摘要:

ABSTRACT.Atherosclerosis is a multifactorial disease. A unified model for the lesion development reveals many connections between the response‐to‐injury hypothesis and the lipid hypothesis. Various cellular uptake mechanisms for native and modified lipoproteins are discussed with respect to foam cell formation and lesion development. The role of arterial smooth muscle cells in atherogenesis is emphasized. Preliminary results of biochemical analyses from the coronary arteries of accidentally died Finnish children and adults reveal that 1) the accumulation of plasma‐derived cholesteryl esters in young children began early in childhood, long before the vessels became macroscopically affected and 2) changes in arterial glycosaminoglycans correlated significantly with the accumulation of cholesteryl e

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1985.tb08885.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

ABSTRACT.The dietary fatty acids include saturated and unsaturated fatty acids of the n‐9, n‐6 and n‐3 families. Their quantity and quality are reflected in the plasma lipoproteins. The platelet and endothelial cell lipid composition also is influenced by the dietary fatty acids. These changes have consequences for cellular lipid and prostanoid metabolism and other cellular functions which could be related to the thrombosis mechanism. A high intake of saturated and n‐9 unsaturated fatty acids induces changes in plasma, platelets and endothelial cells favouring thrombosis and atherosclerosis. By contrast, both n‐6 and n‐3 fatty acids give rise to plasma lipoprotein and cellular lipid composition that counteract atherosclerosis and thrombosis. The ideal balance between the various dietary fatty acids is not known. Experimental and epidemiological studies support the recommendation of a low saturated fat intake with supplement of both n‐6 and ‐3 polyunsatura

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1985.tb08886.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

ABSTRACT.Low density lipoprotein (LDL) is probably the most atherogenic of all the lipoproteins. Several abnormalities in LDL metabolism seem to be associated with coronary heart disease (CHD) one of them being an elevation of plasma LDL concentration. Recent findings suggest that disorders in the metabolism of LDL could be associated with accelerated atherosclerosis even without elevated LDL levels such as increased flux of LDL and changes in the LDL composition. Elevation of plasma LDL levels can be caused by two factors, first, a decrease in the clearance of LDL and second, an overproduction of this lipoprotein. Catabolism of LDL is largely determined by the LDL receptors as clearly shown in patients with familial hypercholesterolemia (FH). In this inherited disease the patients do not have normal LDL receptors and their LDL levels are remarkably elevated. LDL production is also increased in these subjects. In the rest of the population LDL levels are regulated by both the LDL clearance and production rate. The latter also seems to be related to the LDL receptor activity. The conversion of the LDL precursor, very low density lipoprotein (VLDL) to LDL is the most important factor regulating LDL synthesis. When the LDL receptor activity is low a large fraction of VLDL apolipoprotein B (apoB), the major structural protein in VLDL, is converted to LDL, and LDL production is high. On the other hand, only a small part of VLDL apoB is converted to LDL resulting in low LDL synthesis rate in conditions with high LDL receptor activity. The relationships between production and clearance of LDL are, however, more complex. There are individuals who produce a large number of VLDL and LDL particles but maintain LDL concentrations at a normal level by clearing their LDL very effectively. These subjects obviously have another abnormality in lipoprotein metabolism namely an overproduction of apoB. This disorder has been observed in several conditions like obesity, adult‐onset diabetes mellitus, several patients with familial combined hyperlipidemia and some normolipidemic subjects with premature coronary heart disease. In all these conditions increased transport of LDL can be associated with coronary artery disease even in the absence of hypercholesterolemia. This raises the possibility that increased flux of LDL could itself be atherogenic possibly by overloading reverse cholesterol transport. Finally, there is some evidence that LDL particle composition may be important in the process of atherogenesis. High LDL apoB but normal LDL cholesterol levels, hyperapobetalipoproteinemia, has been associated with premature coronary heart disease. Furthermore, variability in LDL composition and particle size indicates that LDL can be heterogenous and raises the possibility that some forms of LDL are more atherogenic than others. In conclusion, the metabolic basis of coronary heart disease, particularly the abnormalities associated with the most atherogenic lipoprotein, LDL, seem to be multiple and indicate a need to expand our views of causal factors in coronary heart diseas

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1985.tb08887.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

ABSTRACT.In the Helsinki Policemen Study based on a cohort of 982 men aged 35—64 years and free of coronary heart disease (CHD) at entry plasma insulin level (fasting, 1‐hour and 2‐hour plasma insulin after oral glucose load) showed during a 9½‐year follow‐up a nonlinear association to the incidence of »hard criteria» CHD events (CHD death or non‐fatal myocardial infarction) with highest incidence in the top decile of plasma insulin. Plasma insulin levels showed positive correlations, besides to blood glucose levels, to body mass index, plasma triglyceride level and blood pressure and inverse correlations to leisure time physical activity and objectively measured physical fitness. In multivariate analyses the predictive value of high plasma insulin with respect to CHD risk was found to be independent of other risk factors, including blood

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1985.tb08888.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

