Haemostatic factors and lipoprotein (a) in three geographical areas in Finland: the Finrisk Haemostasis Study.

BACKGROUND: An increasing volume of evidence suggests that haemostatic factors play a role in the risk of coronary heart disease. It is not known, however, whether between-population differences in haemostatic factors correspond with the differences in mortality related to coronary heart disease. We examined this question in Finland, where, in North Karelia (in the eastern part of the country), the mortality from coronary heart disease is 1.5-1.7 times higher than that in southwestern areas. METHODS: A random sample of 3000 people aged 45-64 years was drawn from the population registers of North Karelia, of the area surrounding Turku and Loimaa in southwestern Finland and of the Helsinki area in southern Finland. Of the 3000 people approached, 79.6% took part in the study. differences in coronary heart disease mortality and morbidity. RESULTS: Factor-VII coagulant activity was significantly higher in North Karelia than in the other areas (P = 0.0008). The fibrinogen level was also higher in North Karelia, although the difference was significant only among non-smokers (P = 0.02). Levels of factor-VII antigen, plasminogen and lipoprotein (a) did not differ between the areas. Within North Karelia, the levels of both factor-VII coagulant activity, and factor-VII antigen were higher in rural areas than in urban areas. Levels of factor-VII coagulant activity, factor-VII antigen and plasminogen were higher in women than in men and increased with age in women but not in men. The fibrinogen level increased with age in both sexes. CONCLUSION: These baseline findings of the Finrisk Haemostasis Study demonstrate that the geographical differences in levels of factor-VII coagulant activity and fibrinogen in Finland are consistent with the population

The rabbit as an animal model of hepatic lipase deficiency.

A natural deficiency of hepatic lipase in rabbits has been exploited to gain insights into the physiological role of this enzyme in the metabolism of plasma lipoproteins. A comparison of human and rabbit lipoproteins revealed obvious species differences in both low-density lipoproteins (LDL) and high-density lipoproteins (HDL), with the rabbit lipoproteins being relatively enlarged, enriched in triacylglycerol and depleted of cholesteryl ester. To test whether these differences related to the low level of hepatic lipase in rabbits, whole plasma or the total lipoprotein fraction from rabbits was either kept at 4 degrees C or incubated at 37 degrees C for 7 h in (i) the absence of lipase, (ii) the presence of hepatic lipase and (iii) the presence of lipoprotein lipase. Following incubation, the lipoproteins were recovered and subjected to gel permeation chromatography to determine the distribution of lipoprotein components across the entire lipoprotein spectrum. An aliquot of the lipoproteins was subjected also to gradient gel electrophoresis to determine the particle size distribution of the LDL and HDL. Both hepatic lipase and lipoprotein lipase hydrolysed lipoprotein triacylglycerol and to a much lesser extent, also phospholipid. There were, however, obvious differences between the enzymes in terms of substrate specificity. In incubations containing hepatic lipase, there was a preferential hydrolysis of HDL triacylglycerol and a lesser hydrolysis of VLDL triacylglycerol. By contrast, lipoprotein lipase acted primarily on VLDL triacylglycerol. When more enzyme was added, both lipases also acted on LDL triacylglycerol, but in no experiment did lipoprotein lipase hydrolyse the triacylglycerol in HDL. Coincident with the hepatic lipase-induced hydrolysis of LDL and HDL triacylglycerol, there were marked reductions in the particle size of both lipoprotein fractions, which were now comparable to those of human LDL and HDL3, respectively.