Search PubMed⌕ Search

Biomedical subjects

A Hamsten

Publications and source records attributed to A Hamsten.

At least 145 records · Page 8Linked to original sources
PubMed1995

Lipoprotein lipase mass and activity in plasma and their increase after heparin are separate parameters with different relations to plasma lipoproteins.

Lipoprotein lipase (LPL) activity and mass in plasma and their increase after heparin administration were measured in 61 men who had suffered myocardial infarction before the age of 45 years and in 69 population-based age- and sex-matched control subjects without coronary heart disease to study the relations between these parameters in plasma and their correlations with plasma lipoproteins in subjects with a wide range of lipoprotein and LPL levels. There was a relatively large amount of LPL protein compared with LPL activity in preheparin plasma, indicating that the majority of circulating LPL is catalytically inactive. LPL mass and activity in postheparin plasma (postheparin minus preheparin values) were highly correlated, and the calculated mean specific activity (0.35 mU/ng) was in the range expected for catalytically active LPL. Hence, heparin releases mainly active LPL. The four LPL parameters (mass and activity in plasma and their increase after heparin administration) were not related to each other, except for postheparin plasma LPL mass and activity, and they showed different correlations with plasma lipoprotein lipid concentrations. There was a strong positive correlation between LPL mass in preheparin plasma and the HDL cholesterol level as well as weak negative relations to VLDL triglyceride and cholesterol concentrations in the patients. In contrast, preheparin LPL activity showed no correlation with the HDL cholesterol level but weak positive relations to VLDL triglyceride and cholesterol concentrations in the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The susceptibility of low density lipoprotein to chemical oxidation is closely related to proneness to biological modification.

U937 is a monocytic cell line dependent on low density lipoprotein (LDL) receptor-mediated uptake of cholesterol for proliferation. However, exposure of U937 cells to LDL also results in an oxidative modification of LDL. We report here that the oxidative modification of LDL by U937 cells results in inhibition of growth and cell death. This finding suggests that analysis of U937 cell growth in presence of LDL may be used to determine the susceptibility of LDL to biological oxidative modification. There was an inverse association between the effect of LDL on U937 cell growth and the rate of degradation of U937 cell-modified LDL in mouse peritoneal macrophages (r = -0.82, p < 0.05) suggesting a coupling between proneness of LDL to develop cytotoxicity and affinity for scavenger receptors. In a group of young post-infarction patients (n = 18) the susceptibility of LDL to chemical oxidation as determined by analysis of the lag phase for formation of conjugated diens in presence of copper ions was compared with the biological modification of LDL as assessed by analysis of U937 cell growth in presence of LDL. The results demonstrated a close relation between the estimates of chemical oxidation and biological modification (r = 0.86, p < 0.005) suggesting that LDL, which is prone to become oxidised by copper also is more prone to become modified by cells in vivo.

Animals↗
PubMed1995

Relationships of insulin and intact and split proinsulin to haemostatic function in young men with and without coronary artery disease.

Glucose intolerance, hyperinsulinaemia, dyslipoproteinaemia and multiple disturbances of haemostatic function are characteristics of young men with premature coronary artery disease. The relations between glucose, insulin and insulin propeptides, in the fasting state, and after an oral glucose load, and haemostatic function were examined in 62 consecutive non-diabetic men with myocardial infarction before the age of 45 and in 41 age-matched healthy men. "True" hyperinsulinaemia, raised plasma concentrations of insulin propeptides, dyslipoproteinaemia, elevated plasma levels of fibrinogen, factor VII antigen (VIIag) and plasminogen activator inhibitor-1 (PAI-1) activity, and lower antithrombin activity (p < 0.05-0.001) characterized the patients. PAI-1 activity was more closely associated with insulin, intact proinsulin and des 31.32 proinsulin in patients than in controls, whereas the plasma levels of fibrinogen, activated factor VII (VIIa) and VIIag were stronger correlated with insulin and insulin propeptides in subjects without coronary artery disease. Very low density lipoprotein (VLDL) triglyceride was a strong determinant of VIIag and PAI-1 activity levels in both cases and controls, whereas VLDL triglyceride in controls and LDL cholesterol in patients related significantly to the plasma fibrinogen concentration. Thus, our data suggests that plasma insulin and insulin propeptides might be involved in the regulation of plasma fibrinogen concentration, factor VII level and plasma PAI-1 activity. However, apolipoprotein B-containing lipoproteins appear to influence the relationships between insulin, insulin propeptides and haemostatic factors in individuals with premature coronary artery disease.

