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Biomedical subjects

H Lithell

Publications and source records attributed to H Lithell.

At least 91 records · Page 5Linked to original sources

Cognitive function, vascular risk factors and education. A cross-sectional study based on a cohort of 70-year-old men.

OBJECTIVES: A low level of education is associated with an increased risk of developing a dementia disorder, as well as with a higher risk of cardiovascular disease. The aim of this study was to investigate the association between education and cardiovascular risk factors, and to study the relation between these factors and cognitive function in elderly men. DESIGN: Cross-sectional population-based study. SETTING: Uppsala, Sweden. SUBJECTS: 504 men aged 69-74 years, participants in a longitudinal health survey concerning cardiovascular risk factors. MAIN OUTCOME MEASURE: Cognitive function as measured by a composite score of 13 standard psychometric tests. RESULTS: A low level of education was associated with poorer cognitive performance, as well as with obesity, smoking, diabetes, high concentrations of serum triglycerides and plasma fibrinogen. In the entire cohort, subjects with obesity, smoking, diabetes or hypertriglyceridaemia showed impaired cognitive test results, independent of socio-economic factors. When stroke cases were excluded, obesity and smoking were still related to impaired cognitive function. CONCLUSIONS: Smoking and obesity with associated metabolic disturbances are inversely related both to educational level and to cognitive function. Cognitive decline of vascular origin is potentially preventable by treatment of risk factors. The question of whether the increased vascular risk contributes to the higher prevalence of cognitive disorders in individuals with low socio-economic status, needs to be further evaluated in longitudinal population-based studies.

Aged↗

Cardiovascular risk factors and electrographical characteristics and abnormalities in middle-aged males.

OBJECTIVES: To evaluate if characteristics and abnormalities found at the electrocardiogram (ECG) are related to common cardiovascular risk factors included in the insulin-resistance metabolic syndrome. DESIGN: Cross-sectional. SETTING: Tertiary university hospital. SUBJECTS: Over 2000 middle-aged males in whom ECG abnormalities were recorded, together with ECG characteristics measured in a random sample of men with no ECG abnormalities (n = 113). INTERVENTIONS: None. RESULTS: All three components of the metabolic syndrome; elevated blood pressure, dyslipidaemia and hyperinsulinaemia were found to be related to the heart rate (P < 0.002) and the QRS-duration (P < 0.01) and inversely to the QoT-interval (P < 0.05), the early diastolic phase (P < 0.05) and the T-wave amplitude (P < 0.02). The components of the metabolic syndrome was furthermore found to be associated with the occurrence of T-wave abnormalities (n = 64, P < 0.01) and to a lesser degree also to the occurrence of Q-waves (n = 21). CONCLUSIONS: The components of the insulin-resistance metabolic syndrome were related both to certain ECG characteristics in subjects with a normal ECG and to some ECG abnormalities. A raised sympathetic activity is likely to be the link between some of the described associations, whilst coronary heart diseases may explain others.

Blood Pressure↗

Circulating angiotensin converting enzyme levels are increased in concentric, but not eccentric, left ventricular hypertrophy in elderly men.

OBJECTIVE: To study the cross-sectional relationship between circulating angiotensin converting enzyme (ACE) activity and echocardiographically determined left ventricular geometry in a study of 380 70-year-old men participating in a health-survey reexamination and 50 patients with hypertension. METHODS: Two-dimensional guided M-mode and Doppler echocardiography. Fluorometric assay of serum ACE activity. RESULTS: The serum ACE activity was higher in the elderly men with left ventricular concentric hypertrophy than it was in men with normal geometry and left ventricular eccentric hypertrophy (32, 27, and 26 U/l, respectively, P < 0.01 for both comparisons before and after adjustment for the 24 h mean arterial pressure, body mass index, and use of antihypertensive medication). The serum ACE activity correlated with the thickness of the left ventricular interventricular septum (r = 0.12, P = 0.0095), the left ventricular relative wall thickness (r = 0.13, P = 0.0053 ), and the total peripheral resistance (r = 0.16, P = 0.0034), but not with the left ventricular mass (r = -0.039, P = 0.45) of these elderly men. The serum ACE activity in the hypertensive patients also correlated with the left ventricular interventricular septum thickness (r = 0.34, P = 0.020) independently of the 24 h mean arterial blood pressure, age, sex, body mass index, and insulin sensitivity. CONCLUSION: Levels of serum ACE activity are associated with left ventricular geometry.

