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Biomedical subjects

J Wikstrand

Publications and source records attributed to J Wikstrand.

At least 73 records · Page 4Linked to original sources

Does microalbuminuria predict cardiovascular events in nondiabetic men with treated hypertension? Risk Factor Intervention Study Group.

The aim of this study was to investigate the predictive value of microalbuminuria (overnight urinary albumin excretion rate 17 to 100 mg/12 h) as a risk factor for future major cardiovascular events in nondiabetic patients with treated hypertension in a prospective study with follow-up time of 3.3 years. Overnight urinary albumin excretion was measured in 345 nondiabetic treated hypertensive men, aged 50 to 72 years, either with a serum cholesterol of > or = 6.5 mmol/L or smokers, or both. Cardiovascular morbidity was closely recorded during the follow-up period. At entry, microalbuminuria was found in 84 patients (24.3%) and 12 patients had macroalbuminuria (3.5%). During the follow-up period there were no differences in new cardiovascular events between patients with microalbuminuria and those with normoalbuminuria. However, an increase in the risk of future major cardiovascular events occurred in patients with urinary albumin excretion above 100 mg/12 h (macroalbuminuria). In a Cox regression analysis urinary albumin excretion was not associated with the incidence of future major cardiovascular events unless a more detailed approach was used, showing that this was the case for urinary albumin excretion above 100 mg/12 h (macroalbuminuria). Calculations with an alternative definition of microalbuminuria and mortality as end-point did not change the principal result. In conclusion, microalbuminuria does not seem to be a predictor of future mortality and cardiovascular morbidity in nondiabetic men with treated hypertension and at high risk of coronary heart disease. However, macroalbuminuria was associated with future major cardiovascular events in this group of patients.

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Microalbuminuria, insulin sensitivity and haemostatic factors in non-diabetic treated hypertensive men. Risk Factor Intervention Study Group.

OBJECTIVE: To examine whether microalbuminuria in non-diabetic, treated hypertensive men is associated with insulin resistance and measures of endothelial function, thrombogenesis and fibrinolysis. DESIGN: Cross-sectional study. SETTING: Outpatient clinic in city hospital. PATIENTS: Ninety-two treated hypertensive men, aged 57-77 years, either with a serum cholesterol of > or = 6.5 mmol L-1 or smokers, or both. Patients with diabetes mellitus or overnight urinary albumin excretion of > 100 mg 12 h-1 were excluded. MAIN OUTCOME MEASURES: Overnight urinary albumin excretion, insulin-mediated glucose disposal (hyperinsulinaemic euglycaemic clamp), blood glucose and plasma insulin during oral glucose tolerance test, fibrinogen, von Willebrand factor and plasminogen activator inhibitor activity. RESULTS: Microalbuminuric patients had increased blood glucose concentrations during the oral glucose tolerance test and higher plasma fibrinogen levels compared with the normoalbuminuric patients. In a randomly selected subgroup (n = 36), insulin-mediated glucose disposal was lower in microalbuminuric than in normoalbuminuric patients, and an inverse relationship between insulin sensitivity and albuminuria (r = -0.37; P = 0.028) was found. This relationship was not significant after adjustment for body-mass index (P = 0.098). In the univariate analyses including all patients, albuminuria was associated with blood glucose, serum creatinine, body-mass index, systolic blood pressure, fibrinogen, von Willebrand factor and cholesterol (negatively). In a multiple regression analysis, only the body-mass index was independently related to urinary albumin excretion. CONCLUSIONS: Microalbuminuria was associated with insulin resistance but obesity was a confounding factor. Relationships between microalbuminuria and fibrinogen as well as von Willebrand factor were found, but only in univariate analysis.

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Carotid artery wall intima-media thickness is associated with insulin-mediated glucose disposal in men at high and low coronary risk.

BACKGROUND AND PURPOSE: The aim of this investigation was to examine the relationship between insulin sensitivity and intima-media thickness in the common carotid artery. METHODS: Ultrasound examinations of the common carotid artery and hyperinsulinemic euglycemic clamp examinations were performed in a group (n = 25) of men aged 57 to 77 years at high risk for atherosclerotic disease (hypertension and at least one of the following factors: hypercholesterolemia and/or smoking) and in an age-matched low-risk group (n = 23) with no cardiovascular risk factors. Subjects with cardiovascular disease or diabetes mellitus were excluded. RESULTS: A significant negative relationship between insulin sensitivity index and common carotid maximum intima-media thickness was observed in both the high-risk group (r = -.45, P < .05) and in the low-risk group (r = -.59, P < .01). CONCLUSIONS: Our results suggest that an increase in intimamedia thickness, as a possible expression of early atherosclerosis, is negatively related to insulin sensitivity.

