antihypertensive drugs in primary care patients.

OBJECTIVE: To determine whether ambulatory blood pressure eight weeks after withdrawal of antihypertensive medication is a more sensitive measure than seated blood pressure to predict blood pressure in the long term. DESIGN: Patients with previously untreated diastolic hypertension were treated with antihypertensive drugs for one year; these were withdrawn in patients with well controlled blood pressure, who were then followed for one year. SETTING: Primary care. SUBJECTS: 29 patients fulfilling the criteria for withdrawal of antihypertensive drugs. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive value of seated and ambulatory blood pressure eight weeks after withdrawal of antihypertensive drugs. RESULTS: Eight weeks after withdrawal of medication, mean diastolic blood pressure returned to the pretreatment level on ambulatory measurements but not on seated measurements. One year after withdrawal of medication, mean diastolic blood pressure had returned to the pretreatment level both for seated and ambulatory blood pressure. For ambulatory blood pressure, the sensitivity and the positive predictive value eight weeks after withdrawal of medication were superior to those for seated blood pressure; specificity and negative predictive value were comparable for both types of measurement. Receiver operating characteristic curves showed that the results were not dependent on the cut off values that were used. CONCLUSION: Ambulatory blood pressure eight weeks after withdrawal of antihypertensive drugs predicts long term blood pressure better than measurements made when the patient is seated.

Characterization of hypertensive subjects who become normotensive during three months of office BP follow-up: comparison with subjects with sustained hypertension and normotensives, and follow-up after two years.

After an observation period of three months, 83% of new hypertensives (n = 84), identified in a population survey, became normotensive. Those with sustained hypertension (n = 14) were compared with 14 initially hypertensives who became normotensive and 14 normotensives, matched for age and sex, using ambulatory and exercise BP and echocardiography (both M-mode and Doppler). The initially hypertensive group (n = 11) was re-examined after two years follow-up. The 24h mean ambulatory and submaximal systolic exercise BP did not differ between sustained (139/92 and 210 mmHg) and initially hypertensives (143/95 and 217 mmHg), being significantly lower in the normotensive group (129/85 and 198 mmHg). Left ventricular mass did not differ between the initially hypertensive and the normotensive groups, being significantly higher in the sustained hypertensives. In both hypertensive groups, as compared with normotensives, the ratio between flow velocity in early and late diastole (E/A ratio) tended to be lower and the early diastolic deceleration time (DT) was significantly shorter. After two years, in the untreated initially hypertensives, office DBP had increased to hypertensive values, without change in ambulatory BP, left ventricular mass or early diastolic deceleration time. The E/A ratio had decreased to a level < 1. We conclude that the subjects who became normotensive after three months office BP follow-up have a BP load and signs of compromised left ventricular diastolic function similar to that of the sustained hypertensives, but without increased left ventricular mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril compared to atenolol in mild to moderate hypertension in a randomized double-blind controlled trial.

After screening a local population in the northern part of The Netherlands for hypertension, 125 patients (116 of whom had not previously used antihypertensive drugs) with a five times elevated diastolic pressure (DP) of between 95 and 130 mmHg were randomized and treated daily either with atenolol 50 mg o.d. (n = 62) or with captopril 25 mg b.i.d. (n = 63) for 2 months under double-blind conditions. During this period the DP fell by 9 mm under atenolol (from 107 +/- 8 to 98 +/- 8) and by 8 mm under captopril (from 107 +/- 7 to 99 +/- 9). The number of responders with a DP = less than 90 mmHg was 21% and 20%, respectively. After 2 months the double-blind period was ended and the patients were submitted to a medication protocol for another 4 months in which an increased dose and additional nifedipine were given to non-responders. The response rate rose to 76% (atenolol/nifedipine combination) and to 60% (captopril/nifedipine combination) - NS. It is concluded that low doses of atenolol and captopril are equally effective in lowering blood pressure in uncomplicated mild to moderate hypertension.

Groningen Hypertension Service: ten years experience in detecting and treating hypertension in a population of 23,340 persons in rural and urban districts in Holland with a special hypertension service.