Adult↗

Adipose tissue lipoprotein lipase and hormone-sensitive lipase. Contrasting findings in familial combined hyperlipidemia and insulin resistance syndrome.

The metabolism of free fatty acids (FFA) is altered in two common atherosclerosis-promoting disorders: familial combined hyperlipidemia (FCHL) and insulin resistance syndrome (IRS). It has been suggested that these two conditions may have a common etiology. The enzymes lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) are rate-limiting steps for the turnover of fatty acids in adipose tissue, because they hydrolyze extracellular triglycerides in lipoproteins (LPL) and intracellular triglycerides in adipocytes (HSL). The present study was undertaken to simultaneously determine the activities of LPL and HSL in subcutaneous adipose tissue from male patients with FCHL and IRS. LPL and HSL activity was investigated in 10 nonobese FCHL patients and compared with 10 matched healthy nonobese subjects, and in 8 essentially normolipidemic IRS patients (who did not have overt diabetes mellitus) and compared with 9 nonobese matched control subjects. LPL activity was 43% lower in patients with IRS (P < .0005), as compared with control subjects, but HSL activity was not significantly different in the two groups, On the other hand, HSL activity was decreased by 45% in FCHL patients (P < .01), as compared with control subjects, but LPL activity was not significantly different in FCHL patients and the control group. In conclusion, triglyceride metabolism in adipose tissue is altered in both FCHL and IRS. However, the abnormalities observed involve impaired function of LPL in IRS and impaired function of HSL in FCHL, suggesting separate etiologies for the altered lipolysis in these conditions, at least in male subjects.

Adipose Tissue↗

Antibodies against cardiolipin and oxidatively modified LDL in 50-year-old men predict myocardial infarction.

Autoantibodies against oxidatively modified low-density lipoproteins (oxLDL) and cardiolipin occur in patients with vascular diseases, including atherosclerosis. The ability of such antibodies to predict myocardial infarction (MI) was investigated in a prospective nested case-control study in which healthy 50-year-old men were followed up for 20 years. Raised levels of antibodies against oxLDL and cardiolipin at 50 years of age correlated positively with the incidence of MI and mortality related to MI 10 to 20 years later. IgG and IgA antibodies against cardiolipin were associated with MI between 50 to 60 years of age and IgG and IgA antibodies against oxLDL with MI at 60 to 70 years of age. Moreover, higher antibody levels were noted in those who died from acute MI in comparison to those who survived. The predictive power of IgA and IgG antibodies was strong and largely independent of that of other strong risk factors. In conclusion, raised levels of antibodies against oxLDL and cardiolipin may predict MI and MI-related death.

Aged↗

Inhibitor index: a novel method for measuring pharmacological inhibition of angiotensin-converting enzyme.

Research into the exact mechanism and site of action of ACE inhibiting compounds has been hampered by methodological difficulties concerning the quantitation of ACE inhibition in tissues. This paper describes an attempt to address this difficulty. ACE activity in serum and uncentrifuged skeletal muscle homogenates was measured with a fluorometric assay before and during treatment in 24 fosinopril-treated and 26 atenolol-treated hypertensives. The absolute difference in activity between the higher and the lower of two different sample dilutions divided by the mean activity was taken to represent competitive inhibition in the sample, "inhibitor index". The reduction in muscle ACE activity coinciding with fosinopril treatment was not statistically significant (-2.6%, p = 0.68). The inhibitor index, however, increased by 46% (p = 0.045) and no change was seen in the atenolol-treated group (-12%, p = 0.51). The change in muscle inhibitor index (but not the reduction in serum ACE activity) correlated inversely with the change in blood pressure (r = -0.50, p = 0.034) and serum aldosterone (r = -0.54, p = 0.031) in the fosinopril group, but not in the atenolol group. In a second study, serum inhibitor index increased by 0.28 (95% CI 0.24-0.32) in 12 trandolapril-treated, but was unchanged in 11 atenolol-treated patients (+0.0097, 95% CI -0.029-0.048). In conclusion, the present study indicates that the inhibitor index described recognizes physiologically relevant ACE inhibition. The value of the method needs to be investigated further.

