Biomedical subjects

H Lithell

Publications and source records attributed to H Lithell.

At least 37 records · Page 2Linked to original sources

PubMed2001

Plasminogen activator inhibitor-1 and relations to fatty acid composition in the diet and in serum cholesterol esters.

High plasminogen activator inhibitor (PAI)-1 levels and poor dietary fat quality are potential risk factors for cardiovascular disease. The aim was to investigate the cross-sectional associations between PAI-1 activity and dietary nutrient intake, focusing on fat quality, in a population-based study of 871 men aged 70 years. The relationship between PAI-1 and the fatty acid composition in serum cholesterol esters (n=381 men) was also studied. The estimated total fat intake was positively associated with PAI-1 activity. The intake of both monounsaturated and polyunsaturated fatty acids was positively associated with PAI-1 activity, whereas the intake of saturated fatty acids was not. In serum cholesterol esters, higher proportions of palmitoleic and dihomo-gamma-linolenic acid, a lower proportion of linoleic acid, and reduced estimated Delta5-desaturase activity were associated with higher PAI-1 levels. These associations were confounded by factors representing the insulin resistance syndrome. PAI-1 activity was positively associated with gamma-linolenic and arachidonic acid, independent of potential confounders. In conclusion, this study demonstrates that dietary intake of unsaturated fatty acids is positively associated with PAI-1 activity, whereas intake of saturated fatty acids is not. The associations present between PAI-1 activity and the fatty acid proportions in serum cholesterol esters are partly influenced by metabolic syndrome-related factors.

Aged↗

PubMed2001

Serum lipid profile improved by ultra-low doses of 17 beta-estradiol in elderly women.

To determine whether ultra-low doses of estradiol (E(2)) affect the serum lipid profile in elderly women, we analyzed changes in serum lipids and lipoproteins in 70 healthy women, 60 yr and older, randomly assigned to parenteral E(2) (7.5 microg per 24 h) delivered by a vaginal ring (Estring; Pharmacia-Upjohn, Malmö, Sweden) or no treatment for 12 months. Baseline serum estrone sulfate (E1S), but not E(2) or serum FSH, was negatively associated with serum total cholesterol (P = 0.026), low-density lipoprotein (LDL) cholesterol (P = 0.053), and apolipoprotein B levels (P = 0.023). Compared with no treatment, Estring treatment yielded nonsignificant increases within the normal postmenopausal range in serum E1S (+16%) and E(2) (+13%), but significantly reduced serum LDL cholesterol by 7.6% (-0.32 mmol/L; 95% confidence interval, -0.58, -0.07; P = 0.014) and LDL to high-density lipoprotein (HDL) ratio by 7.3% (-0.19 mmol/L; 95% confidence interval, -0.44, -0.06; P = 0.030). In Estring users values were significantly reduced in total cholesterol (by 4%), LDL cholesterol (by 7%), LDL to HDL ratio (by 7%), and apolipoprotein B (by 4%), and significantly increased in serum HDL triglyceride (by 25%) but not triglycerides. No significant changes were found in the untreated group. There was a significant interaction between age and both baseline serum E(2)/sex hormone-binding globulin (P = 0.006) and sex hormone-binding globulin (P = 0.009) and a marginal interaction between age and E1S (P = 0.083) with regard to effects on changes in LDL cholesterol levels during Estring treatment. We conclude that ultra-low doses of E(2), which previously were considered to have only local effects, may improve serum lipid profile in elderly women with a pattern and magnitude similar to that reported after conventional estrogen doses or first-generation lipid-lowering agents. The reduction in LDL cholesterol tended to be greater with a combination of high age and low baseline levels of biologically active estrogens.

Cholesterol↗

PubMed2001

In vitro and in vivo studies of a naturally occurring variant of the human p85alpha regulatory subunit of the phosphoinositide 3-kinase: inhibition of protein kinase B and relationships with type 2 diabetes, insulin secretion, glucose disappearance constant, and insulin sensitivity.

In humans, the Met326Ile missense variant of the p85alpha regulatory subunit of the phosphoinositide 3-kinase (PI3K) has been associated with either significant reductions in glucose effectiveness and intravenous glucose tolerance in Caucasians or a significantly higher insulin secretory response in Pima Indians. In the present study, we genotyped 1,190 Caucasian males to evaluate the impact in vivo of the Met326Ile variant of the p85alpha subunit of PI3K on the acute insulin response, intravenous glucose tolerance, insulin-mediated glucose uptake, and the prevalence of type 2 diabetes after 20 years of follow-up. We also expressed the variant in vitro to evaluate the impact on insulin-stimulated activation of protein kinase B (PKB). The Met326Ile variant of p85alpha was not associated with type 2 diabetes or with alterations in insulin secretion, insulin sensitivity, or intravenous glucose tolerance in vivo. Expressed in vitro, the Ile326 and the Met326 variant acted equally as a dominant-negative and prevented (60-70% inhibition) insulin-mediated activation of PKB by inhibiting the phosphorylation of PKB at Thr308. We conclude that the Met326Ile variant of the p85alpha regulatory subunit of PI3K is likely to be as functionally normal in vivo as in vitro.

Aged↗

PubMed2000

Circulating immune complexes in 50-year-old men as a strong and independent risk factor for myocardial infarction.

BACKGROUND: Circulating immune complexes (CICs) and autoantibodies against oxidatively modified LDLs (oxLDLs) and cardiolipin occur in patients with atherosclerosis and myocardial infarction (MI). The ability of such CICs and antibodies to predict myocardial infarction (MI) was investigated in a prospective nested case-control study in which healthy 50-year-old men were followed for 20 years. METHODS AND RESULTS: Two hundred fifty-seven men were included in the study, and 119 developed MI (39 died) between 50 and 70 years of age. One hundred thirty-eight randomly chosen men who did not develop MI up to 70 years of age served as controls. The prevalence of elevated levels of CICs and the concentration of CICs in men who developed MI were higher than in those who remained healthy. The concentration of CICs at age 50 was associated with a marked increased risk for MI, and this risk was independent of other conventionally recognized risk factors. There was a positive correlation between the levels of CIC and IgG antibodies to cardiolipin in men who developed MI. The level of IgG antibodies and the prevalence of elevated IgG and IgM antibodies to cardiolipin were higher in those who developed MI and had CICs than in those without CICs. Among men homozygous for C4 null alleles, those who developed MI had higher concentrations of CICs than did those who remained healthy. CONCLUSIONS: This prospective study shows that CICs alone or in combination with autoantibodies against cardiolipin in healthy males at 50 years of age predict subsequent MI between the age of and 70 years.

Aged↗

PubMed2000

Improved hemorheological properties during infusion of a lipid emulsion (Intralipid) in healthy subjects.

OBJECTIVES: Lipid emulsions are commonly used for nutrition in critically ill patients. In these patients interventions resulting in deteriorated blood rheology and thereby an impaired microcirculation may be deleterious. This study examined the acute hemorrheological effects of the lipid emulsion Intralipid. We have recently shown that hyperinsulinemia exerts a negative effect on erythrocyte deformability, and here the effect of hyperinsulinemia combined with Intralipid was studied. SUBJECTS AND INTERVENTIONS: Eleven healthy subjects received Intralipid (200 mg/ml) intravenously as a bolus injection (0.5 ml/kg) over 10 min and thereafter as a continuous intravenous infusion (90 ml/h) for 4 h combined with heparin (200 U/h) to stimulate lipolysis. During the final 2 h an euglycemic hyperinsulinemic clamp was added. Five subjects underwent the same protocol with the exception that saline was given instead of Intralipid and heparin. MEASUREMENTS AND RESULTS: Whole blood viscosity, plasma viscosity, erythrocyte aggregation tendency and fluidity were measured by rotational viscometry. Compared with basal and control values the Intralipid infusion caused greater erythrocyte fluidity (p < 0.05) and less aggregation tendency (p < 0.05). Whole blood and plasma viscosity remained unchanged. Hyperinsulinemia had no significant effect on the hemorrheological variables measured. CONCLUSIONS: Intralipid has no deleterious effects on blood rheology in healthy subjects. Instead, it leads to improved erythrocyte aggregation tendency and fluidity. If the emulsion exerts the same effects in patients with impaired circulation, the use of Intralipid may be beneficial in these patients.

Adult↗

PubMed2000

Differences in insulin sensitivity and risk markers due to gender and age in hypertensives.

