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Biomedical subjects

J Wikstrand

Publications and source records attributed to J Wikstrand.

At least 109 records · Page 6Linked to original sources

Body weight is more important than family history of hypertension for left ventricular function.

Left ventricular function was studied in young men with a positive family history of hypertension for two generations (n = 15). The findings were compared with three control groups: one age-, sex-, and weight-matched group with a negative family history of hypertension (n = 14); one normotensive control group unselected as regards family history of hypertension (n = 27); and one group also unselected regarding family history of hypertension but selected with blood pressure criteria to have mild blood pressure elevation (n = 59). The group with a positive family history of hypertension, in comparison with the normotensive control group, was heavier, had higher blood pressure, increased left ventricular wall thickness, increased left ventricular mass, and signs of changes in diastolic and systolic left ventricular function. There were no differences in these variables between the group with a positive family history and the other two control groups. Data clearly indicated that subjects with a positive family history of hypertension, as well as subjects with mild blood pressure elevation, were heavier than the normotensive control group. It is not possible to judge, with available data, if the changes in left ventricular morphology and function in the two groups with a different family history of hypertension and in the group with mild blood pressure elevation occurred as a physiological response to the increase in afterload or if the neurohormonal and metabolic disturbances leading to the condition of slight overweight also affected left ventricular function.

Body Mass Index↗

Beta-blockade in the primary prevention of coronary heart disease in hypertensive patients. Review of present evidence.

The aim of this review is to present an overview of the results of randomized primary preventive trials with beta-blockers in patients with hypertension. For statistical and biological reasons, any preventive effect on coronary events is hard to demonstrate in women in these primary preventive trials because of the low incidence of coronary events in middle-aged, white women. Therefore, special attention will be focused on the effect in men. Four beta-blockers have been studied: propranolol, oxprenolol, atenolol, and metoprolol. Results from the Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) trial showed that the risk for coronary events was 24% lower in patients receiving beta-blockade compared with patients receiving diuretics (p less than 0.001). In men, three beta-blockers (propranolol, oxprenolol, and metoprolol) have shown significantly lower risk for coronary events (fatal and nonfatal) in the nonsmoking subgroup. Results from the MAPHY study also indicated a reduction in total and coronary mortality with the beta-blocker as compared with thiazide diuretics. The observed reduced risk for coronary events with beta-blockers as compared with diuretics is probably independent of the reduction in blood pressure. Mechanisms currently under study include antiatherosclerotic effects, antithrombotic effects, anti-ischemic effects, and antifibrillatory effects. It is not possible to judge, with present evidence, if all beta-blockers are equally effective in preventing sudden death and other coronary events.

Adrenergic beta-Antagonists↗

Overtreatment of hypertension in the elderly?

In a representative population sample of 619 70-year-old people, 26% were taking antihypertensive treatment. Twenty per cent (n = 32) of them showed no signs of cardiovascular disease and had a blood pressure of less than 175/95 mmHg. Treatment was withdrawn in 25 of the 32 patients. Casual blood pressure, blood pressure during isometric exercise and left ventricular morphology and function were studied repeatedly over 2 years, using non-invasive methods. A significant increase in mean systolic and diastolic blood pressures was observed in the 14 patients who completed the study. No change was observed with respect to left ventricular morphology and left ventricular diastolic function. A statistically significant decrease in left ventricular fractional shortening, but no clinical signs of congestive heart failure were observed. Withdrawal of antihypertensive treatment in elderly patients free from signs of cardiovascular disease may thus be attempted without harmful effects on cardiovascular function.

Aged↗

Primary prevention with beta-blockade in patients with hypertension: review of results and clinical implications.