The Groningen Hypertension Service (GHS) has demonstrated that provision of training for volunteers, technical assistance and the services of the General Practitioner Laboratory (a private foundation offering laboratory and diagnostic facilities) have enabled large rural and urban districts to be screened for hypertension within a short period of time at low cost. The GHS trained volunteers and paramedics, who assisted with the treatment for six months. The General Practitioner Laboratory evaluated treatment in nearly 600 hypertensive patients, leading to the institution of low-dose therapy and careful investigation of side-effects.

Quality of life on antihypertensive therapy: a randomized double-blind controlled trial of captopril and atenolol.

A randomized double-blind study lasting 2 months was performed with either 25 mg captopril twice a day or 50 mg atenolol once a day in 125 patients with established diastolic hypertension (diastolic blood pressure greater than 95 mmHg) identified during a population screening programme of subjects aged less than 65 years. Quality of life was assessed from self-completed questionnaires. A significant fall in diastolic blood pressure occurred with both captopril (106.7 +/- 7.0 to 98.6 +/- 8.6 mmHg) and atenolol (107.4 +/- 7.5 to 98.2 +/- 8.1 mmHg) but there was no difference between the two drugs in the size of the fall. A measure of the number of symptomatic complaints, the symptom complaint rate, decreased with both drugs, by 1.3% for captopril and 3.1% for atenolol, but the difference between the drugs was not significant [1.8%; 95% confidence interval (Cl) - 1.3%, 4.9%]. There was a significant increase in the reporting of cough and runny nose in those on captopril compared with atenolol. A health index increased by 1.1% with captopril in comparison with no change on atenolol (difference 1.1%; 95% Cl - 2.0%, 4.2%). Psychological well-being was measured using the Symptom Rating Test. The improvement in total score was 1.4% with captopril and 2.3% with atenolol. The difference of 0.9% was not statistically significant (95% Cl - 1.2%, 3.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of labetalol and prazosin combined with atenolol in non-responders to atenolol plus hydrochlorothiazide in uncomplicated hypertension.

After screening two local populations in the northern part of The Netherlands for hypertension, patients with a diastolic pressure (DP) between 95 and 120 mmHg were treated daily either with 50 mg hydrochlorothiazide or 100 mg atenolol. Nonresponders were given the combination and if necessary the dose of atenolol was increased to 200 mg. Non-responders to the latter combination were randomized and treated either with 50 mg hydrochlorothiazide and labetalol or with 50 mg hydrochlorothiazide, 200 mg atenolol and prazosin. If after 1 month a DP less than or equal to 90 mmHg had been reached the patient was reassessed after a further 3 months. If a DP greater than 90 mmHg was found the dose of labetalol or prazosin was increased and the patient was re-examined after 1 month. This protocol was followed until the maximum dose was reached or adverse reactions prevented a further increase in dosage. During 6 months of treatment there was a further drop in systolic and diastolic blood pressures under both regimens of, respectively, 8.6 and 2.4 mmHg for labetalol, and 7.7 and 5.0 mmHg for the prazosin group. At the end of the period the average daily doses of labetalol and prazosin were 1256 mg and 4.3 mg, respectively. There was no significant difference in the average number of complaints between the labetalol and the prazosin group.

Effects of atenolol, labetalol and propranolol on the peripheral circulation in hypertensive patients without obstructive vascular disease.

In an observer-blind, randomised cross-over trial, in 12 patients, the effects on the peripheral circulation of antihypertensive doses of atenolol, labetalol and propranolol and placebo were compared. After a placebo period of at least 4 weeks, patients were allocated at random to one of the three active drug treatments. After active treatment for at least 6 weeks and a fall in diastolic pressure (DP) to less than 90 mmHg subjects were switched to the next medication. At the end of each period, photo-electric plethysmography (PHELP) was done on all fingers of one hand cooled over 4 min in water in steps of 3 degrees C from 33 degrees to 12 degrees C, and subsequently warmed in room air (20 degrees C) for a period of 10 min. Blood flow changes during cooling were expressed as a percentage of the initial PHELP value (% PHELP). Areas under the curves, representing the % PHELP/cooling period and % PHELP/warming-up period, showed that within the temperature range normally encountered in daily life, labetalol preserved finger blood flow significantly better than propranolol and marginally better than placebo. With atenolol, finger blood flow was not significantly different from that during the three other regimens, but there were significantly fewer other side-effects. It is concluded that labetalol may be the drug of choice for hypertensive patients treated with beta-blocking agents whose peripheral arterial circulation seems inadequate at low temperatures.

