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Biomedical subjects

A Hamsten

Publications and source records attributed to A Hamsten.

At least 127 records · Page 7Linked to original sources
PubMed1996

Effects of insulin treatment on cause-specific one-year mortality and morbidity in diabetic patients with acute myocardial infarction. DIGAMI Study Group. Diabetes Insulin-Glucose in Acute Myocardial Infarction.

Diabetic patients with acute myocardial infarction have a poor prognosis, which has been attributed to a higher incidence of congestive heart failure and fatal reinfarction. This study reports on the one-year morbidity and mortality in a randomized study with the aim of testing whether insulin-glucose infusion initiated as soon as possible after onset of myocardial infarction and followed by long-term subcutaneous insulin treatment may have a beneficial effect on outcome in diabetic patients. In all, 306 patients were recruited to the insulin-treated group, while 314 patients served as controls. The overall mortality after one year was 19% in the insulin group compared to 26% among controls (P < 0.05). The treatment effect was most pronounced in patients without prior insulin medication and at low cardiovascular risk. In this stratum the in-hospital mortality was reduced by 58% (P < 0.05) and the one-year mortality by 52% (P < 0.02). The most frequent cause of death in all patients was congestive heart failure (66%), but cardiovascular mortality (congestive heart failure, fatal reinfarction, sudden death and stroke) tended to be decreased in insulin-treated patients. However, this difference did not reach the level of statistical significance. The number of reinfarctions was 53 (28% fatal) in the insulin group compared to 55 (45% fatal) in the control group. The two groups did not differ as regards need for hospital care or coronary revascularization during the year of follow-up. In summary, left ventricular failure and fatal reinfarctions contribute to increased mortality in diabetic patients following acute myocardial infarction. Intensive insulin treatment lowered this mortality during one year of follow-up.

Adult↗
PubMed1996

In vivo demonstration in humans that large postprandial triglyceride-rich lipoproteins activate coagulation factor VII through the intrinsic coagulation pathway.

In vitro studies in purified plasma systems have suggested that triglyceride-rich lipoproteins such as chylomicrons, very low density lipoproteins, and their remnants promote activation of factor VII through activated factor XII (XIIa) and the intrinsic coagulation pathway. We specifically examined the roles of factors XII, XI, and IX in activation of factor VII during alimentary lipemia in vivo in humans and addressed the issue of whether generation of activated factor VII (VIIa) is accompanied by increased thrombin production. For this purpose XIIa, factor IX activation peptide (IXP), VIIa, prothrombin fragment 1 + 2 (F1 + 2), and thrombin-antithrombin complex (TAT) were determined in plasma samples taken before and 3, 6, and 9 hours after intake of a mixed meal type of oral fat load in 24 healthy men The VIIa response to fat intake was also determined in 7 patients with single coagulation-factor deficiency, of whom 2 were deficient in factor XII, 2 in factor XI, and 3 in factor IX. Postprandial activation of factors IX and VII occurred in the healthy individuals, whereas the plasma levels of XIIa did not change in response to the test meal. Of note, plasma concentrations of F1 + 2 were unaltered during alimentary lipemia, and TAT levels showed a small decrease (P < .05) in the 3-hour sample compared with the fasting level, indicating that thrombin generation is not stimulated in the postprandial state, despite the generation of activated factor IX (IXa) and VIIa. Factor VIIa increased in the postprandial period in the 2 factor XII-deficient patients who underwent the oral fat tolerance test but appeared to remain unchanged in the factor XI- and factor IX-deficient patients. Therefore, the current concept that activation of factor XII plays a pivotal role in initiating the sequence of events linking postprandial lipemia to activation of factor VII is contradicted by the present study. Whether activation of factor XI by triglyceride rich lipoproteins initiates these reactions needs to be demonstrated in future studies.

Adult↗
PubMed1996

The antidiabetogenic effect of GLP-1 is maintained during a 7-day treatment period and improves diabetic dyslipoproteinemia in NIDDM patients.

