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Background: The relation between QRS changes during exercise and ischemic heart disease is controversial. The present investigation addressed whether exercise QRS changes are related 1) to myocardial ischemia or necrosis, 2) to possibly confounding factors such as baseline QRS size and changes in heart rate and ST magnitude during exercise, and 3) to the location of scintigraphic defects., Methods: Advanced computerized vectorcardiography (MIDA1000, Ortivus Medical AB, Sweden) was recorded in 71 consecutive patients referred for 201TI exercise myocardial scintigraphy. Maximal exercise tests were performed in the sitting position on a bicycle ergometer. Planar scintigraphic images were obtained immediately after exercise and 4 hours later in three projections, and were evaluated blindly., Results: Exercise QRS changes correlated to baseline QRS size (X, Y, and Z leads; P < 0.005), change in heart rate (X and Y leads; P < 0.01), and ST change at J + 20 ms (X, Y, and Z leads; P < 0.0001). Increased QRS magnitudes in the Y and Z leads correlated to late perfusion defects (P < 0.0001). These correlations remained after correction for baseline QRS size and changes in heart rate and ST magnitude at J+20 ms during exercise (P < 0.0001). No consistent relationships were observed between the location of myocardial perfusion defects and the stress-induced alterations in QRS., Conclusions: Baseline QRS size and changes in heart rate and ST magnitude may have important confounding effects on the QRS response to exercise. However, even after consideration of these factors, the QRS response to exercise was related to late (4 h) scintigraphic myocardial perfusion defects. The findings suggest that the presence of myocardial infarctions or long-lasting ischemia after exercise is associated with increased QRS magnitudes during exercise.

Objective: The aim of the study was to investigate the haemodynamic effects of hormonal changes during the menstrual cycle in 11 hypertensive women aged between 29 and 38 years., Design: In randomized order, the subjects were examined on days 2-7 (follicular phase) and on days 20-24 (luteal phase). All medication was withdrawn on average 5 weeks prior to the experiment. The results in the hypertensive group were compared with those of a control group consisting of 11 normotensive women aged between 21 and 46 years who had earlier taken part in an identical experiment., Methods: A standardized mental stress test and a 24-h ambulatory blood pressure and heart rate recording were performed. RESULTS. Prestress resting heart rate was significantly higher in the hypertensive group and a significant difference was maintained throughout the entire stress experiment. Heart rate, systolic and diastolic blood pressure increased highly significantly in both groups during the exposure to mental stress, but no difference in heart rate or blood pressure reactivity between the normotensive and hypertensive groups was found in either phase. Heart rate reactivity did not differ during the two phases in the hypertensive group, in contrast to our previous findings in normotensives. During 24-h ambulatory recording both groups had slightly but significantly higher heart rate and systolic blood pressure in the luteal phase. In the hypertensives the diastolic blood pressure was also higher in this phase. Both groups had significantly higher serum oestradiol and progesterone levels in the luteal phase., Conclusions: The findings of the present study support the hypothesis that female sex hormones affect cardiovascular control in both normotensive and hypertensive women.

Urinary cortisol output and serum cortisol concentrations were measured in the steady state, under "field" conditions, and during standardized inhibitory and stimulatory tests in premenopausal, obese women, and were analyzed in relation to adipose tissue distribution. Urinary cortisol output was increased under field conditions in women with an elevated waist to hip circumference ratio (WHR) and, in particular, in women with a large abdominal sagittal diameter, indicating visceral fat accumulation. However, dexamethasone inhibition of cortisol secretion was normal. Stimulation with corticotropin analogue and with physical (cold-pressor test) or mental (color-word or mathematic) stress tests also showed elevated responses of serum cortisol, but not of prolactin or growth hormone concentrations. It is suggested that women with visceral fat accumulation have elevated cortisol secretion due to an increased sensitivity along the hypothalamic-pituitary-adrenal axis, and that this may be causing their abnormal fat depot distribution.