Adult↗
PubMed1995

Design features of a five-year Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT).

Young survivors of myocardial infarction represent a poignant challenge to clinical research on atherogenic mechanisms and factors predisposing to and precipitating coronary thrombosis. Young male postinfarction patients are characterized by heavy smoking, dyslipoproteinaemias involving very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL), a family history of premature coronary artery disease, hyperinsulinaemic responses to oral and intravenous glucose challenges, an elevated plasma fibrinogen concentration and defective fibrinolytic function. Based on the multiplicity of metabolic and haemostatic disturbances present in these patients, a double-blind, randomized, placebo-controlled angiographic trial was initiated to determine whether bezafibrate, a clofibrate analogue, retards the progression or facilitates regression of premature coronary atherosclerosis. Men under the age of 45 years who survived a first myocardial infarction were screened for participation in the study. A fasting serum cholesterol value > or = 5.2 mmol/l and/or serum triglycerides > or = 1.6 mmol/l after three months of dietary treatment and angiographically demonstrable lesions in at least one coronary segment were required for inclusion. Treatment with diet and bezafibrate (200 mg t.i.d.) or matching placebo is continued for five years during which time re-angiography is performed after two years and at the end of the study. The primary aim of the trial is a comparison between the bezafibrate and placebo groups for change in mean minimum luminal diameter between the baseline and five-year coronary angiograms. This report presents the design features of the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) and a review of current knowledge of mechanisms underlying premature coronary atherosclerosis and myocardial infarction at a young age.

Adult↗
PubMed1995

Interaction of the lipoprotein lipase asparagine 291-->serine mutation with body mass index determines elevated plasma triacylglycerol concentrations: a study in hyperlipidemic subjects, myocardial infarction survivors, and healthy adults.

A mutation in the lipoprotein lipase (LPL) gene, resulting in the substitution of asparagine by serine at residue 291 (LPL-S291), was found to occur in young survivors of a myocardial infarction from Sweden, combined hyperlipidemic subjects from the United Kingdom, and type III hyperlipidemic subjects from Germany at allelic carrier frequencies no different from those found in companion healthy control subjects (3.63 vs. 3.37; 1.85 vs. 1.60; and 2.00 vs. 1.56%, respectively). In a group of 620 healthy middle-aged men from the United Kingdom with baseline and three subsequent annual lipid measurements, mean plasma triacylglycerol (TG), (but not plasma cholesterol) concentrations in carriers of the mutation were significantly elevated over non-carriers (1.95 vs. 1.61 mmol/l, P = 0.05, and 5.83 vs. 5.65 mmol/l, P = 0.29, respectively). When these healthy control subjects were divided according to tertiles of body mass index (BMI), as expected, non-carriers whose BMI was in the upper two tertiles (BMI > or = 25.0 kg/m2) had higher plasma TG concentrations than those in the lowest tertile (1.90 vs. 1.54 mmol/l), but this difference was much greater in LPL-S291 carriers (2.33 vs. 1.36 mmol/l, P = 0.01, BMI x genotype interaction, P = 0.02). To confirm this effect, a second group of 319 healthy subjects from the United Kingdom was screened for LPL-S291. The allelic frequency of the mutation was found to be 1.88% and the effect on plasma lipid concentrations was very similar to that observed in the first control group (plasma TG, 2.31 vs. 1.27 mmol/l, P < 0.001 for LPL-S291 carriers vs. non-carriers, respectively). As before, those carriers whose BMI was in the top two tertiles for this sample (BMI > or = 23.3 kg/m2) had higher plasma TG concentrations than non-carriers (2.31 vs. 1.42 mmol/l). Thus, the LPL-S291 variant may predispose individuals to elevated plasma TG concentrations under conditions such as increased BMI.