OBJECTIVE: To investigate the long-term antidiabetogenic effect of glucagon-like peptide 1 (GLP-1) and its influence on diabetic dyslipoproteinemia, patients with NIDDM were treated with GLP-1 subcutaneously for 1 week. RESEARCH DESIGN AND METHODS: Twelve patients participated in the study. The 1st week of the study, all of them were on intensive insulin treatment and from day 8, four were randomized to a control group continuing with insulin, and eight to a treatment group where GLP-1 was given at meals together with regular insulin from day 8 to 12. On days 13 and 14, they were only given GLP-1 at meals. NPH insulin at bedtime was given throughout the study. RESULTS: In the GLP-1-treated patients, the doses of regular insulin, given to keep a satisfactory blood glucose control, were reduced compared with treatment with insulin only. GLP-1 virtually inhibited the early increase in blood glucose after the meals, whereas an increase of approximately 2 mmol was seen during an optimized insulin treatment. In agreement with the short half-life of the peptide, 2-h postprandial plasma insulin levels were significantly decreased both at day 12 and 14, suggesting that there was not enough GLP-1 left to stimulate endogenous insulin release and compensate for the decrease in the dose of exogenous insulin. Therefore, the effect of GLP-1 was lost before the next meal, resulting in increased preprandial blood glucose values at lunch and dinner. The concentration of VLDL triglycerides decreased already during the 1st week. This decrease persisted during the 2nd week when GLP-1 was included in the treatment. No changes were observed in the levels of LDL and HDL cholesterol. The LDL particle diameter increased from a mean of 22.3 to 22.6 nm (P < 0.01) in response to insulin treatment. A further increment to 22.9 nm (P < 0.05) was seen after GLP-1 treatment. The LDL particle size did not change in the control group. Lipoprotein lipase activity was decreased by 27% and hepatic lipase was reduced by 13% in the GLP-1-treated group. CONCLUSIONS: We confirm the antidiabetogenic effect of GLP-1 in NIDDM patients. This effect was maintained during 7 days, which implies that the patients did not develop tolerance during this treatment period. Intensive insulin treatment, leading to normotriglyceridemia, increased the mean LDL particle diameter, which is likely to lower the risk of future coronary heart disease in patients with NIDDM. Furthermore, an additive effect of GLP-1 is indicated. Hence, this study gives additional evidence that GLP-1 may be useful as an agent for treating NIDDM.

Blood Glucose↗
PubMed1996

Accumulation of large very low density lipoprotein in plasma during intravenous infusion of a chylomicron-like triglyceride emulsion reflects competition for a common lipolytic pathway.

Very low density lipoproteins (VLDL) are produced in the liver and contain apolipoprotein (apo) B-100 and endogenous lipids. By contrast, ingestion of fat leads to formation of chylomicrons containing apoB-48 secreted from the intestine. In this study, a 60-min intravenous infusion of a chylomicron-like triglyceride emulsion was given to healthy young men to examine whether competition between chylomicrons and VLDL for the same lipolytic pathway explains the increase in VLDL seen after meals. The responses of two major VLDL subfractions were determined by measuring the concentrations of apoB-100 in fractions of triglyceride-rich lipoproteins with Svedberg flotation rates of 60-400 (large VLDL) and 20-60 (small VLDL) that were separated from plasma by density gradient ultracentrifugation. A threefold elevation in plasma triglycerides was observed during the infusion together with a consistent linear increase of large VLDL. The rate at which large VLDL accumulated in plasma differed markedly among individuals and was not enhanced by doubling of the infusion rate. The response of small VLDL was more heterogeneous; however, a decrease was seen in most subjects. The combined pattern for the two VLDL species is what would be expected if large VLDL particles are the precursors of smaller VLDL species and if lipolysis of large VLDL is inhibited through competition from the triglyceride emulsion. The extent to which the triglyceride emulsion inhibited the lipolysis of VLDL and/or influenced the synthesis rate of large VLDL was estimated from simultaneous stable isotope studies. The emulsion caused a 75-90% block of the conversion of large VLDL apoB to small VLDL apoB and there was no sign of enhanced synthesis of large VLDL after infusion of the triglyceride emulsion. The corollary of these findings is that chylomicrons and their remnants impede the normal lipolytic degradation of VLDL and could thereby be indirectly implicated in the generation of atherogenic remnant lipoproteins.

