Effects of guar gum in male subjects with hypercholesterolemia

Fourteen male subjects with hypercholesterolemia received daily supplementation with granulated guar gum or placebo, 15 g/day, during 12 wk in a double-blind, cross-over trial. A statistically significant reduction in serum total cholesterol (7.27 +/- 0.24 versus 8.23 +/- 0.26 mmol/l, mean +/- SEM, p less than 0.01) which was mainly due to a reduction in low-density lipoprotein cholesterol concentration (4.70 +/- 0.19 versus 5.32 +/- 0.23 mmol/l, p less than 0.05) was observed after 6 wk on guar gum as compared with placebo. Between 6 and 12 wk on guar gum the serum cholesterol and low-density lipoprotein cholesterol levels increased in most subjects, and after 12 wk the difference from placebo was no longer statistically significant. Serum high-density lipoprotein cholesterol levels were unaffected by guar gum. Serum and lipoprotein triglycerides showed no significant changes during the study, and the body weight of the subjects remained unchanged. Serum calcium, magnesium, phosphate, and iron levels, and urinary calcium excretion were not affected by guar gum supplementation. No severe side effects were observed, necessitating reduction of the dose or stopping the treatment. It is concluded that the hypocholesterolemic effect of guar gum seems to decrease during prolonged dietary supplementation. Further controlled studies are needed before the dose response and the long-term effects of guar gum in hypercholesterolemia can be evaluated.     

The effects of guar gum, sugar beet fibre and wheat bran supplementation on serum lipoprotein levels in normocholesterolaemic volunteers

The effect of dietary supplementation with guar gum, sugar beet fibre (SBF) and wheat bran on serum lipoprotein leveh was assessed in normocholesterolemic men. Each fibre preparation was incorporated into bread and subjects ate half a loaf a day which provided 20 g of the fibre preparation. Each bread was eaten for 14 days with a 21-dey rest period between each stage of the study. Twelve subjects consumed each type of fibre-supplemented bread.
During fibre supplementation dietary non-starch polysaccharide (NSP) intake increased significantly (P < 0.025) and the mean daily fat and energy intakes increased but not significantly. Serum total cholesterol levels were reduced by an average of 11.7% (s.e. 1.8) (P<0.01) during guar supplementation and 4.6% (s.e. 1.9) (P < 0.025) during SBF supplementation. Bran supplementation was without effect. Mean HDL cholesterol, serum triglycerides and plasma glucose and insulin levels were unaffected by supplementation with any of the fibres. Mean serum total bile acids were significantly reduced by guar (P < 0.01) and SBF (P < 0.025) but not bran supplementation. Mean apo B levels were only significantly reduced by guar (P < 0.05). Apo A1 levels were not affected by any of the fibres. There was a significant correlation between apo B and total cholesterol levels (P<0.01) and between apo A1 and HDL cholesterol levels (P < 0.01) throughout each stage of the trial.
This study demonstrates that dietary supplementation with 20 g guar or sugar beet fibre has a favourable effect on both cholesterol and apoprotein levels.     

Effects of guar gum and wheat bran on lipid metabolism of rats.

The effects of guar gum and wheat bran on blood and liver lipid levels of rats were measured. In experiment 1, rats were fed ad libitum a 55% sucrose diet containing 0, 15 or 25% wheat bran for 3 weeks. Postprandial plasma triglyceride, liver triglyceride and liver cholesterol values in rats fed the sucrose diet with wheat bran were significantly lower than values for rats fed the diet without wheat bran. Neither fasting plasma triglyceride nor cholesterol values were altered by wheat bran. In experiment 2, rats were meal-fed one of four experimental diets for 3 weeks: sucrose, sucrose-cholesterol, sucrose-cholesterol-bran or sucrose-cholesterol-guar gum. Rats fed sucrose-cholesterol-guar gum diet had significantly lower fasting plasma total cholesterol, liver triglyceride and liver cholesterol values, but higher plasma high density lipoprotein (HDL) cholesterol values than those fed sucrose-cholesterol diet. These values were similar for the sucrose-cholesterol and sucrose-cholesterol-bran groups. Fasting plasma triglyceride levels were not altered by wheat bran or guar gum. These studies indicate that while guar gum lowers fasting plasma total cholesterol and raises HDL cholesterol, wheat bran does not.     

The relation of high density lipoprotein cholesterol and its subfractions to apolipoprotein A-I and fasting triglycerides: the role of environmental factors. The Atherosclerosis Risk in Communities (ARIC) Study.

