Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(02)09678-2.pdf

Childhood obesity: public-health crisis, common sense cure

The apo E locus contributes to determining the variation in plasma cholesterol levels of healthy and diseased populations. It also influences the expression of hyperlipidemia and appears to modulate the susceptibility to atherosclerosis in a complex multifactorial interaction. There is evidence that the presence of apo E2 is protective, whereas that of apo E4 predisposes to coronary artery disease. The burden of proof, however, lies on future, well-designed clinical trials and prospective studies. The study of the biological significance of the apo E polymorphism in humans has emphasized the importance of gene-gene and gene-environment interactions in the pathogenesis of hyperlipidemia and atherosclerosis. The apo E polymorphism involves the coding region of the apo E gene and results in alterations of the gene product which, in turn, either directly or secondarily affect the metabolic fate of the lipoprotein particles. Rapid advances in knowledge over the last decade have provided a metabolic explanation for the observation of the opposite effects of the epsilon 4 and the epsilon 2 alleles on lipoprotein levels. Apo E2 has lower receptor binding affinity which results in delayed clearance of apo E2-bearing lipoprotein particles from plasma. Apo E4 is distributed differently from apo E3 between VLDL and HDL, is degraded more rapidly than apo E3, and may enhance the catabolism of E4-bearing particles, leading to other alterations in lipoprotein metabolism which result in elevated levels of LDL. In view of the significant opposite impacts of the epsilon 4 and the epsilon 2 alleles on plasma LDL cholesterol concentrations, it is evident that determination of the apo E phenotype will become a useful adjunct to the assessment of the cardiovascular risk profile of an individual. In addition, the relationship between the epsilon 2 allele and type III hyperlipoproteinemia provides a valuable model for the study of complex genetic interactions in the pathogenesis of hyperlipidemia. The further study of apo E and its interactions shows great promise for a deeper comprehension of the pathogenesis of atherosclerosis.

Apolipoprotein E polymorphism and atherosclerosis.

Background Motivational Interviewing is a well-known, scientifically tested method of counselling clients developed by Miller and Rollnick and viewed as a useful intervention strategy in the treatment of lifestyle problems and disease.

Aim To evaluate the effectiveness of motivational interviewing in different areas of disease and to identify factors shaping outcomes.

Design of study A systematic review and meta-analysis of randomised controlled trials using motivational interviewing as the intervention.

Method After selection criteria a systematic literature search in 16 databases produced 72 randomised controlled trials the first of which was published in 1991. A quality assessment was made with a validated scale. A meta-analysis was performed as a generic inverse variance meta-analysis.

Results Meta-analysis showed a significant effect (95% confidence interval) for motivational interviewing for combined effect estimates for body mass index, total blood cholesterol, systolic blood pressure, blood alcohol concentration and standard ethanol content, while combined effect estimates for cigarettes per day and for HbA1c were not significant. Motivational interviewing had a significant and clinically relevant effect in approximately three out of four studies, with an equal effect on physiological (72%) and psychological (75%) diseases. Psychologists and physicians obtained an effect in approximately 80% of the studies, while other healthcare providers obtained an effect in 46% of the studies. When using motivational interviewing in brief encounters of 15 minutes, 64% of the studies showed an effect. More than one encounter with the patient ensures the effectiveness of motivational interviewing.

Conclusion Motivational interviewing in a scientific setting outperforms traditional advice giving in the treatment of a broad range of behavioural problems and diseases. Large-scale studies are now needed to prove that motivational interviewing can be implemented into daily clinical work in primary and secondary health care.

Motivational interviewing: a systematic review and meta-analysis

The PPARs: from orphan receptors to drug discovery.

Conjugated linoleic acid is a collective term used to designate a mixture of positional and geometric isomers of linoleic acid in which the double bonds are conjugated. Unlike linoleic acid, there is a paucity of information regarding the effect of dietary conjugated linoleic acid on plasma lipoproteins and aortic atherosclerosis. Therefore, fifty hamsters were divided into five groups of ten and fed 0 (Control), 0.06 (LOW), 0.11 (MEDIUM), and 1.1 (HIGH) en% conjugated linoleic acid or 1.1 en% linoleic acid. Blood samples were taken at 4, 8 and 11 weeks for plasma lipid analyses and for plasma tocopherol assay at sacrifice. Animals fed the conjugated linoleic acid-containing diets collectively had significantly reduced levels of plasma total cholesterol, non-high density lipoprotein cholesterol, (combined very low and low density lipoprotein) and triglycerides with no effect on high density lipoprotein cholesterol, as compared to CONTROLs. Linoleic acid-fed animals relative to CONTROLs also had reduced plasma total cholesterol, non-high density lipoprotein cholesterol and triglycerides, but only the latter was statistically significant. Compared to the CONTROL group, plasma tocopherol/total cholesterol ratios determined from plasma pools for the LOW, MEDIUM and HIGH conjugated linoleic acid and linoleic acid groups were increased by 48%, 48%, 86% and 29%, respectively, suggesting a tocopherol-sparing effect, at least for the conjugated linoleic acid treatment. Morphometric analysis of aortas revealed less early atherosclerosis in the conjugated linoleic acid and linoleic acid-fed hamsters compared to the CONTROL group.

