Impact of diabetes on treatment-induced changes in left ventricular structure and function in hypertensive patients with left ventricular hypertrophy. The LIFE study.

BACKGROUND AND AIM: Diabetes is associated with left ventricular hypertrophy (LVH) and impaired systolic function in hypertensive patients, but less is known about its impact on LVH regression and functional improvement during antihypertensive treatment. METHODS AND RESULTS: We performed annual echocardiography in 730 non-diabetic and 93 diabetic patients (aged 55-80 years) with hypertension and electrocardiographic LVH during 4.8-year losartan- or atenolol-based treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Baseline mean blood pressure (BP) and LV mass did not differ between groups. Diabetic patients had higher body mass index and pulse pressure, and lower LV ejection fraction, midwall shortening, stress-corrected midwall shortening, and estimated glomerular filtration rate (all p<0.05), and were more likely to have albuminuria. Despite comparable BP reduction in diabetic and non-diabetic groups during treatment (33/18 vs. 28/16mmHg (ns)), diabetes was associated with higher prevalence of persistent LVH (47 vs. 39%, p<0.05). In multivariate analyses, diabetes independently predicted less LV mass reduction and less improvement in stress-corrected LV midwall shortening (both p<0.01). CONCLUSION: Among hypertensive patients with LVH, diabetes is associated with more residual LVH and less improvement in systolic LV function by echocardiography over 4.8 years of antihypertensive treatment.

Characteristics of 9194 patients with left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint Reduction in Hypertension.

-Losartan was the first available orally administered selective antagonist of the angiotensin II type 1 receptor developed for the treatment of hypertension. The Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality. Patients with essential hypertension, aged between 55 and 80 years, and ECG-documented left ventricular hypertrophy (LVH) were included. Altogether, 9223 patients in Scandinavia, the United Kingdom, and the United States were randomized from June 1995 through April 1997, and 9194 remain after exclusion of a study center at which irregularities were discovered. This population of hypertensives (mean systolic/diastolic blood pressure, 174.4/97.8 mm Hg) with LVH comprises women (54.1%) and men, mostly retired from active work (mean age, 66.9 years), with a high prevalence of overweight (mean body mass index, 28.0 kg/m2), diabetes mellitus (12.3%), lipid disorders (18.0%), and symptoms or signs of coronary heart disease (15.1%). There were fewer current smokers (<17%) than in the general population, and approximately 7% were nonwhite. Almost 30% of participants had been untreated for at least 6 months when screened for the study. Only 1557 persons who entered the placebo run-in period of 14 days were excluded, predominantly because of sitting blood pressures above or below the predetermined range of 160-200/95-115 mm Hg and ECG-LVH criteria not met. By application of simple 12-lead ECG criteria for LVH (Cornell voltage QRS duration product formula plus Sokolow-Lyon voltage read by a core laboratory), hypertensive patients with LVH with an average 5-year coronary heart disease risk of 22.3% according to the Framingham score were identified. This population is now being treated (goal, <140/90 mm Hg) in adherence with the protocol for at least 4 years after final enrollment (ie, through April 2001) and until at least 1040 patients suffer myocardial infarction, stroke, or cardiovascular death.

Effect of sodium depletion on plasma renin concentration before and during adrenergic beta-receptor blockade with propranolol in normotensive man.

Plasma renin levels have been used to discriminate between different forms of hypertension, but how to define the normal range of plasma renin levels has not been agreed upon. Sodium depletion stimulates renin release. Evaluation of plasma renin would, therefore seem possible only in relation to sodium balance. Plasma renin concentration and concurrent daily sodium excretion were determined in 33 healthy normotensive subjects (control group) ingesting high, normal and low sodium diets. A well-defined hyperbolic relationship was found between the two variables indicating that the physiologic level of plasma renin concentration depends on the state of sodium balance. An increase in plasma potassium concentration may reduce plasma renin concentration, but this appeared to be overruled by the stimulating effect of sodium depletion. To examine whether beta-adrenergic stimulation contributes to the increase in plasma renin concentration during sodium depletion, the relationship between plasma renin concentration and concurrent sodium excretion was studied during beta-receptor blockade with propranolol. In 20 healthy normotensive subjects in whom beta-receptor blockade was verified by a significant reduction in pulse rate, the same hyperbolic relationship was found between plasma renin concentration and sodium excretion as in the control group showing that sodium depletion stimulates renin release independent of sympathetic nervous activity.