In order to find new ischaemic parameters, the spatial changes of the Frank vectorcardiogram were continuously analysed with a new, highly precise vectorcardiographic method during, and immediately after a maximal exercise test. This was done in 18 young healthy males, and 18 patients with scintigraphic reversible ischaemia. During exercise, different patterns between the groups were noted for the changes in the mean QRS magnitude in the Y-lead (P less than 0.005), the QRS-integral (P less than 0.05), and the QRS-duration (P less than 0.05). Immediately after exercise, several QRS parameters in the normal group continued to change according to the same pattern as during exercise (P less than 0.05), which was in contrast with the patterns of the ischaemic group (P less than 0.01). The spatial ST difference at J+20 ms discriminated well between the groups, especially when corrected for QRS-magnitudes at rest and heart rate (P less than 0.0005). In short, this pilot study supports previous findings in that changes in amplitude and duration of the QRS complex during exercise discriminated between healthy young males and patients with ischaemic heart disease. Moreover, rapid discriminating changes were seen in the QRS segment during cessation of exercise. These changes deserve attention since they may be of importance for the conflicting results on the diagnostic value of QRS changes during exercise.

Hypertrophic adaptation of the left ventricle and blood vessels is a prominent feature of established essential hypertension. Presence of left ventricular hypertrophy in hypertension increases, independently of other risk factors, the risk for a number of the most important cardiovascular hypertensive complications. Available evidence indicates that left ventricular hypertrophy develops in close parallel with the peripheral vascular changes. Structural involvement can be detected already in early phases of borderline hypertension. The pathophysiology of structural changes in hypertension appears to be dependent on a complex interplay between genetic, hemodynamic, and humoral-metabolic factors.

A male fat distribution pattern with abdominal obesity increases the risk for hypertension and cardiovascular disease, and is closely linked to a number of metabolic aberrations including insulin resistance. Recent observations suggest that changes in the peripheral vasculature may be of pathophysiological importance for the development of hypertension and its associated metabolic disturbances. We therefore investigated the hemodynamic correlates of abdominal obesity. A central fat distribution was found to be associated with a specific hemodynamic profile, characterized by elevated total peripheral resistance and lower cardiac output. In response to sympathoadrenal activation during mental stress, the normal cardiac output-dependent pressor response was reversed into a systemic vasoconstrictor response. There was a direct relationship between degree of abdominal obesity (expressed as waist-hip ratio) and fasting serum insulin. Furthermore, the stress-induced increase in total peripheral resistance correlated positively with fasting serum insulin concentration, whereas there was an inverse relation between serum insulin and cardiac output and heart rate. In a second study, the circulatory responses to stress during physiological hyperinsulinemia were investigated. During hyperglycemic hyperinsulinemia the central hemodynamic response to stress was changed into a systemic vasoconstrictor response. In the forearm the physiological vasodilation during stress was markedly attenuated, suggesting that insulin may have peripheral vascular effects. In conclusion, central obesity is associated with a specific hemodynamic pattern characterized by higher total peripheral resistance and lower cardiac output, and a vasoconstrictor response to psychosocial stress. This hemodynamic response pattern may be related to insulin metabolism.

Essential hypertension is closely related to conditions with impaired glucose tolerance and hyperinsulinemia. To evaluate a possible interaction between the sympathetic nervous system and carbohydrate ingestion on the circulatory responses to psychosocial stress, we compared the hemodynamic effects of an oral glucose challenge with those observed after placebo in 10 glucose-tolerant, normotensive young men at rest and during standardized mental stress. After glucose, resting cardiac output increased by 20% (p less than 0.05), which was mainly due to an increased heart rate (+14%; p less than 0.001). Since total peripheral resistance decreased by 13% (p less than 0.02), mean arterial pressure was unaffected by glucose. In spite of this, glucose loading was associated with a slight increase in systolic blood pressure and a gradual decrease of diastolic blood pressure. Resting forearm blood flow was unaffected by glucose. The stress response after placebo was characterized by the expected increase in cardiac output and mean arterial pressure, and an unchanged total peripheral resistance. By contrast, in the postprandial state the pressor response to stress was solely dependent on an increased systemic vascular resistance, and cardiac output was unaffected by stress. After glucose, the stress-induced muscular vasodilation in the forearm was reduced to 40% of that observed after placebo (p less than 0.01). Thus, acute carbohydrate administration has significant hemodynamic effects in humans. Furthermore, during the postprandial period there is a marked alteration of the pattern of the circulatory responses to psychosocial stress, characterized by attenuated muscular vasodilation and a rise in systemic vascular resistance.