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Urinary albumin excretion is associated with the intima-media thickness of the carotid artery in hypertensive males with non-insulin-dependent diabetes mellitus.

OBJECTIVE: To examine the relationship between urinary albumin excretion and ultrasonographically assessed morphology of the common carotid artery in hypertensive men with and without non-insulin-dependent diabetes mellitus. DESIGN: Cross-sectional study. SETTING: An outpatient clinic in a city hospital. PATIENTS: Hypertensive male patients (n = 25) with non-insulin-dependent diabetes mellitus and non-diabetic hypertensive male patients (n = 94) aged 50-72 years, randomly selected from a larger study group. MAIN OUTCOME MEASURES: Overnight urinary albumin excretion and B-mode ultrasound examinations of the carotid artery. RESULTS: Among the diabetic patients the logarithm of the overnight urinary albumin excretion was independently and significantly associated with the common carotid artery intima-media thickness, which was also true after adjustment for concomitant cardiovascular disease. In the non-diabetic group there was no association between intima-media thickness and urinary albumin excretion. No relationship between the occurrence of plaque and urinary albumin excretion was observed in any of the study groups. The results were reproducible at a re-examination after 3 years using the same methods. CONCLUSION: Among the hypertensive men with non-insulin-dependent diabetes mellitus, an independent and significant relationship, reproducible after 3 years, was found between urinary albumin excretion and the intima-media thickness of the common carotid artery. No such relationship was found in the group of non-diabetic hypertensive males.

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A randomized study of quality of life during multiple risk factor intervention in treated hypertensive men at high cardiovascular risk.

OBJECTIVE: To examine the effect on quality of life in hypertensive men of a multiple risk factor intervention programme compared with that of usual care. DESIGN: A prospective, open, randomized, parallel-group study with allocation either to a comprehensive multiple risk factor modification programme or to usual care. SETTING: An outpatient clinic in a city hospital. PATIENTS: Five hundred and eight treated hypertensive men, aged 50-72 years, with at least one of the following: serum cholesterol > or = 6.5 mmol/l, smoking habit or diabetes mellitus. INTERVENTION: Nutritional advice, behavioural treatment principles and drug therapy. MAIN OUTCOME MEASURES: Minor symptoms evaluation profile (MSEP) was used to measure change in quality of life. RESULTS: The intervention programme led to sustained effects on lifestyle-related variables such as hypercholesterolaemia, body mass index and smoking habits, whereas diastolic blood pressure and HbA1c remained unchanged. The change in the MSEP during follow-up did not differ between the intervention and the usual care groups. There was a close relationship between the measurements of the three MSEP dimensions at baseline and at follow-up (P < 0.0001). None of the potential risk factors measured at entry was significantly associated with change in the three MSEP dimensions during follow-up. CONCLUSION: The multiple risk factor intervention programme directed towards smoking habits, hypercholesterolaemia and the metabolic control of diabetes mellitus in treated hypertensive men at high cardiovascular risk was not associated with an impaired quality of life compared with that in a control group. The method used, the MSEP, has previously been found to be a reliable method with good validity, and this study's results provide further evidence of its validity.

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Carotid artery wall morphology, haemostatic factors and cardiovascular disease. An ultrasound study in men at high and low risk for atherosclerotic disease.

The aim of this study was to examine whether there was a relationship between haemostatic factors and ultrasound-assessed morphology of the common carotid artery and cardiovascular disease in 57- to 77-year-old men at high risk for atherosclerotic disease (hypertension and at least one of the following risk factors: hypercholesterolaemia, smoking, diabetes mellitus). They were divided into one group with (n = 59) and one group without (n = 70) manifest cardiovascular disease. An age-matched reference group with no cardiovascular risk factors was used as a comparison (n = 51). Significant associations, independent of smoking, were found between plasma fibrinogen and both the maximal intima-media thickness and the occurrence of plaque in the high-risk group. High-risk patients with clinical signs of cardiovascular disease had higher levels of plasma fibrinogen and prothrombin 1 + 2 fragment compared with both high-risk patients without concomitant cardiovascular disease and low-risk subjects. Plasminogen activator inhibitor, von Willebrand factor and thrombin/antithrombin complex were increased in the high-risk group with signs of cardiovascular disease in comparison with the low-risk group. In conclusion the results indicate that plasma fibrinogen may be operative in the development of atherosclerosis. Clinical signs of cardiovascular disease were associated with increased plasma levels of fibrinogen, von Willebrand factor, plasminogen activator inhibitor, thrombin/antithrombin complex and prothrombin 1 + 2 fragment.