ABSTRACT.Two types of end‐point measurement are presently available in clinical trials of the effect of treatment of hyperlipidaemia on cardiovascular disease; these are the incidence of clinical events and the arteriographic assessment of progression or regression of atherosclerosis. These approaches are briefly reviewed. In the present trial, 25 hyperlipidaemic men with symptomatic femoral atherosclerosis underwent biplanar femoral arteriography at baseline. They were then randomised into treatment and usual‐care groups; treatment was individualized, comprising a lipid‐lowering diet with cholestyramine, nicotinic acid or clofibrate as appropriate for the lipoprotein disorder. Mean cholesterol and triglyceride levels were 19% and 37% lower in the treatment group. Arteriography was repeated after a mean period of 19 months. With attention to blinding of observers, changes in arteriograms were quantitated using computerised image analysis and visual methods, and expressed both by patient and by arterial segment. All end‐points were in conformity and showed a lower rate of progression of arterial disease in the treatment group, and a higher frequency of segmental regression in treated patients. In this small trial of patients with functionally‐significant atherosclerosis, effective treatment of hyperlipidaemia favourably affected the course of the arteria

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1985.tb08889.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

ABSTRACT.Coronary heart disease (CHD) mortality has decreased markedly in the U.S.A., Finland, Australia and other countries. Although the data are lacking, a decline in incidence is likely. Possible reasons include increased dietary consumption of essential fatty acids and decreased consumption of saturated fat and cholesterol, reduction in smoking, increased control of high blood pressure and increase in exercise. Not all countries fit this schema. Sweden has an increased CHD mortality which is not easily explained. Japan has had a continued decline in CHD mortality despite apparent increases in dietary fat. In the U.K., a decrease in CHD mortality began late, but there are encouraging signs both of changes in life style and of decreased mortality.

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1985.tb08890.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

ABSTRACT.Medical and epidemiological research into the aetiology of CHD has drawn attention to the likely causal role of certain risk factors, especially elevated serum (LDL) cholesterol and blood pressure levels, and smoking. Conventional trials to establish the causality have come up against problems of feasibility and study design. Community‐based studies have considerable potential in introducing changes to the general lifestyle and risk factors in large numbers of people (since the risk factors are closely related to the way of life and other features of the community). Thus a well evaluated community‐based study can augment our knowledge on the role of the risk factors. Furthermore, a community study examines how the existing service structure and community resources can be used and assesses the overall feasibility and consequences of such an intervention.The North Karelia project, started in eastern Finland in 1972, has been a major communitybased study on the prevention of CHD. The results of the 10‐year evaluation of the project illustrate the feasibility and consequences of the approach. During the 10‐year period 1972—82 the following net changes (i.e. adjusted for changes in the reference area) occurred in the risk factor means of the population aged 30—59 in North‐Karelia: —28% for smoking (p<.001), —3% for serum cholesterol (p<.001) and —3% for systolic BP (p<.001). During the period 1974—79 the age‐standardized CHD mortality of men aged 30—64 was reduced by 22% in North Karelia, 12% in the reference area and 11% in the rest of Finland (p<.05 compared with NK). Other results of the evaluation are also presented to support the feasibility of the approach and to demonstrate that the programme has led to a number of positive changes in the health

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1985.tb08891.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

ABSTRACT.There is increasing evidence that nutritional factors are critical in the pathogenesis of essential hypertension typical for acculturated societies. These factors include sodium, potassium, calcium, alcohol, and type and level of fat in the diet. More research is needed, however, before the role of various nutrients in the prevention and treatment of hypertension will be ascertained.

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1985.tb08892.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

ABSTRACT.In clinical studies in dyslipidaemic patients gemfibrozil has produced falls in LDL and VLDL of 10—20% and 30—50%, respectively, but a rise in HDL of 15—25%. Gemfibrozil also produces increases in both Apo AI and AII, and in kininogen and prekallikrein. Side‐effects are not a major problem. The Helsinki Heart Study has compared the effects of gemfibrozil with those of placebo in a group of 4080 dyslipidaemic Finnish men aged 40—55. The results are not yet available but there is reason to believe that the probable level of coronary risk reduction will be at least as great as that reported by the Lipid Research Clinics Study Coronary Primary Prevention Trial (

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1985.tb08893.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

ABSTRACT.High blood pressure (HBP) in the range 90—104 DBP (»mild») has been shown to carry a sizeable excess risk of coronary death, at least in countries with atherogenic diets. Effective treatment to control HBP should result in lowering CHD risk.Early trials comparing drug treatment vs placebo in such hypertensives were generally too small or too limited to demonstrate this, although overall trends favored treatment. The U.S. Hypertension Detection and Follow‐up Program (HDFP), a population based trial with 10,940 patients, did demonstrate large reductions in CHD mortality and in nonfatal CHD, as measured by a variety of indices. A subsequent large trial, the Multiple Risk Factor Trial (MRFIT), found benefit in reducing CHD deaths for most hypertensives, but for the subgroup with resting ECG abnormalities, CHD deaths were greater in the Special Intervention than in the Usual Care group. The overall findings of the several studies indicate benefit of effective antihypertensive treatment in reducing CHD mortality and morbidity for most hypertensives with DBP 90—104. However, need to highlight a number of other aspects of anti‐hypertensive treatment is indicated: use of lowest drug level possible to achieve BP normalization; need to control all major CHD risk factors in hypertensives; need to utilize nutritional means to further both these aims; need to monitor and counteract unwanted metabolic effects of antihypertensive dru

ISSN:0001-6101    

DOI:10.1111/j.0954-6820.1985.tb08894.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY