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Of the highest priority for preventive medicine in Europe is to achieve a major reduction in coronary heart disease (CHD) and other manifestations of atherosclerosis. To this end a policy based upon reduction of risk factors has been formulated by experts from 19 countries: it employs complementary strategies directed to CHD-prone populations as a whole and to individuals at particular risk. The population strategy includes improved nutrition, avoidance of smoking, blood pressure reduction and promotion of suitable exercise. These should be based upon health education for all age groups and actions by governmental and supranational agencies (including implementation of food labelling, smoking control measures and wide provision of exercise facilities). Only measures directed to the population can reach the large proportion of people at mild to moderate risk of CHD. To provide care for individuals at particular risk of CHD, case finding requires that risk factor assessment, including measurement of plasma cholesterol and blood pressure, be included in full medical examinations. The relative merits of other modes of case finding, including selective screening and general screening, are discussed. Decisions concerning management of elevated lipid levels should be influenced by overall cardiovascular risk, by a family history of CHD and by age. Lipid lowering dietary and drug therapy should take these variables into account in addition to the extent and type of the hyperlipidaemia. Cholesterol levels exceeding about 5.2 mmol l-1 (200 mg dl-1) deserve consideration, and the goal of therapy should be to reduce levels towards this value. For most persons with levels of 5.2-6.5 mmol l-1 (200-250 mg dl-1) dietary advice and correction of other risk factors are appropriate, i.e. management comprises reinforcement of population strategy. Dietary recommendations for the control of hyperlipidaemia are reviewed, and indications for drug therapy are presented. Non-pharmacological methods for reducing mildly elevated blood pressure are discussed, and reduction of CHD risk in diabetes is reviewed. Implementation of these recommendations will be furthered by their endorsement by cardiologists and other physicians.
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PMID:Strategies for the prevention of coronary heart disease: a policy statement of the European Atherosclerosis Society. 381 42

Lipoproteins were isolated by sequential ultracentrifugation, and the concentrations and compositions were determined in nondiabetic (ND), borderline diabetic (BD), and diabetic (D) Macaca nigra males consuming a chow ration. The total concentrations and components of the VLDL and IDL increased significantly with metabolic deterioration (P less than 0.01). Concentrations and components of LDL increased in the BD and D monkeys, but changes were not statistically significant. The HDL2 and HDL3 particles were virtually unchanged among the three different metabolic groups. The VLDL was the major carrier of the triglycerides, especially in D monkeys. Cholesterol was present predominantly in the LDL. The LDL-cholesterol to HDL-cholesterol ratio increased in the BD and D monkeys, owing mainly to increases in the LDL-cholesterol content. Apoprotein antisera showed apoprotein B in the VLDL, IDL, and LDL, apoprotein E in the VLDL and IDL, and apoprotein A-I in the HDL2 and HDL3 fractions. Because Macaca nigra consume a nonatherogenic, low-cholesterol, low-fat ration, the changes in lipoproteins, particularly in VLDL and IDL, are attributable to metabolic alterations associated with diabetes.
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PMID:Lipoprotein patterns in nondiabetic, borderline diabetic, and diabetic Macaca nigra. 382 73

The major atherosclerosis risk factors hypertension, diabetes, hyperlipidemia and cigarette smoking are examined along with blood vessel anatomy, hemodynamics, histopathology and known experimental results. A common factor of blood vessel hypoxia, specifically endothelial and intimal hypoxia, is shown to exist. Arguments are presented suggesting endothelial hypoxia as the commonest initiating event for atherosclerosis. Cholesterol appears to be a secondary and opportunistic villain. Explanations are given for the lack of increased atherosclerosis risk in familial lipoprotein lipase deficiency (type I hyperlipoproteinemia) and for the increased incidence and severity of atherosclerosis in the human abdominal aorta in comparison with the thoracic aorta. It is suggested that effective prevention of atherosclerosis can be accomplished by lowering blood pressure and blood glucose, among others, even though these may be within acceptable normal limits. Suggestions are given for experiments to test the hypothesis of hypoxia being the major initiating factor in atherosclerosis.
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PMID:Mechanisms of atherogenesis: endothelial hypoxia proposed as the major initiator. 385 84

