CEPHEUS SA: a South African survey on the undertreatment of hypercholesterolaemia.

AIM: The aim of the CEntralised Pan-South African survey on tHE Under-treatment of hypercholeSterolaemia (CEPHEUS SA) was to evaluate the current use and efficacy of lipidlowering drugs (LLDs), and to identify possible patient and physician characteristics associated with failure, if any, to achieve low-density lipoprotein cholesterol (LDL-C) targets. METHODS: The survey was conducted in 69 study centres in South Africa and recruited consecutive consenting patients who had been prescribed LLDs for at least three months. One visit was scheduled for data collection, including fasting plasma lipid and glucose levels. Physicians and patients completed questionnaires regarding their knowledge, awareness and perceptions of hypercholesterolaemia and the treatment thereof. RESULTS: Of the 3 001 patients recruited, 2 996 were included in the final analyses. The mean age was 59.4 years, and 47.5% were female. Only 60.5 and 52.3% of patients on LLDs for at least three months achieved the LDL-C target recommended by the NCEP ATP III/2004 updated NCEP ATP III and the Fourth JETF/South African guidelines, respectively. Being male, older than 40 years, falling into the lower-risk categories, compliance with the medication regimen, and patient knowledge that the LDL-C goal had been reached, were associated with the highest probability of attaining LDL-C goals. CONCLUSION: The results of this survey highlight the sub-optimal lipid control achieved in many South African patients taking lipid-lowering therapy.

Effects of dietary corn and olive oil versus coconut fat on biliary cholesterol secretion in rats.

We have studied the effects of dietary corn and olive oil versus coconut fat on bile formation and fluidity of hepatic plasma membranes in rats. After 4 weeks of feeding the purified diets containing 9% (w/w) of the test fats, there was no difference in plasma cholesterol concentration between the dietary groups. The amount of free and esterified cholesterol in the liver was significantly higher in rats fed either corn oil or olive oil as compared with coconut fat. In the rats fed olive oil, but not in those fed corn oil this was associated with lower rates of biliary phospholipid excretion. Bile flow was not differently influenced by the three dietary fats. Hepatic plasma membranes of the rats fed corn or olive oil contained more cholesterol and less phospholipids than those on coconut fat, which was, however, not accompanied by changes in fluidity of the membranes. These results indicate that in rats the type of dietary fat can induce considerable changes in hepatic cholesterol metabolism without affecting plasma cholesterol concentrations, and without consistent effects on biliary cholesterol secretion.

Effects of dietary cholesterol on bile formation and hepatic processing of chylomicron remnant cholesterol in the rat.

We have studied the coupling between hepatic uptake of chylomicron remnant cholesteryl ester and biliary excretion of cholesterol and bile acids in rats, after feeding them a cholesterol-free (control) or a high-cholesterol diet (1% wt/wt) for 2 wk. We equipped rats with permanent catheters in the bile duct, duodenum and heart to allow experiments in unanesthetized, unrestrained animals. Cholesterol feeding induced a 20% increase in plasma cholesterol concentration, a threefold increase in hepatic bile acid synthesis and a 27% increase in bile acid pool size, whereas biliary excretion of cholesterol was decreased by 50%. The enlarged bile acid pool contained relatively less cholic acid and more chenodeoxycholic acid and muricholic acids. [3H]cholesteryl ester-labeled chylomicron remnants (150 micrograms protein per rat) were injected intracardially, and blood and bile were collected for a period of 22 hr. Plasma disappearance of remnants was significantly delayed by cholesterol feeding, probably caused by competition with diet-induced beta-very low density lipoproteins for hepatic uptake. In control rats biliary excretion of chylomicron remnant-derived radioactivity (50% in free cholesterol and 50% in bile acids) showed an initial peak 1 hr after injection (2.4% dose per hour). A second peak (90% in bile acids), amounting to 1.5% of the dose per hour, appeared 11 hr after injection. Total 22-hr excretion of 3H was 22% of the dose. In cholesterol-fed rats chylomicron remnant-derived radioactivity appeared more rapidly in bile, with a peak 1 hr after injection, amounting to 3.5% of the dose per hour. In this case radioactivity was mainly present as bile acid. Total excretion in 22 hr was 27% of the dose. We conclude that chylomicron remnant uptake by the liver is efficiently coupled to bile acid synthesis and biliary excretion, thus providing an efficient pathway for removal of intestine-derived cholesterol. After cholesterol feeding, chylomicron remnant cholesteryl ester is more efficiently converted to bile acids, a mechanism which may contribute to the resistance of rats to diet-induced elevation of plasma cholesterol. In contrast, biliary excretion in the form of free cholesterol, the second main excretory pathway, is significantly decreased by a high-cholesterol diet.

Dietary fish oil-induced changes in intrahepatic cholesterol transport and bile acid synthesis in rats.

