Causal relationship between removal efficiency of low density lipoproteins and their composition following cholesterol feeding and cholestyramine therapy

The origin of cholesterol-rich low density lipoprotein (LDL) in diet-induced hypercholesterolemia was investigated by simultaneous examination of LDL composition and ¹²⁵I-LDL plasma clearance in control and in cholesterol-fed rabbits treated or not with cholestyramine. The results show a straight relationship between LDL plasma clearance and the cholesterol ester/triglyceride ratio among the three experimental groups. Cholesterol-fed rabbits present a marked increase in the cholesterol ester/triglyceride ratio of LDL associated with an impairment in the catabolism of LDL, isolated from normal rabbits, as indicated by their fractional catabolic rate (FCR). Both parameters, cholesterol ester content and FCR of the LDL remain intermediate in cholesterol-fed rabbits treated with cholestyramine. The intravascular transformation of labeled LDL from normal rabbits was evaluated by the study of changes in their density profile. The increase in modal density of LDL after 7 hours of exposure in the blood stream is accentuated in cholesterol fed-rabbits. Therefore the intravascular transformation of LDL depends on the removal efficiency of the recipient animals. Taken together the findings support the hypothesis that abnormal LDL mainly results from supplementary intravascular degradation as a consequence of increased lifetime. Additional data concerning the composition of the very low density lipoproteins (VLDL) and intermediate density lipoproteins (LDL) are given. Cholestyramine has clear preventive effects on the alteration of these lipoproteins following cholesterol feeding suggesting that the mechanism proposed for LDL alteration is involved in the appearance of the other apo-B- containing lipoproteins.     

The Role of Dietary Supplementation with Plant Sterols and Stanols in the Prevention of Cardiovascular Disease

Several studies have shown that increased levels of low-density lipoprotein (LDL) cholesterol predict cardiovascular events. The Adult Treatment Panel II (ATP II) introduced the principle of therapeutic lifestyle changes, including plant sterols/stanols for the management of LDL cholesterol. Plant sterols and stanols in fat matrices effectively lower LDL cholesterol levels in hypercholesterolemic, diabetic, and healthy human volunteers. Recent studies also show that sterols (2 g/d) lower LDL cholesterol even when incorporated in nonfat matrices. In addition, they may reduce biomarkers of oxidative stress and inflammation. Plant sterols and stanols exert their hypocholes-terolemic effects possibly by interfering with the uptake of both dietary and biliary cholesterol from the intestinal tract. Present evidence is accumulating to promote their use for lowering LDL cholesterol levels, as a first line of therapy (as well as adjunctive therapy) in patients on statin therapy.     

Phytosterols,Phytostanols, and Lipoprotein Metabolism

The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL) cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%–10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a) or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL) cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein particles will be diminished.     

Incorporation of Lean Red Meat into a National Cholesterol Education Program Step I Diet: A Long-Term,Randomized Clinical Trial in Free-Living Persons with Hypercholesterolemia

Objective: Clinicians often recommend that intake of all meat, particularly red meat, be reduced in conjunction with a low-fat, low-cholesterol diet to reduce low-density lipoprotein (LDL) cholesterol. This study was designed to determine the long-term effects of lean red meat (beef, veal and pork) compared to lean white meat (poultry and fish) consumption on lipoprotein concentrations in free-living hypercholesterolemic subjects consuming a National Cholesterol Education Program (NCEP) Step I diet.

Methods: A randomized, crossover design was utilized. Hypercholesterolemic men and women (LDL cholesterol between 3.37 and 4.92 mmol/L) (triglycerides <3.96 mmol/L) (n = 145) were counseled to consume ≥80% of their 170 g/d meat intake as either lean red meat or lean white meat for two 36-week phases, separated by a four-week washout period of free meat selection. Subjects were instructed to follow an NCEP Step I diet throughout the study.

Results: There were no significant differences in lipid concentrations between the lean red meat and lean white meat phases. LDL cholesterol was 4.02 ± 0.04 (SEM) and 4.01 ± 0.04 mmol/L in the white and red phases, respectively; this represented a decrease of ～2% from baseline concentrations (p < 0.01). Total cholesterol also declined by 1% from baseline (p < 0.05), and high-density lipoprotein (HDL) cholesterol rose over the study period by ～2% to ～3% from baseline to reach concentrations of 1.37 ± 0.03 mmol/L and 1.38 ± 0.03 mmol/L in the white and red phases, respectively (p < 0.001). Triglycerides were not altered by treatment.