1. To evaluate the short-term reproducibility of heart rate, oscillometrically determined blood pressure, antecubital venous plasma catecholamine concentrations and subjective responses to strictly standardized mental arithmetic, we performed two identical tests 1 h apart in 14 young, healthy and normotensive male subjects (age 22-35 years). 2. Heart rate and blood pressure responses to the two stress tests were highly correlated, when expressed both as correlations between levels attained during stress (rs greater than 0.80 throughout) and as absolute reactivity measures (all rs greater than 0.75). Also, subjective stress responses were highly correlated, when considering both levels during stress and reactivity (r = 0.97 and r = 0.85, respectively). Stress levels of catecholamines were correlated, but the change scores (reactivity) were unrelated. 3. The measurement error SD for heart rate was 2.6 and 3.0 beats/min for reactivity and stress levels, respectively. The corresponding SD for blood pressure ranged between 2.7 and 4.4 mmHg. Subjective stress experience showed an SD of a similar magnitude. The responses of plasma catecholamine concentrations were subject to considerable variability. 4. It is concluded that haemodynamic and subjective stress responses and stress levels during the mental arithmetic stress test show acceptable reproducibility and high test-retest correlations. However, stress-induced changes in venous plasma catecholamine concentrations show low reproducibility.

To study the effect of sex hormones on the hemostatic responses to stress, blood samples were collected before, during, and after 20 min of mental stress from 9 healthy, non-smoking female volunteers, examined in the follicular and luteal phase. Mental stress caused significant increases in heart rate, blood pressure, and plasma catecholamines. In addition, analysis of variance indicated significant changes of leukocyte count, hematocrit, fibrinogen, von Willebrand factor antigen, t-PA activity and antigen in response to the stress test. However, in contrast to a male group previously investigated, there were no significant changes in factor VII coagulant activity in either menstrual phase. Overall the responses were more pronounced in the luteal as compared to the follicular phase. The findings support the concept that both gender and physiological variations in female sex hormones may modulate hemostatic responses to psychosocial stress.

Circulating epinephrine may facilitate neural release of norepinephrine both during and after periods of sympathoadrenal activation by stimulation of prejunctional beta-adrenergic receptors. The present study was undertaken to examine possible effects and aftereffects of epinephrine on the hemodynamic reactivity to mental stress. To this end, two strictly standardized mental stress tests were performed in 14 normotensive men during and 1 hour after double-blind infusion of epinephrine (50 ng x kg-1 x min-1) or placebo given in random order. During epinephrine infusion, the systolic pressor response to psychosocial stress was augmented (+17 versus +10 mm Hg during epinephrine and placebo, respectively; p = 0.02). This was associated with an attenuated post-stress recovery, with the result that the stress exposure induced a prolonged elevation of systolic blood pressure. Heart rate was elevated and diastolic blood pressure lowered during epinephrine infusion without any change in the reactivity to stress. One hour after the end of the epinephrine infusion resting heart rate was still maintained on a higher level independently of level of arousal, but heart rate and blood pressure responses to stress were unaffected. The findings are consistent with the hypothesis that high circulating epinephrine levels amplify pressor responses to mental stress but do not support the suggestion that short-term infusion of epinephrine causes prolonged augmentation of blood pressure responses to psychosocial stress.

The effects of cholinergic blockade on haemodynamic reactivity to standardized mental stress has been studied in nine normotensive males during infusion of atropine (bolus dose 10 micrograms x kg-1 followed by a constant-rate infusion of 0.02 microgram x kg-1 x min-1) or placebo given in a randomized order on two different days. Partial cholinergic blockade increased resting heart rate by 25-30 beats per minute. The magnitude of the heart rate response to stress (reactivity) however was unaffected by the atropine infusion. Also, in four subjects who received a higher dose of atropine (approximately 1.8-1.9 mg), heart rate responses to stress were the same as during placebo infusion. Cholinergic blockade was associated with a small but prolonged increase in diastolic blood pressure. These findings suggest that parasympathetic withdrawal does not contribute to the tachycardia caused by mental arithmetic, and that the pattern of neurogenic activation may differ from that elicited during a classic defence-alarm reaction and by somatomotor activation.

1. The haemodynamic effects of hormonal changes during the menstrual cycle were examined in 11 normotensive women (age 20-46 years). The subjects were studied on days 2-8 (follicular phase) and days 18-26 (luteal phase) in a randomized order. A standardized mental stress test and a 24 h recording of ambulatory blood pressure and heart rate were performed. 2. Pre-stress resting levels of heart rate and blood pressure were similar during the two phases of the menstrual cycle. 3. During mental stress, the heart rate response was significantly greater during the luteal phase than during the follicular phase (14.7 versus 9.7 beats/min; P less than 0.05). 4. Blood pressure, plasma catecholamine concentrations and subjective stress experience increased significantly in response to stress, without any significant differences between the two phases. 5. During 24 h ambulatory monitoring, higher levels of systolic blood pressure and heart rate were observed in the luteal phase than in the follicular phase (P less than 0.005 and P less than 0.0001, respectively). 6. These data indicate that cyclic variations in female sex hormones not only affect systolic blood pressure and heart rate, but also alter the haemodynamic responses to psychosocial stress.