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The efficacy of multiple risk factor intervention in treated hypertensive men during long-term follow up. Risk Factor Intervention Study Group.

OBJECTIVE: To examine the feasibility and efficacy of a multifactorial intervention programme directed towards hypercholesterolaemia, smoking, and diabetes mellitus in treated hypertensive patients after more than 3 years' follow-up and to describe the incidence of cardiovascular complications. DESIGN: Open, randomized, parallel-group study with allocation either to a comprehensive multiple risk factor modification programme or to usual care. SETTING: Outpatient clinic in a city hospital. PATIENTS: A total of 508 male patients with treated hypertension, aged 50-72 years, with at least one of the following: serum cholesterol > or = 6.5 mmol L-1, smoking or diabetes mellitus. INTERVENTION: Individually given advice and group meetings based on nutritional advice and behavioral treatment principles. Drug therapy could be instituted to achieve the treatment goals in the intervention group: serum total cholesterol below 6.0 mmol L-1, no smoking, and HbA1c below 6.0%. Diastolic blood pressure below 90 mmHg was the treatment goal in both groups. MAIN OUTCOME MEASUREMENTS: Serum cholesterol, HbA1c, diastolic blood pressure, smoking. Cardiovascular end-points were recorded. RESULTS: The net changes were (change intervention--change usual care): serum cholesterol -5.0% (95% confidence interval, -7.6 to -2.3%), 17.6% more stopped smoking (P = 0.04); diastolic blood pressure and HbA1c remained unchanged. The incidence of stroke was lower in the intervention group compared with the usual-care group: 2.0 and 6.7%, respectively (P = 0.017). CONCLUSION: The intervention programme was comparatively successful with regards to the effects on hypercholesterolaemia and smoking habits. An unexpected decrease in the stroke incidence was observed in the intervention group compared with the usual-care group.

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Ultrasound evaluation of atherosclerotic manifestations in the carotid artery in high-risk hypertensive patients. Risk Intervention Study (RIS) Group.

The aim of this study was to evaluate whether high-risk hypertensive patients (n = 137) had larger far-wall common carotid artery intima-media thickness than a control group (n = 37) and to study whether intima-media thickness was related to other signs of atherosclerotic disease. The results showed that intima-media thickness was significantly larger in the hypertension group than in the control group. Lumen diameter and mean cross-sectional area of the intima-media complex were larger both for hypertensive patients with a positive history of manifest clinical cardiovascular disease and for hypertensive patients with no such history than in the control group. There was a significant relationship between far-wall common carotid artery intima-media thickness and plaque status (visual scoring, no, small, moderate/large) in the carotid artery region. In univariate analyses, low diastolic blood pressure and high pulse pressure were both significantly related to plaque status. In multivariate analyses, pulse pressure was significantly and independently related both to common carotid artery intima-media thickness and to plaque status in the carotid artery region. In multivariate analyses, there was also an independent relationship between age and common carotid artery intima-media thickness, between smoking status and plaque status, and between a positive history of manifest clinical cardiovascular disease and plaque status. In conclusion, common carotid artery intima-media thickness and lumen diameter were increased in elderly high-risk hypertensive patients, in whom more than one third of the patients also had a moderate to large plaque in the carotid artery region.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗

Abnormalities in the renin-angiotensin-aldosterone system in normotensive subjects with a positive family history of hypertension.

Non-hypertensive men with a positive family history of hypertension in two generations (N = 16) were compared with weight-matched (N = 13) and lean (N = 12) control groups with a negative family history of hypertension with respect to the activity of the renin-angiotensin-aldosterone system at baseline and during an oral glucose tolerance test. Blood pressure was measured phonographically after 30 min of semirecumbent rest and the oral glucose tolerance test was performed after a 10-h overnight fast with 100 g of glucose given orally. Blood samples were drawn from a peripheral catheter at baseline, 30 and 120 min after the glucose challenge. Systolic and diastolic blood pressures did not differ between subjects with a positive or a negative family history of hypertension. At baseline, blood glucose and plasma insulin were similar in the three groups while the group with a positive family history of hypertension had a significantly lower plasma renin activity (PRA) (0.85 +/- 0.09 compared with the weight-matched but not with the lean control group (1.36 +/- 0.13 and 1.06 +/- 0.15 ng AI.ml-1.h-1; p < 0.01 and NS, respectively). The PRA increased significantly after the glucose challenge in all groups (p < 0.01), while the plasma aldosterone concentration decreased after 30 min and then showed an increase at 120 min. The PRA response was less pronounced in the group with a positive family history of hypertension compared with the weight-matched and lean control groups (p < 0.05 and p < 0.01, respectively). Serum potassium did not change significantly in either group after the glucose challenge. Urinary sodium excretion was similar in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

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Low-dose angiotensin II increases glucose disposal rate during euglycemic hyperinsulinemia.