Conclusions: Consumption of lean red meat or lean white meat, as part of an NCEP Step I diet, is similarly effective for reducing LDL cholesterol and elevating HDL cholesterol concentrations in free-living persons with hypercholesterolemia.     

Soy constituents: modes of action in low-density lipoprotein management

Reviewed here are the modes of action of soy components used as ingredients in foods, which can lower plasma levels of low-density lipoprotein (LDL) and cholesterol, which are markers for the risk for atherosclerosis. Soy ingredients act via more than one mode of action including the following: LDL absorption suppression, cholesterol efflux stimulation, LDL resorption stimulation, LDL oxidation prevention, LDL particle size increase, cholesterol synthesis reduction, and bile secretion increase. Individual genetics, lifestyle, and nutrition habits alter LDL management and a better understanding of the various modes of actions of soy ingredients may facilitate the composition of effective ingredient cocktails. The optimization of food components offers further alternatives to LDL management to augment drug therapy for patients who are unable to reach their target LDL cholesterol levels or who are suffering from side effects or drug insensitivity.     

Systematic Review of Anthocyanins and Markers of Cardiovascular Disease

Anthocyanins are dietary flavonoids commonly consumed in the diet, which have been suggested to have a preventative effect on cardiovascular disease (CVD) development among epidemiological studies. We systematically reviewed randomized controlled trials (RCTs) testing the effects of purified anthocyanins and anthocyanin-rich extracts on markers of CVD (triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and blood pressure) in both healthy and diseased populations. Eligible studies included RCTs of adults published in English. We searched PubMed, Web of Science Core Collection, and BIOSIS Previews for relevant articles from inception until 1 July 2014. Twelve RCTs representing 10 studies were included in this review. Supplementation with anthocyanins significantly improved LDL cholesterol among diseased individuals or those with elevated biomarkers. Supplementation did not significantly affect other markers of CVD in either healthy individuals or those with elevated markers. No adverse effects of anthocyanins were reported across studies at levels up to 640 mg/day. Limitations of trials in the qualitative analyses include short trial duration and large variability in the dose administered within the trials. Longer-duration trials assessing dose response are needed to adequately determine whether an effect of supplementation exists.     

Conjugated linoleic acid reduces early aortic atherosclerosis greater than linoleic acid in hypercholesterolemic hamsters

Thirty-six male F₁B hamsters, 10 weeks of age, were divided into 3 groups of 12 based on similar body weights. The experimental diets comprised of a chow-based hypercholesterolemic diet supplemented with 20% coconut oil, 2% safflower oil, and 0.12% cholesterol (HCD); the HCD plus either 1% CLA as the free fatty acid (CLA), or 1% LA as the free fatty acid (LA) and were fed for 12 weeks. Plasma total cholesterol (TC) and nonHDL-C (very low- and low-density lipoprotein cholesterol) were significantly lower in the CLA and LA relative to the HCD (P < 0.05). The CLA had significantly less maximum number of dienes formed relative to the LA and HCD (P < 0.05). The CLA developed significantly less early aortic atherosclerosis relative to both the HCD and LA (P < 0.05). Thus it appears CLA reduces the development of early aortic atherosclerosis to a greater degree than LA possibly through changes in LDL oxidative susceptibility in hypercholesterolemic hamsters.     

Increased dietary cholesterol does not increase plasma low density lipoprotein when accompanied by an energy-restricted diet and weight loss

BACKGROUND: Diets enriched with dietary cholesterol, frequently from eggs, have been shown to produce a small but variable increase in plasma low density lipoprotein (LDL) cholesterol. There is evidence to suggest that energy-restricted diets, that may contain a relatively high proportion of fat and cholesterol, can attenuate the cholesterol-raising effect of dietary cholesterol on plasma LDL. AIM OF THE STUDY: To determine the combined effects of increased dietary cholesterol and weight loss produced by energy restriction on plasma LDL cholesterol and lipoproteins. METHODS: A randomized, controlled, parallel study was performed in two groups of free-living volunteers on an energy-restricted diet for 12 weeks, one group was instructed to consume two eggs a day (n = 24), the other, to exclude eggs (n = 21). Dietary advice on energy restriction was based on the British Heart Foundation guidelines on how to lose weight for men and women. RESULTS: Energy intake fell by 25 and 29% in the egg-fed and non-egg-fed groups, resulting in a moderate weight loss of 3.4 kg (P < 0.05) and 4.4 kg (P < 0.05), respectively. The daily intake of dietary cholesterol increased significantly in the egg-fed group from 278 to 582 mg after 6 weeks. The concentration of plasma LDL cholesterol decreased in the non-egg-fed groups after 6 weeks (P < 0.01) and in the egg-fed and non-egg-fed at 12 weeks relative to baseline. There were no other significant changes in plasma lipoproteins or LDL particle size. CONCLUSIONS: An increased intake of dietary cholesterol from two eggs a day, does not increase total plasma or LDL cholesterol when accompanied by moderate weight loss. These findings suggest that cholesterol-rich foods should not be excluded from dietary advice to lose weight on account of an unfavorable influence on plasma LDL cholesterol.     