Long-term central hemodynamic effects at rest and during exercise of losartan in essential hypertension.

BACKGROUND: Losartan reduces blood pressure in patients with essential hypertension, but the long-term central hemodynamic effects at rest and during exercise are not known. METHODS AND RESULTS: After 8 months of losartan treatment (50 to 100 mg daily, mean 82 mg), intra-arterial pressure was reduced from 165/102 mm Hg to 145/91 mm Hg at rest and from 193/104 mm Hg to 179/96 mm Hg during 100 W exercise in 28 patients with essential hypertension. Cardiac index and heart rate remained unchanged, but total peripheral resistance index was reduced 12% to 15%. Stroke index was unchanged at rest but increased 7% to 9% during exercise. Twenty-four-hour ambulatory blood pressure was reduced 10% to 13%. Left ventricular mass was reduced 27% in patients with left ventricular hypertrophy (n = 18). CONCLUSION: Losartan lowers blood pressure by reducing total peripheral resistance at rest and during exercise but cardiac pump function is unchanged or slightly improved. In patients with left ventricular hypertrophy, losartan induces a sizeable reduction in left ventricular mass.

Cardiac biochemical markers after cardioversion of atrial fibrillation or atrial flutter.

BACKGROUND: Cardioversion or defibrillation of cardiac arrhythmias is often necessary in acutely ill cardiac patients. The electrical current may cause elevation of biochemical markers used to diagnose acute myocardial infarction. Therefore it is important to find cardiac markers with high specificity for myocardial necrosis. The purpose of this study was to assess the effects of elective cardioversion of atrial fibrillation or flutter on troponin T and I among conventional markers in patients with no evidence of acute ischemia. METHODS AND RESULTS: Fifty-seven consecutive patients underwent 1 to 4 direct current shocks (mean cumulative energy 407 J, range 100 to 920 J) under general anesthesia. At baseline, all had normal troponin levels; 50 patients (mean age 68 years, range 33 to 84 years) had normal cardiac enzymes and were included in the final analysis. Blood samples were drawn at baseline, and 1 to 2, 6 to 8, and 20 to 24 hours after cardioversion. The troponin levels were unaffected by cardioversion in all patients, whereas creatine kinase and myoglobin increased more than 10-fold. Creatine kinase MB mass and aspartate aminotransferase were above reference limits in 18% and 24% of patients, respectively, 20 to 24 hours after cardioversion. There was a significant association between elevated creatine kinase, myoglobin, and creatine kinase MB levels with cumulated energy delivered as well as when possible confounders such as age and sex were adjusted for. High international normalized ratio with warfarin use was associated with increased levels of creatine kinase, aspartate aminotransferase, lactate dehydrogenase, and myoglobin. CONCLUSIONS: The increase of conventional biochemical markers after direct current cardioversion is positively associated with cumulative energy delivered and international normalized ratio (INR) values; neither influences levels of the cardiac troponins.

Is sodium restriction effective treatment of borderline and mild essential hypertension? A long-term haemodynamic study at rest and during exercise.

Blood pressure (BP) may fall during moderate sodium restriction in patients with essential hypertension (EH). Few data are available on the haemodynamic changes associated with sodium restriction and exercise data are lacking. We studied the long-term haemodynamic effect of reduced sodium intake in 19 men aged 16-51 years with mild and borderline EH. Cardiac output (CO; by Cardiogreen) and intra-arterial BP were measured at rest and during exercise before and after 9 months therapy. Sodium excretion was reduced by 75 mmol/24 h (36%) from a mean of 209 mmol/24 h and the sodium:potassium (Na:K) ratio fell by 0.75 from 2.17. Intra-arterial pressures fell by 3-5% (P less than 0.05) at rest, both supine and sitting, and during 50, 100 and 150 W bicycle exercise. Body weight and body fluid volumes (isotope dilution) remained unchanged. Haemodynamically, the fall in BP was due to reduction in CO ranging from 7-12% at rest and during exercise, while total peripheral resistance (TPR) rose by 4-10%. Stroke volume and heart rate fell by 2-9%. We conclude that moderate sodium restriction was not an efficient treatment in our patients with borderline and mild EH. The slight reduction in BP was associated with a fall in CO but without reduction of TPR. Thus, the main haemodynamic disturbance of established EH, that is an increase in TPR, was not normalized by 9 months sodium restriction.