The MAPHY primary prevention study in hypertensive men aged 40-64 years with diastolic blood pressure above 100 mm Hg showed that total mortality, sudden cardiovascular death, and the pooled incidence of fatal and definite nonfatal coronary events were significantly lower in patients randomized to metoprolol (n = 1,609) than in patients randomized to diuretics (n = 1,625) (p = 0.028, p = 0.017, and p = 0.001, respectively). The publication of the mortality results aroused great interest as well as a number of comments in the literature. The aim of this review is to present comments on the study design, results, and clinical implications of primary preventive studies performed with beta-blockers in hypertension. Statistical analyses of the MAPHY study results convincingly show a substantially lower risk for coronary events in patients on metoprololin relative terms, about a 25% reduction compared with diuretics-with beneficial preventive effects on coronary events both in smokers and nonsmokers. Supporting evidence for the MAPHY study results are available from several other clinical studies in hypertensive men and also from experimental, clinical, and animal studies. The results indicate that the difference in mortality and coronary events in the studies performed probably is mediated via mechanisms other than blood pressure control. Benefits have been attributed to the beta1-blockade of treatment, and evidence suggests that relatively lipophilic beta-blockers are best documented. Cardioselectivity appears to be an advantage for the risk reduction in smokers and also concerning side effects and quality of life. Thus, available data support the choice of a beta-blocker as antihypertensive therapy in patients with increased risk for coronary events unless contraindications limit the choice of these agents. Furthermore, primary prevention and risk reduction in hypertensives is dependent not only on the choice of the antihypertensive agent but also on improved detection and management of the other cardiovascular risk factors.

Adrenergic beta-Antagonists↗

Coronary artery disease can be prevented by antihypertensive therapy: experiences from the MAPHY Study.

The present randomized primary prevention study in hypertensive men aged 40-64 years (n = 3,234) was aimed at investigating whether metoprolol given as initial treatment would prevent coronary artery disease (CAD) better than thiazide diuretics. Two hundred fifty-five patients had a definite CAD event during the 15,730 patient-years of follow-up; 25% of these events were fatal, and 38% were definite acute myocardial infarctions. The incidence of CAD was significantly lower during follow-up in patients randomized to metoprolol than in patients randomized to diuretics: 111 vs. 144 cases (p = 0.001). Stroke mortality was significantly lower in the metoprolol group than in the diuretic group, but the overall stroke incidence was similar in the two treatment groups. A majority of events occurred among smokers in both treatment groups although only one-third of patients were smokers at baseline. Blood pressure (BP) control was similar in the two treatment groups; therefore, the difference between the groups in CAD events is mediated via mechanisms other than the BP-reducing effect of metoprolol.

Adult↗

Renal sensitivity to angiotensin II in type 1 diabetes.

The role of the renin angiotensin system for the regulation of kidney function in diabetes mellitus is uncertain. Results from studies in diabetic animals suggest that a reduced activity in this system contributes to the renal hyperperfusion and hyperfiltration in diabetes. The renal sensitivity to angiotensin II in diabetic patients is also unknown. Changes in renal hemodynamics were measured after infusion of two low doses of angiotensin II in ten young type 1 diabetic patients without complications and in ten healthy controls. The renin and angiotensin II levels were found to be the same in both groups. The baseline glomerular filtration rate was higher in the diabetics. During the highest angiotensin II dose, the 51Cr-EDTA and PAH clearance decreased 14 +/- 15 and 157 +/- 118 ml/min in the diabetics and 14 +/- 15 and 146 +/- 109 in the controls respectively. The changes in blood pressure and renal vascular resistance or sodium excretion did not differ between the groups. A malfunction of the renin angiotensin system is thus unlikely as a cause of the glomerular hyperfiltration in type 1 diabetes.

Adult↗

Radiological heart enlargement in treated hypertensive men: a comparative study of chest X-ray examination and M-mode echocardiography.

Twenty-five hypertensives with no history of myocardial infarction and with a radiologically determined heart enlargement were examined with M-mode echocardiography and compared with a normotensive control group (n = 41). All except two of the hypertensive patients were on a beta-blocker based antihypertensive treatment regime. The relative heart volume on X-ray was significantly larger in the hypertensives, 562 ml m-2 body surface area (BSA), compared to the normotensives, 408 ml m-2 BSA (P less than 0.001). Both left ventricular diameter (LVD) in end-diastole and end-systole and left arterial (LA) diameter were significantly larger in the hypertensives (56 vs. 51 mm, P less than 0.01; 35 vs. 31 mm, P less than 0.01; 46 vs. 42 mm, P less than 0.01, respectively) as was the LV mass (296 vs. 203 g, P less than 0.001). The end-systolic wall stress (ESWS) was significantly greater in the hypertensives. Despite these findings resting left ventricular fractional shortening was the same and showed a similar correlation with ESWS (r = 0.79 and r = 0.77, respectively) in both groups. Hence, left ventricular systolic performance was not impaired in the hypertensives compared to the normotensives. These results show that an enlarged cardiac silhouette on the chest X-ray in hypertensive subjects with beta-blocker based drug therapy must be interpreted with caution and must not, a priori, be judged as a sign of an impaired systolic cardiac function.