To determine the importance of emotional stress for relative polycythaemia, we studied 11 subjects with the Type A and 11 subjects with the Type B behaviour patterns during short-term mental stress. All subjects were healthy, normotensive non-smoking young males aged 20-34 yr. without any medication. During rest there were no significant differences in heart rate, blood pressure, or plasma catecholamines between the two groups, but the A-group had significantly higher haemoglobin concentration (147 vs 140 g/l; p less than 0.005) and haematocrit (43.8 vs 42.1%: p = 0.05) than the B-group. In the whole group, there was a positive correlation between resting diastolic blood pressure and haemoglobin concentration (r = 0.53; p less than 0.05). In response to 10 min of mental arithmetic, haematocrit, haemoglobin and erythrocyte count rose approximately 2% (p less than 0.001 throughout). The stress-induced changes were not significantly different between the A- and B-groups. It is concluded that mild relative polycythaemia could be induced by acute emotional stress. In subjects with the Type A behaviour pattern a slight haemoconcentration is present already at rest, which further increases during stress.

This was a double-blind multicenter study to compare the efficacy, tolerability and effects on the quality of life with isradipine and atenolol in the treatment of essential hypertension. Of 588 patients entering the 6-week placebo run-in period, 549 were eligible for randomization to receive either isradipine or atenolol for 8 weeks. If, at the end of this period, diastolic blood pressure (DBP) remained greater than 90 mm Hg, then both agents were given in combination for a further 10 weeks. Tolerability and quality of life were assessed repeatedly during the placebo and active-treatment phases. A subgroup of 30 patients were followed by 24-h ambulatory blood pressure monitoring, and their results are now being analyzed. In another subgroup of 26 patients, maximum exercise capacity, as determined by ergometer bicycle-testing, was measured once during placebo and twice during active treatment. At the end of the 24-week study period, both isradipine and atenolol as monotherapy had produced significant decreases in blood pressure. There were no significant differences overall between the compounds in quality-of-life and side-effect profiles, although there was a relative absence of ankle edema and headache with isradipine. Furthermore, patients receiving isradipine had no change in performance on exercise testing whereas patients on atenolol had a significant decrease (p less than 0.01).

Endothelin-1 was infused into the non-dominant brachial artery in two male subjects. We then monitored intra-arterial mean blood pressure, right atrial pressure, the heart rate and forearm blood flow (by plethysmography). Endothelin-1 at a dose of 5 x 10(-14) to 5 x 10(-9) mol, infused over 5 min periods, elicited no major changes in mean arterial pressure, heart rate and right atrial pressure. We observed an initial increase in forearm blood flow, followed by dose-dependent decreases of 25, 34 and 42% at 5 x 10(-11) to 5 x 10(-9) mol. A higher dose of endothelin-1, 5 x 10(-8) mol, given to only one of the subjects, elicited sweating and vomiting. In this subject, mean arterial pressure, right atrial pressure and the heart rate did not change, while forearm blood flow increased transiently. A deep muscular pain developed in the forearm receiving the endothelin-1 infusion after 30 min (maximum 2 h, duration 10 h), and this pain was intensified by touch and muscle contractions. The force of muscle contractions in the forearm was markedly reduced and a visible oedema developed. In order to investigate the mechanisms of oedema formation, endothelin-1 (10(-10) to 5 x 10(-8) mol/l) was given intra-arterially in a rat hindquarter preparation which was perfused at a constant flow rate. In the rat, endothelin-1 increased both pre- and postcapillary resistance, leading to an increase in capillary hydrostatic pressure and a marked net transcapillary fluid transfer from the perfusate to tissue. There was no sign of increased vascular permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

In recent years, there has been increasing interest in incorporating the concept of "Quality of Life" in the evaluation of medical interventions. The lack of a general definition which can function as a basis for the scientific evaluation of medical treatment is, however, a problem. The definition proposed in this paper contains three main factors: Subjective well-being, Health and Welfare. "Subjective well-being" is the central component in the evaluation of Quality of Life, referring to the individual's perception of his life situation, "Health" is a subjective as well as objective evaluation of physical and mental status, while "Welfare" reflects the objective environmental factors. Thus, the evaluation of Quality of Life in medicine should ideally address these three main factors. Although the importance of any particular component may vary, subjective well-being and health should always be included.