Acute haemodynamic effects of perindoprilat in essential hypertension at rest and during exercise.

The acute haemodynamic effect of perindoprilat was examined at rest, supine and sitting, and during 100 W bicycle exercise in 12 patients (mean age 42 years) with essential hypertension. Intra-arterial blood pressure and the heart rate were recorded continuously. Cardiac output was measured by dye dilution (Cardiogreen) and blood volume was determined by radio-iodinated (125I) human serum albumin. Two hours after a slow (3 min) intravenous injection of perindoprilat, blood pressure was reduced in all patients (P less than 0.01)--at rest sitting from 175/108 to 153/97 mmHg (11%)--because of reduction in total peripheral resistance index (f = 2.63; P less than 0.05). Only minor changes were seen in the heart rate, stroke index and cardiac output. The fall in blood pressure was significantly (P less than 0.05) correlated with blood volume (r = 0.65) and pretreatment total peripheral resistance index (r = 0.59).

Haemodynamic effects of nifedipine in essential hypertension at rest and during exercise.

Fifteen males with previously untreated essential hypertension in WHO stage I, aged 20-64 years were studied on an outpatient basis. Oxygen consumption, heart rate, cardiac in a in a supine and sitting position and during steady state work at 50, 100 and 150 W. Following the haemodynamic study, nifedipine (long-acting form) 40-80 mg daily was given as the sole drug for 3-12 months (mean 11 months) whereupon the haemodynamic study was repeated. Systolic, diastolic and mean arterial pressures fell about 17% at rest supine and sitting and from 15 to 10% at the three different workloads (P less than 0.001). All but one patient demonstrated a fall in mean arterial pressure of 10 mmHg or more. The fall in pressure was associated with a statistically significant (P less than 0.05) reduction in total peripheral resistance (17% during rest and 10 to 16% during exercise). There were no statistically significant changes in oxygen consumption, heart rate, cardiac index or stroke index.

Long-term effects on central haemodynamics and body fluid volumes of ketanserin in essential hypertension studies at rest and during dynamic exercise.

The long-term haemodynamic effects of ketanserin, a new serotonin-antagonist, was examined in 13 patients of both sexes (age range 24-62 years) with mild and moderate essential hypertension (EH). Cardiac output (CO) and intra-arterial blood pressure (BP) were measured at rest and during exercise before and after nine months of therapy. On ketanserin the mean casual BP was lowered by 15/21 mmHg to 152/91 mmHg and five of the 13 patients became 'normotensive' (BP less than 140/90 mmHg). The intra-arterial systolic pressure fell by 5-8% and the diastolic pressure by 5-11% from pretreatment levels at rest supine, sitting and during 50, 100 and 150 W exercise. The fall in BP was associated with a reduction in CO at rest while during exercise both a fall in CO and in total peripheral resistance contributed to the hypotensive effect. The fall in CO was due to a reduction in heart rate (average: -4 to 8 beats/min). The stroke volume remained unchanged in all settings and oxygen consumption was not affected by the drug. Body weight and body fluid volumes did not change significantly. Eight patients complained of drowsiness and lack of concentration. It is concluded that in mild and moderate EH ketanserin induces a moderate BP reduction associated with a fall in CO. There is no large vasodilating effect after long-term ketanserin treatment either at rest or during exercise. Ketanserin does not influence body fluid balance. The incidence of side-effects is high.

Combined captopril and hydrochlorothiazide therapy in severe hypertension: long-term haemodynamic changes at rest and during exercise.

