Acta cardiologica. Supplementum最新文献

Hypercholesterolemia is the result of an imbalance between two basic cholesterol homeostatic mechanisms. One is related to intercellular and the other to extracellular cholesterol homeostasis. The human organism gives always absolute priority to the intracellular homeostasis. The naturally occurring balance between both systems can be disturbed: 1) By genetic factors, one of them located on chromosome 19 and governing the number of LDL-receptors on the cell membrane (liver, arterial wall, adrenals, fibroblasts, etc.). Total genetic absence of malfunction of LDL-receptors is seen in homozygote familial hypercholesterolemia, with ischemic heart disease between ages 2 and 25. Less harmful situations arise from heterozygote familial hypercholesterolemia and from other genetic defects (among them those located at the gene of apo E on chromosome 19 and of apo AI on chromosome 11). 2) By nutritional factors decreasing or totally blocking the number of active LDL-receptors. This has been demonstrated in the rabbit, hamster, dog, baboon and humans. Overloading the organism with dietary cholesterol and saturated fat is one extremely common factor in western societies. Certain fats (omega-6 and omega-3 polyunsaturated, and oleic acid) may be beneficial. Other factors are generally of lesser importance. 3) By a combination in different proportions of 1) and 2). Severe dietary overloading with cholesterol and saturated fat in the rabbit results in early atherosclerotic lesions resembling almost totally those produced by the genetic absence of LDL-receptors (Watanabe rabbit). In humans from western countries the serum LDL-level is more related to environmental factors, whereas the HDL-level is more related to genetic factors. Age is an important factor integrating the effects of genetics and environmental deviations. The influence of sex is also important. Serum cholesterol in western countries is increasing markedly with age, but this growth of serum cholesterol with age is totally different between sexes. Serum cholesterol is on the average only equal in both sexes at ages 3, 10, 25 and 50. It is higher in males between ages 25 and 50 and higher in females between ages 3 to 10, 10 to 25 and above 50 years. In general females are less susceptible to higher cholesterolemia than males except at very old ages (above 80-85 years). Together with other observations of sex linked differences this points to the influence of a sex linked chromosome, most probably the X-chromosome. The susceptibility of females in a given population decreases with decreasing levels of infectious diseases, the opposite is true for males.(ABSTRACT TRUNCATED AT 400 WORDS)

In adults of Western societies the positive relationship between blood pressure and body weight has often been demonstrated, both cross-sectionally and longitudinally. This correlation is even stronger in children and early adulthood. In most studies in children, the association between age and blood pressure disappears after controlling for weight. Association must be differentiated from causation. It has however been shown in several intervention studies that treatment of obesity by weight loss decreases blood pressure substantially both in hypertensive and normotensive subjects. Although combining results from several intervention trials is difficult this is the only practical way to get an overall estimate of the hypotensive response to be expected from weight reduction. In the studies presently reviewed, a decrease in weight by 1 kg resulted in a reduction in blood pressure by 3.4/1.3 mm Hg in hypertensive patients and in normotensive subjects the corresponding reductions averaged 1.4 mm Hg and 0.6 mm Hg for systolic and diastolic pressure, respectively.

The clinical consequences of atherosclerosis differ substantially by time, by place and by person. The between population variation can largely be explained by differences in the classical risk factors. Within a population it becomes more difficult to predict atherosclerosis risk solely on the basis of blood pressure, serum cholesterol and smoking. On the individual level risk prediction becomes even more hazardous. Among the long list of less well documented or more controversial risk indicators physical activity and psychosocial variables are of prime importance. In epidemiological research the association between physical inactivity and atherosclerosis is modest compared to the classical risk factors. Physical inactivity does not necessarily precede the atherosclerosis process. However a majority of prospective epidemiological surveys performed has found physical inactivity to be a risk factor. The ability of physical inactivity or physical fitness to predict atherosclerosis events has been reproducible when applied crossculturally but the consistency with clinical pathological studies is poor. Regular exercise most likely helps to decrease other risk factors. Therefore the inclusion of regular exercise in one's life style makes good sense for many reasons. Concerning the psychosocial variables there is overwhelming evidence to accept that they play a role in the development of atherosclerosis as well as in the occurrence and recurrence of its clinical consequences. However major problems exist to quantify in a standardized way these psychosocial factors across or within populations and in a given individual. Various hypotheses relating atherosclerosis to stress, social support, personality pattern, psychological traits or life events have been tested in epidemiological, experimental and clinical studies. In a majority of these, significant associations were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Although the historical debate between Pickering and Platt has never been settled, most scientists have felt that hypertension should not be defined as a disease state, qualitatively different from normotension with a sharp dividing line in between them. Still, in clinical practice, there is a need for well defined limits which one should initiate therapeutic actions that should not be taken below such a limit. In fact, in trying to escape to setting up a sharp limit, clinicians have tried to find a level above which benefits of decreasing blood pressure could outweigh the potential harm caused by the therapeutic interventions. However even in that way, finding such a limit is a most difficult enterprise; it has necessitated many large trials which certainly have not resolved yet all our questions. First, one should realize that blood pressure by itself is not a constant value; following blood pressure over a certain period shows its large variations from "normotensive" ranges to clearly "hypertensive" levels in the same individual. As soon as one is spoiled by this type of information, it becomes hardly conceivable to define someone's blood pressure without ambulatory recordings of some kind. This is also valid for finding the above mentioned limit of therapeutic benefit; an European International multicenter studied is being set up in this respect (HOME BP). Moreover, whatever the definition of blood pressure, its relationship to mortality, morbidity and organ damage, also, is not a constant one.(ABSTRACT TRUNCATED AT 250 WORDS)