Men run a higher risk for cardiovascular disease than women, even if hypertensive. This has been attributed to a more pronounced central (abdominal) fat distribution in men as well as menopausal state in women. The hypothesis to be tested in hypertensives was that men have more pronounced insulin resistance and other cardiovascular risk factors than pre-menopausal, but not post-menopausal, women. We carried out a cross-sectional observation study of middle-aged hypertensives of both sexes, divided into two age groups, below or over 50 years of age. The study was performed in untreated out-patients, visiting a hypertension policlinic, in Uppsala, Sweden. Three hundred men and 170 women with a mean age of 57 years were investigated. Measurements were taken by: physical examination (body mass index, waist-to-hip ratio, blood pressure); intravenous glucose tolerance test (IVGTT); euglycaemic hyperinsulinaemic clamp; and blood sampling for lipoprotein lipid fractions, uric acid, and free fatty acids. The results were that pre-menopausal women showed a higher insulin-mediated glucose disposal (7.6 vs5.8 mg/kg/min; P < 0. 01), and lower fasting glucose (4.9 vs 5.2 mmol/l; P < 0.05) than men, as well as a more advantageous lipoprotein profile. However, in post menopausal women insulin sensitivity decreased and the lipoprotein profile deteriorated. Women still showed higher levels of high-density lipoprotein (HDL)-cholesterol, and men a higher waist-to-hip ratio and levels of uric acid, in both age groups. It was concluded that post-menopausal hypertensive women are relatively more insulin resistant than pre-menopausal ones in comparison with men in the same age group and with the same degree of overall obesity. Journal of Human Hypertension (2000) 14, 51-56.

Age Factors↗

PubMed2000

Induction of insulin resistance by beta-blockade but not ACE-inhibition: long-term treatment with atenolol or trandolapril.

The effects on glucose metabolism by the beta-blocker atenolol and the angiotensin-converting enzyme (ACE)-inhibitor trandolapril were investigated in a randomised double-blind parallel group study of patients with primary hypertension. Twenty-six patients were treated with 50-100 mg atenolol and 27 patients with 2-4 mg trandolapril o.d. Intravenous glucose tolerance tests, euglycaemic hyperinsulinaemic clamps and serum lipid measurements were performed after 8 and 48 weeks of active treatment. After 48 weeks insulin sensitivity was reduced by 23% by atenolol while it remained unchanged during trandolapril treatment (+0.5%, P = 0.0010 for difference between treatments, ANCOVA). The effect on triglycerides (+22% vs -8.5%) and high-density lipoprotein cholesterol (-13% vs +0.7%) also differed significantly between atenolol and trandolapril. Results after 8 weeks were similar. Glucose tolerance was not affected by either drug. Atenolol reduced diastolic blood pressure (DBP) better than trandolapril (-15.3 mm Hg vs -6.6 mm Hg for supine DBP after 48 weeks, P = 0.012). The difference in effect on insulin sensitivity between the drugs corresponded to 25% of the baseline values of insulin sensitivity, and persisted over 48 weeks of treatment. The choice of antihypertensive treatment could influence the risk of diabetes associated with treated hypertension. Journal of Human Hypertension (2000) 14, 175-180.

Adrenergic beta-Antagonists↗

PubMed2000

The impairment in endothelial function induced by non-esterified fatty acids can be reversed by insulin.