This brief review summarizes the background and principles for the development of a new psychometric instrument (Assessment of Symptoms and Psychological Effects in Cardiovascular Therapy--ASPECT Scale). The test consists of two parts, one for assessment of three aspects of global well-being (hedonic tone, relaxation, and activity) and one for evaluation of 34 commonly experienced symptomatic side-effects of cardiovascular drugs. All items are assessed by visual-analogue scales, and six clusters of symptoms have been identified: cardiac symptoms, central nervous system or cognitive symptoms, fatigue, local/cutaneous symptoms, sleeping disturbances, and other symptoms.

Tests used to evaluate the impact of drug therapies on mood and well-being need to be more sensitive than standard psychiatric tests, and specific procedures for the construction and validation of such instruments have been developed. Suitable questions are selected from an initial pool of possible test items and a questionnaire is formed. This undergoes a pretest procedure to eliminate any unclear or offensive questions and is then evaluated in a suitable group of patients for validity, responsiveness (i.e. sensitivity) and reproducibility. Using tests developed in this way, it has been shown that the transfer of hypertensive patients from standard triple therapy to placebo is accompanied by an increase in perceived well-being. Subsequent treatment with enalapril produced a further small increase in well-being. These and other results indicate that although angiotensin-converting enzyme (ACE) inhibitors may not have positive mood elevating properties, they are beneficial in terms of quality of life during treatment.

The long-term efficacy of isradipine, a new dihydropyridine calcium antagonist with marked vascular selectivity, was evaluated in 17 patients with essential hypertension. All had a supine diastolic blood pressure of greater than 95 mmHg with 10 mg pindolol once daily. After a short-term, double-blind, dose-finding, crossover comparison with addition of isradipine or placebo twice daily, they continued on pindolol and their optimal dose of isradipine in a single-blind, long-term follow-up study. Eighteen patients were recruited but one male patient discontinued treatment after 2 weeks due to ankle oedema and will not be accounted for in the overall evaluation. There were 11 males and six females with a mean age of 56 +/- 10 years. In the short-term study on the optimal dose of isradipine (5.1 mg twice daily) blood pressure was lowered by 24/18 mmHg (P less than 0.001). No change in heart rate was seen despite the substantial drop in blood pressure. In the long-term study the patients were seen for a mean follow-up time of 12.5 months (range 4-17 months). After the longest follow-up time mean arterial pressure was 107.0 +/- 7.4 compared with 120.1 +/- 8.2 mmHg after placebo baseline [delta = 13 mmHg (11%), P less than 0.001, n = 17]. The heart rate was unchanged (delta = 0.2 beats/min, 95% confidence limits -3, +3), and so was ankle circumference (delta = 0.12 cm, 95% confidence interval, -1, +1). On the other hand, mean weight was reduced by 2 kg from 90 kg (P less than 0.05, n = 17).(ABSTRACT TRUNCATED AT 250 WORDS)

The antihypertensive effect of pafenolol, a new beta 1-selective adrenoceptor blocker without intrinsic sympathomimetic activity and three times more selective than metoprolol, was evaluated. Twenty-three patients with essential hypertension, mean age 49 years (range 21-62), were randomized after a 4-week placebo run-in period (double-blind) to 4 weeks of either placebo, pafenolol 50 mg or 100 mg once daily. A submaximal exercise test was performed before and at the end of the treatment period. Pafenolol 50 mg and 100 mg significantly reduced recumbent and standing blood pressure compared with baseline with a mean reduction of 17/14 and 10/12 mm Hg on pafenolol 50 mg and 15/10 and 14/10 mm Hg on pafenolol 100 mg, respectively. Heart rate, both at rest and during exercise, was significantly reduced (p less than 0.05) on pafenolol 100 mg compared with placebo. The reduction in exercise heart rate (percent) was dose dependent and significantly correlated to the log plasma concentration of pafenolol (r = 0.60; p less than 0.05). It can be concluded that pafenolol had a clinically relevant antihypertensive effect when given once daily. No difference between 50 and 100 mg could be demonstrated, thus suggesting that 50 mg may be the preferred dose for antihypertensive treatment.