Adult↗
PubMed1996

Gemfibrozil reduces thrombin generation in patients with combined hyperlipidaemia, without influencing plasma fibrinogen, fibrin gel structure or coagulation factor VII.

A double-blind, placebo-controlled, cross-over study was conducted in 21 men with combined hyperlipoproteinaemia to examine if lipid-lowering treatment with gemfibrozil (10-12 weeks) affects blood coagulation and fibrin gel structure at rest or during mental stress. Gemfibrozil lowered plasma triglycerides by 57 +/- 4%, whereas high density lipoprotein (HDL) cholesterol increased by 22 +/- 5%. Gemfibrozil lowered the triglyceride content of low density lipoprotein (LDL). Gemfibrozil reduced the plasma concentrations of thrombin-antithrombin complex (TAT) and prothrombin fragment F1 + 2 (F1 + 2), both at rest and during mental stress. However, there were no effects of gemfibrozil treatment on the plasma concentrations of fibrinogen, factor VII antigen, activated factor VII (VIIa) or activated factor XII (XIIa), or on fibrin gel structure. Acute mental stress per se did not influence coagulation factors, reaction products or fibrin gel structure, or their responses to the study drug. Thus, gemfibrozil reduced thrombin generation in men with combined hyperlipoproteinaemia, without influencing the plasma levels of fibrinogen, VIIa and XIIa, or fibrin gel structure. Attenuation of thrombin generation may contribute to the primary-preventive effects of gemfibrozil on coronary heart disease.

Adult↗
PubMed1996

Proneness to formation of tight and rigid fibrin gel structures in men with myocardial infarction at a young age.

The native fibrin gel structure formed in vitro from plasma samples was examined by liquid permeation of hydrated fibrin gel networks in 38 unselected men who had suffered a myocardial infarction before the age of 45 years and in 88 age-matched population-based control men. Both the fibrin gel porosity (permeability coefficient, Ks) and the calculated fiber mass-length ratio varied considerably within the two groups, but were generally lower in the patients. Ks was 8.3 +/- 5.2 cm2 x 10(9) (mean +/- SD) in the patient group and 12.5 +/- 5.7 cm2 x 10(9) among controls (p < 0.001). The corresponding figures for fiber mass-length ratio were 13.1 +/- 7.7 and 16.5 +/- 7.5 Dalton/ cm x 10(-13), respectively (p < 0.01). Around 50% of the patients had Ks values below the 10th percentile of the control group. A strong inverse correlation was seen between plasma plasminogen activator inhibitor-1 (PAI-1) activity and Ks (r = -0.603, p < 0.001) or fiber mass-length ratio (r = -0.565, p < 0.001) in the patient group. Corresponding weaker associations of PAI-1 with fibrin gel properties were also present in the control group. In addition, inverse relationships of very low density lipoprotein (VLDL) triglyceride concentrations to Ks (r = -0.362, p < 0.001) and fiber mass-length ratio (r = -0.283, p < 0.01) were found among the controls. Proneness to formation of tight and rigid fibrin gel networks with abnormal architecture in vitro is in vivo associated with myocardial infarction at a young age. Impaired fibrinolytic function secondary to a raised plasma PAI-1 activity level is associated with abnormal fibrin gel structure.

Adult↗
PubMed1995

Insulin, intact and split proinsulin, and coronary artery disease in young men.

