PubMed HealthSearch

Biomedical subjects

V Rasi

Publications and source records attributed to V Rasi.

At least 19 recordsLinked to original sources

Symptoms of chronic bronchitis, haemostatic factors, and coronary heart disease risk.

Positive association has been suggested between a variety of infections and coronary heart disease. Disturbances in blood coagulation system may form a link between infections and coronary heart disease. The aim of this study was to analyze whether chronic bronchitis, defined by the occurrence of symptoms, is associated with selected haemostatic factors in a cross-sectional population study of 2379 Finnish men and women aged between 45 and 64 years. Plasma fibrinogen level was significantly higher, 3.70 versus 3.35 g/l (P < 0.001) in men and 3.64 versus 3.44 g/l (P < 0.001) in women, among subjects with symptoms of chronic bronchitis than among those without symptoms. The association was independent of age, smoking, body mass index, physical exercise, and alcohol consumption. Also plasminogen was higher among men with symptoms than among those without but the difference disappeared after adjustment for age and smoking. Factor VII coagulant activity and factor VII antigen level did not differ between subjects with and without symptoms. Thus, fibrinogen may be associated with a possible mechanism to link chronic bronchitis to coronary heart disease risk, even though the causality of the association cannot be verified in a cross-sectional study.

Blood Coagulation Factors

Protein C in the treatment of coagulopathy in meningococcal disease.

OBJECTIVE: To evaluate the clinical and laboratory effects of the substitution of protein C (PC) as an adjunct to conventional therapy in the treatment of purpura fulminans associated with meningococcal sepsis. DESIGN: case series. SETTING: Medical and medical-surgical intensive care units of two university hospitals. PATIENTS: Three patients with purpura fulminans and multiple organ failure caused by Neisseria meningitidis. INTERVENTION: Intravenous administration of PC concentrate (100 IU/kg every 6 to 8 hrs). MEASUREMENTS AND MAIN RESULTS: The administration of PC resulted in normal or above normal levels of the plasma PC activity in all patients. The laboratory and clinical parameters reflecting the severity of coagulopathy improved during the treatment, as did peripheral ischemia and the clinical manifestations of multiple organ failure. No adverse events were noted. One patient died of cerebral edema. CONCLUSION: The administration of PC had a beneficial effect on coagulopathy and peripheral gangrene formation associated with meningococcal disease and showed no adverse effects.

Adult

Intra- and interindividual variability of hemostatic factors and traditional cardiovascular risk factors in a three-year follow-up.

Elucidation of the key role of thrombosis in cardiovascular disease events has arisen considerable interest in hemostatic factors and in the repeatability of their determinations. Data on long-term repeatability has, however, remained scanty. We examined twice 208 men and 265 women in North Karelia, eastern Finland. The baseline examination was a part of the FINRISK 1992 Hemostasis Study and the age-range of participants was between 45-64 years. The re-examination took place three years later in 1995. Both surveys followed the same protocol and were carried out during the same season. Spearman rank correlation coefficients between 1992 and 1995 measurements of fibrinogen, factor VII coagulant activity (FVII:C), factor VII antigen (FVII:Ag), and plasminogen were among men 0.72, 0.77, 0.46 and 0.56, respectively. For total cholesterol, HDL-cholesterol, triglycerides and diastolic blood pressure the corresponding coefficients were 0.74, 0.83, 0.66, and 0.54. In women, the coefficient of fibrinogen was lower than in men, 0.62, otherwise the results were similar. Of men belonging to the highest quarter of fibrinogen, FVII:C, FVII:Ag and plasminogen in 1992, 65%, 60%, 53% and 60% belonged to the highest quarter of respective distributions also in 1995. In women, the corresponding proportions were 64%, 65%, 46% and 58%. The modest repeatability of FVII:Ag and plasminogen was mainly due to the high intraindividual variability. However, in comparisons of plasma levels between two groups, relatively small sample sizes seemed to give adequate statistical power to detect possible differences in FVII:Ag and plasminogen. In conclusion, the long-term repeatability of fibrinogen and FVII:C is similar to that of triglycerides and even better than that of diastolic blood pressure, but somewhat lower than the repeatability of total cholesterol. FVII:Ag and plasminogen did not have very good repeatability and more than one measurement of them should be considered if they are used as predictors of cardiovascular disease in prospective studies.

Cardiovascular Diseases

Association of the fatty acid composition of serum phospholipids with hemostatic factors.