Angiotensin-Converting Enzyme Inhibitors↗

How do we treat, or not treat, high blood pressure in the oldest old? A practice study in Swedish geriatricians.

No clear guidelines exist for the treatment of hypertension in the oldest old (age 80+). While on the one hand the benefits of antihypertensive treatment in stroke prevention are greatest in very old people, on the other hand the adverse effects of treatment are more frequent in these frail, elderly patients. What is optimum blood pressure (BP) in healthy old patients, and in old patients with stroke or dementia? This study aimed to describe physicians opinions regarding BP treatment in geriatric patients. Of 462 Swedish geriatricians sent a postal questionnaire, 350 responded. In answer to the question what stage they would initiate treatment in a healthy, 82-year-old female patient, more than half responded that they would start treatment at higher BP levels (systolic BP >180 mmHg or diastolic BP >100 mmHg) than is recommended for younger elderly. Opinion varied on ideal BP in the case of a recent minor stroke, or dementia. Findings from epidemiological studies concerning the relations between BP and stroke and dementia are discussed. We conclude that further research is needed in this area.

Aged↗

The serum cholesterol ester fatty acid composition but not the serum concentration of alpha tocopherol predicts the development of myocardial infarction in 50-year-old men: 19 years follow-up.

A low serum tocopherol concentration and a low proportion of linoleic acid in plasma cholesterol esters have been reported to be associated with coronary heart disease. This study was undertaken to evaluate the predictive importance of the serum cholesterol ester fatty acid composition and serum tocopherol concentration in addition to established risk factors for myocardial infarction. The study comprised 2322 fifty-year-old men who participated in a health survey in 1970-1973 regarding risk factors for coronary heart disease. The proportions of myristic, palmitic, palmitoleic, and dihomogammalinolenic acid were significantly higher in 1970-1973 in subjects who suffered myocardial infarction during the following 19 years, while the proportion of linoleic acid was lower, than in those who remained healthy. Serum tocopherol did not differ significantly between the groups. LDL/HDL ratio, systolic blood pressure, and arachidonic acid/dihomogammalinolenic acid ratio were significant independent discriminators between cases and controls in a stepwise logistic regression analysis. This study suggests that middle-aged men who later develop a myocardial infarction are characterized not only by conventional risk factors but also by an altered fatty acid composition of serum cholesterol esters, with a low arachidonic to dihomogammalinolenic acid ratio, indicating reduced delta 5 desaturase activity. This may imply that changes in the quality of dietary fat intake, or an altered capacity to metabolize fatty acids in the body, could precede the development of coronary heart disease.

Biomarkers↗

Effects of hydrochlorothiazide and captopril on lipoprotein lipid composition in patients with essential hypertension.

OBJECTIVE: Effective antihypertensive agents may differ in their capacity to reduce cardiovascular risk because they induce potentially atherogenic alterations in lipoprotein composition. PATIENTS: To assess this possibility, the effects of five months' treatment with either hydrochlorothiazide (HCTZ) or the converting enzyme inhibitor captopril (CAPT) on lipoprotein lipid composition were compared in thirty normolipidaemic patients with essential hypertension (EH). RESULTS: The sixteen patients treated with HCTZ showed the expected directional alterations in plasma TG (+31%), HDL2-C (-16%), and CHOL (+7.6%); in contrast TG and CHOL were unchanged after captopril in fourteen patients and their HDL2-C declined (-16%). Neither drug altered lipoprotein core lipid composition, but small increases were observed in the HDL2 sphingomyelin/lecithin ratio after both agents. The plasma free (unesterified) cholesterol (FC) lecithin (L) ratio, a new index of cardiovascular risk, was abnormally increased before treatment and was not altered by either drug. CONCLUSION: These findings indicate that HCTZ and CAPT treatment have small, but demonstrable effects on lipoprotein surface lipid composition in patients with EH that are confined to the HDL2 subfraction.