Captopril is an orally active converting enzyme inhibitor lowering blood pressure (BP) in different types of hypertension. A combination of captopril and a diuretic is often used in the treatment of severe hypertension. We have examined the chronic haemodynamic effect of combined captopril and hydrochlorothiazide treatment at rest and during 50 and 100 W dynamic exercise in 12 patients with severe therapy resistant essential hypertension. Blood pressure was measured intra-arterially before and after a mean treatment period of 8.7 months. Cardiac index (CI) was measured by dye dilution (Cardiogreen) and body fluid volumes by radioisotope dilution techniques. During rest sitting BP was reduced by 31/17 mmHg (15%) from a pretreatment value of 205/119 mmHg. Total peripheral resistance index (TPRI) fell 17% whereas CI, heart rate (HR) and stroke index (SI) did not show any significant changes. The fall in mean arterial pressure (MAP) was slightly less during exercise (12%) and the BP reduction was associated with a fall in CI and SI of 15 and 17%, respectively and no fall in TPRI. No significant changes were observed in body fluid volumes.

Nisoldipine. Central haemodynamics at rest and during exercise in essential hypertension: acute and chronic studies.

Calcium blockers may reduce contractility of vascular smooth muscle as well as that of myocardial cells. Therefore, falls in both total peripheral vascular resistance (TPR) and cardiac output (CO) might be responsible for a fall in blood pressure (BP) caused by calcium blockers in essential hypertension. We have studied the acute and chronic haemodynamic effects of nisoldipine (a new calcium blocker) in 19 patients with essential hypertension at rest in the supine and sitting positions and during 100-W dynamic exercise to investigate whether CO might be compromised by acute and chronic calcium blockade. Intra-arterial pressure, CO (by Cardiogreen), stroke volume, heart rate and TPR were measured hourly after the first dose of 10 mg nisoldipine (acute study) and then after 1 year of nisoldipine treatment (mean dose 25 mg; chronic study). The maximal first dose response was seen after 1 h, i.e. a fall in intra-arterial pressure (9%) and TPR (19%) and a reflex rise in heart rate (9%) and CO (12%). The effects levelled off during the next 2 h. After 1 year of treatment there was a more marked reduction in BP: at rest intra-arterial pressure fell (14% supine, 16% sitting) due to fall in TPR (19%) but without significant changes in heart rate or CO; during 100-W exercise, intra-arterial pressure fell (14%) due to reduction in both TPR (7%) and CO (6%). In conclusion, nisoldipine lowers BP by reducing TPR, both acutely and chronically. The initial reflex tachycardia and rise in CO disappear during long-term treatment, probably due to resetting of the baroreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

The Bergen blood pressure study: offspring of two hypertensive parents have significantly higher blood pressures than offspring of one hypertensive and one normotensive parent.

OBJECTIVE: To study blood pressure and antihypertensive drug treatment in subjects with contrasting family histories of hypertension. SUBJECTS AND METHODS: We grouped 520 offspring examined in 1990 (mean +/- SD age 36 +/- 7 years) according to their parents' blood pressure screened in 1963-1964 as offspring of two normotensive (systolic/diastolic blood pressure < 135/70 mmHg) parents (group 1); offspring of one hypertensive (> or = 145/95 mmHg) and one normotensive (<135/70 mmHg) parent (group 2); and offspring of two hypertensive (> or = 140/90 mmHg) parents (group 3). Offspring blood pressure was measured with a conventional mercury sphygmomanometer by one observer. The mean of the last two of three seated measurements was used for analyses. Drug treatment was determined by interview. RESULTS: Mean +/- SD blood pressure was lowest in group 1 (121 +/- 12/72 +/- 10 mmHg), intermediate in group 2 (125 +/- 12/76 +/- 9 mmHg) and highest in group 3 (135 +/- 15/85 +/- 11 mmHg), P<0.01 for each. Of the subjects in groups 1, 2 and 3, 1.3, 2.4 and 11.7%, respectively, were taking antihypertensive drugs (P<0.01). CONCLUSIONS: Screening blood pressure in parents has implications for offspring blood pressure almost 30 years later. Offspring of hypertensive parents have higher blood pressure and are given antihypertensive drugs at higher rates than the offspring of normotensive parents. Also, substantial differences were seen between the offspring of one and of two hypertensive parents. Thus, risk associated with a family history of hypertension varies with the definition of the family history. To obtain maximum contrast in the predisposition to high blood pressure, comparative studies in offspring of hypertensive and normotensive families should be based on blood pressure data from both parents.

Comparison of the angiotensin II antagonist losartan with the angiotensin converting enzyme inhibitor enalapril in patients with essential hypertension.