To study the metabolic effects of angiotensin II we examined the glucose disposal rate and calf blood flow in healthy men (n = 39) during euglycemic hyperinsulinemia followed by a period with simultaneous angiotensin II infusion at a low dose (0.1 ng/kg/min). Angiotensin II infusion abruptly increased the glucose disposal rate significantly as compared with glucose disposal rate during euglycemic hyperinsulinemia only. There were no differences in blood glucose or plasma insulin between the euglycemic hyperinsulinemic and the angiotensin II infusion period. During hyperinsulinemia alone, blood pressure was unchanged while calf muscle blood flow increased significantly as compared with the baseline period, while during the angiotensin infusion the systolic blood pressure increased and calf blood flow decreased significantly as compared with the hyperinsulinemic period. We conclude that angiotensin II within physiological range stimulates insulin-mediated glucose uptake in healthy men. The mechanisms are, however, unclear, but changes in blood flow are probably not responsible for the observed effects.

Adult↗

Effects of long-term antihypertensive treatment and aging on renal function and albumin excretion in primary hypertension.

The effects on renal function and urinary albumin excretion of 7 years of antihypertensive treatment compared to the effects of normal aging were studied in a random sample of 40 men with newly diagnosed primary hypertension and in 17 normotensive men of the same age, respectively. The hypertensives were treated with metoprolol either as monotherapy (n = 21) or combined with hydrochlorothiazide or hydralazine. Glomerular filtration rate (GFR; inulin clearance), renal blood flow (RBF; para-aminohippurate clearance), renal vascular resistance (RVR), and the 24 h urinary albumin excretion were determined. GFR was significantly reduced from 104 +/- 15 mL/min (mean +/- SD) to 86 +/- 20 mL/min (P < .001) in the hypertensive group, but the reduction was not significantly greater than in the normotensive group. As judged from the study of a subgroup of the hypertensives, most of the decrease in GFR occurred early as an immediate drug-induced, functionally explained decrease. The changes in RBF and RVR after 7 years of treatment did not differ significantly from those due to normal aging. RVR remained higher and RBF remained lower in the hypertensives than in the normotensives. The urinary albumin excretion in the hypertensives was significantly reduced after 7 years but remained higher than in the normotensives. In conclusion, the changes in renal function and hemodynamics seen after long-term treatment with metoprolol in primary hypertension were not significantly different from the changes caused by normal aging in normotensives.

Aging↗

Reduced left ventricular distensibility in normotensive men with a positive family history of hypertension.

Left ventricular (LV) morphology and function (echocardiography) were assessed in a population-derived sample of young normotensive men with a positive (PFH, n = 15) or negative (NFH, n = 29) family history of hypertension for at least two generations. Since subjects with PFH were overweight (mean weight, 89 kg), the control group was divided into one group with mild overweight (n = 15) and one lean control group (n = 14). Blood pressure, cardiac output, and calculated total peripheral resistance did not differ between the groups. LV mass was significantly increased (P < .05 to .01) in the two groups, with overweight, compared with the lean control group and in multivariate analysis body mass index (BMI), the primary determinant for LV mass (r = 0.63, P < .001). Neither LV contractility nor LV relaxation time index differed between the groups. Left ventricular distensibility (a/H ratio), which was moderately related to BMI, systolic blood pressure, and the renal vascular sensitivity to angiotensin II (r = 0.34, P < 0.03), was reduced compared with the control groups. This difference persisted after adjusting for BMI and blood pressure. The present study shows that in normotensive subjects with a positive family history of hypertension the increased LV mass was primarily dependent on weight, irrespective of heredity. However, the observed reduction in LV distensibility remained after adjusting for weight, suggesting that diastolic abnormalities may occur before hypertension in subjects likely to later develop the clinical condition.

Aldosterone↗

Atherosclerotic changes in the femoral and carotid arteries in familial hypercholesterolemia. Ultrasonographic assessment of intima-media thickness and plaque occurrence.