大豆蛋白对大鼠血浆胆固醇影响及作用机制

目的探讨膳食大豆蛋白对高胆固醇模型大鼠血浆胆固醇及其相关血脂指标的影响及可能的作用机制。方法4周龄断乳雄性Wistar大鼠，诱导高胆固醇模型28d后，按体重和血浆总胆固醇浓度均衡分为2组，分别喂饲含酪蛋白和大豆蛋白的纯合成高脂饲料56d。结果酪蛋白组和大豆蛋白组大鼠TC、甘油三酯（TG）、载脂蛋白B（apoB）含量显著降低，粪胆汁酸排泄量增高。但对高密度脂蛋白胆固醇（鼢L—C），载脂蛋白AⅠ（apoA—Ⅰ）zk平无影响；同时可见，大豆蛋白可以增强大鼠肝脏3-羟基-3-甲酰基CoA（HMG—CoA）还原酶及低密度脂蛋白受体（LDL—R）基因的表达。结论大豆蛋白可通过影响apoB、HMG—CoA还原酶及LDL—R基因的表达来改变血浆胆固醇水平，其作用机制还需进一步探讨。     

Unscrambling the research: Eggs, serum cholesterol and coronary heart disease

The role of dietary cholesterol in raising plasma cholesterol levels has been debated over the past 25 years. Consequently, eggs, as a food high in dietary cholesterol, have been targeted as a food to limit when advising patients on a diet to lower serum cholesterol levels. The aim of the present review was to evaluate the literature to address the effects of dietary cholesterol from eggs on serum cholesterol levels and risk of coronary heart disease. An increase in dietary cholesterol from eggs by 100 mg daily, equivalent to half a medium egg or three to four eggs a week, results in an increase of approximately 0.05 mmol/L in LDL cholesterol. Adding 100 mg of cholesterol per day (equivalent to three to four eggs a week) to a high saturated fat diet caused an increase in LDL cholesterol of 0.061 ± 0.006 mmol/L, whereas adding the same quantity of cholesterol to a low saturated fat diet caused an increase in LDL cholesterol of only 0.036 ± 0.004 mmol/L (P = 0.03). Despite the small increase in LDL‐cholesterol levels with increasing egg intake, most epidemiological studies have shown little or no association between egg intake and risk of coronary heart disease. However, the impact of dietary cholesterol for people with type 2 diabetes has been poorly studied. In conclusion, in a healthy Western population, there is insufficient evidence to excessively restrict egg intake as part of a healthy diet. Eggs should be considered in a similar way as other protein‐rich foods and selected as part of a varied diet that is low in saturated fat and contains a variety of cardio‐protective foods such as fish, wholegrains, fruits, vegetables, legumes and nuts.     

Dietary Cholesterol Affects Plasma Lipid Levels,the Intravascular Processing of Lipoproteins and Reverse Cholesterol Transport without Increasing the Risk for Heart Disease

The associations between dietary cholesterol and heart disease are highly controversial. While epidemiological studies and clinical interventions have shown the lack of correlation between cholesterol intake and cardiovascular disease (CVD) risk, there is still concern among health practitioners and the general population regarding dietary cholesterol. In this review, several clinical studies utilizing cholesterol challenges are analyzed in terms of changes that occur in lipoprotein metabolism resulting from excess consumption of cholesterol. Dietary cholesterol has been shown to increase both LDL and HDL in those individuals who respond to a cholesterol challenge without altering the LDL cholesterol/HDL cholesterol ratio, a key marker of CVD risk. Further, dietary cholesterol has been shown to increase only HDL with no changes in LDL with average cholesterol consumption and during weight loss interventions. Ingestion of cholesterol has also been shown to increase the size of both LDL and HDL particles with the associated implications of a less atherogenic LDL particle as well as more functional HDL in reverse cholesterol transport. Other changes observed in lipoprotein metabolism are a greater number of large LDL and decreases in small LDL subfractions. All this information put together points to specific roles of dietary cholesterol in substantially altering intravascular processing of lipoproteins as well as reverse cholesterol transport.     