Adolescent↗
PubMed1994

Postprandial lipoproteins and progression of coronary atherosclerosis.

The relations between triglyceride-rich lipoproteins, alimentary lipaemia and coronary heart disease (CHD) have remained obscure and much debated. We studied the basal and postprandial plasma levels of chylomicron remnants and very low density lipoproteins (VLDL) of varying particle size in 32 male postinfarction patients (mean (S.D.) age 48.8 (3.2) years) and in 10 age-matched control men. The selective quantification of postprandial intestinal and hepatic lipoproteins was accomplished by determining apolipoproteins B-48 and B-100 in lipoprotein subfractions of Svedberg flotation (Sf) rates > 12 before and 3, 6 and 12 h after an oral fat load. Since all patients had undergone two coronary angiographies with an intervening time interval of around 5 years, lipoprotein fractions were examined in relation to the global severity as well as the rate of progression of coronary lesions. The postprandial plasma levels of small chylomicron remnants (Sf 20-60 apolipoprotein B-48) were found to relate distinctly to the rate of progression of coronary lesions between the angiographies (r = 0.51, P = 0.01). Adjustment for the possible confounding effect of the HDL cholesterol and dense LDL apolipoprotein B concentrations did not substantially alter the strength of this association. Neither the increment of plasma triglyceride during the postprandial period nor the concentrations of other lipoprotein fractions closely reflected the amount of small chylomicron remnants in the circulation or correlated with progression of coronary lesions. Our data suggest that small chylomicron remnants are implicated in the progression of coronary artery disease.

Apolipoprotein B-100↗
PubMed1994

Clinical and biochemical factors associated with prognosis after myocardial infarction at a young age.

OBJECTIVES: This study examined the effect of metabolic disturbances, hemostatic function, coronary artery disease severity and left ventricular function on the long-term prognosis after myocardial infarction in men < 45 years old. BACKGROUND: Heavy smoking; dyslipoproteinemias involving very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL); a family history of premature coronary artery disease; hyperinsulinemic responses to oral and intravenous glucose challenges; and defective fibrinolytic function characterize the young postinfarction patient, but the influence of these features on the long-term prognosis is virtually unknown. METHODS: Measurements of hemostatic function and metabolic and angiographic indicators of risk were included in a prospective cohort study of variables predictive of reinfarction, cardiac death and major coronary events within 6 to 9 years in 108 unselected nondiabetic men with a first myocardial infarction before age 45 years. RESULTS: During follow-up, 20 patients had sudden cardiac death, and 53 had a major coronary event (reinfarction, sudden cardiac death, bypass surgery or intervention by catheterization). In multivariate analysis, VLDL and global coronary atherosclerosis score predicted reinfarction; plasma plasminogen activator inhibitor-1 (PAI-1) activity and global coronary stenosis score predicted cardiac death; and VLDL triglyceride levels, global coronary atherosclerosis score and age predicted any major coronary event. CONCLUSIONS: This prospective cohort study shows that hypertriglyceridemia, impaired fibrinolytic capacity secondary to plasma PAI-1 activity elevation and extensive coronary artery disease increase the risk of recurrences in men with a first myocardial infarction before age 45 and contribute to the relatively poor long-term prognosis in this patient group.

Adult↗
PubMed1994

Relationships of thrombosis and fibrinolysis to atherosclerosis.

The importance of the haemostatic system in predisposing to or precipitating coronary heart disease has gained increasing recognition. Major advances have been made in our understanding of the mechanisms resulting in hypercoagulability and impaired fibrinolytic function. Emphasis is placed on the role of dyslipoproteinaemia and insulin resistance.

Arteriosclerosis↗
PubMed1994

Associations of genotypes at the apolipoprotein AI-CIII-AIV, apolipoprotein B and lipoprotein lipase gene loci with coronary atherosclerosis and high density lipoprotein subclasses.