Adrenergic beta-Antagonists↗

Atrial natriuretic peptide (ANP) in relation to blood pressure: a study in middle-aged men with normal and elevated blood pressure.

In order to investigate the potential role of atrial natriuretic peptide (ANP) in mild to moderate essential hypertension, a study was conducted in groups of normotensive and hypertensive middle-aged men born in 1926 and 1927. Venous plasma concentrations of immunoreactive ANP (irANP) were studied in relation to measurements of cardiac structure and function, urinary electrolytes as well as some cardiovascular hormones. Plasma irANP did not differ between normotensive controls (31 +/- 14 pmol l-1) and borderline or untreated hypertensive patients. However, irANP concentrations were slightly but significantly (P less than 0.05) lower in the borderline (26 +/- 8 pmol l-1) compared to the untreated established hypertensives (35 +/- 14 pmol l-1). No relationships were found between irANP and blood pressure, indices of left ventricular structure and function or hormone parameters in subgroups or the whole study group. Our data do not support the view that plasma irANP is increased in uncomplicated essential hypertension, since our groups of borderline or established hypertensive middle-aged men without major cardiac involvement did not differ in irANP concentrations compared to normotensive controls. Thus, during the development or in the early stages of essential hypertension, ANP secretion does not seem to be abnormal.

Antihypertensive Agents↗

Decreased coronary heart disease in hypertensive smokers. Mortality results from the MAPHY study.

The present primary prevention study aimed at investigating whether metoprolol given as initial antihypertensive treatment would lower cardiovascular complications of high blood pressure to a greater extent than thiazide diuretics. Patients were randomized to metoprolol (n = 1,609, 8,110 patient-years) or a thiazide diuretic (n = 1,625, 8,070 patient-years). At randomization, 535 patients in the metoprolol group and 524 patients in the diuretic group were classified as smokers. Blood pressure control during follow-up was equally effective regardless of smoking habits at randomization. Cardiovascular and coronary heart disease mortality was three to four times higher in smokers than in nonsmokers, underlining the importance of smoking as a risk factor. Total and cardiovascular mortality were significantly lower for the metoprolol group than for the thiazide diuretic group in the whole study population (p = 0.028 and p = 0.012), as well as in smokers (p = 0.013 and p = 0.016). Coronary heart disease mortality was significantly lower for patients on metoprolol than for patients on diuretics in the whole study population (p = 0.048) as well as in smokers (p = 0.021). The results suggest that initial antihypertensive therapy with metoprolol is associated with a lesser incidence of total, cardiovascular, and coronary heart disease mortality as compared with initial diuretic treatment, both in the whole study population and in smokers. The favorable effect of metoprolol must be mediated via mechanisms other than the blood pressure-lowering effect of metoprolol because equal blood pressure control was achieved with both types of medication, irrespective of smoking habits at randomization.

Adult↗

Cardiovascular and renal effects of long-term antihypertensive treatment.

To study whether restoration of a normal circulatory system could be achieved with antihypertensive treatment, 13 hypertensive men with structural cardiovascular changes and 37 normotensive control subjects were investigated by echocardiography, apexcardiography, plethysmography, inulin and p-amino-hippurate clearance, and determination of 24-hour urinary excretion of albumin, first at age 49 years and again seven years later. All men were untreated at the first investigation. Immediately thereafter, therapy with the cardioselective beta-adrenoceptor blocker metoprolol tartrate was initiated in the hypertensive men. Seven years of antihypertensive treatment resulted in (1) normalization of central and peripheral hemodynamic variables, (2) reversal of left ventricular hypertrophy in proportion to achieved blood pressure control, (3) normalization of systolic wall stress and a well-preserved systolic left ventricular function, (4) normalization of diastolic left ventricular function, and (5) normalization of increased microalbuminuria and a decrease in renal vascular resistance, with no change in glomerular filtration rate compared with control subjects. In conclusion, the findings strongly indicate that regression of cardiovascular structural changes can be achieved with long-term antihypertensive treatment.