Cholesterol and bile acid metabolism was examined in nonobese, spontaneously diabetic (NOD) female mice before and after the development of diabetes. After the development of glucosuria, the plasma and liver cholesterol levels, gallbladder bile weight after 5-h fasting, biliary cholesterol, phospholipid and bile acid concentrations, the lithogenic index, the pool size of bile acids, and fecal sterol excretion markedly increased, but fecal bile acid excretion and fractional turnover rates for the cholic acid and chenodeoxycholic acid groups decreased. The distribution percentage of bile acids in the small intestine did not change, but it increased in the gallbladder and decreased in the large intestine. One striking finding was a change in the bile acid composition: increases were recorded in cholic and deoxycholic acids while decreases occurred in bile acids derived from chenodeoxycholic acid, such as beta-muricholic and ursodeoxycholic acids in the bile and alpha-muricholic, beta-muricholic, omega-muricholic, and hyodeoxycholic acids in the feces. Therefore, the cholic acid group/chenodeoxycholic acid group (CA/CDCA) ratio increased in the bile, feces, and small and large intestines after the development of diabetes. These changes were very similar to those observed in alloxan-treated mice, suggesting that the changes found in NOD mice are caused by insulin deficiency.
Diabetes 1985 Jan
PMID:Altered bile acid metabolism in nonobese, spontaneously diabetic (NOD) mice. 396 56

The contribution of dietary cholesterol to hypercholesterolemia in diabetic rats fed chow ad libitum was evaluated. Diabetes was induced with streptozotocin, and the intake, absorption, and subsequent tissue distribution of dietary cholesterol were measured. Absorption was measured as the difference between [3H]cholesterol intake and fecal 3H-labeled neutral sterol excretion, using both [14C]sitosterol (added to diet) and [14C]cholesterol (added to feces) as recovery markers. [3H]Cholesterol absorption was underestimated by 1-3% using [14C]sitosterol as a recovery standard, due to the 7-8% absorption of sitosterol. After 3 weeks of diabetes, rats were hyperphagic, thereby increasing dietary cholesterol intake 2-fold. [3H]Cholesterol absorption was significantly increased from 69% in controls to 78% in diabetics, whereas [14C]sitosterol absorption was unaffected. With increased dietary cholesterol intake and decreased whole body cholesterol synthesis (Diabetes. 1983. 32: 811-819), influx from diet equaled for exceeded influx from synthesis. The amounts of 3H-labeled neutral sterol recovered from the small intestine, periphery, and plasma were increased 3- to 4-fold in the diabetic rats. Furthermore, the degree of hypercholesterolemia in diabetic rats was directly related to the fraction of plasma cholesterol derived from the diet. We conclude that the 2.3-fold increase in absorbed dietary cholesterol resulting from hyperphagia and, to a lesser extent, from increased fractional absorption, contributes to the hypercholesterolemia of diabetic rats fed chow ad libitum.
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PMID:Evaluation of the contribution of dietary cholesterol to hypercholesterolemia in diabetic rats and of sitosterol as a recovery standard for cholesterol absorption. 403 27