Administration, Oral↗

Increase in muscle nerve sympathetic activity after glucose intake is blunted in the elderly.

Muscle nerve sympathetic activity (MSA; involved in blood pressure regulation) was recorded by microneurography in the peroneal nerve for 90 min after ingestion of 100 g D-glucose in three groups of healthy subjects: young subjects (mean age 26 years) and 70-year-old men with normal and reduced insulin sensitivity as assessed by euglycaemic insulin clamp. Muscle nerve sympathetic activity at rest was lowest in the young and highest in the insulin-resistant subjects (burst frequencies 19.8 +/- 6.0, 47.7 +/- 7.0 and 55.1 +/- 11.5 bursts/min for the three groups, respectively). The young subjects responded to glucose intake with a pronounced increase in MSA, a response that was blunted in the elderly and weakest in the insulin-resistant subjects. A similar relationship was observed during a Valsalva manoeuvre, indicating that the blunted response in the elderly is a generalized phenomenon. Blood pressure remained stable in the young subjects but fell slightly and significantly in the elderly subjects. It is concluded that old subjects utilize their total capacity for MSA close to maximum at rest. Thus, the reserve for response to stimuli normally evoking a strong increase in MSA is restricted. This restriction may contribute to postprandial hypotension in the healthy elderly.

Adult↗

Relationship between diastolic hypertension and myocardial morphology and function in elderly males with diabetes mellitus.

The existence of a distinct diabetic cardiomyopathy, characterized by a raised left ventricular mass, has previously been suggested. However, as diabetes mellitus is associated with both left ventricular hypertrophy and hypertension a confounding effect of raised blood pressure in diabetic patients has to be considered. In the present cross-sectional study an echocardiographical examination was performed as part of a health screening survey in 582 males, aged 70 years. After the exclusion of subjects with coronary heart disease or those on regular antihypertensive treatment, 30 normotensive subjects with diabetes were compared with 10 subjects with non-insulin-dependent diabetes (NIDDM) and a diastolic blood pressure 90 mm Hg or more and 203 normotensive control subjects with normal glucose tolerance. Both groups with NIDDM showed a significantly increased left atrial diameter (4.4 +/- 0.7 vs 4.0 +/- 0.5 cm, p < 0.05) and an increased atrial component in diastole (A-wave, p < 0.01) compared to the control subjects. Left ventricular mass was, however, only marginally and not significantly elevated in the diabetic subjects when compared to the healthy control subjects (133 +/- 19 and 133 +/- 28 vs 128 +/- 25 g/m2). Only in the subjects with concomitant diabetes and a raised blood pressure was the intraventricular septum significantly enlarged (p < 0.05). Thus, in the present sample no distinct diabetic cardiomyopathy with an increased left ventricular mass, independent of the influence of hypertension could be detected. The myocardial alterations in these diabetic males were restricted to an increased left atrial size and an impaired diastolic function.

Aged↗

Metabolic effects of doxazosin and enalapril in hypertriglyceridemic, hypertensive men. Relationship to changes in skeletal muscle blood flow.

In a previous open study on the metabolic effects of doxazosin in patients with essential hypertension, subgroup analysis indicated that subjects with an accumulation of risk factors for coronary heart disease (high VLDL triglycerides, low HDL cholesterol and high fasting blood glucose) seemed to benefit most from the metabolic actions of doxazosin treatment. Those results formed the basis of this double-blind, parallel-group study undertaken to elucidate the metabolic effects of 6 months of doxazosin and enalapril treatment in patients with both essential hypertension and hypertriglyceridemia. Insulin sensitivity was measured with the euglycemic hyperinsulinemic clamp method. Hemodynamic evaluation included measurements of office and ambulatory blood pressure and ultrasonic measurements of femoral artery blood flow. Both drugs significantly reduced both office BP and 24-h ambulatory BP. Office systolic BP was significantly better reduced by enalapril. Doxazosin, in contrast to enalapril, significantly increased insulin sensitivity (by 21%, P = .02). It also reduced serum-triglycerides (by 23%, P = .01), VLDL triglycerides (by 30%, P = .008) and VLDL cholesterol (by 24%, P = .02). This lipid-lowering effect of doxazosin was accompanied by an increase in both plasma lipoprotein lipase activity and the elimination rate of an intravenous fat emulsion load. Neither treatment significantly increased femoral artery blood flow. It is speculated that without measurably increasing blood flow in conduit vessels such as the femoral artery, doxazosin, by capillary recruitment, may prolong the transit time for the blood over the muscle bed, which could explain the increased glucose disposal and increased lipoprotein lipase activity.