It has been suggested that the fatty acid composition of serum phospholipids is an independent risk factor for cardiovascular disease. We examined the association of the fatty acid composition of serum phospholipids with fibrinogen, factor VII antigen (FVII:Ag), factor VII coagulant activity (FVII:C), plasminogen, and lipoprotein(a) [Lp(a)] in 338 men and 363 women 45 to 64 years old. Palmitic acid, the most abundant saturated fatty acid, was positively associated in univariate analyses with plasminogen, which explained 5.2% of its variance among men (P<.0001) and 5.8% among women (P<.0001). Linoleic acid, which is the most abundant polyunsaturated fatty acid, was negatively associated with plasminogen and fibrinogen. This explained 1.1% of the variance in fibrinogen among men (P=.04) and 3.2% among women (P=.0006) and 4.1% of the variance in plasminogen in both sexes (P<.0001). Dihomogammalinolenic acid was positively associated with FVII:Ag and explained 3.7% of its variance among men (P=.0003) and 4.6% among women (P<.0001). Furthermore, dihomogammalinolenic acid was positively and significantly associated with FVII:C, fibrinogen, and plasminogen among women but not among men. All these associations remained significant after adjustment for multiple potential confounding factors such as age, smoking, serum lipids, and body mass index. In conclusion, our findings suggest that linoleic acid, palmitic acid, and dihomogammalinoleic acid are significant independent determinants of hemostatic profile. It is not clear, however, to what extent these results reflect the effects of fatty acids on coagulation and to what extent they reflect the activity of inflammatory processes in the arteries.

8,11,14-Eicosatrienoic Acid

Fibrinogenemia Tampere--a dysfibrinogenemia with defective gelation and thromboembolic disease.

Fibrinogen Tampere was found in a woman with severe thromboembolic disease. The thrombin induced clotting time of her plasma and purified fibrinogen was slightly prolonged. The activation of fibrinogen Tampere appeared to be normal but subsequent gelation was defective. We studied fibrin gels formed at different ionic strengths and at different fibrinogen and calcium concentrations by liquid permeation, turbidity, and 3D laser microscopy. Crosslinking was studied by SDS-gel electrophoresis. The gels formed from fibrinogen Tampere were at ionic strength above 0.2 much tighter and had lower fiber mass-length ratios than normal gels as judged by permeability and turbidity data. At ionic strength 0.15 and at different calcium concentrations analysis by permeability showed the same results for fibrinogen Tampere as for normal gels. Analysis by turbidity at ionic strength 0.15 suggested swelling of the fibers at low calcium concentrations. 3D microscopy revealed perturbed clot architecture under all conditions. In fibrin gels from fibrinogen Tampere, the gamma-chain crosslinking was normal but the crosslinking of alpha-chains was delayed at ionic strength 0.2 and also at lower ionic strengths on lowering the calcium concentration. The abnormal gelation may be due to a mutation in the fibrinogen molecule. Tendency to form tight fibrin gels and/or insufficient crosslinked fibrin matrix may be pathogenetic in this thrombotic disease.

Adult

Haemostatic and other cardiovascular risk factors, and socioeconomic status among middle-aged Finnish men and women.

BACKGROUND: The higher morbidity and mortality due to cardiovascular diseases (CVD) in lower social classes has been shown repeatedly in Finland. Lower socioeconomic groups also have a more adverse CVD risk factor profile. The association between socioeconomic factors and risk of CVD is only partly explained by the traditional risk factors. Fibrinogen may be of particular importance as an underlying mechanism that mediates this association. MATERIAL AND METHODS: The association of socioeconomic status (SES), as measured by years of education and family income with coronary risk factors was studied among a random population-based sample (N = 2365) of Finnish men and women aged 45 to 64. Subjects were studied in three parts of Finland; North Karelia, the Helsinki area, and South-West Finland, in connection with a larger cardiovascular monitoring programme. Years of education was divided into four categories (< or = 7, 8-9, 10-12, > or = 13) and family income into quartiles. The coronary risk factors studied were serum total cholesterol, HDL-cholesterol, triglycerides, blood pressure, prevalence of hypertension, smoking, body mass index (BMI), waist-to-hip ratio, prevalence of obesity, alcohol use and the following haemostatic factors: plasma fibrinogen, factor VII coagulant activity (factor VII:C), factor VII antigen (factor VII:Ag) and plasminogen. RESULTS: Adjusting for age and area of residence, both men and women of low SES tended either to have more adverse risk factor levels or there was no association. The only exception was proportion of heavy drinkers, which was higher among higher social class women. The inverse association of SES were especially strong and consistent with smoking among men, and with BMI in both sexes. Of the haemostatic factors studied, plasma fibrinogen was inversely associated with SES in both sexes. The association disappeared after adjustment for smoking among men but not among women. Among women, plasma factor VII:Ag was inversely associated with income. No other statistically significant associations of haemostatic factors with SES were observed. CONCLUSIONS: Low SES groups had more adverse levels of most of the CVD risk factors. Haemostatic factors appeared to be associated with SES especially among women.