Cross-sectional analysis of four general representative populations of middle-aged adults in the United States in 1986-1989 provides estimates of the close relation of high density lipoprotein cholesterol (HDL cholesterol) to its major structural apolipoprotein (apolipoprotein A-I) and to fasting plasma triglyceride levels. HDL cholesterol differences of approximately 0.4 mg were associated with 1-mg differences in apolipoprotein A-I; differences of 20% in HDL cholesterol (reductions) were associated with triglyceride doublings. Variation in apolipoprotein A-I and triglyceride concentration together accounted for 66% of the population variance in HDL cholesterol. The uniformity of this pattern in the four race-sex groups studied suggests an important role of triglyceride-cholesterol transfer as a determinant of HDL cholesterol. The fundamental relations observed among HDL cholesterol, apolipoprotein A-I, and triglycerides were unaltered by levels of factors under personal volition. The volitional factors appeared to influence HDL cholesterol indirectly: Obesity and physical activity were affected primarily through their associations with triglycerides, and alcohol use and smoking through associations with apolipoprotein A-I. The association of alcohol use with elevated HDL cholesterol was attenuated in persons with greater body mass.     

Effects of diets rich in fermentable carbohydrates on plasma lipoprotein levels and on lipoprotein catabolism in rats

This study was conducted to examine the effects of a combination of several dietary fibers (5% guar gum, 5% apple pectin, 15% wheat bran, 22% soybean fiber) and crude potato starch (23%) on plasma lipids and lipoproteins and on liver lipid concentration in rats fed a diet containing either 15% lard or 5% oil with or without dietary cholesterol/cholic acid. Male Wistar rats ate the test diets for 3 wk. The incorporation of fiber and crude potato starch into the diet resulted in a significant enlargement of the cecum; it also increased the concentration of volatile fatty acids and the pool of acetate, propionate and butyrate. Feeding this fermentable carbohydrate decreased plasma cholesterol and triglyceride levels in rats given a low fat diet and prevented the expected rise in plasma cholesterol and triglycerides in rats fed cholesterol/cholic acid or lard. Further studies of high density lipoprotein (HDL) composition, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase) activity and 125I-labeled human low density lipoprotein (LDL) turnover were done in the group fed the low fat diet without added cholesterol/cholic acid. The study of the HDL fraction in rats fed a diet rich in fermentable carbohydrates demonstrated a decrease in the HDL1 subpopulation and in the proportion of apolipoprotein E. Plasma clearance of intravenously injected 125I-labeled LDL was faster in rats fed this diet than in rats fed the fiber-free diet. In the liver, cholesterol and triglyceride levels were depressed whereas the activity of HMG-CoA reductase was increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Time course for the changes of serum lipoproteins and apolipoprotein T concentrations after major surgical trauma in man

Trauma induces changes in the serum lipoprotein pattern in man. A characteristic apolipoprotein, named apolipoprotein T existing in its isoforms T-I to T-IV, in the high density lipoprotein (HDL) fraction of serum, also appears in response to trauma. In this report eight patients operated on for abdominal aortic aneurysms were studied concerning the time dependency in changes of serum lipoproteins and the appearance of apolipoprotein T. Blood samples for lipoprotein analysis were taken preoperatively, postoperatively on days 1, 2, 4, 6 and thereafter twice a week until discharge from the hospital. The serum lipoprotein concentrations were compared with those from a group of healthy men. The most striking abnormalities were found in serum VLDL where both concentrations of triglycerides and cholesterol decreased during the first 2 days by more than 50%, compared to the initial level, and remained low for about 1 week. Also the concentration of LDL cholesterol in serum decreased about 40% from the preoperative value during the first days. Serum HDL cholesterol either increased during the first 2 days in those patients with a low preoperative concentration or stayed on a subnormal level during the first 4 days. After day 4 the serum HDL cholesterol decreased and reached the minimum level on days 10 to 13. Already on day 1 after trauma apolipoprotein T had reached a high level in order to stay high for several weeks. The apolipoprotein T isoforms had different appearance with time and varied independently of serum cholesterol in HDL.     