OBJECTIVE: To evaluate the blood pressure lowering efficacy as well as tolerability and safety of the angiotensin II antagonist losartan compared with that of the angiotensin converting enzyme inhibitor enalapril in patients with mild-to-moderate essential hypertension. DESIGN AND METHODS: The study was a multicentre, double-blind, double-dummy, randomized, parallel study. Patients (n = 407) with diastolic blood pressure > or = 95 and < or = 120 mmHg at the end of a 2-week baseline placebo period were randomly allocated to receive either 50 mg losartan once a day or 20 mg enalapril once a day for 12 weeks. Blood pressure, clinical and laboratory safety, specific symptoms including coughing determined using a symptoms questionnaire and metabolic variables were examined at baseline and at weeks 6 and 12. RESULTS: Both losartan and enalapril decreased systolic and diastolic blood pressure from baseline at weeks 6 and 12. Blood pressure changes from baseline at trough (22-26 h after the dose) did not differ between the two groups in the per-protocol analysis. Response to treatment at trough was excellent or good (diastolic blood pressure < 90 mmHg or reduction in diastolic blood pressure of 10 mmHg) in 51 and 53% of the patients in the losartan and enalapril groups, respectively. Enalapril administration increased dry coughing symptoms whereas losartan did not. The incidence of dry coughing was 1.0 and 12.2% as a spontaneously reported discomfort at week 12 and 3.0 and 15.1% as a clinical adverse experience in the losartan and enalapril groups, respectively. The difference from baseline at week 12 in the incidence of dry coughing between the two groups was 14.9% as a specific symptom in the symptoms questionnaire. Losartan reduced serum uric acid concentration, whereas effects on other metabolic parameters did not differ between the groups. CONCLUSIONS: Losartan is an effective and well-tolerated antihypertensive drug showing similar blood-pressure-lowering efficacy to that of enalapril at trough. However, in contrast to enalapril, losartan does not increase the incidence of dry coughing. Thus, the angiotensin II antagonist losartan provides a promising new approach to treatment of hypertension.

Sodium excretion and blood pressure in middle-aged men in the Sogn County: an intra- and interpopulation study.

Blood pressure (BP) and daily sodium excretion were measured in 262 males aged 35-54 years from three separate districts of the Sogn county in Norway. Averages for mean arterial pressure and sodium excretion were 103.4 mmHg and 192.4 mmol/24 h respectively, which is similar to the excretion rates in most other Western societies. Interpopulation (between groups) analysis revealed statistically significant differences in sodium excretion and BP between the three districts, but no significant correlation was found between individual sodium excretion rates and the respective BPs (within group analysis). The mean urinary sodium/potassium ratio (Na/K) was significantly lower in the district with the lower BP level, but there was no statistically significant correlation between individual Na/K ratios and BP. The lack of significant correlation between sodium excretion and BP in the within group analysis as opposed to the between groups comparison could be due to large intra-individual variation of sodium excretion.

Clinical evaluation of the Accutracker II ambulatory blood pressure monitor: assessment of performance in two countries and comparison with sphygmomanometry and intra-arterial blood pressure at rest and during exercise.

In order to assess the Accutracker II (Suntech Medical Instruments, Raleigh, North Carolina, USA), a relatively new ambulatory blood pressure (BP) monitor, versus standard forms of BP measurement, we compared same- and contralateral-arm measurements made, via a t-tube connected to a mercury column sphygmomanometer, by two clinicians using a teaching stethoscope and by intra-arterial recordings. Average systolic BP values obtained using the Accutracker II were similar to both the mercury column and intra-arterial determinations, but average diastolic BP values were lower than both the average mercury column (2.8 +/- 4.2 mmHg, P less than 0.001) and intra-arterial measurements (2.0 +/- 4.7 mmHg, P less than 0.02). During isometric exercise and 100-watt bicycle exercise, there were greater limits of agreement for the differences in BP between the Accutracker II and the intra-arterial transducer than were observed for the resting measurements, but these differences were no greater than those observed between intra-arterial and clinician-determined BP measurements. The clinical performance of the Accutracker II was assessed using 119 hypertensive subjects (84 in Norway and 35 in the USA) who wore the monitor for 24 h. While there was good-to-excellent data return in both countries, there were significantly less error codes secondary to excessive arm motion observed in Norway. Our data demonstrate that the Accutracker II is quite accurate compared with both the mercury column and intra-arterial methods of measuring BP, and performs well during 24 h outpatient activities. Our findings also indicate certain geographical differences which may be important in the performance of ambulatory BP-monitoring studies.