Blood Proteins

Association of hormone replacement therapy with hemostatic and other cardiovascular risk factors. The FINRISK Hemostasis Study.

The risk of cardiovascular diseases in women is small until menopause but increases considerably afterwards. When all age groups are considered, cardiovascular diseases are responsible for approximately half of the total mortality in women. It has been suggested that hormone replacement therapy (HRT) in perimenopausal and postmenopausal women could be useful in the prevention of cardiovascular diseases, but its effects are insufficiently known. We performed a cross-sectional study on the associations of menopause and HRT with cardiovascular risk factors, in particular with hemostatic factors, on female participants of the FINRISK Hemostasis Study. The participants, aged 45 to 64 years, were recruited from the Finnish population register by random sampling from three geographically defined areas. The participation rate of women was 83.2%. Of the 1202 women included in the study, 29.2% were current users of HRT. Differences in cardiovascular risk factors by menopausal status and by HRT use were examined after adjustment for age, study area, current smoking, body mass index, self-reported diabetes, and years of education. Postmenopausal women not using exogenous sex hormones had on average a total cholesterol level 0.5 mmol/L (8.9%) higher and an LDL cholesterol level 0.4 mmol/L (11.4%) higher than premenopausal women. Women reporting irregular menstruation (presumably due to perimenopause) had higher adjusted plasma fibrinogen, factor VII coagulant activity, and factor VII antigen than women with regular menstruation or no menstrual periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation

Deficiency in the A-subunit of coagulation factor XIII: two novel point mutations demonstrate different effects on transcript levels.

Congenital deficiency in coagulation factor XIII is a rare autosomal recessive bleeding disorder. Although the defect was characterized over 30 years ago, little is known about the molecular basis of the disorder. Here, we show two novel point mutations in the gene of the A-subunit of factor XIII in the genetically isolated population of Finland. All eight factor XIII-deficient families identified in Finland were studied. The exons of the gene of A-subunit were amplified individually by polymerase chain reaction and subsequently screened by single-strand conformation polymorphism. Sequence analysis of the abnormally migrating fragments showed two point mutations resulting in an amino acid alteration. A C-to-T transition at Arg-661 in exon XIV created a premature stop codon. This mutation was detected in six of the eight families, thus being the major alteration causing FXIII deficiency in Finland. In two of the six families, the patients were compound heterozygotes with the Arg-661-Stop mutation in one allele and either a T-to-C point mutation in exon VI or a thus far uncharacterized mutation in the other allele. The T-to-C transition in exon VI resulted in a substitution of threonine for methionine 242. The transition was found in one family only, where it was in the heterozygote form combined with the Arg-661-Stop mutation. To evaluate the consequences of these mutations, steady-state FXIII mRNA levels were quantitated by solid-phase minisequencing. In addition to the termination of translation 70 amino acids before the initial stop codon, the Arg-661-Stop mutation causes a 10- to 30-fold reduction in FXIII mRNA levels. This is also likely to result in a low translation level in the truncated polypeptide. In contrast, Met-242-Thr mutation does not seem to affect the level of mRNA. Here, the absence of a functional and immunodetectable protein is probably caused by an altered conformation of the mutant polypeptide, resulting in early degradation of the defective protein.

Adolescent

Haemostatic factors and prevalent coronary heart disease; the FINRISK Haemostasis Study.