Vitamin D Supplementation Ameliorates Hypoinsulinemia and Hyperglycemia in Static Magnetic Field–Exposed Rat

The purpose of this study is to evaluate the effects of vitamin D supplementation on glucose and lipid metabolism in static magnetic field (SMF)–exposed rats. Rats exposed to SMF (128 mT; 1 h/day) during 5 consecutive days showed an increase in plasma glucose level and a decrease in plasma insulin concentration. By contrast, the same treatment failed to alter body weight and plasmatic total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels. Interestingly, supplementation with vitamin D (1,600 IU/100 g, per os) corrected and restored glycemia and insulinemia in SMF-exposed rats. The same treatment had no effects on lipid metabolism.     

Evaluation of a high-fiber diet in hyperlipidemia: a review.

Epidemiologic studies of cardiovascular mortality rates in different countries have suggested that dietary fiber may play a protective role. Within a similar population, a large intake of fiber is associated with a lower relative risk of death from coronary heart disease. Dietary fiber may be separated into at least two types: insoluble, which includes cellulose, hemicellulose, and lignin; and soluble, including pectin and gums. Laxative effects appear to predominate with insoluble fibers such as wheat bran, with little change in plasma lipid levels in most studies. Pectin, guar gum, and oat bran (soluble fibers) have been reported to have hypocholesterolemic effects in both animals and man, with the effect being proportional to the degree of cholesterol elevation. Other gums, specifically those from locust bean and karaya, have a similar effect, with the decrease in total cholesterol due primarily to a decrease in the low-density lipoprotein cholesterol fraction. While some studies have shown continued improvement over a period of months, this has not been uniformly found. Both normal and elevated triglyceride levels appear to be more resistant to change with dietary fiber. An increase of dietary carbohydrate as a source of fiber may be associated with an increase in triglyceride levels. Fiber may, however, offer some protection against an increase in cholesterol and triglyceride levels in subjects fed diets containing large amounts of sucrose. Although rats fed oat bran, guar gum, or pectin had lower levels of hepatic and blood triglycerides, humans with hypercholesterolemia fed oat bran or guar showed no effect on their triglycerides.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of a high-fiber diet in hyperlipidemia: a review

Epidemiologic studies of cardiovascular mortality rates in different countries have suggested that dietary fiber may play a protective role. Within a similar population, a large intake of fiber is associated with a lower relative risk of death from coronary heart disease. Dietary fiber may be separated into at least two types: insoluble, which includes cellulose, hemicellulose, and lignin; and soluble, including pectin and gums. Laxative effects appear to predominate with insoluble fibers such as wheat bran, with little change in plasma lipid levels in most studies. Pectin, guar gum, and oat bran (soluble fibers) have been reported to have hypocholesterolemic effects in both animals and man, with the effect being proportional to the degree of cholesterol elevation. Other gums, specifically those from locust bean and karaya, have a similar effect, with the decrease in total cholesterol due primarily to a decrease in the low-density lipoprotein cholesterol fraction. While some studies have shown continued improvement over a period of months, this has not been uniformly found. Both normal and elevated triglyceride levels appear to be more resistant to change with dietary fiber. An increase of dietary carbohydrate as a source of fiber may be associated with an increase in triglyceride levels. Fiber may, however, offer some protection against an increase in cholesterol and triglyceride levels in subjects fed diets containing large amounts of sucrose. Although rats fed oat bran, guar gum, or pectin had lower levels of hepatic and blood triglycerides, humans with hypercholesterolemia fed oat bran or guar showed no effect on their triglycerides.(ABSTRACT TRUNCATED AT 250 WORDS)     

Orange juice decreases low-density lipoprotein cholesterol in hypercholesterolemic subjects and improves lipid transfer to high-density lipoprotein in normal and hypercholesterolemic subjects

Orange juice (OJ) is regularly consumed worldwide, but its effects on plasma lipids have rarely been explored. This study hypothesized that consumption of OJ concentrate would improve lipid levels and lipid metabolism, which are important in high-density lipoprotein (HDL) function in normolipidemic (NC) and hypercholesterolemic (HCH) subjects. Fourteen HCH and 31 NC adults consumed 750 mL/day OJ concentrate (1:6 OJ/water) for 60 days. Eight control subjects did not consume OJ for 60 days. Plasma was collected before and on the last day for biochemical analysis and an in vitro assay of transfers of radioactively labeled free-cholesterol, cholesteryl esters, phospholipids, and triglycerides from lipoprotein-like nanoemulsions to HDL. Orange juice consumption decreased low-density lipoprotein cholesterol (160 ± 17 to 141 ± 26 mg/dL, P < .01) in the HCH group but not in the NC group. HDL-cholesterol and triglycerides remained unchanged in both groups. Free-cholesterol transfer to HDL increased (HCH: 4.4 ± 2 to 5.6 ± 1%, NC: 3.2 ± 2 to 6.2 ± 1%, P< .05) whereas triglyceride (HCH 4.9 ± 1 to 3.1 ± 1%, NC 4.4 ± 1 to 3.4 ± 1%, P< .05) and phospholipid (HCH 21.6 ± 2 to 18.6 ± 3%, NC 20.2 ± 2 to 18.4 ± 2%, P < .05) transfers decreased in both groups. Cholesteryl-ester transfer decreased only in HCH (3.6 ± 1 to 3.1 ± 1%, P < .05), but not in NC. In control subjects, plasma lipids and transfers were unaltered for 60 days. Thus, by decreasing atherogenic low-density lipoprotein cholesterol in HCH and increasing HDL ability to take up free cholesterol in HCH and NC, OJ may be beneficial to both groups as free-cholesterol transfer to HDL is crucial for cholesterol esterification and reverse cholesterol transport.     