Spontaneously hypertensive rats of the Okamoto strain (SHR) were compared with inbred normotensive rats of the Wistar-Kyoto strain (WKY) and with normally bred Wistar rats (NT) in tests on the audiogenic immobility reaction (freezing), open-field behavior in a dark and an enlightened arena respectively, auditory startle response and male sexual behavior. Compared to the WKYs the SHRs showed increased locomotion and rearing in the open-field situations, reduced startle response and shortened immobility reaction. The SHRs differed in the same way from the NT rats with the exception for motor activity in the dark arena, where no differences were observed. The WKY rats showed less motor activity than the NT animals. Both SH and WKY rats showed shorter latency time for ejaculation than the NT rats. The characteristics of the behavior patterns displayed by the SH rats were interpreted as indicating a reduced propensity for fear reactions in this strain of rats compared to the WKY and NT strains used in the present study.

The objective of this placebo controlled double-blind multicentre (six centres) trial was to investigate the safety and efficacy of ICI 141,292 (Visacor), a new selective beta 1-adrenoceptor antagonist with modest intrinsic sympathomimetic activity (ISA), in hypertensive patients. Fifty-nine patients with mild essential hypertension were randomized to two of five treatment alternatives (placebo, 50 mg, 100 mg 200 mg or 300 mg of ICI 141,292) each given once daily for 2 weeks with a 4 week placebo period before (run in) and in between (wash out) active periods. Thus, each of the five treatments was evaluated in 20-24 patients. After 2 weeks (24 h after last dose) the reduction in recumbent blood pressure for all doses except 50 mg of ICI 141,292 was statistically significant and in the order of 6/4 mm Hg. Standing systolic blood pressure was reduced in a dose-dependent way but only significant for 200 mg of ICI 141,292 (8 mm Hg). Heart rate changes (delta) less than 4 beats/min) were not statistically significant for any dose. It is concluded that ICI 141,292 was well tolerated and had a significant but weak antihypertensive effect which might be explained by too much beta 1-adrenoceptor ISA.

In 47 patients admitted to the coronary care unit (CCU) at Sahlgren's Hospital in Göteborg, Sweden, due to acute myocardial infarction (MI) the intensity of pain independently assessed by the patient and by the nurse on duty was evaluated during the first 24 hours in CCU. Pain was assessed according to a modified numerical rating scale graded from 0-10, where 0 meant no pain and 10 meant the most severe pain. A positive correlation between the patients' and nurses' assessments was found (r = 0.76; P less than 0.001). However, the nurses under-estimated the patients' pain in 23% of the situations and over-estimated it in 20%. Over-estimation was particularly found when heart rate and blood pressure increased. Many patients scoring their pain to fairly high degrees were not given pain-relieving treatment. Treatment with morphine did not cause substantial pain relief in a substantial number of patients. A significantly positive correlation was found between the patients' and nurses' assessments of pain, although under-estimation as well as over-estimation occurred. A few patients with severe pain were not treated and when treatment was given it was often ineffective.