BACKGROUND: Glucose intolerance and hyperinsulinemia are common disturbances in nondiabetic men with premature coronary artery disease (CAD). To investigate the relation between insulin-like molecules and severity of coronary atherosclerosis, 62 consecutive nondiabetic men presenting with a first myocardial infarction before the age of 45 were studied along with 41 healthy, age-matched, male, population-based control subjects. METHODS AND RESULTS: Specific two-site immunoradiometric assays were used to distinguish intact proinsulin, (des 31,32) proinsulin, and "true" insulin in fasting plasma and during an oral glucose tolerance test (OGTT). Global coronary atherosclerosis and number and severity of distinct stenoses were determined in the patients in 15 proximal coronary arterial segments by use of separate semiquantitative classification systems. The patients had a two- to threefold increase in insulin and insulin propeptide concentrations in the fasting state as well as during the OGTT. Severity of coronary atherosclerosis correlated significantly (P < .05 to P < .01) with basal proinsulin (r = .40) and the proinsulin area under the curve (AUC) (r = .34), basal insulin (r = .31), basal C peptide (r = .30), and the glucose AUC (r = .30). In multiple stepwise regression analysis including insulin-like molecules, major plasma lipoproteins, and lipoprotein subfractions, basal proinsulin (increase in R2 = .09) and dense LDL triglycerides (increase in R2 = .10) predicted 19% of the variation of the global coronary atherosclerosis score after adjustment for age, body mass index, fasting insulin concentration, and VLDL triglycerides. CONCLUSIONS: This study shows that young, nondiabetic, male survivors of myocardial infarction are truly hyperinsulinemic during an OGTT and suggests a close association between proinsulin and coronary atherosclerosis.

Adrenergic beta-Antagonists↗
PubMed1995

Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction.

Increased plasminogen-activator inhibitor 1 (PAI-1) activity is a common finding in patients with coronary heart disease. Here we provide evidence for an independent, etiological role of PAI-1 in myocardial infarction. The 4G allele of a recently described common 4/5-guanine-tract (4G/5G) polymorphism in the PAI-1 promoter is associated with higher plasma PAI-1 activity. The prevalence of the 4G allele is significantly higher in patients with myocardial infarction before the age of 45 than in population-based controls (allele frequencies of 0.63 vs. 0.53). Both alleles bind a transcriptional activator, whereas the 5G allele also binds a repressor protein to an overlapping binding site. In the absence of bound repressor, the basal level of PAI-1 transcription is increased.

Adult↗
PubMed1995

Common variation in the gene for apolipoprotein B modulates postprandial lipoprotein metabolism: a hypothesis generating study.

We have carried out a pilot study to examine the influence on postprandial lipid and lipoprotein metabolism of common genetic variation in the gene coding for apolipoprotein (apo) B, in a previously described group of 30 individuals who had survived a myocardial infarction (MI) before the age of 45 (normo (NTG)- and hypertriglyceridaemic (HTG) patients) and 11 age-matched healthy individuals. Postprandial lipid or lipoprotein levels were examined by genotypes in the three groups separately and after adjustment for fasting triglycerides (TG) in the whole group combined. For the signal peptide polymorphism in the apo B gene, individuals with one or more SP-24 alleles had a 38% smaller mean area under curve (AUC) (P = 0.06) for postprandial large chylomicron remnants and a 29% smaller mean AUC (P = 0.01) for large very low density lipoproteins (VLDLs) compared to individuals homozygous for the wild type SP-27 allele. Previously in this patient group, small chylomicron remnants (apo B-48 levels in the Sf 20-60 range) were found to relate significantly and positively to progression of coronary atherosclerosis suggesting that these lipoproteins are implicated in progression of atherosclerosis. For the apo B Val591-Ala polymorphism (Ag a1/d), individuals homozygous for the V591 allele had a 33% greater AUC for Sf 20-60 postprandial triglycerides (P = 0.006), with higher postprandial levels of both apo B-48- and apo B-100-containing lipoproteins in this fraction. This pilot study gives insight into the mechanisms of the previously reported associations between polymorphisms in the apo B gene and fasting plasma lipids and lipoproteins.