Dyslipidaemia, with elevations of circulating triacylglycerols (triglycerides) and non-esterified (free) fatty acids, and hyperinsulinaemia are often found in the same subjects, the so-called 'insulin resistance syndrome'. The present study aims to investigate how elevated levels of non-esterified fatty acids, hyperinsulinaemia and the combination of these factors affects endothelium-dependent vasodilatation (EDV). Ten volunteers were examined on two occasions. Intralipid (plus heparin) or saline (0.9% NaCl) was infused for 4 h. During the final 2 h, euglycaemic hyperinsulinaemia (80+/-4 m-units/l) was imposed. EDV and endothelium-independent vasodilatation were evaluated in the forearm by local intra-arterial infusion of methacholine or sodium nitroprusside at baseline and after 2 and 4 h. Forearm blood flow was measured by venous occlusion plethysmography. Lipid oxidation was determined by measuring plasma malondialdehyde levels. Infusion of Intralipid plus heparin increased the concentration of non-esterified fatty acids to 2.6+/-1.2 mmol/l and decreased EDV from 27.6+/-8.7 to 21.0+/-5.7 ml x min(-1) x 100 ml(-1) tissue (P < 0.01). This effect was completely reversed by hyperinsulinaemia (P < 0.01). Hyperinsulinaemia alone increased EDV (to 30.4+/-9.5 ml x min(-1) x 100 ml(-1) tissue; P < 0.01), while endothelium-independent vasodilatation was unaltered by the interventions. Infusion of Intralipid plus heparin increased malondialdehyde levels from 0.67+/-0.22 to 1.2+/-0.37 micromol/l (P < 0.001), while hyperinsulinaemiadid not change the malondialdehyde level. In conclusion, an acute increase in serum levels of non-esterified fatty acids increased lipid oxidation and decreased EDV. The effect on EDV of non-esterified fatty acids could be reversed by hyperinsulinaemia.

Adult↗

PubMed2000

Relationships between muscle morphology and insulin sensitivity are improved after adjustment for intra-individual variability in 70-year-old men.

The purpose of this investigation was to examine to what extent variability in the muscle morphology and insulin sensitivity influence the correlation between them. Reproducibility of muscle characteristics was estimated in duplicate biopsies from the same thigh of 23 subjects from a cohort of 70-year-old men. The coefficient of variation (CV) for different characteristics of muscle morphology was between 11 and 42% in duplicate biopsies. Coefficient of variation for markers of insulin sensitivity ranged between 12 and 39%. The variability reflected by intra-class correlation ranged from 0.23 to 0.60 for muscle morphology and from 0.68 to 0.96 for estimates of insulin sensitivity. The correlation analysis between muscle morphology and insulin resistance was performed in a sample of 515 men from the cohort, correlation coefficients were calculated with (rtrue) and without (r) adjustment for intra-individual variation. Insulin sensitivity showed a positive relationship with percentage of type I fibres (rtrue=0.33, r=0.21; P < 0.0001) and capillary density (rtrue=0.43, r=0.21; P < 0. 0001) and negative correlations with percentage of type IIB fibres (rtrue=-0.35, r=-0.24; P < 0.0001). Capillary density was inversely correlated to insulin. Thus, an obvious improvement of the correlation was seen after correcting intra-individual variation. In conclusion, owing to the low degree of reproducibility of muscle morphology variables and insulin sensitivity, implying a noticeable underestimation of correlations, the r-values should be adjusted for within-subject variation in order to demonstrate a more accurate estimate of the strength of the relationships studied.

Aged↗

PubMed2000

Evaluation of endothelium-dependent vasodilation in the human peripheral circulation.

Flow-mediated vasodilation (FMD) in the brachial artery measured by ultrasound, and the increase in forearm blood flow (FBF) induced by local infusion of a muscarinic-receptor agonist have both frequently been used to evaluate endothelium-dependent vasodilation (EDV) in the human forearm. The present study intended to evaluate the relationship between these techniques and to investigate if vasodilation induced by the muscarinic receptor-agonist methacholine (MCh) was owing to production of nitric oxide (NO). FMD during hyperaemia was assessed by ultrasound and FBF was measured by venous occlusion plethysmography during local infusion of MCh or L-arginine in the human forearm. Both these methods were applied in 26 individuals. In another 12 individuals forearm arterial and venous plasma concentrations of nitrate/nitrite (NOx) were measured together with FBF before and during local MCh infusion. While the change in brachial artery diameter induced by sublingually given nitroglycerine and the vasodilatory response to sodium nitroprusside (SNP) given locally in the forearm were significantly correlated (r = 0.70, P < 0.01), FMD showed no relationship with the vasodilation evoked by MCh (r = -0.03) or L-arginine (r = 0.04). The five-fold increase in FBF during MCh infusion was associated with a significant increase in venous plasma NOx concentrations (P < 0.05) and a more than 11-fold increase in forearm NOx-release (P < 0.01). Thus, a significant relationship between the two methods regarding the evaluation of endothelium-independent vasodilation evoked by NO-donors was found, but no relationship was found between the two methods regarding the evaluation of endothelium-dependent vasodilation. Furthermore, vasodilation induced by MCh in the forearm seems to be induced by NO-release.