Association studies were carried out in a sample of 86 patients from Sweden who had survived a myocardial infarction (MI) at a young age and 93 age-matched healthy individuals, to compare the impact of polymorphisms at the apolipoprotein (apo) AI-CIII-AIV gene cluster on among-individual differences in plasma lipid and lipoprotein traits, the five high density lipoprotein (HDL) subclasses (2b to 3c), lipoprotein lipase (LPL) activity and presence and progression of atherosclerosis. Individuals were genotyped for four polymorphisms; 5'apoAI (G/A-75), 3'apoAI (PstI; P +/-), apoCIII (C/T1100) and apoCIII (PvuII; V +/-), using PCR-based techniques. Allele frequencies were similar in healthy individuals and patients (frequencies of alleles in combined population: 5'apoAI-A-75 = 0.14, 3'apoAI-P- = 0.05, apoCIII-T1100 = 0.27 and apoCIII-V- = 0.18). In the healthy individuals, levels of low density lipoprotein (LDL) triglycerides were significantly associated with genotypes of the apoCIII-PvuII polymorphism (p = 0.02), but no other associations were found between lipids or HDL subclasses and single polymorphisms in the apoAI-CIII-AIV gene cluster. Levels of triglycerides and very low density lipoprotein (VLDL) triglycerides were significantly higher in the presence of the haplotype defined by the presence of apoCIII-T1100 and common alleles of the other three polymorphisms, explaining 5.8% and 7.8% (p = 0.03 and 0.01), respectively, of sample variance. In the patients, no associations were found between lipids or HDL subclasses and variation at the apoAI-CIII-AIV gene cluster. Associations were also examined between levels of HDL subclasses and variation at the apoE (common isoforms), apoB (signal peptide and XbaI polymorphisms) and lipoprotein lipase (PvuII, HindIII and Serine447/Stop polymorphisms) gene loci. In the patient group only, levels of protein in HDL2b, HDL2a and HDL3b subclasses were significantly associated with genotypes of the LPL-HindIII polymorphism (22.1, 19.3 and 11.4%, respectively, of sample variance; p < 0.05). Finally, associations were examined between genotypes at the apoAI-CIII-AIV gene cluster and the extent of coronary atherosclerosis. Global severity of atherosclerosis at the first angiography was weakly associated with genotypes of the apoCIII-C/T1100 polymorphism, presence of the T1100 allele being associated with 53% lower median score (1.6 vs 0.75; p = 0.09).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Activation of coagulation factor VII during alimentary lipemia.

Dietary studies have established a connection between plasma lipoproteins and coagulation factor VII. The present study was undertaken to specifically examine whether factor VII is activated during alimentary lipemia and to investigate the relations of factor VII mass and activity state with fasting and postprandial lipoproteins and free fatty acids (FFAs). Factor VII levels were therefore determined in plasma samples taken before and after intake of a standardized, oral fat load of a mixed-meal type in 33 men (mean age +/- SD, 48.8 +/- 3.2 years) with a previous myocardial infarction at a young age and 10 healthy, age-matched control subjects. A panel of methods for factor VII determination was used to ensure that changes in all potentially existing forms of the factor during alimentary lipemia would be included. Substantial activation of factor VII was found to occur during alimentary lipemia, whereas the number of factor VII molecules remained constant or even appeared to decrease after the test meal. Activation of factor VII was more pronounced in control subjects than patients, and the proportion of activated factor VII molecules was higher in control subjects. Interestingly, factor VII activation, which correlated quantitatively with the degree of postprandial triglyceridemia, seemed to be related to FFA production during lipolysis of triglyceride-rich lipoproteins that were generated in response to fat intake. Postheparin plasma lipoprotein lipase activity was lower in patients, which could offer one explanation why factor VII activity was lower during alimentary lipemia in these subjects despite their exaggerated postprandial triglyceridemia. Thus, activation of coagulation factor VII during alimentary lipemia may result in a procoagulant state that is likely to promote the formation of a coronary thrombus in individuals with established coronary artery disease.

