Influence of cholesterol on survival after stroke: retrospective study.

Dyker AG, Weir CJ, Lees KR.

University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow.

OBJECTIVE: To investigate the association between serum cholesterol concentration and cerebrovascular disease. DESIGN: Retrospective study. SETTING: Acute stroke unit of inner city general hospital. SUBJECTS: 977 patients with acute stroke. MAIN OUTCOME MEASURES: Serum total cholesterol concentration, type of stroke investigated by computed tomography or magnetic resonance imaging, three month outcome (good (alive at home) or bad (dead or in care)), long term mortality. RESULTS: After adjustment for known prognostic factors, higher serum cholesterol concentrations were associated with reduced long term mortality after stroke (relative hazard 0.91 (95% confidence interval 0.84 to 0.98) per mmol/l increase in cholesterol) independently of stroke type, vascular territory and extent, age, and hyperglycaemia. Three month outcome was also influenced independently by serum cholesterol (P = 0.024). CONCLUSIONS: Our data suggest an association between poor stroke outcome and lower serum cholesterol concentration. Until a prospective controlled study has confirmed the benefits of lowering cholesterol concentration in elderly subjects, the application of cholesterol lowering guidelines cannot be justified as secondary prevention of acute stroke.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9169402&dopt=Abstract cholesterol




The effect of vitamin C in high doses on plasma and biliary lipid composition in patients with cholesterol gallstones: prolongation of the nucleation time.

Gustafsson U, Wang FH, Axelson M, Kallner A, Sahlin S, Einarsson K.

Department of Surgery, Danderyd Hospital, Sweden.

Vitamin C deficiency in guinea pigs leads to cholesterol supersaturation of bile and formation of cholesterol gallstones. It has been suggested that there may also exist an association between vitamin C and cholesterol gallstones in man, but such a relationship has not been studied in gallstone patients. In order to study the possible effects of vitamin C on gallstone disease in humans, plasma lipid levels, hepatic cholesterol metabolism, biliary lipid composition, cholesterol saturation and nucleation time of gallbladder bile were analysed in 16 consecutive gallstone patients, who were planned for laparoscopic cholecystectomy and were treated with vitamin C (500 mg, four times a day) for 2 weeks before surgery. The plasma concentration of vitamin C increased by 42% in the treatment group. The concentrations of plasma lipids did not differ before and after vitamin C treatment; nor did the plasma levels of lathosterol and 7 alpha-hydroxy-4-cholesten-3-one, reflecting cholesterol and bile acid synthesis respectively. The relative concentrations of cholesterol, bile acids and cholesterol concentration of bile did not differ significantly between the two groups, but the relative concentration of phospholipids was slightly higher in the treated group. The bile acid composition was changed; the percentage of cholic acid being lower and those of deoxycholic acid, ursodeoxycholic acid and lithocholic acid higher in the vitamin C-treated patients compared with the untreated group. The nucleation time was significantly longer in the treatment group (7 days) compared with the untreated group (2 days). Our findings indicate that vitamin C supplementation may also influence the conditions for cholesterol gallstone formation in humans.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9179545&dopt=Abstract cholesterol




Gene-diet interactions and plasma lipoproteins: role of apolipoprotein E and habitual saturated fat intake.

Campos H, D'Agostino M, Ordovas JM.

Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. hcampos hsph.harvard.edu

To test whether plasma lipoprotein levels and low density lipoprotein (LDL) particle size are modulated by an interaction between habitual saturated fat intake and apolipoprotein E (APOE) genotype, we studied 420 randomly selected free-living Costa Ricans. The APOE allele frequencies were 0.03 for APOE2, 0.91 for APOE3, and 0.06 for APOE4. The median saturated fat intake, 11% of energy, was used to divide the population into two groups, LOW-SAT (mean intake 8.6% energy) represents those below median intake, and HIGH-SAT (mean intake 13.5%) represents those above median intake. Significant interactions between APOE genotype and diet were found for VLDL (P = 0.03) and HDL cholesterol (P = 0.02). Higher saturated fat intake was associated with higher VLDL cholesterol (+29%) and lower HDL cholesterol (-22%) in APOE2 carriers, while the opposite association was observed in APOE4 carriers (-31% for VLDL cholesterol and +10% for HDL cholesterol). Higher saturated fat intake was associated with smaller LDL particles (-2%, P < 0.05) in APOE2 carriers, and larger LDL particles (+2%, P < 0.05) in APOE4 carriers, but the gene-diet interaction was not statistically significant (P = 0.09). Higher saturated fat intake was associated with higher LDL cholesterol in all genotypes (mean +/- SEM, LOW-SAT 2.61 +/- 0.05 vs. HIGH-SAT 2.84 +/- 0.05 mmol/L, P = 0.009). These data suggest that the APOE2 allele could modulate the effect of habitual saturated fat on VLDL cholesterol and HDL cholesterol in a population with an average habitual total fat intake of less than 30%. Copyright 2001 Wiley-Liss, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11119301&dopt=Abstract cholesterol




Associations of HDL2 and HDL3 subfractions with ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study.