Hypocholesterolemic activity of some Indian gums

Indian gums and pectin were added to a diet causing hypercholesterolemia in rats. Gum guar, gum acacia and pectin showed hypolipidemic activity while gum karaya did not. The reduction in serum cholesterol was primarily due to decrease in LDL+VLDL fractions. HDL cholesterol and triglyceride levels were not affected. Increased excretion of fecal steroids was noted with each source of fibre. Trace element content of serum was not affected by these gums but gum karaya and gum guar altered copper and iron and pectin and cellulose altered iron bioavailability.     

MODERATE DOSES OF ALCOHOLIC BEVERAGES WITH DINNER AND POSTPRANDIAL HIGH DENSITY LIPOPROTEIN COMPOSITION

Moderate alcohol consumption is associated with a reduced riskof coronary heart disease. In this study, postprandial changesin plasma lipids, high-density lipoprotein (HDL) compositionand cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyltransferase (LCAT) activity levels were investigatedin response to moderate alcohol consumption. A dose of 40 gof alcohol was consumed as beer, wine or spints by eight healthymiddle-aged men before and during dinner thus simulating socialdrinking. Lipid parameters were studied before, and at 1, 3,5, 9, and 13 h after dinner. An alcohol- induced elevation ofplasma triglycerides was observed at 3 and 5 h after dinner,but total plasma cholesterol and apolipoprotein B were hardlyaffected. HDL lipids changed during the postprandial phase afteralcohol consumption, HDL triglycerides were elevated at 5 and9 h, RDL phospholipids were elevated at 9 and 13 h, and HDLcholesterol was elevated at 13 h. A 6% increase in the concentrationof apolipoprotein A-II was observed at 13 h. Plasma LCAT activitywas slightly increased 9 h after dinner, but CETP activity levelswere not affected. The LCAT changes appeared similar for allthree alcoholic beverages. It is concluded that moderate alcoholconsumption with dinner affects plasma triglyceride concentrationas well as HDL composition.     

Different effects of zinc and copper deficiency on composition of plasma high density lipoproteins in rats

Male Sprague-Dawley rats (six per group) were fed an egg white-based diet containing 0 or 5 micrograms/g Cu with 1, 10, 100 or 1000 micrograms/g Zn. After 6 wk of feeding, the rats were killed, and the tissues were processed for trace element, lipid and lipoprotein analysis. Copper deficiency was associated with a higher concentration of plasma free cholesterol, high density lipoprotein (HDL) cholesterol and HDL apolipoproteins. Plasma total cholesterol was not significantly affected. No significant differences were noted in HDL lipid composition. However, HDL apo E and apo A-I concentrations were higher with copper deficiency. Lecithin:cholesterol acyltransferase (LCAT) was not affected in a consistent manner by copper status. Varying the amount of zinc in the diet did not produce significant changes in plasma total cholesterol, plasma free cholesterol, HDL cholesterol, or HDL apolipoprotein concentrations. However, HDL from zinc-deficient rats were enriched in free cholesterol and depleted in triglycerides. Furthermore, the concentration of HDL apo C increased as the level of dietary zinc increased.     