Dietary conjugated linoleic acid reduces plasma lipoproteins and early aortic atherosclerosis in hypercholesterolemic hamsters.

Dietary fat intake and the risk of coronary heart disease in women

Our laboratory has reported that the hypolipidemic effect of rice bran oil (RBO) is not entirely explained by its fatty acid composition. Because RBO has a greater content of the unsaponifiables, which also lower cholesterol compared to most vegetable oils, we wanted to know whether oryzanol or ferulic acid, two major unsaponifiables in RBO, has a greater cholesterol-lowering activity. Forty-eight F 1 B Golden Syrian hamsters ( Mesocricetus auratus ) (BioBreeders, Watertown, MA) were group housed (three per cage) in cages with bedding in an air-conditioned facility maintained on a 12-h light/dark cycle. The hamsters were fed a chow-based hypercholesterolemic diet (HCD) containing 10% coconut oil and 0.1% cholesterol for 2 weeks, at which time they were bled after an overnight fast (16 h) and segregated into 4 groups of 12 with similar plasma cholesterol concentrations. Group 1 (control) continued on the HCD, group 2 was fed the HCD containing 10% RBO in place of coconut oil, group 3 was fed the HCD plus 0.5% ferulic acid and group 4 was fed the HCD plus 0.5% oryzanol for an additional 10 weeks. After 10 weeks on the diets, plasma total cholesterol (TC) and non-high-density lipoprotein cholesterol (HDL-C) (very low- and low-density lipoprotein) concentrations were significantly lower in the RBO (−64% and −70%, respectively), the ferulic acid (−22% and −24%, respectively) and the oryzanol (−70% and −77%, respectively) diets compared to control. Plasma TC and non-HDL-C concentrations were also significantly lower in the RBO (−53% and −61%, respectively) and oryzanol (−61% and −70%, respectively) diets compared to the ferulic acid. Compared to control and ferulic acid, plasma HDL-C concentrations were significantly higher in the RBO (10% and 20%, respectively) and oryzanol (13% and 24%, respectively) diets. The ferulic acid diet had significantly lower plasma HDL-C concentrations compared to the control (−9%). The RBO and oryzanol diets were significantly lower for plasma triglyceride concentrations compared to the control (−53% and −65%, respectively) and ferulic acid (−47% and −60%, respectively) diets. Hamsters fed the control and ferulic acid diets had significantly higher plasma vitamin E concentrations compared to the RBO (201% and 161%, respectively) and oryzanol (548% and 462%, respectively) diets; the ferulic acid and oryzanol diets had significantly lower plasma lipid hydroperoxide levels than the control (−57% and −46%, respectively) diet. The oryzanol-fed hamsters excreted significantly more coprostenol and cholesterol in their feces than the ferulic acid (127% and 120%, respectively) diet. The control diet had significantly greater aortic TC and FC accumulation compared to the RBO (115% and 89%, respectively), ferulic acid (48% and 58%, respectively) and the oryzanol (74% and 70%, respectively) diets. However, only the RBO and oryzanol diets had significantly lower aortic cholesterol ester accumulation compared to the control (−73% and −46%, respectively) diet. The present study suggests that at equal dietary levels, oryzanol has a greater effect on lowering plasma non-HDL-C levels and raising plasma HDL-C than ferulic acid, possibly through a greater extent to increase fecal excretion of cholesterol and its metabolites. However, ferulic acid may have a greater antioxidant capacity via its ability to maintain serum vitamin E levels compared to RBO and oryzanol. Thus, both oryzanol and ferulic acid may exert similar antiatherogenic properties, but through different mechanisms.

Rice bran oil and oryzanol reduce plasma lipid and lipoprotein cholesterol concentrations and aortic cholesterol ester accumulation to a greater extent than ferulic acid in hypercholesterolemic hamsters.

Background A variety of studies have noted seasonal variation in blood lipid levels. Although the mechanism for this phenomenon is not clear, such variation could result in larger numbers of people being diagnosed as having hypercholesterolemia during the winter. Methods We conducted a longitudinal study of seasonal variation in lipid levels in 517 healthy volunteers from a health maintenance organization serving central Massachusetts. Data collected during a 12-month period for each individual included baseline demographics and quarterly anthropometric, blood lipid, dietary, physical activity, light exposure, and behavioral information. Data were analyzed using sinusoidal regression modeling techniques. Results The average total cholesterol level was 222 mg/dL (5.75 mmol/L) in men and 213 mg/dL (5.52 mmol/L) in women. Amplitude of seasonal variation was 3.9 mg/dL (0.10 mmol/L) in men, with a peak in December, and 5.4 mg/dL (0.14 mmol/L) in women, with a peak in January. Seasonal amplitude was greater in hypercholesterolemic participants. Seasonal changes in plasma volume explained a substantial proportion of the observed variation. Overall, 22% more participants had total cholesterol levels of 240 mg/dL or greater (≥6.22 mmol/L) in the winter than in the summer. Conclusions This study confirms seasonal variation in blood lipid levels and suggests greater amplitude in seasonal variability in women and hypercholesterolemic individuals, with changes in plasma volume accounting for much of the variation. A relative plasma hypervolemia during the summer seems to be linked to increases in temperature and/or physical activity. These findings have implications for lipid screening guidelines. Further research is needed to better understand the effects of a relative winter hemoconcentration.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/216973/ioi30014.pdf

Seasonal variation in serum cholesterol levels: treatment implications and possible mechanisms.