Alleles↗
PubMed1995

Association of insulin and insulin propeptides with an atherogenic lipoprotein phenotype.

A characteristic lipoprotein phenotype, including hypertriglyceridemia, a low high-density lipoprotein (HDL) cholesterol concentration, and a predominance of small, dense low-density lipoprotein (LDL) particles, is linked to insulin resistance and hyperinsulinemia. Individuals with these characteristics are supposed to be at increased risk of developing coronary heart disease (CHD). To address this issue further, relations between basal and postload glucose, insulin and insulin propeptide concentrations and subfractions of apolipoprotein (apo) B-containing lipoproteins were examined in 62 consecutive Swedish nondiabetic men who had experienced a first myocardial infarction before the age of 45. A total of 41 age-matched, population-based healthy men were investigated as controls. Highly specific immunoradiometric assays were used for measuring intact proinsulin and des 31,32proinsulin levels. In all, 39% of the patients were found to be glucose-intolerant, and basal and postload hyper(pro)insulinemia were characteristic features irrespective of glucose tolerance category. Hypertriglyceridemic (HTG) lipoprotein phenotypes with a low HDL cholesterol concentration dominated among the patients, and hyperinsulinemia was linked to hypertriglyceridemia and putatively atherogenic lipoprotein traits, such as increased particle numbers of small very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) and triglyceride enrichment of LDL. The corollary of these findings is that insulin resistance is a characteristic feature of young postinfarction patients and is accompanied by a complex atherogenic lipoprotein phenotype, new components of which are an abundance of small cholesteryl ester-rich VLDL and an elevated LDL triglyceride concentration.

Adult↗
PubMed1995

Fibrinolysis and atherosclerosis.

The link between impaired fibrinolytic function and CHD has been reinforced considerably in the past couple of years. This has been achieved by a combination of epidemiological, clinical, cell biological and molecular biological studies. The molecular mechanisms for the identified associations between more established risk factors for atherosclerotic disease and impaired fibrinolytic function now need to be disentangled to promote the design of specific drugs that may pave the way for intervention. The possibility that some of the observed relations are epiphenomena should also not be disregarded. The concept of genotype-specific differences in the susceptibility of the individual to common metabolic disturbances needs to be examined in greater detail. Basic research on the role of fibrinolysis in atherosclerosis and its thrombotic complications should be given high priority, because the modulation of fibrinolytic function is likely to become an important approach to prevention.

Animals↗
PubMed1995

Postprandial lipoprotein metabolism and atherosclerosis.

The metabolism of chylomicrons and their remnants is a highly facilitated route to distribute energy from the diet for storage in adipose tissue or immediate use in the muscles. It has been proposed that chylomicron remnants are atherogenic, and a delayed clearance of chylomicron remnants seems to be associated with compositional abnormalities of other cholesterol-rich lipoproteins. Furthermore, the plasma concentration of chylomicron remnants is very low compared with all other major lipoprotein species. These arguments suggest that the metabolism of chylomicrons may not be directly implicated in atherogenesis, but it may instead enhance the atherogenicity of endogenous lipoproteins. This review critically examines the current literature in this field.

Arteriosclerosis↗
PubMed1995

Cellular processing of apolipoprotein B-containing lipoproteins from young post-infarction patients and healthy controls.