Psyllium improves dyslipidaemia,hyperglycaemia and hypertension,while guar gum reduces body weight more rapidly in patients affected by metabolic syndrome following an AHA Step 2 diet

The aim of this study was to comparatively evaluate the long-term effects of psyllium husk and guar gum supplementation on metabolic syndrome (MS) components. We randomised 141 MS patients to soluble psyllium husk powder or guar gum 3.5 g t.i.d. to be taken 20 min before the main 2 meals, or to a standard diet for a cumulative period of 6 months. Both fibres significantly improved body mass index (−7.2% vs. −6.5%), fasting plasma glucose (−27.9% vs. −11.1%) and insulin (−20.4% vs. −10.8%), HOMA Index (−39.2% vs. −16.7%), glycated haemoglobin (−10.4% vs. −10.3%), low-density lipoprotein cholesterol (−7.9% vs. −8.5%) and apolipoprotein B (−10.5% vs. −5.6%), after 6 months of treatment. Only the psyllium supplementation exerted a significant improvement on plasma triglyceride concentration (−13.3%) and systolic (−3.9%) and diastolic blood pressure (−2.6%). No significant difference was observed regarding the standard diet group in comparison to the baseline. On the basis of our data, psyllium could be more strongly indicated for patients that have to reduce a large number of cardiovascular risk factors, while guar gum could be more rapidly efficacious in strengthening the effect of diets aimed at reducing body weight.     

Naringin supplementation lowers plasma lipids and enhances erythrocyte antioxidant enzyme activities in hypercholesterolemic subjects

BACKGROUND AND AIMS: Preliminary studies have shown that naringin has a potent lipid-lowering effect and antioxidant capacity in high-cholesterol diet fed animals. Accordingly, the present study was conducted to investigate the effect of naringin on hypercholesterolemic subjects. METHODS: A hypercholesterolemic group (n=30) and healthy control group (n=30) were established based on the plasma cholesterol levels in the subjects, then all subjects received naringin (400mg/capsule/day) with regular meals for a period of 8 weeks. RESULTS: In the hypercholesterolemic subjects, naringin supplementation was found to lower the plasma total cholesterol by 14% and low-density lipoprotein cholesterol concentrations by 17%, while the plasma triglyceride and high-density lipoprotein cholesterol concentrations remained unaffected. The apolipoprotein B levels in the hypercholesterolemic subjects were significantly lowered after naringin treatment, yet no change was observed in the apolipoprotein A-1 levels. The erythrocyte superoxide dismutase and catalase activities in the hypercholesterolemic group were significantly increased, whereas the glutathione peroxidase activity and plasma TBARS levels were not different from the baseline measurements. Meanwhile, naringin supplementation had no affect on plasma lipids, apolipoproteins, and TBARS levels or antioxidant enzyme activities in the control group. CONCLUSIONS: Therefore, these data suggest that naringin may play an important role in lowering plasma cholesterol and regulating the antioxidant capacity in hypercholesterolemic subjects.     

Permutation analyses of familial association arrays for lipoprotein concentrations in families of the Stanford Five City Project

Permutation models are introduced as a formal method for assigning significance to association matrices that assess the correlation of spouse, parent-offspring, and sibling similarity over an entire class of data transformations (usually, the class of all increasing functions). Analysis of 218 nuclear families who participated in the Stanford Five City Project revealed that parent and offspring triglyceride concentrations correlated more strongly when data transformations emphasized contrasts among low to moderate levels, and that high density lipoprotein (HDL) cholesterol correlated more strongly between family members with relatively higher HDL cholesterol concentrations. Application of family weights to the association matrices revealed a tendency for greater correlation among sibling triglyceride concentrations in larger families. Parent-child, mother-child, father-child, parent-daughter, and sibling total cholesterol concentrations correlated significantly for all monotonically increasing transformations (designated strong association), and father-daughter and parent-son cholesterol concentrations correlated significantly for most increasing transformations of the data (moderate association). There were fewer significant associations for plasma triglyceride concentrations: parent-child and sibling (both strong), parent-daughter and mother-daughter (both moderate), and mother-child (weak). HDL cholesterol showed no strong or moderate familial associations and was weakly associated only among siblings. Thus, concordance in familial lipoprotein levels appears to be restricted to a narrower range of values for triglycerides and HDL cholesterol than total cholesterol levels, possibly reflecting in part the influences of diet or other environmental factors on specific regions of the HDL cholesterol or triglyceride distributions in casual blood samples.     