Adult↗

PubMed2000

N-terminal atrial natriuretic peptide and left ventricular geometry and function in a population sample of elderly males.

OBJECTIVES: To investigate the relationships between N-terminal atrial natriuretic peptide (N-ANP) and left ventricular geometry and function. DESIGN: A cross-sectional study of a population-based cohort. SETTING: Follow-up of a health survey in Uppsala county, Sweden. SUBJECTS: Two hundred and five men aged 70. MAIN OUTCOME MEASURES: A Delfia sandwich immunoassay was used to measure the plasma levels of N-ANP. M-mode and Doppler echocardiographic examinations were used to measure left ventricular dimensions, mass, geometry and systolic function and to classify the subjects into four groups (normal geometry, concentric remodelling, concentric hypertrophy or eccentric hypertrophy). Left ventricular systolic dysfunction was defined as a left ventricular ejection fraction </= 0.40. RESULTS: Plasma levels of N-ANP were significantly increased in subjects with left ventricular dysfunction compared to healthy subjects (702 +/- 486, n = 14 vs. 277 +/- 201 pmol L-1, n = 118, P < 0.0001), but there was a great overlap between the groups. N-ANP differed significantly between the four different left ventricular geometric groups (P = 0.02) with the highest N-ANP levels in the subjects with left ventricular eccentric hypertrophy (n = 40). However, N-ANP levels were no longer significantly associated with left ventricular geometry when taking the ejection fraction into account. CONCLUSIONS: This study showed that N-ANP levels were significantly elevated in subjects with left ventricular dysfunction, as well as in subjects with left ventricular hypertrophy. However, the increase in N-ANP seen in the eccentric hypertrophy group was mainly due to a decreased ejection fraction.

Aged↗

PubMed2000

Twenty-four hour ambulatory blood pressure in a population of elderly men.

OBJECTIVES: The principal aim was to study ambulatory and office blood pressure in a population of elderly men. We also wanted to describe the prevalence of hypertension and investigate the blood pressure control in treated elderly hypertensives. DESIGN: A cross-sectional study of a population of elderly men, conducted between 1991 and 1995. SUBJECTS: Seventy-year-old men (n = 1060), participants of a cohort study that began in 1970. MAIN OUTCOME MEASURES: Office and 24 h ambulatory blood pressure. RESULTS: Average 24 h blood pressure in the population was 133 +/- 16/75 +/- 8 mmHg, and daytime blood pressure 140 +/- 16/80 +/- 9 mmHg. Corresponding values in untreated subjects (n = 685) were 131 +/- 16/74 +/- 7 and 139 +/- 16/79 +/- 8, respectively. An office recording of 140/90 mmHg corresponded to an ambulatory pressure of 130/78 (24 h) and 137/83 mmHg (daytime) in untreated subjects. In subjects identified as normotensives according to office blood pressure (n = 270), the 95th percentiles of average 24 h and daytime blood pressures were 142/80 and 153/85 mmHg, respectively. The prevalence of hypertension, defined as office blood pressure greater than or = 140/90 mmHg, was 66%. Despite treatment, treated hypertensives (n = 285) showed higher office (157/89 vs. 127/76 mmHg) and 24 h ambulatory (138/78 vs. 122/71 mmHg) pressures than normotensives (P < 0.05). Fourteen per cent of the treated hypertensives had an office blood pressure < 140/90 mmHg. CONCLUSIONS: Our results provide a basis for 24 h ambulatory blood pressure reference values in elderly men. The study confirms previous findings of a high prevalence of hypertension at older age. It also indicates that blood pressure is inadequately controlled in elderly treated hypertensives.

Aged↗

PubMed2000

Blood pressure changes in relation to sodium and calcium status in induced hyperinsulinemia.