Drug Therapy, Combination↗

Primary prevention with metoprolol in patients with hypertension. Mortality results from the MAPHY study.

The present study of primary prevention in white men aged 40 to 64 years attempts to investigate whether a beta-blocker given as initial antihypertensive treatment would lower total mortality to a greater extent than thiazide diuretics. Patients were randomized to metoprolol (n = 1609, 8110 patient-years) or a thiazide diuretic (n = 1625, 8070 patient-years). The median follow-up time was 4.2 years. The mean dose of metoprolol was 174 mg/d, and of thiazide diuretics, 46 mg/d of hydrochlorothiazide or 4.4 mg/d of bendroflumethiazide. Identical control of blood pressure was achieved using a fixed therapeutic schedule. Total mortality was significantly lower for metoprolol than for thiazide diuretics because of fewer deaths from coronary heart disease and stroke. Total mortality was also significantly lower in smokers randomized to metoprolol. The benefit demonstrated in patients treated with metoprolol seems to have important implications for clinical practice.

Adult↗

New concepts in the treatment of elderly hypertensive patients.

Present evidence from several secondary and primary prevention trials indicates that if antihypertensive treatment is initiated with a cardioselective beta-blocker such as metoprolol, a better preventive effect on total mortality, cardiovascular mortality, and atherosclerotic complications can be expected than if diuretics are used as initial therapy. Results from a large-scale, multicenter international study have shown that a regimen in which antihypertensive treatment is initiated with metoprolol once daily is effective, safe, and well tolerated in elderly hypertensive patients. This might be of particular importance since a steep increase in cardiovascular mortality and other atherosclerotic complications is seen with age. In many elderly hypertensive patients, symptoms of heart failure might be caused by poor filling in stiff hearts rather than ineffective systolic contractions. By reducing heart rate with use of a cardioselective beta-blocker, diastole will be prolonged; this will improve filling and hence stroke volume and will increase coronary flow. Long-term treatment with metoprolol has also been found to reduce left ventricular systolic wall stress, reverse hypertrophy, improve left ventricular compliance, decrease the stiffness of large arteries, reduce total peripheral resistance, and reduce albuminuria. The improvement in the stiffness of the large arteries might be of particular clinical importance in elderly patients who have isolated systolic hypertension.

Aged↗

Primary prevention in patients with hypertension: comments on the clinical implications of the MAPHY Study. Metoprolol Atherosclerosis Prevention in Hypertensives Study.

The MAPHY Study was conducted to investigate whether metoprolol, a relatively beta 1-selective beta-blocker, given as initial antihypertensive treatment, would lower cardiovascular complications of high blood pressure to a greater extent than do thiazide diuretics as initial treatment at similar blood pressure control. In a controlled, randomized, stratified primary prevention study (n = 3234; 16,180 patient-years) in white men (40 to 64 years old) with mild to moderate uncomplicated hypertension, a treatment schedule starting antihypertensive treatment with metoprolol was compared with treatment starting with a thiazide diuretic. The two treatment groups were well matched in blood pressure and other major clinical characteristics at randomization, as well as at the last follow-up during treatment. Total mortality was significantly lower in patients randomized to metoprolol. At the median follow-up time (4.2 years) 28 deaths occurred in the metoprolol group and 54 in the diuretic group--a difference of 48% in total mortality (95% confidence limit, ranging from 68% to 17%), mainly because of a highly significant reduction in coronary heart disease at this point in time. The benefit demonstrated with metoprolol seems to have important implications for clinical practice and public health policy, since hypertension and coronary heart disease are major health problems worldwide.

Adult↗

Different patterns of cellular sodium turnover in essential hypertension.