The purpose of this study was to evaluate the potentiating effect of hydrochlorothiazide (HCTZ) 12.5 or 25 mg once daily when added in a placebo-controlled double-blind randomized study of patients with essential hypertension, whose diastolic blood pressure (DBP) was not adequately controlled (DBP > 90 mmHg) following 6 weeks of single-blind treatment with the angiotensin converting enzyme (ACE) inhibitor enalapril, 20 mg once daily. Forty-eight patients started the first period with enalapril after 4 weeks on placebo. In 13 patients DBP fell to < or = 90 mmHg after enalapril for 6 weeks. In this group supine mean arterial pressure (MAP) was reduced by 13% (P < 0.01). In the patients whose DBP was > 90 mmHg after 6 weeks on enalapril (n = 32) the average supine MAP fell by 9% (P < 0.001). After 3 weeks there was no further drop in blood pressure (BP). Addition of HCTZ to the 32 patients with DBP > 90 mmHg caused a significant further drop in supine BP by 13/7 mmHg with 12.5 mg and by 15/7 mmHg with 25 mg. Seven patients discontinued the study, none due to side effects on enalapril alone. Well-being, assessed with a special questionnaire, was significantly better with enalapril as monotherapy compared with previous treatment, but not different from well-being during the placebo periods. It is concluded that 20 mg enalapril once daily lowered BP effectively and was well tolerated. The maximum BP lowering effect was seen within 3 weeks. Addition of HCTZ caused a significant, and clinically relevant, further drop in BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Atenolol and metoprolol are the two most widely used beta 1-adrenoceptor antagonists in the treatment of essential hypertension. Differences in their physico-chemical properties have been the basis of a number of clinical studies whose primary or secondary objective has been to compare subjective well-being during treatment with these beta-selective blockers. The results are, however, contradictory, mainly due to factors such as open study design, different dose regimens and dissimilar study populations. The aim of the present study was to evaluate and compare subjective well-being during treatment with atenolol (50 mg o.d.) and metoprolol CR (100 mg o.d.) in a randomized double-blind, cross-over study (2 x 6 weeks) in hypertensives not previously treated with either of the drugs studied. Two self-administered questionnaires (MSE-profile and Jern quality of life questionnaire) were filled in both before randomization and before follow up visits at 1, 3 and 6 weeks in each treatment period. Furthermore, subjective symptoms, blood pressure and heart rate were monitored. At the end of the study, patients were requested to state what treatment they preferred. Atenolol and metoprolol CR were found to be equally effective in reducing blood pressure (from 159/98 to 144/87 and 144/88 mm Hg, respectively, n = 74). The MSE-profile and the Jern quality of life questionnaire could not detect any differences between the two treatments as regards general well-being. Other subjective symptoms (e.g. diarrhoea, bradycardia, cold hands and feet) were uncommon and equally distributed among atenolol and metoprolol patients. 31 of the patients preferred metoprolol CR, 23 atenolol, while 20 had no preference.(ABSTRACT TRUNCATED AT 250 WORDS)

The concept of quality of life is used to determine clinically relevant aspects of subjective symptoms and well-being, and refined psychometric instruments are now being developed to assess changes in well-being during pharmacological therapy. In order to evaluate general well-being, subjective symptoms and common side effects during cardiovascular therapy, workers at this hospital have designed a quality of life questionnaire. This consists of a generic section for the evaluation of 3 global aspects of well-being (hedonic tone, activity and relaxation) and a specific symptoms section for assessing 21 common side effects of cardiovascular drugs. The test is based on visual analogue scales. This questionnaire was used in a Swedish subsample (n = 211) of the epanolol versus metoprolol study in patients with stable angina pectoris (VISA 1). In this double-blind crossover study, there were no significant differences between epanolol and metoprolol as regards general well-being with this sample size. The frequency of some specific symptoms (fatigue, sleep disturbances, vivid dreams and cold digits) was somewhat lower during epanolol treatment, but the differences did not attain statistical significance.

To study the effects of standardized mental stress (arithmetic and the Stroop color word test) on plasma coagulation and fibrinolysis, blood samples were obtained before, during, and after 20 minutes of mental stress from 10 healthy, non-smoking young males aged 22 to 30 years. Reactions were compared with those observed during physical exercise and infusion of adrenaline. Both von Willebrand factor antigen and factor VIII coagulant activity increased significantly in response to mental stress (95 +/- 28 vs 123 +/- 56%; p less than 0.05 and 125 +/- 54 vs 217 +/- 170%; p less than 0.05, respectively). There was also a significant increase of factor VII coagulant activity (86 +/- 31 vs 108 +/- 51%; p less than 0.05). Furthermore, mental stress caused an activation of the fibrinolytic system with an elevation of tissue plasminogen activator activity and tissue plasminogen activator antigen (0.80 +/- 0.48 vs 1.23 +/- 0.96 IU/ml; p = 0.076 and 4.38 +/- 1.87 vs 5.78 +/- 2.58 IU/ml; p less than 0.01). Fibrinogen concentration increased during stress (1.95 +/- 0.29 vs 2.11 +/- 0.27 g/l; p less than 0.05). Similar but more pronounced responses were observed during exercise and adrenaline infusion. Parallel to the increases in coagulation and fibrinolytic factors there were significant increases in heart rate, and systolic and diastolic blood pressure. It is concluded that mental stress has significant effects on plasma coagulation and fibrinolysis, and that it could thus affect important risk factors for cardiovascular disease.