The activities of beta-Hydroxy-beta-methylglutaryl CoA reductase (HMG CoA reductase), Acyl CoA: Cholesterol-O-acyltransferase (ACAT) and cholesterol 7 alpha-hydroxylase, the major enzymes involved in cholesterol metabolism, were determined in diabetic and non-diabetic rats after vagotomy and compared with those of sham-operated controls. Hepatic cholesterol levels and serum lipid profiles were also examined. In the non-diabetic animals vagotomy produced a significant increase in HMG CoA reductase (the rate limiting enzyme of cholesterol biosynthesis), and ACAT (the enzyme responsible for intracellular esterification) activities, while the activity of cholesterol 7 alpha-hydroxylase (which catalyses the rate determining step of bile acid biosynthesis) was significantly decreased. These rats had higher levels of free and esterified cholesterol in the liver and serum cholesterol levels were also increased in comparison with sham-operated animals. Vagotomized diabetic rats had similar HMG CoA reductase activity, but significantly reduced ACAT and reduced cholesterol 7 alpha-hydroxylase activity in comparison with sham-operated diabetic rats. There were significant alterations in hepatic and serum cholesterol fractions in both normal and diabetic rats after vagotomy. The results suggest that vagotomy leads to an increased rate of cholesterol synthesis and a decreased rate of cholesterol utilization, thus providing a possible mechanism for excessive cholesterol accumulation. These results are discussed in relation to alterations in cholesterol metabolism found in diabetic autonomic neuropathy.
Diabetes Res 1985 Nov
PMID:Cholesterol metabolism: regulatory effects of the vagus in the normal and diabetic animal. 407

The triglyceride, cholesterol, and phospholipid contents of heart papillary muscle were measured in groups of obviously healthy and diseased females and males on whom either routine or forensic necropsies were performed. In healthy men the triglyceride content was 1.77 +/- 1.30 mg/g of wet weight and in women 1.25 +/- 0.48 mg/g wet weight. The corresponding values for cholesterol were 1.07 +/- 0.24 mg/g and 1.21 +/- 0.22 mg/g and those for phospholipids 17.70 +/- 5.15 mg/g and 19.65 +/- 10.21 mg/g. The differences between the sexes were not significant. The hypertensive or cardiac hypertrophy group had about the same or slightly lower means for lipid content. In the cholelithiasis group, women had significantly high triglyceride values (3.38 +/- 2.36 mg/g). The cholesterol values were not significantly elevated in either men or women. In the diabetic group, triglycerides were significantly increased both in men (mean 8.12 +/- 0.54 mg/g) and in women (6.85 +/- 5.66 mg/g). The cholesterol mean values were also high in both sexes, but the rise was not significant because of the great variation. In the coronary atheroma group, both male and female hospital cases had high triglyceride contents (mean 4.48 +/- 4.25 mg/g and 3.65 +/- 3.94 mg/g) whereas the forensic cases had only slightly elevated or normal values. Cholesterol assays paralleled the triglyceride ones, but phospholipids showed an inverse trend. The results showed that the lipid content of papillary muscle was increased in diseases where disturbances of lipid metabolism are evident, as in diabetes and cholelithiasis. In coronary atheroma only those cases with advanced obstruction of the arteries were associated with abnormal values of papillary lipids. No increase of the lipid content with age alone was found, nor was there any correlation with obesity.
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PMID:Triglycerides, cholesterol, and phospholipids in normal heart papillary muscle and in patients suffering from diabetes, cholelithiasis, hypertension, and coronary atheroma. 426 65

The prevalence of diabetes, the interrelationship of blood glucose, serum insulin, and lipids, and their relationship to ischemic heart dise ase in a rural Jamaican community were investigated. The people were mo stly of West African descent. Occupations were primarily agricultural w ith much physical labor. Approximately 80% of total claories in their d iet were from carbohydrates. Of 696 25-64 year old persons, a response rate of 77.3% was achieved. The patients, after an overnight fast, drank a 7-oz bottle of Glucola which was the equivalent of a 100 gm glucose load. Electrocardiograms (EKGs), blood pressure readings, a chest X-ray, and skinfold tests for obesity were done. A family history was obtained. Blood and urine specimens were taken before the glucose was given. 1 hour after the glucose was given, blood and urine specimens were also taken. Those with blood glucose of 180 mg% or more were given a 3-hour glucose tolerance test. Of the 525 persons who had the 1-hour test, 23 were found to be glycosuric. Of these, 11 were not shown to be diabetic by the 3-hour glucose test. Of the 502 with negative urines, 34 were positive on blood tests. The rates increased with age, except in the oldest age groups (p less than .05 for males and p less than .001 for females). There was no relationship between the number of live births and the 1-hour blood glucose tests. There was neither increase in the diagnosis of diabetes nor increase in variance with number of children. The known diabetics were fatter and had higher triglycerides than others. Cholesterol was higher in all male diabetics but not in females. Only 2 persons experiencing effort pain had EKG changes. Data from this study indicate that no statistically significant association exists between levels of glycemia and blood pressure or prevalence of cardiovascular disease. The physical fitness acquired from walking and working in a hilly area may be a factor.
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PMID:The prevalence of diabetes in a rural population of Jamaican adults. 466 90