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity was measured in fibroblasts incubated with large (Sf > 60) and small (Sf 20-60) very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) particles, at similar protein concentrations, from young post-infarction patients and healthy controls. The results showed that apolipoprotein (apo) B-containing lipoproteins (VLDL, IDL, LDL) from patients suppressed HMG-CoA reductase activity to a similar extent compared to apo B-containing lipoproteins from controls. When all subjects taken together were grouped according to triglyceride levels, it was found that small VLDL from hypertriglyceridaemic individuals suppressed the HMG-CoA reductase activity more than small VLDL from normotriglyceridaemic individuals. The opposite pattern was seen for LDL. The lipoprotein composition was related to the respective HMG-CoA reductase activity. In addition to a positive association between the cholesterol content of small VLDL and LDL, and the inhibition of HMG-CoA reductase activity, the apo C I and C II content of small VLDL and IDL was inversely related to the suppression of HMG-CoA reductase activity. This study shows that the cellular processing of apo B-containing lipoproteins in young post-infarction patients and healthy controls is heterogeneous and dependent on the composition of the lipoprotein.

Adult↗
PubMed1995

Long-term prognostic significance of M mode echocardiography in young men after myocardial infarction.

OBJECTIVE: To evaluate the power of measurements of left ventricular size and function for predicting long term (82 month) mortality by performing echocardiography in 97 men who had survived an acute myocardial infarction. SETTING: University hospital specialising in cardiology. PARTICIPANTS: 97 consecutive male patients who had survived a myocardial infarction. MAIN OUTCOME MEASURES: The additive prognostic value of functional measurements to that provided by primary risk factors (smoking habits and lipoprotein levels), radiological heart size, exercise capacity, and number of major coronary arteries with haemodynamically significant stenoses was evaluated. An echo index was calculated from three echocardiographic variables (yielding one score point each if: left ventricular diameter at the end of diastole (LVDD) > or = 5.7 cm, left ventricular fractional shortening < or = 24%, and E point-separation (EPSS) > or = 10 mm). MAIN OUTCOME: 17 cardiac deaths occurred during follow up. RESULTS: Univariate analysis showed that treatment with loop diuretics for heart failure (P < 0.01), LVDD (P < 0.01), left ventricular diameter at the end of systole (LVDS) (P < 0.001), left atrial diameter (P < 0.001), fractional shortening (P < 0.05), and echo index (P < 0.001) were all associated with cardiac death. Angiographically determined regional wall motion disturbances (P < 0.005) and angiographic ejection fraction (P < 0.001) were also associated with cardiac death, as was the number of major coronary arteries with significant stenosis (P < 0.05). When all significant echocardiographic variables from univariate analysis were entered into Cox proportional hazards survival analysis, LVDS and left atrial diameter contributed independently to the prediction of cardiac death. If angiographic data were also entered into the model, the echo index made an independent contribution to the prediction of cardiac death. CONCLUSIONS: Among young male patients with a previous myocardial infarction, a simple M mode echocardiographic examination can identify high and low risk patients and improve the prediction of cardiac death made from clinical information, exercise test, chest x ray and angiographically determined ejection fraction.

Adult↗
PubMed1995

Quantification of postprandial triglyceride-rich lipoproteins in healthy men by retinyl ester labeling and simultaneous measurement of apolipoproteins B-48 and B-100.

The metabolism of chylomicrons, very-low-density lipoprotein (VLDL), and their remnants in the postprandial state was studied in normolipidemic healthy men by measuring apoB-48 and apoB-100 and retinyl palmitate (RP) in fractions of triglyceride-rich lipoproteins after a mixed meal type of oral fat load supplemented with vitamin A. ApoB-48 was present at low concentrations in the fasting plasma samples in most subjects and increased in response to the test meal in Svedberg's flotation rate (Sf) > 20 lipoprotein fractions. Concomitantly, the level of Sf 60 to 400 apoB-100 (large VLDL) had doubled at 3 hours and returned to baseline at 9 hours. The number of apoB-48-containing lipoprotein particles did not exceed 20% of the total number of apoB-containing lipoproteins contained in Sf 12 to 400 fractions at any time point after fat intake. The peak plasma level of RP was delayed compared with the peak plasma concentration of apoB-48, suggesting that retinyl ester labeling of chylomicrons is questionable as a means of quantifying postprandial triglyceride-rich lipoproteins of intestinal origin. Approximately 2000 and 4000 RP molecules were carried in each chylomicron particle in the 3- and 6-hour samples, respectively, in contrast to the remnant fractions in which 100 to 600 RP molecules were found for each lipoprotein particle. The limited RP exchange between lipoprotein particles indicates that the smaller intestinal lipoproteins do not originate primarily from larger Sf > 400 chylomicron particles but instead are secreted directly into the Sf 20 to 400 fraction and subsequently converted to smaller chylomicron remnants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Coagulation factor VII mass and activity in young men with myocardial infarction at a young age. Role of plasma lipoproteins and factor VII genotype.