B-mode ultrasound is increasingly used in clinical research to study the atherosclerotic process in the carotid arteries. The present investigation evaluated the feasibility of measuring intima-media thickness in the common femoral artery and assessed whether such measurement might provide further information on the extent of the atherosclerotic process in patients with familial hypercholesterolemia. A further aim was to study the relationship between the intima-media thickness of the common carotid artery and the occurrence of plaque in the carotid and femoral arteries. The results showed an increased intima-media thickness in the far wall of the common femoral artery in patients with familial hypercholesterolemia compared with the control subjects (P < .01). The results also showed a clear relationship between the thickness of the intima-media complex in the common carotid artery and the prevalence of plaque in the carotid and femoral arteries. This may be interpreted as an indication that an increase in intima-media thickness in the common carotid artery at least partly expresses a generalized atherosclerotic process. The atherosclerotic changes appeared to be more advanced in the femoral artery compared with the carotid artery. In future studies, therefore, valuable information on different stages of atherosclerotic changes may be achieved by combining information from B-mode recordings from both the carotid and femoral arteries.

Adult↗

Cost-effectiveness of antihypertensive treatment: metoprolol versus thiazide diuretics.

The aim of the present analysis was to calculate the cost-effectiveness of metoprolol versus thiazide diuretics in middle-aged men with mild to moderate uncomplicated hypertension. The analysis was based on the Metoprolol Atherosclerosis Prevention in Hypertensives (MAPHY) study, a randomised trial which showed a significantly lower risk for coronary events in patients taking metoprolol than in patients on thiazide diuretics. The main analysis was based on Swedish costs, but the costs were also varied in a special sensitivity analysis. Metoprolol was shown to be cost-saving compared with thiazide diuretics when both direct and indirect costs of morbidity were included. When only direct costs were included, the cost per life-year gained was $US2400. The result of the present analysis suggests that metoprolol is to be preferred to thiazide diuretics from a cost-effectiveness standpoint in the treatment of mild to moderate hypertension in middle-aged men. These findings regarding cost-effectiveness should, however, not be extrapolated to patient groups not included in the MAPHY trial.

Benzothiadiazines↗

Body fat distribution and left ventricular morphology and function in obese females.

OBJECTIVE: To study left ventricular function and morphology in non-hypertensive obese females and to relate the findings to body mass index (BMI) and to an index of body fat distribution (waist:hip ratio). DESIGN: Cross-sectional study. SETTING: Obesity unit in city hospital. SUBJECTS: Healthy obese females (n = 22) with BMI > 25 and < 40 kg/m2 and a non-obese, age-matched control group (n = 20) with BMI < 25 kg/m2. MAIN OUTCOME MEASURES: Blood pressure and non-invasive indices of left ventricular morphology and diastolic and systolic function. RESULTS: The obese group had significantly higher blood pressure, larger left ventricular end-diastolic diameter, greater left ventricular mass; larger left atrial size, signs of decreased left ventricular distensibility and prolonged left ventricular relaxation time index, and signs of supernormal systolic left ventricular function (as judged from the relationship between fractional shortening and end-systolic wall stress) than the non-obese controls. The results also indicated that left ventricular wall thickness and mass were well adapted to the increase in afterload, as judged by analyses of end-systolic wall tension and end-systolic wall stress. CONCLUSION: In confirmation of several previous studies, obesity was closely associated with an increase in blood pressure and left ventricular mass, and with early signs of disturbed left ventricular diastolic function. Left ventricular wall thickness and mass were well adapted to the increase in afterload; thus, we could not identify any non-afterload-dependent effect of an increase in BMI or waist:hip ratio on left ventricular hypertrophy.

Adipose Tissue↗

A view from Europe.

The pharmacologic approach to coronary protection, defined here as the prevention or delay of sudden death and myocardial infarction (without negatively affecting noncardiac mortality), is critically discussed. The value of pharmacologically treating mild hypertension and mild hypercholesterolemia is questioned, and the need for well-designed, randomized clinical trials with definitive endpoints to determine a drug's cardioprotective capability is emphasized. Based on such studies, it is concluded that some (but perhaps not all) beta-receptor antagonists as well as aspirin have been shown to protect against sudden cardiac death. Trials of thiazide diuretics, calcium antagonists, and angiotensin-converting enzyme inhibitors have not shown a reduction in sudden cardiac death, despite having individual benefits with respect to other aspects of cardiovascular disease. The demonstration that some beta blockers are cardioprotective is discussed in terms of the pathophysiology of sudden cardiac death, and differences in the pharmacokinetic profiles of individual agents.

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