Insulin increases renal sodium reabsorption which may contribute to hypertension. However, acute insulin administration may result in vasodilation. The aim of the present study was to investigate effects on blood pressure and alterations in ion status during hyperinsulinemia. Blood pressure and serum sodium and ionized calcium concentrations were measured before and at the end of euglycemic hyperinsulinemic clamp tests performed in 45 patients with essential hypertension. Both the systolic and the diastolic blood pressure decreased, by 4% (p < 0.05) and 3% (p < 0.05), respectively. Circulating ionized calcium concentration increased by 2% (p < 0.001), and the ratio between circulating sodium and ionized calcium concentrations decreased. The changes in circulating sodium concentration correlated to changes in systolic blood pressure (SBP; r = 0.36, p = 0.05). Both ionized calcium concentrations and the ratio between circulating sodium and ionized calcium concentrations correlated to changes in SBP during hyperinsulinemia (r = -0.41, p = 0.03, r = 0.56, p < 0.01, respectively). The changes in ion status were not significantly correlated to age, body mass index or insulin sensitivity. In conclusion, a more pronounced increase in circulating ionized calcium concentration and reduction in the ratio between sodium and ionized calcium concentrations was associated with a greater blood pressure decline during the hyperinsulinemic clamp test when performed in hypertensive patients.

Aged↗

PubMed2000

The association between low diastolic blood pressure in middle age and cognitive function in old age. A population-based study.

BACKGROUND: previous longitudinal studies have shown an inverse relation between blood pressure and cognitive function. OBJECTIVE: to determine the association between mid-life blood pressure and performance in different areas of cognitive function in late life. SUBJECTS AND METHODS: we recruited 502 men, aged 69-74 years, from a population-based cohort in Uppsala, Sweden. Blood pressure had been measured at age 50 and we examined performance in 13 psychometric tests about 20 years later. RESULTS: after the 39 men with a previous stroke had been excluded, there was an inverse relation between diastolic blood pressure at age 50 and performance 20 years later in the digit span test, the trail-making tests and in verbal fluency. The relationships were significant, independently of age, education and previous occupational level. Men within the lowest category of diastolic blood pressure (< or = 70 mmHg, n = 59) showed the best results. Baseline blood pressure levels were not linked to performance in tasks on vocabulary, verbal learning and memory or figure copying. CONCLUSIONS: low blood pressure in mid-life indicates a low long-term cerebrovascular risk and is associated with higher late-life performance in cognitive tests that mainly assess subcortico-frontal cognitive functions.

Aged↗

PubMed2000

Prediction models for insulin resistance in the polycystic ovary syndrome.

Women with the polycystic ovary syndrome (PCOS) have a high prevalence of insulin resistance, with consequent increased risk of metabolic diseases later in life. An early metabolic screening would therefore be of clinical relevance. By using stepwise regression analysis on several variables obtained in 72 women with PCOS, we constructed simple and reliable mathematical models predicting insulin sensitivity, as measured by the euglycaemic hyperinsulinaemic clamp. The normal ranges of insulin sensitivity were calculated from 81 non-hirsute, normally menstruating women with normal ovaries, and similar body mass index (BMI) and age as the women with PCOS. Measured variables included BMI, waist and hip circumferences, truncal-abdominal skin folds, circulating concentrations of gonadotrophins, androgens, sex hormone-binding globulin (SHBG), triglycerides, total cholesterol and cholesterol subfractions, fasting insulin, C-peptide and free fatty acids. The three best prediction models included waist circumference, together with insulin (model I: R(2) = 0.77), serum triglycerides (model II: R(2) = 0.65), and the subscapularis skin fold (model III: R(2) = 0. 64). Using reference limits for insulin sensitivity obtained in the 81 normal pre-menopausal women, the models identify insulin resistant women with PCOS. These simple and inexpensive models are potentially useful in clinical practice as an early screening in women with PCOS.

Adolescent↗

PubMed2000

Epidemiological and clinical studies on insulin resistance and diabetes.