Patients with borderline hypertension tend to suppress expression of anger and hostility. However, if anything, they are psychologically hyperresponsive. The blood pressure elevation is maintained neurogenically in many with borderline hypertension. Consequently, it is tempting to postulate that suppressed anger causes neurogenic increases in blood pressure. Available data are inadequate to substantiate this hypothesis. It is equally plausible that neurogenic factors affect emotions, behavior and blood pressure. The terms specificity and directionality are introduced and defined to facilitate a better understanding of this important area of research.

In 47 patients admitted to the coronary care unit (CCU) at Sahlgren's Hospital because of acute myocardial infarction (MI), we evaluated the intensity of pain before admission and during the first 24 hours in the CCU and the delay time between the onset of symptoms and the decision to go to the hospital. Pain was assessed according to a modified visual analogue scale graded from 0 to 10, where 0 meant no pain and 10 meant the most severe pain. Patients generally scored their maximal pain before admission higher than their pain in the CCU. The maximal pain before admission did not seem to differ between patients with larger and smaller infarcts, estimated from maximal serum enzyme activity, whereas patients with larger infarcts tended to have more intensive pain in the hospital despite consuming more analgesics during the first 3 hours and the first 24 hours in the CCU. The time between onset of symptoms and decision to go to the hospital was not influenced by the intensity of pain before admission, but patients with larger infarcts made their decision much faster than those with smaller infarcts. In conclusion, infarct size, a major determinant of the initial prognosis, appeared to influence the initial pain course in the CCU and to markedly affect the delay time between onset of symptoms and the decision to seek medical care.

To study haematological effects of emotional stress, blood samples were obtained from 29 healthy, normotensive, non-smoking males aged 20-34 years before, during and after 10 min of mental arithmetic. There were significant increases in peripheral blood cell count, haemoglobin concentration, and haematocrit in response to mental stress. Parallel to these changes significant increases in heart rate, and systolic and diastolic blood pressure were observed. The relative increments of leucocyte (8%) and platelet (3.5%) count were significantly higher than the increase in haemoglobin concentration (2%). There was a significant positive correlation between the blood pressure increase and the mobilization of leucocytes, whereas the increase in erythrocyte count, haemoglobin concentration, and haematocrit showed significant positive correlations with heart rate reactivity. It is concluded that mental stress causes an increase in leucocyte and platelet count that could not solely be accounted for by the concurrent haemoconcentration.

Several large-scale studies have recently drawn attention to the fact that arterial hypertension frequently is inadequately controlled and that therapeutic alternatives other than the commonly employed stepped-care treatment may be needed in order to obtain normotension. For this reason PN 200-110, a new dihydropyridine calcium antagonist--at two different dose levels (average 3.8 mg b.i.d. or 5.7 mg b.i.d.)--or placebo was added in a double-blind cross-over trial to pindolol, 10 mg per day, in 20 patients with essential hypertension, after an initial 3-week placebo period. Ionized calcium in serum was determined repeatedly during the study. From an initial level of 157/100 mm Hg, PN 200-110 at the first dose level reduced blood pressure by 14/11 mm Hg (p less than 0.01/0.001) and at the second dose level reduced blood pressure by 22/18 mm Hg (p less than 0.001/0.001). The reduction in mean arterial pressure was significantly correlated to age (=0.050, p less than 0.05). There was no significant increase in heart rate, nor were there any significant correlations between ionized calcium and the effect of PN 200-110 nor between the changes in ionized calcium and the changes in blood pressure. Adverse effects were few and mild. One patient had to be withdrawn because of side effects, probably not related to the investigated drugs. Thus, addition of PN 200-110 to hypertensive patients treated with pindolol caused highly significant and clinically relevant further reductions in arterial pressure. The results show that a combination of this kind offers the possibility of good blood pressure control.

1. Psycho-emotional profiles were compared with invasive haemodynamic findings in a population sample of 37 young men (mean age 27 years) with mild blood pressure elevation and in 21 matched normotensive controls. 2. In comparison with normotensive controls, subjects with hyperkinetic blood pressure elevation had higher irritability levels, more guilt feelings and more psychic distressful symptoms. 3. In subjects with blood pressure elevation and normokinetic circulation structural vascular changes were found, and their psycho-emotional profiles showed high irritability levels but not significantly increased guilt or anxiety. 4. These results indicate a relationship between psychological factors and haemodynamic patterns in mild blood pressure elevation. A psychosomatic aetiology in hyperkinetic blood pressure elevation is suggested, and the psychological findings are compatible with a gradual development from hyperkinetic to normokinetic blood pressure elevation.