Hepatic cholesterol metabolism was studied in rats fed purified diets supplemented (9% wt/wt) with either fish oil (FO) (n-3 fatty acids) or corn oil (CO) (n-6 fatty acids) for 4 wk. Rats were equipped with permanent catheters in heart, bile duct, and duodenum to allow studies under normal feeding conditions. [3H]-cholesteryl oleate-labeled small unilamellar liposomes, which are rapidly endocytosed by hepatocytes, were intravenously injected to label intrahepatic cholesterol pools, and plasma and bile were collected. FO as compared to CO induced a lowering of plasma cholesterol levels by 38% and of triglyceride levels by 69%. This reduction in plasma lipids in FO rats was accompanied by: (a) an increased bile acid pool size (28%); (b) a fourfold increase in the ratio cholic acid/chenodeoxycholic acid in bile; (c) increased biliary excretion of cholesterol (51%); (d) accelerated excretion of endocytosed free cholesterol into bile; (e) accelerated incorporation of endocytosed cholesterol in bile acids; (f) a significant increase in the bile acid-independent fraction of bile flow; and (g) a threefold increase in hepatic alkaline phosphatase activity. The results show that FO induces changes in transport and metabolic pathways of cholesterol in the rat liver, which result in a more rapid disposition of plasma-derived cholesterol into the bile.

The value of the routine chest roentgenogram in the cardiological evaluation of infants and children. A prospective study.

The value of the routine chest roentgenogram was studied in 284 patients, newly admitted to our paediatric outpatient department. Emergency patients were excluded from the study. In 141 cases the initial diagnosis after history, physical examination and ECG was "no heart disease", while in 143 cases it was "heart disease". After a follow up of up to 4 years, 170 children appeared to have "no heart disease" and 114 definite heart disease. In 7.7% of cases the chest roentgenogram made at the first visit to the outpatient department led to a change in policy, whereas in only 3.8% was the chest roentgenogram in someway helpful in establishing the correct diagnosis. Amongst those children with initial diagnosis of innocent murmur, the chest roentgenogram led to a diagnosis of "heart disease" in only 2.8% of cases. It is concluded that for the differentiation "heart disease" or "no heart disease", a chest X-ray film is not indicated. In children with "heart disease" the chest X-ray film is also of little value, and is mostly to be used only for documentation.

Short- and long-term effects of biliary drainage on hepatic cholesterol metabolism in the rat.

The present study concerns short- and long-term effects of interruption of the enterohepatic circulation (EHC) on hepatic cholesterol metabolism and biliary secretion in rats. For this purpose, we employed a technique that allows reversible interruption of the EHC, during normal feeding conditions, and excludes effects of anaesthesia and surgical trauma. [3H]Cholesteryl oleate-labelled human low-density lipoprotein (LDL) was injected intravenously in rats with (1) chronically (8 days) interrupted EHC, (2) interrupted EHC at the time of LDL injection and (3) intact EHC. During the first 3 h after interruption of the EHC, bile flow decreased to 50% and biliary bile acid, phospholipid and cholesterol secretion to 5%, 11% and 19% of their initial values respectively. After 8 days of bile diversion, biliary cholesterol output and bile flow were at that same level, but bile acid output was increased 2-3-fold and phospholipid output was about 2 times lower. The total amount of cholesterol in the liver decreased after interruption of the EHC, which was mainly due to a decrease in the amount of cholesteryl ester. Plasma disappearance of LDL was not affected by interruption of the EHC. Biliary secretion of LDL-derived radioactivity occurred 2-4 times faster in chronically interrupted rats as compared with the excretion immediately after interruption of the EHC. Radioactivity was mainly in the form of bile acids under both conditions. This study demonstrates the very rapid changes that occur in cholesterol metabolism and biliary lipid composition after interruption of the EHC. These changes must be taken into account in studies concerning hepatic metabolism of lipoprotein cholesterol and subsequent secretion into bile.

Dietary cholesterol and fats at a young age: do they influence cholesterol metabolism in adult life?

The effects of dietary cholesterol and fats on cholesterol metabolism later in life were studied in Mongolian gerbils. Three groups were given a basic diet with soybean oil, palm kernel oil amounting to 8.75% (w/w), or the basic diet only. In three other groups, cholesterol (0.05%) was added to the above diets. Measurements were done in animals of the third generation on the diets. On all diets, teh serum cholesterol of the sucklings was increased as compared to the young that were suckled by mothers on the basic diet only, while body cholesterol was highest in sucklings of mothers on the basic diet or palm-kernel-oil-enriched diets. When the diets were replaced by the basic diets at 6 months of age, serum cholesterol was still increased at 12 months of age in animals previously fed on the cholesterol-enriched diets. Tissue cholesterol did not differ. However, after a challenge with cholesterol at that age, the differences in serum cholesterol were not significantly different.

Effects of dietary cholesterol in the Mongolian gerbil and the rat: a comparative study.

To come to a better understanding of the diet-induced cholesterol-ester storage in the gerbil liver, the reactions of the gerbil to 0.2% of cholesterol in the diet during 4 weeks were compared with those of the rat consuming the same diet. The major reason for the increased hepatic cholesterol-ester storage in the cholesterol-fed gerbil is the low cholesterol turnover in this species. This contrasts with the rat. Although faecal acidic steroid excretion can be slightly increased during cholesterol feeding in the gerbil, this increase is not sufficient to compensate for the quantity of dietary cholesterol when administered at the 0.2% level.

Long-term and short-term effects of dietary cholesterol and fats in the Mongolian gerbil.

In long-term and short-term experiments with Mongolian gerbils the effects of various dietary fats and different amounts of cholesterol on progeniture and liver pathology were studied. In contrast to palm kernel oil, with 8.75% (w/w) of sunflower seed oil we observed fewer litters and a decreased survival of the sucklings. On 0.2% of cholesterol we observed severe hypercholesterolemia and storage of cholesterol ester in the liver, ultimately leading to cirrhosis. On 0.05% for 6 months the gerbils stayed in good health. Progeniture was unaffected on this level of intake.