The effect of milk and skim milk intake on serum lipids and apoproteins in young females

The effect of milk and skim milk intake on serum lipid and apoprotein levels was investigated in young females with consideration of each subject's menstrual period. When milk and dairy products were not allowed, the serum cholesterol concentration tended to decrease in high density lipoprotein (HDL) and very low density lipoprotein (VLDL), the triglyceride concentration tended to increase in HDL and low density lipoprotein (LDL), the phospholipid concentration showed no change, and the apoB, apoC-III and apoE significantly decreased. In the milk group, VLDL cholesterol and phospholipid concentrations were increased with a significant increase in the apoB concentration after intake of 200 ml/day of milk for one menstrual period, and these levels did not change when the milk intake was doubled. VLDL phospholipid increased and apoE decreased after the intake of 20 g/day of skim milk, and LDL cholesterol and HDL phospholipid concentrations tended to decrease when the skim milk intake was doubled.     

Dietary fibre, fish and blood lipids

The effects of dietary fibre and fish consumption on the concentration of the components of blood lipids are discussed. Fibres such as pectin, guar gum and rolled oats reduce serum cholesterol and low density lipoprotein cholesterol, whereas cellulose and wheat bran do not. Fish or fish oils reduce plasma triglyceride concentration, but dietary fibre has no effect. Fish oils may also reduce serum cholesterol and increase high density lipoprotein cholesterol, but these effects are less well defined.     

Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized,double-blind,placebo-controlled trial.

The objective of this study was to evaluate the effects of daily dietary supplementation with 1.25 g or 2.5 g of docosahexaenoic (DHA), in the absence of eicosapentaenoic acid (EPA), on serum lipids and lipoproteins in persons with combined hyperlipidemia (CHL) [serum low-density lipoprotein cholesterol (LDL-C) 130 to 220 mg/dL and triglycerides 150 to 400 mg/dL].

After a 6-week dietary stabilization period, subjects entered a 4-week single-blind placebo (vegetable oil) run-in phase. Those with adequate compliance during the the run-in were randomized into one of three parallel groups (placebo, 1.25, or 2.5 g/day DHA) for 6 weeks of treatment. Supplements were administered in a triglyceride form contained in gelatin capsules. Primary outcome measurements were plasma phospholipid DHA content, serum triglycerides, high-density lipoprotein cholesterol (HDL-C). LDL-C and non-HDL-C.

The DHA content of plasma phospholipids increased dramatically (2 to 3 fold) in a dose-dependent manner. Significant (p < 0.05) changes were observed in serum triglycerides (17 to 21% reduction) and HDL-C (6% increase) which were of similar magnitude in both DHA groups. Non-HDL-C [+1.6 (NS) and +5.7% (p < 0.04)] and LDL-C [+9.3% (NS) and +13.6% (p < 0.001)] increased in the DHA treatment groups. All lipid effects reached an apparent steady state within the first 3 weeks of treatment.

Dietary DHA, in the absence of EPA, can affect lipoprotein cholesterol and triglyceride levels in patients with combined hyperlipidemia. The desirable triglyceride and HDL-C changes were present at a dose which did not significantly increased non-HDL-C or LDL-C. These preliminary findings suggest that dietary supplementation with 1.25 g DHA/day, provided in a triglyceride form, may be an effective tool to aid in the management of hypertriglyceridemia.     

Investigating Effects of Plasma Apolipoprotein E on Ischemic Heart Disease Using Mendelian Randomization Study

Background: Observationally plasma apolipoprotein E (apoE) is positively associated with ischemic heart disease (IHD). A Mendelian randomization (MR) study suggesting apoE is unrelated to cardiovascular mortality did not consider specific isoforms. We used MR to obtain estimates of plasma apoE2, apoE3 and apoE4 on IHD, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides and apolipoprotein B (apoB). Methods: We obtained independent genetic instruments from proteome genome-wide association studies (GWAS) and applied them to large outcome GWAS. We used univariable MR to assess the role of each isoform and multivariable MR to assess direct effects. Results: In univariable MR, apoE4 was positively associated with IHD (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01 to 1.09), but apoE2 and apoE3 were less clearly associated. Using multivariable MR an association of apoE2 with IHD (OR 1.16, 95% CI 0.98 to 1.38) could not be excluded, and associations of apoE3 and apoE4 with IHD were not obvious. In univariable MR, apoE2 and apoE4 were positively associated with apoB, and a positive association of apoE2 with LDL cholesterol could not be excluded. Using multivariable MR apoE2 was positively associated with LDL cholesterol, and associations with apoB could not be excluded. After adjusting for apoB, no direct effects of apoE isoforms on IHD were evident. Conclusions: Plasma apoE2 and apoE4 may play a role in lipid modulation and IHD. Whether apoE could be a potential therapeutic target requires further clarification when larger genetic studies of apoE isoforms are available.