Adult↗
PubMed1994

Dyslipoproteinemic changes in borderline hypertension.

The present study examined plasma lipoprotein, lipoprotein lipase, hepatic lipase, and insulin levels in men with borderline hypertension (diastolic blood pressure 85 to 94 mm Hg) compared with age-matched normotensive control subjects (diastolic blood pressure less than or equal to 80 mm Hg, n = 75 + 75). High-density lipoprotein (HDL) subclasses were determined in a subset (n = 45 + 45). While total and low-density lipoprotein cholesterol levels were similar, levels of very-low-density lipoprotein (VLDL) cholesterol and triglycerides (0.46 versus 0.41 mmol/L, P = .027, and 1.0 versus 0.85 mmol/L, P = .031) and total triglycerides (1.53 versus 1.33 mmol/L, P = .009) were elevated and HDL cholesterol was reduced in the borderline group compared with the normotensive group (1.17 versus 1.26 mmol/L, P = .043). The HDL subclass HDL2b concentration was lower (0.16 versus 0.24 mmol/L, P = .006), while HDL3b and HDL3c concentrations were higher in the borderline group (0.38 versus 0.32 mmol/L, P = .016, and 0.19 versus 0.16 mmol/L, P = .042). Significantly higher activities of hepatic lipase in the borderline group (282 versus 232 mU/mL, P = .024) and significant correlations between lipoprotein lipase activity and VLDL and HDL concentrations suggest an involvement of these enzymes in the development of these differences. When adjusted for body mass index or insulin level, all differences disappeared, except for HDL3b and HDL3c concentrations, which remained significantly elevated. These results indicate that dyslipoproteinemic changes are present in early hypertension. Although most of these changes are related to obesity, alterations in HDL profile were not explained by influences of body mass index and insulin.

Adult↗
PubMed1994

Impaired glucose and insulin metabolism in borderline hypertension.

This study investigated glucose and insulin metabolism in borderline hypertension (BHT) defined as repeated diastolic blood pressures (DBP) of 85-94 mmHg. Seventy-five BHT and 75 age-matched normotensive (NT, DBP < or = 80 mmHg) men were recruited from a population screening programme. Plasma lipoproteins were determined and an oral glucose tolerance test was performed (WHO criteria). Fasting insulin was significantly higher in the BHT group (17.2 vs 14.2 mU/ml, p < 0.001), whereas fasting blood glucose levels were similar in the two groups, indicating a reduced insulin sensitivity. The BHT group had significantly lower levels of HDL cholesterol and higher levels of plasma triglycerides, VLDL cholesterol and VLDL triglycerides. When adjusted for BMI these differences disappeared, whereas the basal insulin levels remained significantly elevated (F = 10.7, p < 0.001). These results indicate that an altered glucose and insulin metabolism is present already in the early stages of hypertension. They also suggest that these disturbances are only partly dependent on BMI. This supports the hypothesis that reduced insulin sensitivity could be of importance in the early phases of essential hypertension.

Adult↗
PubMed1994

Haemostatic factors and inhibitors and coronary artery bypass grafting: preoperative alterations and relations to graft occlusion.

Graft closure remains a major problem after coronary artery bypass surgery. While a number of graft characteristics influencing the risk of occlusion have been defined, the role of haemostatic factors and inhibitors has not been studied in detail. The present study examined the time course of changes in blood coagulation and fibrinolytic function after coronary artery bypass grafting in 20 consecutive patients. Pre- and postoperative determinations of haemostatic factors and inhibitors were also related to the presence of graft occlusion assessed by angiography at three months after surgery. A broad panel of haemostatic tests was used preoperatively, on the first, third and eight postoperative days, and at three months after surgery. A particular emphasis was placed on fibrinogen, factor VII activity, von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) activity, anticoagulant proteins C and S, thrombin-antithrombin complex and D-dimer. A marked activation of the coagulation cascade was noted postoperatively along with enhanced degradation of cross-linked fibrin. The degree of activation of blood coagulation and fibrinolysis differed widely between individuals and appeared to relate only partly to the acute phase reaction produced by the surgical trauma. Preoperative values of haemostatic factors and inhibitors showed fairly weak associations with the levels of postoperative determinations.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗
PubMed1994

Elevated levels of factor VII activity in the postprandial state: effect of the factor VII Arg-Gln polymorphism.