Chitooligosaccharides decreases plasma lipid levels in healthy men

Chitosan, which is derived from chitin, has drawn much attention due to its low toxicity and potential use in medical and pharmaceutical applications. The biological activities of chitosan have been shown to depend on its molecular weight (MW) and degree of deacetylation. In this study, we investigated whether oral chitooligosaccharides, which are easily absorbed into the body, can reduce the plasma level of lipid in smokers and non-smokers because smoking is a high-risk factor for cardiovascular diseases. All healthy men (11 smokers and 8 non-smokers) consumed 500 mg of chitooligosaccharides in water twice daily before a meal (breakfast and dinner) over a 6-week period. Total cholesterol and low-density lipoprotein cholesterol levels were significantly decreased in both the smoker group and non-smoker group when compared with baseline. These results suggest that low MW chitooligosaccharides would be an effective dietary supplement for lowering cholesterol level.     

Effectiveness of Written Dietary Advice for Improving Blood Lipids in Primary Care Adults—A Pragmatic Randomized Controlled Trial (MYDICLIN)

Lifestyle management is the first line of treatment for moderately elevated blood lipids in healthy individuals. We investigated the effectiveness of providing food-based written advice for lowering low-density lipoprotein (LDL) cholesterol (intervention) or triglycerides (control) in a pragmatic randomized controlled trial with two parallel arms from 2018–2019 at a rural primary health care center. We sent feedback letters after 3 weeks and 6 months. Out of the 113 adult primary care patients randomized, 112 completed the study. There were no differences between the intervention and control groups for changes in LDL cholesterol after 3 weeks (mean ± standard deviation −0.21 ± 0.38 vs. −0.11 ± 0.34 mmol/L, p = 0.45) or 6 months (−0.05 ± 0.47 vs. 0.02 ± 0.41 mmol/L, p = 0.70) (primary outcome). Following the advice to consume plant sterols and turmeric was associated with a reduction in LDL cholesterol after 3 weeks. Following the advice to consume less carbohydrates was associated with reduced triglycerides. In the intervention arm, 14 individuals (25%) reduced their LDL cholesterol by ≥10% after three weeks. Their reduction was attenuated but maintained after six months (−7.1 ± 9.2% or −0.31 ± 0.38 mmol/L, p = 0.01 compared with baseline). They differed only in higher adherence to the advice regarding turmeric. In conclusion, this undemanding intervention had little effect on blood lipids for most individuals.     

阿托伐他汀不同用法降低血清总胆固醇和低密度脂蛋白胆固醇效果观察

目的 探讨社区高胆固醇血症患者隔日与每日口服阿托伐他汀20 mg治疗3个月对降低血清总胆固醇(total cholesterol , TC)和低密度脂蛋白胆固醇( low density lipoprotein cholesterol , LDL-C )浓度的影响。方法 连续入选2014年1月至2017年5月门诊收治的高胆固醇血症患者158例,按电脑随机数字表法分为隔日口服阿托伐他汀组(79例,阿托伐他汀20mg隔天口服1次)和每日口服阿托伐他汀组(79例,阿托伐他汀20 mg每天口服1次),疗程均为3个月,所有患者在治疗前、治疗3个月后分别测定血清三酰甘油(triacylglycerol , TG)、TC、LDL-C 、高密度脂蛋白胆固醇(high density lipoprotein cholesterol , HDL-C )浓度,同时对2组的血糖、肝功能、肾功能、肌酸激酶进行检测比较。结果 2组在治疗3个月后的TG、TC、LDL-C与治疗前比较,均有明显降低,差异均有统计学意义(P<0.05 ; P<0.01);2组间比较,差异无统计学意义(P>0.05)。结论 隔日口服与每日口服阿托伐他汀20 mg降低血清总胆固醇和低密度脂蛋白胆固醇浓度疗效相似,隔日口服不良反应少,减少了服药次数,节约了药费开支。     

Lipid Responses to a Dietary Docosahexaenoic Acid Supplement in Men and Women with Below Average Levels of High Density Lipoprotein Cholesterol

Objective: To assess fasting lipid responses to a docosahexaenoic acid (DHA) supplement in men and women with below-average levels of high-density lipoprotein (HDL) cholesterol.