Oryzanol is a class of nonsaponifiable lipids of rice bran oil (RBO). More specifically, oryzanol is a group of ferulic acid esters of triterpene alcohol and plant sterols. In ex- periment 1, the mechanisms of the cholesterol-lowering action of oryzanol were investigated in 32 hamsters made hypercho- lesterolemic by feeding chow-based diets containing 5% co- conut oil and 0.1% cholesterol with or without 1% oryzanol for 7 wk. Relative to the control animals, oryzanol treatment re- sulted in a significant reduction in plasma total cholesterol (TC) (28%, P < 0.01) and the sum of IDL-C, LDL-C, and VLDL-C (NON-HDL-C) (34%, P < 0.01). In addition, the oryzanol- treated animals also exhibited a 25% reduction in percent cho- lesterol absorption vs. control animals. Endogenous cholesterol synthesis, as measured by the liver and intestinal HMG-CoA re- ductase activities, showed no difference between the two groups. To determine whether a lower dose of oryzanol was also efficacious and to measure aortic fatty streaks, 19 hamsters in experiment 2 were divided into two groups and fed for 10 wk chow-based diets containing 0.05% cholesterol and 10% co- conut oil (w/w) (control) and the control diet plus 0.5% oryzanol (oryzanol). Relative to the control, oryzanol- treated hamsters had reduced plasma TC (44%, P < 0.001), NON-HDL-C (57%, P < 0.01), and triglyceride (TG) (46%, P < 0.05) concentrations. Despite a 12% decrease in high density lipoprotein cholesterol (HDL-C) (P < 0.01), the oryzanol-treated animals maintained a more optimum NON-HDL-C/HDL-C pro- file (1.1 ± 0.4) than the control (2.5 ± 1.4; P < 0.0075). Aortic fatty streak formation, so defined by the degree of accumulation of Oil Red O-stained macrophage-derived foam cells, was re- duced 67% (P < 0.01) in the oryzanol-treated animals. From these studies, it is concluded that a constituent of the non- saponifiable lipids of RBO, oryzanol, is at least partially respon- sible for the cholesterol-lowering action of RBO. In addition, the cholesterol-lowering action of oryzanol was associated with significant reductions in aortic fatty streak formation. Lipids 32, 303-309 (1997). The cholesterol-lowering effect of rice bran oil (RBO) has re- cently been reported by several investigators (1-7). A num- ber of studies have suggested that the nonsaponifiables in the RBO may play a very important role in the cholesterol-low- ering effect of RBO (1-3,5-8). When the nonsaponifiable lipids extracted from RBO were fed to rats in an amount equivalent to that in the RBO (2), similar cholesterol-lower- ing effects were observed. When oryzanol, a constituent of the nonsaponifiable lipids in RBO, was added to a diet con- taining purified RBO (8), it further decreased the serum total cholesterol (TC) level in rats compared to purified alone, sug- gesting that the hypocholesterolemic activity of RBO is at- tributable to oryzanol and to some other components in the nonsaponifiable matter. A study in nonhuman primates demonstrated that serum cholesterol levels decreased as the level of RBO in the diet increased, and this reduction in serum cholesterol level was not entirely explained by the fatty acid composition of the dietary lipids, suggesting a component of RBO other than its fatty acid content was responsible for its hypocholesterolemic effect (5). RBO, unlike most vegetable oils, contains a relatively high proportion of nonfatty acid components (the nonsaponifiable lipids). Refined RBO may contain 1.5-2.6% of nonsaponifi- able lipids, and crude RBO may contain up to 5% of non- saponifiable lipids (9). In contrast, most common refined veg- etable oils contain only 0.3-0.9% of nonsaponifiable lipids (10). The nonsaponifiables of RBO contain sterols (43%), triterpene alcohols (28%), 4-methyl sterols (10%), and less polar components (19%) (11). In the crude oil, about 20% of the nonsaponifiables of RBO are in the form of ferulic acid es- ters, which are a mixture of esters of ferulic acid (4-hydroxy-

Robert J. Nicolosi

Papers

Dietary conjugated linoleic acid reduces plasma lipoproteins and early aortic atherosclerosis in hypercholesterolemic hamsters.

Dietary fat intake and the risk of coronary heart disease in women

Rice bran oil and oryzanol reduce plasma lipid and lipoprotein cholesterol concentrations and aortic cholesterol ester accumulation to a greater extent than ferulic acid in hypercholesterolemic hamsters.

Seasonal variation in serum cholesterol levels: treatment implications and possible mechanisms.

Oryzanol decreases cholesterol absorption and aortic fatty streaks in hamsters