Adult↗

The blood pressure response to antihypertensive treatment with lisinopril or bendrofluazide is related to the calcium and magnesium contents in skeletal muscle.

To evaluate the association between skeletal muscle mineral balance and effect of antihypertensive treatment, 37 patients with essential hypertension, randomly treated with either lisinopril or bendrofluazide, were investigated with skeletal muscle biopsies before and after 6 months of treatment. The ratio between calcium and magnesium concentrations in skeletal muscle prior to treatment predicted the blood pressure response during active treatment (r = -0.38, P < .02). During treatment the change in blood pressure was related to the change in muscle Ca/Mg ratio (r = 0.35, P < .05), especially in the patients treated with lisinopril. Thus, an association between the calcium and magnesium balance in skeletal muscle and the blood pressure response to antihypertensive treatment was found in the present study.

Analysis of Variance↗

Urapidil treatment decreases plasma fibrinogen concentration in essential hypertension.

The effects of antihypertensive drugs on cardiovascular metabolic risk factors were monitored in 42 patients with essential hypertension (diastolic blood pressure [DBP] >95 mm Hg). In a double-blind randomized parallel-group study, they were treated with atenolol 50 mg once per day (n = 25) or urapidil 60 mg twice per day (n = 17), a peripheral alpha1-receptor blocker with an additional central serotonin 1A (5HT1A) receptor agonistic effect, for 12 weeks. Plasma fibrinogen concentration decreased by 24% (P < .0001) during urapidil treatment and by 9% (P = .05) during atenolol treatment, with the effects of the two drugs differing significantly. Plasminogen activator inhibitor (PAI) activity tended to increase by 17% (nonsignificant [NS]) in the atenolol-treated group and to decrease by 4% (NS) in the urapidil group. Differences between the effects of the two drugs on very-low-density lipoprotein (VLDL) triglycerides (TG) and on total TG were significant. During urapidil medication, these two parameters were reduced by 22% and 13%, respectively, but the changes were nonsignificant (P = .11 and P = .14, respectively). In contrast, atenolol treatment caused a significant increase in both VLDL TG and total TG of 31% and 21%, respectively. Hemoglobin A1c (HbA1c) increased by 4% (P = .06) during atenolol treatment, but was unaffected by urapidil. There were no significant changes within or between atenolol- and urapidil-treated groups regarding glucose disposal on an oral glucose tolerance test (OGTT) or the insulin sensitivity index on a hyperinsulinemic-euglycemic clamp test. In conclusion, urapidil treatment was characterized by neutral or favorable effects on several variables associated with the metabolic syndrome. Atenolol treatment had neutral properties in some metabolic aspects, but deleterious effects on lipid status.

Adrenergic alpha-Antagonists↗

Left ventricular hypertrophy and geometry in a population sample of elderly males.