Methods: This randomized, double-blind, controlled clinical trial included 57 subjects, 21–80 years of age, with fasting HDL cholesterol concentrations ≤44 mg/dL (men) and ≤54 mg/dL (women), but ≥35 mg/dL. Subjects were randomly assigned to receive either 1.52 g/day DHA from capsules containing DHA-rich algal triglycerides or olive oil (control) for six weeks.

Results: There were no significant differences between groups in baseline lipid values. The DHA supplemented group showed significant changes [?43 (DHA) vs. ?14 (controls) mg/dL, p = 0.015] and percent changes [?21% (DHA) vs. ?7% (controls), p = 0.009] in triglycerides, total (12 vs. 3 mg/dL; p = 0.021 and 6% vs. 2%; p = 0.018) and low-density lipoprotein (17 vs. 3 mg/dL; p = 0.001 and 12% vs. 3%; p = 0.001) cholesterol concentrations, and in the triglyceride to HDL cholesterol ratio (?1.33 vs. ?0.50, p = 0.010), compared with controls. In addition, there was a significant reduction in the percentage of LDL cholesterol carried by small, dense particles in the DHA supplemented group (changes = ?10% vs. ?3%, p = 0.025).

Conclusions: Supplementation with 1.52 g/d of DHA in men and women with below-average HDL cholesterol concentrations raised the LDL cholesterol level, but had favorable effects on triglycerides, the triglyceride/HDL cholesterol ratio and the fraction of LDL cholesterol carried by small, dense particles. Further research is warranted to evaluate the net impact of these alterations on cardiovascular risk.     

Sex Differences in the Impact of the Mediterranean Diet on LDL Particle Size Distribution and Oxidation

Sex differences have been previously highlighted in the cardioprotective effects of the Mediterranean diet (MedDiet). The objective of this study was to investigate whether sex differences also exist with regard to LDL particle size distribution and oxidation. Participants were 37 men and 32 premenopausal women (24–53 years) with slightly elevated LDL-C concentrations (3.4–4.9 mmol/L) or total cholesterol/HDL-C ≥5.0. Variables were measured before and after a four-week isoenergetic MedDiet. Sex differences were found in response to the MedDiet for the proportion of medium LDL (255–260 Å) (p for sex-by-time interaction = 0.01) and small, dense LDL (sdLDL; <255 Å) (trend; p for sex-by-time interaction = 0.06), men experiencing an increase in the proportion of medium LDL with a concomitant reduction in the proportion of sdLDL, while an opposite trend was observed in women. A sex difference was also noted for estimated cholesterol concentrations among sdLDL (p for sex-by-time interaction = 0.03), with only men experiencing a reduction in response to the MedDiet. The MedDiet marginally reduced oxidized LDL (oxLDL) concentrations (p = 0.07), with no sex difference. Results suggest that short-termconsumption of the MedDiet leads to a favorable redistribution of LDL subclasses from smaller to larger LDL only in men. These results highlight the importance of considering sex issues in cardiovascular benefits of the MedDiet.     

A cholesterol-lowering VLP vaccine that targets PCSK9

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory protein that controls cholesterol homeostasis by enhancing endosomal and lysosomal degradation of the low-density lipoprotein receptor (LDL-R). Mutations that cause increased activity of PCSK9 are associated with hypercholesterolemia, atherosclerosis and early cardiovascular disease (CVD), whereas individuals with loss-of-function mutations in PCSK9 are apparently healthy but are hypocholesterolemic and have a dramatically decreased risk of CVD. In this study, we generated virus-like particle (VLP)-based vaccines targeting PCSK9. Mice and macaques vaccinated with bacteriophage VLPs displaying PCSK9-derived peptides developed high titer IgG antibodies that bound to circulating PCSK9. Vaccination was associated with significant reductions in total cholesterol, free cholesterol, phospholipids, and triglycerides. A vaccine targeting PCSK9 may, therefore, be an attractive alternative to monoclonal antibody-based therapies.     