The relationships between casual and ambulatory blood pressure measurements and central hemodynamics in essential human hypertension.

OBJECTIVE: To determine the association between ambulatory blood pressure (ABP) and central hemodynamics in hypertensive patients and between the area under the 24-h blood pressure curve and the hemodynamic indexes. PATIENT POPULATION: Forty untreated essential hypertensive patients (28 previously untreated, 12 withdrawn from therapy for > 12 weeks). METHODS: Patients underwent casual and 24-h ABP monitoring and invasive measurements of central hemodynamics. Central measures of ABP included 24-h mean, awake, and sleep values guided by activity journals. The ABP data were modeled by Fourier series and the ability of the smoothed and unsmoothed data to predict hemodynamics was compared. Individual blood pressure curves were analyzed by calculating the area under the curve using different threshold awake and sleep values to test the correlations between this form of blood pressure load and hemodynamics. RESULTS: Hemodynamic measures were not predicted by casual blood pressure but were related to ABP. Total peripheral resistance was strongly predicted by the area under the diastolic blood pressure (DBP) curve using an awake threshold of 90 mmHg and a sleep threshold of 80 mmHg (r = 0.56, P < 0.001). Data smoothing using Fourier transformation did not alter any correlations between ABP and hemodynamics. Exercise stroke index, an indicator of cardiac function impaired in early hypertensive heart disease, was also best predicted by area under the DBP curve using the same thresholds as above (r = -0.56, P < 0.001). CONCLUSIONS: These data imply that integrated areas under the ABP curve are related to hemodynamic hypertensive indexes and could be used to assess the extent of hypertensive burden in clinical trials.

Double-blind, parallel, comparative study on quality of life during treatment with amlodipine or enalapril in mild or moderate hypertensive patients: a multicentre study.

OBJECTIVE: To compare tolerance, antihypertensive efficacy and impact on quality of life of amlodipine and enalapril in patients with mild or moderate hypertension. DESIGN: Multicentre, double-blind, double-dummy, comparative trial in general practice. Three phases were conducted: 4 weeks on placebo, 12 weeks of dose adjustment (amlodipine or enalapril) and a 38-week maintenance period. PATIENTS: Four hundred and sixty-one patients of both sexes were enrolled; 451 were available for efficacy evaluation at the end of the trial. TREATMENT: The patients were allocated to either amlodipine (231) or enalapril (230) treatment. If at the end of dose adjustment (amlodipine 5-10 mg/day, enalapril 10-40 mg/day) diastolic blood pressure was > or = 95 mmHg, hydrochlorothiazide (25-50 mg/day) was added (27 amlodipine patients and 45 enalapril patients). MAIN OUTCOME MEASURES: Blood pressure changes after 1 year of treatment; between- and within-group changes in quality of life as assessed by psychological general well-being, social and sexual functioning, health-risk perception, alertness, behaviour, and impact of symptom and side effects. RESULTS: Indices on quality of life were unchanged or increased (2-9%) in both groups. Blood pressure was normalized or reduced by > or = 10 mmHg in 204 (90%) and 190 (85%) patients on amlodipine and enalapril, respectively. Cough was the most frequently reported adverse event in the enalapril group (13%) and oedema in the amlodipine group (22%). Only eight (4%) patients on amlodipine and nine (4%) on enalapril were withdrawn because of drug-related adverse events. CONCLUSION: At similar blood pressure reduction in mild and moderate hypertension, quality of life is equally well maintained on amlodipine and enalapril therapy.

Long-term haemodynamic effects of amlodipine at rest and during exercise in essential hypertension.