Erythrocyte sodium turnover was studied in 22 men aged 56 years who had been treated for hypertension for 7 years. Investigations were performed during treatment, and 1 and 4 weeks after withdrawal of therapy, and when hypertension had returned (blood pressure greater than or equal to 170/105 mmHg). Hypertension returned early in 11 patients (group A) and late in 11 patients (group B). There was no difference in blood pressure, therapy, body weight or peripheral resistance between the groups, but group A had a greater left ventricular mass. Intra-erythrocyte sodium was determined by flame photometry. Sodium influx and the rate constant of sodium efflux were calculated from uptake values of 22Na. In group B the return of hypertension was accompanied by a tendency for an increase in intra-erythrocyte sodium and a decrease in sodium efflux. In group A opposing changes were seen, so that significant differences occurred in sodium efflux and intra-erythrocyte sodium between the groups occurred at the reappearance of hypertension. The results are compatible with the appearance of a membrane abnormality in patients with a slow return of hypertension, whereas other mechanisms, e.g. increased sympathetic activity, may be associated with the more rapid rise in blood pressure in the other group.

Antihypertensive Agents↗

Dyspnoea of cardiac origin in 67 year old men: (1). Relation to systolic left ventricular function and wall stress. The study of men born in 1913.

The relation between dyspnoea of presumed cardiac origin and disturbed left ventricular systolic function was studied in a group of 67 year old men from the general population of Gothenburg, Sweden. Forty two men with cardiac dyspnoea were identified and 45 controls were randomly selected from a screened cohort of 644 men. Dyspnoea was graded according to the World Health Organisation standard, and M mode echocardiography, carotid pulse tracing, an apex cardiogram, and phonocardiography were used to evaluate the grade of dyspnoea and its relation to systolic time intervals, left ventricular ejection indices, and wall stress. The dyspnoea grade was significantly related to the left ventricular end systolic dimension, to septal and posterior wall fractional thickening, and to ejection indices such as fractional shortening. The dyspnoea grade was also significantly correlated with the ratio of end systolic wall stress to end systolic volume index. There was a close relation between end systolic wall stress and mean velocity of circumferential fibre shortening adjusted for heart rate. This relation did not clearly show reduced inotropy in the dyspnoeic men. There was no relation between the degree of dyspnoea and the systolic time intervals. Among the systolic variables obtained by echocardiography the only abnormal finding in mild to moderate dyspnoea was an increased end systolic dimension. The grade of cardiac dyspnoea seemed to be related to the degree of systolic left ventricular dysfunction, which was considerably impaired in severe dyspnoea. In population studies left ventricular end systolic dimension and fractional shortening may provide sufficient information on systolic function without the need to assess variables that are independent of load.

Aged↗

Dyspnoea of cardiac origin in 67 year old men: (2). Relation to diastolic left ventricular function and mass. The study of men born in 1913.

The relation of cardiac dyspnoea to diastolic left ventricular dysfunction was examined in a sample of 67 year old men from the general population of Gothenburg, Sweden. Forty two men with cardiac dyspnoea and 45 controls were selected from the screened cohort of 644 men. M mode echocardiography, apexcardiography, and phonocardiography were used to evaluate heart sounds, diastolic time intervals, aortic root motion (atrial emptying index); peak rate of change in left ventricular dimension, left atrial and ventricular size; and left ventricular mass. There was a significant relation between dyspnoea grade and left ventricular mass and posterior wall thickness. Dyspnoea grade also correlated significantly with the amplitude of the rapid filling wave and the third heart sound, atrial emptying index and left atrial size, the pulmonary component of the second heart sound, and the dimension of the right ventricle. In mild to moderate dyspnoea fractional shortening was normal, but posterior wall thickness and left atrial dimension were increased. The time from the second heart sound to the O point of the apexcardiogram, adjusted for heart rate, was significantly prolonged in mild to moderate dyspnoea, but not in severe dyspnoea. There was a significant decrease of rate adjusted isovolumic relaxation time, probably secondary to altered loading conditions, in severe dyspnoea, but not in mild to moderate dyspnoea. When the effect of systolic function was excluded multivariate analyses showed that the relation between dyspnoea grade and left atrial dimension persisted. The finding that diastolic abnormalities of the heart contributed to the generation of cardiac dyspnoea may have implications for treatment.

Aged↗