BACKGROUND: Recent studies have shown that left ventricular geometric adaptation to hypertension is complex. The spectrum of geometric adaptations in a general population and its relationship to systolic and diastolic function has, however, not been investigated. OBJECTIVES AND METHODS: This echocardiographic and Doppler study investigated the relationships between left ventricular geometric shape (normal, concentric remodelling, concentric hypertrophy and eccentric hypertrophy) and left ventricular systolic and diastolic function in a population sample of 584 males aged 70 in Uppsala, Sweden. The influences of hypertension, coronary heart disease and diabetes mellitus were also evaluated. RESULTS: Sixteen percent of the healthy population (n = 167) demonstrated the presence of left ventricular hypertrophy (mainly eccentric). Subjects with hypertension (n = 115) showed an increased left ventricular mass (eccentric left ventricular hypertrophy 31%, concentric left ventricular hypertrophy 15%), when compared with healthy subjects (P < 0.001). Subjects with coronary heart disease (n = 32) without hypertension also showed an increased left ventricular mass (most often eccentric) (P < 0.05). Using Doppler determinations of cardiac index, no differences were found in cardiac index between the geometric groups. Raised total peripheral resistance, increased blood pressure and enlarged left atrium were found in both concentric and eccentric left ventricular hypertrophy (P < 0.01-0.05). Disturbed diastolic function was seen with a prolongation of the isovolumic relaxation time in eccentric (P < 0.01) and increased atrial-dependent left ventricular filling in concentric left ventricular hypertrophy (P < 0.05). CONCLUSION: Alterations in left ventricular geometry were common in this population-based study of elderly males, both in healthy subjects and in subjects with hypertension or coronary heart disease. Raised total peripheral resistance and left ventricular diastolic dysfunction were common findings in both concentric and eccentric left ventricular hypertrophy.

Aged↗

Elevated ambulatory day-time blood pressure in women with polycystic ovary syndrome: a sign of a pre-hypertensive state?

The aim of this study was to evaluate office and 24 h blood pressures in women with polycystic ovary syndrome (PCOS) and normal controls in relation to insulin sensitivity. Office blood pressure, insulin sensitivity (euglycaemic hyperinsulinaemic clamp) and body fat distribution (skin-folds, waits:hip ratio) were investigated in 36 women with PCOS and 55 controls [body mass index (BMI) for PCOS patients, mean (confidence interval) 26.3 (24.6-28.2); controls, 25.1 (24.0-26.9)], and ambulatory 24 h blood pressure was recorded in representative subgroups of 17 and 16 women respectively. Compared with the controls, the women with PCOS had higher day-time systolic (mean +/- SD, 126 +/- 11 versus 119 +/- 12 mm Hg, P < 0.05) and mean arterial blood pressures (92 +/- 7 versus 86 +/- 7 mm Hg, P < 0.05) in ambulatory recordings, and greater increases in pulse rate (70%; P < 0.05) from night to day-time recordings, whereas the groups did not differ significantly in day-time diastolic blood pressure (74 +/- 6 versus 70 +/- 6 mm Hg, P = 0.05) or in night-time recordings. The women with PCOS had a more pronounced truncal-abdominal fat distribution (P < 0.05) and a lower insulin-mediated glucose disposal (P < 0.01) during the clamp. The increased day-time blood pressures in women with PCOS persisted after adjusting for BMI, body fat distribution and insulin resistance. It is concluded that women with PCOS have an increased prevalence of labile blood pressure, which may indicate a pre-hypertensive state, adding a further risk factor for cardiovascular disease in these women.

Androgens↗

Long-term trends in incidence of and mortality from acute myocardial infarction and stroke in women: Analyses of total first events and of deaths in the Uppsala Health Care Region, Sweden.

We studied the trends from 1969 to the mid-1980s in the incidence and mortality of acute myocardial infarction and stroke in Swedish women residing in the Uppsala Health Care Region. We used data from the Inpatient Care and Causes of Death registers to obtain total first event incidence and mortality rates. In our population, there were 20,182 acute myocardial infarctions and 30,462 stroke events, and 17,359 and 21,336 deaths, respectively. We found an average overall annual increase of 1.3% in the age-standardized incidence of acute myocardial infarction during the 1970s, followed by decreasing rates during the early 1980s. Mortality was virtually unchanged. Notably, among women 45-49 years of age, we observed a rising trend during the whole period, whereas in the oldest age groups, the increase slowed and reversed in the latter years. Both the incidence and mortality for stroke declined steadily: the age-standardized incidence fell by an average of 2.1% per year for all stroke and 7.8% for intracerebral hemorrhage. The falling rate of stroke was best explained by birth cohort effects, with a 30% reduction in women born in 1920 and later as compared with those born in 1890. We conclude that important changes in Swedish women's cardiovascular health have taken place and that increasing cigarette smoking and hypertensive treatment are major determinants.

Adult↗