Dietary cholesterol, eggs and coronary heart disease risk in perspective

Summary  The idea that dietary cholesterol increases risk of coronary heart disease (CHD) by turning into blood cholesterol is compelling in much the same way that fish oil improves arthritis by lubricating our joints! Dietary cholesterol, chiefly in the form of eggs, has long been outlawed as a causative agent in CHD through its association with serum cholesterol. However, the scientific evidence to support a role for dietary cholesterol in CHD is relatively insubstantial in comparison with the incontrovertible link between its circulating blood relative in low density lipoprotein (LDL) cholesterol and CHD. Interpretation of the relationship between dietary cholesterol and CHD has been repeatedly confounded by an often inseparable relationship between dietary cholesterol and saturated fat. It has also been exaggerated by the feeding of unphysiologically high intakes of eggs. Nonetheless, numerous studies have shown that dietary cholesterol can increase serum LDL-cholesterol, but the size of this effect is highly variable between individuals and, according to over 30 years of prospective epidemiology, has no clinically significant impact on CHD risk. Variation in response to dietary cholesterol is a real phenomenon and we can now identify nutrient–gene interactions that give rise to this variation through differences in cholesterol homeostasis. More importantly, to view eggs solely in terms of the effects of their dietary cholesterol on serum cholesterol is to ignore the potential benefits of egg consumption on coronary risk factors, including obesity, diabetes and metabolic syndrome. Cardiovascular risk in these conditions is largely independent of LDL-cholesterol. These conditions are also relatively unresponsive to any LDL-cholesterol raising effects of dietary cholesterol. Treatment is focused primarily on weight loss, and it is in this respect that eggs may have a new and emerging role in facilitating weight loss through increased satiety.     

Implications of the obesity epidemic for lipid-lowering therapy: non-HDL cholesterol should replace LDL cholesterol as the primary therapeutic target

Obesity, metabolic syndrome and diabetes are conditions with increasing prevalence around the world. Cardiovascular risk in diabetics is often so high as to overlap with event rates observed in those with established coronary disease and this has lead to diabetes being classified as a coronary risk equivalent. However, despite the elevated risk of cardiovascular events associated with diabetes and the metabolic syndrome, these patients often have normal low density lipoprotein (LDL) cholesterol despite frequent increases in apolipoprotein B, triglycerides and nonhigh density lipoprotein (HDL) cholesterol. In contrast to LDL cholesterol, non-HDL cholesterol represents cardiovascular risk across all patient populations but is currently only recommended as a secondary target of therapy by the ATP III report for patients with hypertriglyceridemia. This article provides an overview of the studies that shown non-HDL cholesterol to be superior to LDL cholesterol in predicting cardiovascular events and presents the case for non-HDL cholesterol being the more appropriate primary target of therapy in the context of the obesity pandemic. Adopting non-HDL cholesterol as the primary therapeutic target for all patients will conceivably lead to an appropriate intensification of therapy for high risk patients with low LDL cholesterol.     

Apolipoprotein E polymorphism and plasma lipid, lipoprotein, and apolipoprotein levels in Italian children.

We have investigated the effect of apolipoprotein (apo) E polymorphism on serum lipid, lipoprotein, and apolipoprotein levels in a sample of 195 children, aged 8-11 years, from Sezze, Central Italy. The relative frequencies of e2, e3, and e4 alleles were 0.062, 0.867, and 0.072, respectively. Variation at the apo E gene locus explained 5.1% of the sample variance in serum total cholesterol levels, 7.6% in low-density lipoprotein (LDL) cholesterol levels, 7.3% in apo B levels, and 14.1% in high-density lipoprotein-apo E (HDL-E) levels. The effect of the e2 allele was to lower levels of total cholesterol, LDL-cholesterol, and apo B and to raise levels of HDL-E, while the effect of the e4 allele was the opposite. Variation at the apo E gene locus was not associated with differences in serum triglyceride, HDL-cholesterol, or apo AI levels. The effects of common apo E polymorphisms and genetic variation associated with the PvuII RFLP of the apo B gene on serum apo B levels were additive, explaining 11.3% of the phenotypic variance in this sample. When the effect of apo E polymorphism on serum lipid traits was estimated in boys and girls separately, variation at the apo E gene locus explained 10.4, 13.3, 13.3, and 13.5% of the phenotypic variance in serum total cholesterol, LDL-cholesterol, apo B, and HDL-E levels, respectively, in boys, while in girls only the effect on HDL-E levels (19.3%) reached statistical significance. This study has demonstrated that genetic variations at the apo E locus contribute to the determination of serum lipid, lipoprotein, and apolipoprotein levels in youths and that the effects are gender specific.