Cholesterol of high density lipoproteins (Ch HDLP) was assayed in primary hyperlipoproteinemia (HLP) in patients with coronary heart disease (CHD) and in secondary HLP that developed in the presence of chronic glomerulonephritis with the nephrotic syndrome, hypothyrosis, diabetes mellitus, and lipoprotein metabolism disturbances innduced by longterm oral contraceptive adminnistration. In patients with primary HLP and the nephrotic syndrome, the Ch HDLP level was found to be reduced, this reduction being more manifest in hypertriglyceridemia; the reverse correlation between Ch HDLP and triglyceride content in the blood was observed. In patients with diabetes mellitus and hypothyrosis, Ch HDLP concentration was found to grow parallel with hypertriglyceridemia degree. Simultaneously, hypertriglyceridemia and hyper-Ch-HDLP were found in the blood under the effect of OCs. High levels of Ch HDLP during OC intake were found to depend on accumulation of cholesterol ethers in them, whereas in diabetes mellitus and hyperalphalipoproteinemia, detected in male subjects during prophylactic examinations, high levels of Ch HDLP were found to be related to the accumulation of free cholesterol. Study of the ratio of free and bound cholesterol in HDLP allows a differentiation between physiologic and pathologic hyper-Ch-HDLP; in physiologic hyperalphaproteinemia, cholesterol ethers were found to accumulate in HDLP, in pathologic ones, free cholesterol. At the same time, study of the cholesterol/phospholipid ratio gives an idea of the ability of HDLP to take hold of cholesterol from the peripheral cell membranes. Except for estrogen-induced lipoprotein metabolism disturbances, hyperalphalipoproteinemia in HLP is a sign or progressing lipoprotein metabolism disturbances. (author's modified)
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PMID:[High density lipoprotein cholesterol in secondary hyperlipoproteinemias]. 620 50

We studied the aortic histology of 28 Macaca nigra males and females, from 6 to more than 20 years old, normal and manifesting various degrees of spontaneous diabetes. Correlations of several metabolic and hormonal indicators of diabetes severity with gross and microscopic findings in the aortas demonstrated direct associations with the severity of atherosclerosis. Mild to relatively severe aortic lesions were present. These monkeys showed many changes similar to those observed in medium and large arteries of diabetic humans. Intimal proliferation, prominent extracellular fibers as part of the intimal thickening, and lipid deposition--mostly in extracellular locations--were particularly evident. Significant relationships were observed when glucose clearance, insulin secretion, and fasting glucose levels were correlated with all aortic microscopic findings. Cholesterol concentrations had no correlation with the histological state of the aortas, and triglyceride levels correlated only with aortic lipid content and intimal thickness. Aortic pathologic changes increased with age; diabetics had significantly greater changes than nondiabetics. Macaca nigra can be useful in the study of how diabetes affects the development of atherosclerosis without the influence of an atherogenic diet.
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PMID:Correlations of aortic histology with gross aortic atherosclerosis and metabolic measurements in diabetic and nondiabetic Macaca nigra. 638 May 10


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