In Uppsala, extensive epidemiological and clinical studies on insulin resistance and diabetes have been ongoing for the past 30 years. A prospective cohort study of men born 1920-24, living in Uppsala County, was initiated during 1969-74 (the Uppsala Longitudinal Study of Adult Men, ULSAM). Risk factors for cardiovascular disease were examined in 2,322 men, and re-examinations have been performed every 10 years. At the first follow-up, when the men were 60 years old, insulin resistance was found to be a risk factor for development of hypertension and diabetes. In addition, treatment with antihypertensive medication was an independent risk factor for development of diabetes. These findings resulted in a series of clinical studies on metabolic effects of antihypertensive agents. At the second follow-up, when the men were 70 years old, the development of hypertension and diabetes was once again in focus, but at this time, cross-sectional and prospective studies of other cardiovascular determinants, such as circadian blood pressure pattern, left ventricular geometry and function, muscle morphology, ion status, fibrinolysis and cognitive function, were also performed. The cohort has furthermore been linked to the Swedish census and hospital discharge and cause of death registries, it has been used for studies on relationships between birth weight and cardiovascular disease, and genetic analyses have been performed, taking advantage of the long observation time obtained in this cohort. The cohort is currently being re-examined for the third time, and will hopefully continue to provide valuable information on the epidemiology of diabetes and cardiovascular disease in the future.

Aged↗

PubMed2000

Polymorphism in the glycogen-associated regulatory subunit of type 1 protein phosphatase (PPP1R3) gene and insulin sensitivity.

A polymorphism (PP1ARE) in the 3'-untranslated region of the gene encoding the glycogen-associated regulatory subunit of type 1 protein phosphatase PPP1R3 is associated with insulin resistance in Pima Indians. The aim of this study was to investigate whether two common variants in the PPP1R3 gene, Asp905Tyr and PP1ARE, are associated with reduced insulin sensitivity or can predict the development of impaired glucose tolerance (IGT) or type 2 diabetes during a 20-year follow-up period in 696 50-year-old Caucasian men. The allelic frequency of Tyr905 was 0.11 (95% CI 0.09-0.13) and of PP1ARE 0.34 (0.31-0.37) and the two polymorphisms were in linkage disequilibrium (chi2 = 46, P < 0.0001, Fisher's exact test). None of the polymorphisms was associated with the development of IGT or type 2 diabetes, but the PP1ARE polymorphism was weakly correlated to whole-body insulin sensitivity (r = -0.08, P = 0.04). In conclusion, we found no evidence in Swedish men that the PP1ARE or the Asp905Tyr variants over a 20-year period predict the development of IGT or type 2 diabetes, but the PP1ARE polymorphism could have a higher penetrance in other populations.

Alleles↗

PubMed2000

Study on COgnition and Prognosis in the Elderly (SCOPE): baseline characteristics.

The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multi-centre, prospective, randomized, double-blind, parallel-group study. The primary objective of SCOPE is to assess the effect of the angiotensin II type 1 (AT1) receptor blocker, candesartan cilexetil 8-16 mg once daily, on major cardiovascular events in elderly patients (70-89 years of age) with mild hypertension (DBP 90-99 and/or SBP 160-179 mmHg). The secondary objectives of the study are to test the hypothesis that antihypertensive therapy can prevent cognitive decline (as measured by the Mini Mental State Examination, MMSE) and dementia, and to assess the effect of therapy on total mortality, myocardial infarction (MI), stroke, renal function, and hospitalization. A total of 4964 patients from 15 participating countries were recruited during the randomization phase of SCOPE, exceeding the target population of 4000. The mean age of the patients at enrolment was 76 years, the ratio of male to female patients was approximately 1:2, and 52% of patients were already being treated with an antihypertensive agent at enrolment. The majority of patients (88%) were educated to at least primary school level. At randomization, mean sitting blood pressure values were SBP 166 mmHg and DBP 90 mmHg, and the mean MMSE score was 28. Previous cardiovascular disease in the study population included myocardial infarction (4%), stroke (4%) and atrial fibrillation (4%). Men, more often than women, had a history of previous MI, stroke and atrial fibrillation. A greater percentage of men were smokers (13% vs 6% in women) and had attended university (11% vs 3% of women). Of the randomized patients, 21% were 80 years of age. In this age group smoking was less common (4% vs 10% for 70-79-year-olds) and fewer had attended university (4% vs 7% for 70-79-year-olds). The incidence of MI was similar in both age groups. However, stroke and atrial fibrillation had occurred approximately twice as frequently in the older patients. The patients' mean age at baseline was similar in the participating countries, and most countries showed the approximate 1:2 ratio for male to female patients. There was also little inter-country variation in terms of mean SBP, DBP or MMSE score. However, there was considerable regional variation in the percentage of patients on therapy prior to enrolment.

Aged↗