We examined the association of haemostatic factors with prevalent coronary heart disease (CHD) in the population-based FINRISK Haemostasis Study. Of the 2365 participants aged 45-64 years, 88 men and 44 women with prevalent CHD were identified. The participants with CHD were older and had lower high density lipoprotein cholesterol, higher triglycerides and higher body mass index than the participants without CHD. Men with CHD had significantly higher plasma fibrinogen (P < 0.0001, adjusted for age and smoking) and lipoprotein (a) (Lp (a), P = 0.001, adjusted for age) concentrations than those without CHD. Among women, the findings were consistent with those of men, but only fibrinogen reached the conventional level of statistical significance (P = 0.04). No difference was observed in factor VII antigen, factor VII activity or in plasminogen. The association of Lp (a) with prevalent CHD was dependent on fibrinogen concentration (P = 0.02 for the interaction-term) and on non-HDL cholesterol concentration (P = 0.01 for the interaction-term). These cross-sectional results do not prove causality, but they demonstrate a considerable accumulation of prevalent CHD among persons with high Lp (a), fibrinogen and non-HDL cholesterol.

Antigens

The effects of saturated fat and n-6 polyunsaturated fat on postprandial lipemia and hemostatic activity.

The effect of different fat loads on postprandial lipemia and hemostatic activity was examined in 10 middle-aged men using 3 different meals. One meal was rich in saturated fatty acids (cream), the other rich in n-6 polyunsaturated fatty acids (sunflower oil) and the third was fat-free containing only carbohydrates. Lipoprotein lipids and hemostatic parameters were measured during fasting and 2, 4, 6 and 8 h after the test meal. In fasting samples, several hemostatic parameters were significantly associated with lipoprotein lipids. Most notable were the strong associations of fibrinolysis parameters tissue plasminogen activator antigen and plasminogen activator inhibitor activity (PAI-1) with total and very low density lipoprotein (VLDL) triglycerides. During lipemia, the associations were approximately similar or slightly weaker than in the fasting state. Both fat loads resulted in similar postprandial lipid responses: VLDL and high density lipoprotein (HDL) triglycerides reached maximum at 4 h after the meal. VLDL cholesterol also increased 4 and 6 h after the fat loads. HDL3 cholesterol declined after the fatty meals but no change was observed in the HDL2 fraction. The fat-free meal gave no significant lipid changes during the time course studied. Factor VII activity (F VII:C) increased 6 and 8 h after the fatty meals, whereas a decrease was observed after the fat-free meal. The changes (+/- S.D.) at 8 h after cream, sunflower oil and fat-free meal were 5.2 +/- 3.3, 3.3 +/- 4.2 and -5.8 +/- 7.9 percentage points, respectively, and the effect of the meal on the changes was statistically significant (F (8,99) = 2.99, P = 0.0048). F VII antigen (F VII:Ag) tended to decline during the day but there was no difference between the meals. Factor VIII activity (F VIII:C) was highest after the polyunsaturated fat meal and lowest after the fat-free meal. PAI-1 declined during the day and the decline tended to be steepest after the fat-free morning meal. The effect of the meal on the changes in lipoprotein lipids and hemostatic factors varied significantly between individuals. In conclusion, postprandial lipemia after a single fatty meal was associated with procoagulatory change in F VII:C but there was no difference between saturated fat and n-6 polyunsaturated fat.

Adult

Anaesthesia affects plasma concentrations of vasopressin, von Willebrand factor and coagulation factor VIII in cardiac surgical patients.

Operative stress may affect haemostatic mechanisms through hormonal systems. As the endocrine stress response to surgery may be modulated by anaesthesia, we have altered stress hormone concentrations by using either opioid or inhalation based anaesthesia to study haemostatic mechanisms in cardiac surgical patients. Thirty patients undergoing coronary artery surgery were allocated randomly to receive fentanyl (non-stress group) or enflurane (stress group) as the main anaesthetic agent. After cardiopulmonary bypass (CPB), plasma arginine vasopressin (AVP) concentrations were significantly (P < 0.001) greater in the stress group (81.8 (46.9-142.9) pg ml-1, mean with 95% confidence limits) than in the non-stress group (5.8 (3.3-10.2) pg ml-1). Plasma noradrenaline and adrenaline concentrations increased similarly in both groups after CPB. Plasma concentrations of both von Willebrand factor (stress: 1.56 (1.33-1.79) IU ml-1; non-stress: 1.00 (0.76-1.25) IU ml-1) and coagulation factor VIII: C (stress 1.15 (0.87-1.44) IU ml-1; non-stress: 0.69 (0.55-0.80) IU ml-1) were significantly (P < 0.01) greater in the stress group than in the non-stress group after CPB. The results indicate that there is a temporal relationship between the increased plasma concentrations of AVP and von Willebrand factor and factor VIII: C. It is not clear if this indicates a causal relationship. However, variable stress control by anaesthesia may modify haemostasis in cardiac surgical patients.

Adult