The long-term haemodynamic responses to amlodipine, a new long-acting calcium antagonist, were studied both at rest and during exercise in 18 patients (mean age 43 years) with essential hypertension. Blood pressure was measured intra-arterially, cardiac output by dye dilution and heart rate by electrocardiogram. After 11 months of treatment with 5-10 mg amlodipine once daily (mean dose 9 mg/day), mean arterial pressure was reduced by 14% sitting at rest. The reduction in blood pressure was associated with a marked reduction in the total peripheral resistance index (TPRI) of 19% (P less than 0.001). Similar responses were seen supine at rest and during 50W, 100W and 150W bicycle exercise. No significant changes were seen in heart rate. There was a slight increase in stroke index, and cardiac index was preserved at rest and during exercise with a slight trend towards an increase. In 10 of the patients, blood pressure was monitored by a portable blood pressure recorder (Accutracker II, Suntech Medical instruments, Raleigh, North Carolina, USA). Blood pressure was well controlled throughout the full 24 h period after one daily dose. In conclusion, amlodipine exerts a clear antihypertensive effect, both at rest and during exercise, through reduction in the TPRI and without a fall in cardiac pump function. No changes in heart rate were seen and there was no tendency for a reduction in the stroke index during 8 min of exercise at 150 W; on the contrary there was a trend towards an increase. The incidence of side-effects was low (ankle oedema in two patients).

Comparison of long-term hemodynamic effects at rest and during exercise of lisinopril plus sodium restriction versus hydrochlorothiazide in essential hypertension.

To investigate whether sodium restriction might replace thiazides in promoting blood pressure (BP) reduction by angiotensin-converting enzyme inhibitors, the long-term hemodynamic effect of lisinopril plus sodium restriction versus lisinopril plus hydrochlorothiazide was compared at rest and during dynamic exercise in 2 groups of essential hypertensive patients. Mean pretreatment intraarterial BP at rest sitting was 177/107 mm Hg. The patients were randomly allocated to lisinopril combined with either low salt diet (low salt group, n = 13) or hydrochlorothiazide (diuretic group, n = 12). After 1 year of treatment the mean dose of lisinopril was 25 mg in both groups. In the low salt group sodium excretion was reduced from 188 to 129 mmol/24 hours (p less than 0.01). In the diuretic group sodium excretion was unchanged with a mean dose of hydrochlorothiazide of 19 mg. BP was reduced (p less than 0.001) in both groups: at rest 16 and 21% and during exercise 10 and 13% in the low salt and the diuretic groups, respectively. Total peripheral resistance was reduced (p less than 0.05) in both groups: at rest 14 and 7% and during exercise 8 and 5% in the low salt and the diuretic groups, respectively. Overall cardiac output was reduced (p less than 0.05) in the diuretic group but remained unchanged in the low salt group. Thus, lisinopril--either in combination with a diuretic or sodium restriction--induces marked reduction in BP due to decreases in peripheral vascular resistance both at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of four ambulatory blood pressure monitors and measurements by clinicians versus intraarterial blood pressure at rest and during exercise.

The accuracy of 4 different ambulatory blood pressure (BP) monitors was assessed by comparing them to simultaneous intraarterial BP (contralateral brachial artery) during rest, isometric and dynamic (bicycle) exercise in 48 hypertensive patients undergoing invasive hemodynamic evaluation. The differences between the intraarterially determined BP and values obtained by the various monitors were then compared to differences between BP measured directly and by 2 clinicians using a standard mercury column in 10 additional hypertensive patients. The monitors studied were the Accutracker II (auscultatory with mandatory electrocardiographic gating), Colin ABPM 630 (auscultatory or oscillometric), Del Mar Pressurometer IV (auscultatory with optional electrocardiographic gating) and SpaceLabs 90202 (oscillometric). During rest, the differences between intraarterially and clinician-determined systolic and diastolic BP were 4 +/- 8 and -4 +/- 6 mm Hg, respectively. The Accutracker II and Colin ABPM 630 using the auscultatory method showed less disparity and closer limits of agreement (2 standard deviations of the mean difference) with intraarterial BP than the clinicians' measurements, whereas the other units showed similar or greater limits of agreement. During both isometric and dynamic exercise, mean BP differences between intraarterial and clinician determinations were similar to those at rest but the limits of agreement increased. The limits of agreement between intraarterial and monitor-derived BP also increased during exercise compared to differences observed at rest. The Accutracker II and Colin ABPM 630 using the auscultatory method had limits of agreement with intraarterial BP that were either similar to or less than the clinician's, whereas the Colin monitor using the oscillometric method and the Del Mar Pressurometer IV showed greater disparity.(ABSTRACT TRUNCATED AT 250 WORDS)