Factor VII (FVII) coagulant activity has been proven to be associated with the risk of future fatal coronary heart disease (CHD) in middle-aged men. Recent studies have emphasized the role of triglyceride-rich lipoproteins and FVII genotype in determining plasma levels of FVII protein and activity. The present study was undertaken to examine whether FVII activity state and protein concentration in fasting plasma are altered in young men with proven myocardial infarction (MI) and examined the relations of FVII to subfractions of apo B-containing lipoproteins and the Arg-->Gln polymorphism in the FVII gene. Activated FVII (FVIIa) was determined by a clotting assay using soluble, recombinant, truncated tissue factor. A total of 94 men with a first MI before the age of 45 (mean age +/- SD, 39.6 +/- 4.5 years) were included in the study along with 99 population-based, age-matched control subjects. In addition to FVIIa and FVII antigen (FVII:Ag), a panel of FVII activity assays were included for comparison with previous work in this field. The plasma level of FVII:Ag was higher in patients than in control subjects when the entire groups were compared (537 +/- 128 versus 479 +/- 93 ng/mL, P < .001), the differences being accounted for by patients with hypertriglyceridemic lipoprotein phenotypes. In contrast, FVIIa was similar in patients and control subjects (4.6 +/- 1.4 versus 4.3 +/- 1.3 ng/mL, NS), which means that the proportion of FVIIa molecules was unaltered or even lower in the patients. As expected, the Arg-->Gln polymorphism significantly influenced both FVII mass and activity levels. In addition, presence of the Gln allele appeared to be associated with a lower proportion of fully active FVII molecules. The polymorphism also affected the relation between the plasma concentration of VLDL and FVII:Ag. The triglyceride content and particle number of all VLDL subfractions, irrespective of particle size, correlated fairly strongly with FVII mass determinations but not at all with FVIIa. HDL cholesterol concentration, on the other hand, presumably reflecting the efficiency of lipoprotein lipase-mediated lipolysis of VLDL, related significantly to the FVIIa level. The Arg-->Gln polymorphism, independent of lipoprotein effects, explained 5% to 10% of the variation in FVII mass and activity. In conclusion, the present findings speak against a role of FVII as a risk factor for CHD, because a significantly increased potential for activation of coagulation (ie, raised basal concentration of FVIIa) was not observed among young postinfarction patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Association between circulating immune complexes, complement C4 null alleles, and myocardial infarction before age 45 years.

One hundred patients who had survived a myocardial infarction before the age of 45 years and 90 age- and sex-matched healthy individuals were investigated for circulating immune complexes (CICs) and the presence of complement C4 null alleles (C4Q0). CICs were found in increased concentrations in 20% of patients and 6.7% of control subjects. Patients and control subjects had the same prevalence of C4Q0. CICs were present in all patients and in 36% of the control subjects homozygous for C4Q0. Patients and control subjects heterozygous for C4Q0 had CICs in 71% and 0%, respectively. The high prevalence and a high concentration of CICs were particularly associated with C4A*Q0. Patients homozygous for C4A*Q0 had concentrations of LDL that were lower than found in other patients. The increased concentration of CICs associated with genetic deficiencies of the complement factor C4 might thus be an additional etiological factor for the development of chronic vascular damage and premature myocardial infarction.

Adult↗