Comparison of atenolol 50 mg and 100 mg as initial treatment in uncomplicated mild to moderate hypertension.

After screening a local population in the northern part of The Netherlands for hypertension, 59 patients with a diastolic pressure (DP) between 95 and 130 mmHg were randomized and treated either with 50 mg atenolol (n = 29) or 100 mg atenolol (n = 30) for 1 month. There was no significant difference between the two treatments, neither in the fall in systolic and diastolic pressures nor in the number of complaints reported. It is concluded that in the initial treatment of uncomplicated mild to moderate hypertension, 100 mg atenolol has no advantage over a 50 mg dose.

Comparison of hydrochlorothiazide and atenolol as initial treatment in uncomplicated hypertension.

After screening a local population in the northern part of The Netherlands for hypertension, 119 patients with a diastolic pressure (DP) between 95 and 120 mmHg were randomised and treated either with 50 mg hydrochlorothiazide (n = 59) or 100 mg atenolol (n = 60). After 1 month of treatment 6 patients in the hydrochlorothiazide group and 24 patients in the atenolol group had reached a DP less than or equal to 90 mmHg (p less than 0.001). 43 of the 50 non-responders to hydrochlorothiazide were switched to atenolol and 30 of the 35 non-responders to atenolol were changed to hydrochlorothiazide. One month after the switch 19 patients in the atenolol group and 2 patients in the hydrochlorothiazide group had reached a DP less than or equal to 90 mmHg (p less than 0.001). After 6 months of treatment 32 of the 43 atenolol responders and 7 of the 8 hydrochlorothiazide responders were still receiving the same medication, as their DP was still less than or equal to 90 mmHg. Non-responders to either medication were given the combination (n = 46). 21 patients now became normotensive as did a further 10 after increasing the dose of atenolol to 200 mg. Thus, in all 70 patients had a blood pressure less than or equal to 90 mmHg after treatment for 4 months. Both drugs induced a significant reduction in the total of number of complaints after 1 month of treatment. They did not differ from each other. The reduction was seen both in responders and non-responders and persisted during treatment for 6 months. It is concluded that in terms of short-term efficacy the cardioselective, hydrophilic beta adrenoceptor-blocking drug atenolol is preferable to hydrochlorothiazide in the treatment of uncomplicated hypertension.

Comparison of labetalol, propranolol and hydralazine in hypertensive out-patients.

In a randomized cross-over trial the combination labetalol/hydrochlorothiazide was compared with the combination of propranolol/hydralazine/hydrochlorothiazide in 34 uncomplicated hypertensive patients, who were not satisfactorily controlled with hydrochlorothiazide 50 mg alone. The elevated diastolic pressure (D.P.) in 27 patients responded satisfactorily to the labetalol schedule and in 28 patients to the propranolol/hydralazine schedule. No difference was found in the rate of decrease of D.P., nor in the disappearance of hypertension-related complaints. Although the duration of the washout between treatments was at least one month, treatment was significantly more efficacious during the second period. Labetalol pre-treatment especially seemed to enhance the effect of subsequent propranolol/hydralazine administration. Side effects due to therapy were rare and were not related to any particular treatment. The median daily dose of labetalol in responders was 600 mg and that of propranolol/hydralazine 120/60 mg (in both therapies hydrochlorothiazide 50 mg was given in addition). Patients showed a slight preference for the labetalol medication. It is concluded that labetalol/hydrochlorothiazide and propranolol/hydralazine/hydrochlorothiazide are equally satisfactory in the treatment of uncomplicated hypertension.