A genetic polymorphism (Arg/Gln353) of coagulation factor VII was recently identified and shown to be associated with differences in basal factor VII coagulant activity. Postprandial lipaemia seems to exert an acute but evanescent effect on the activity of factor VII, and the influence of the Arg/Gln353 polymorphism on factor VII activation during postprandial lipaemia was therefore studied in male post-infarction patients [age 48.8 +/- 3.3 years (mean +/- SD)] with Arg/Arg (n = 23) and Arg/Gln (n = 8) genotypes. Factor VII antigen (VIIag) and activity along with plasma lipoproteins were determined before and after intake of a mixed meal-type of oral fat load. Patients with the Arg/Gln genotype had basal VIIag and activated factor VII (VIIa) levels 75% and 48%, respectively, of those of patients homozygous for the Arg allele. In absolute terms, VIIa increased more in homozygotes for the Arg allele (delta 0-6 h VIIa 1.76 +/- 1.48 ng/ml) than in heterozygotes (0.60 +/- 0.27 ng/ml) in response to fat intake, but the percentage increase in VIIa molecules did not differ significantly between subjects with Arg/Arg and Arg/Gln genotypes (37 +/- 32% versus 27 +/- 15%). This suggests that the influence of the Arg/Gln polymorphism on factor VII activity is mainly accounted for by differences in the basal factor VII protein level between genotypes. Since most of our lives are spent in the postprandial state, possession of the factor VII-Gln353 allele is likely to confer protection against coronary heart disease by reducing the amount of VIIa produced in response to fat intake.

Arginine↗
PubMed1994

Determination of apolipoproteins B-48 and B-100 in triglyceride-rich lipoproteins by analytical SDS-PAGE.

The present work describes a procedure for determining apolipoproteins (apo) B-100 and B-48 in subfractions of triglyceride-rich lipoproteins by analytical sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) with Coomassie staining. The chromogenicity of the two apoB species was found to be almost equal, and independent of lipoprotein particle size. Both proteins were sensitive to overloading of the gel, which resulted in low dye uptake. This was particularly evident for apoB-48. The precision of this analytical SDS-PAGE-based procedure to determine the plasma concentrations of apoB-100 and B-48 in triglyceride-rich lipoproteins was found to be appreciably low (coefficients of variation ranging between 3.1 and 14.1%).

Apolipoprotein B-100↗
PubMed1994

Relationship of tissue factor pathway inhibitor activity to plasma lipoproteins and myocardial infarction at a young age.

Tissue factor pathway inhibitor (TFPI) activity was quantified in two cohorts of young male post-infarction patients and in population-based control subjects to explore the relationships between TFPI activity and plasma lipoproteins and to address the issue of coordinate regulation of factor VII and TFPI in hyperlipidaemia and premature coronary heart disease (CHD). Participants were investigated in the fasting state and after an oral fat load. Basal TFPI activity and factor VII antigen (VIIag) levels were found to be increased in the patients (TFPI activity 1.25 +/- 0.23 vs 1.17 +/- 0.20 U/ml, p < 0.05; VIIag 537.7 +/- 127.7 vs 479.4 +/- 93.4 ng/ml, p < 0.001). The parallel increase was accounted for by patients with hypertriglyceridaemic lipoprotein phenotypes. In contrast, the level of activated factor VII (VIIa) neither differed significantly between patients and controls, nor between patients with different lipoprotein phenotypes. The elevated TFPI activity in the patients was closely associated with the plasma level of dense low density lipoprotein (LDL) particles (r = 0.46, p < 0.001) and with the plasma concentration of the small, dense high density lipoprotein (HDL) subspecies HDL3b (r = 0.34, p < 0.01).

Adult↗