Lamarche B, Moorjani S, Cantin B, Dagenais GR, Lupien PJ, Despres JP.

Lipid Research Center, CHUL Research Center, Ste-Foy, Quebec, Canada.

Individuals with elevated plasma concentrations of HDL cholesterol are at lower risk for ischemic heart disease (IHD). Whether the cardioprotective effects of HDL can be attributed to one or both HDL subfractions (HDL2 and HDL3) remains, however, controversial. The relationship of HDL subfractions to the incidence of IHD was investigated in a sample of 1169 French-Canadian men younger than 60 years and living in the Quebec City suburbs. Between 1980 to 1981 and 1990, 83 of the 944 men with complete follow-up in 1990 (80.8%) had a first IHD. Men who developed IHD had lower HDL, HDL2, and HDL3 cholesterol concentrations at baseline than men who remained free from IHD. Adjusted relative risk (RR) of IHD was calculated among quartiles of HDL cholesterol and HDL subfractions with the use of Cox survival models. Men in the fourth quartile of HDL2 (RR = 0.21; 95% confidence interval [CI], 0.08 to 0.56) and HDL3 cholesterol distributions (RR = 0.37; 95% CI, 0.15 to 0.94) were at lower risk for IHD than men in the first quartile. Despite the fact that the respective contributions of HDL2 and HDL3 to IHD risk were of the same magnitude in a multivariate model that included both subfractions, the contribution of the HDL2 subfraction was statistically significant (standardized RR = 0.84; 95% CI, 0.74 to 0.95), whereas it did not reach significance for HDL3 (standardized RR = 0.87; 95% CI, 0.69 to 1.11). Neither the linear combination of HDL2 and HDL3 nor their ratio provided further information on the risk of IHD compared with HDL cholesterol alone or with the ratio of total to HDL cholesterol. From a statistical standpoint, the present data suggest that the HDL2 subfraction may be more closely related to the development of IHD than the HDL3 subfraction. However, the qualitative difference in the relative predictive value of each subfraction was trivial, since it only corresponded to a modest quantitative difference. Thus, the possibility that a significant proportion of the cardioprotective effect of elevated HDL cholesterol levels may be mediated by the HDL3 subfraction still cannot be excluded. Finally, from a clinical point of view and within the limits of resolution provided by these data, the measurement of HDL subfractions does not appear to provide any additional information on the risk of IHD than HDL cholesterol alone or the ratio of total to HDL cholesterol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9194760&dopt=Abstract cholesterol




Alterations in plasma lipids, lipoproteins and high density lipoprotein subfractions in peripheral arterial disease.

Mowat BF, Skinner ER, Wilson HM, Leng GC, Fowkes FG, Horrobin D.

Department of Molecular and Cell Biology, University of Aberdeen, Marischal College, UK. d.mcb aberdeen.ac.uk

The concentrations of the major lipoprotein classes and of high density lipoprotein (HDL) subfractions in 63 male patients with arteriosclerosis of the lower limbs (claudication) were determined and compared with values from 63 healthy controls. The patients with peripheral arterial disease (PAD) had reduced levels of total HDL-cholesterol and HDL2b of large particle size, increased levels of small HDL3c particles and a high ratio of total plasma-cholesterol to HDL-cholesterol (coronary risk factor). The PAD patients, however, had lower levels of low density lipoprotein (LDL)-cholesterol but higher concentrations of very low density lipoprotein (VLDL)-cholesterol and plasma triglyceride than healthy subjects. This study therefore suggests that in PAD, the protective effect of HDL may be more important than the atherogenic effect of LDL. It further suggests that while HDL-cholesterol HDL2b and the ratio of total plasma-cholesterol to HDL-cholesterol may provide valid indices for identifying individuals at risk of PAD, other factors, such as LDL and total cholesterol, may not provide such an appropriate risk indicator.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9199268&dopt=Abstract cholesterol




Influence of two apo A4 polymorphisms at codons 347 and 360 on non-fasting plasma lipoprotein-lipids and apolipoproteins in Asian Indians.

Saha N, Wang G, Vasisht S, Kamboh MI.

Department of Human Genetics Graduate School of Public Health, University of Pittsburgh, PA 15261, USA.

Apolipoprotein A-IV (apo A-IV, protein; apo A4, gene) is a major constituent of triglyceride-rich and high-density lipoprotein particles and may, therefore, play an important role in lipid metabolism. We studied the distribution of two apo A4 polymorphisms at codons 347 (alleles A and T) and 360 (alleles 1 and 2) in relation to plasma lipoprotein-lipid and apolipoprotein levels in 176 non-fasting male blood donors from New Delhi, Northern India. The frequencies of the T allele at codon 347 and the 2 allele at codon 360 were 0.12 and 0.03 respectively. Carriers of the T allele (AT and TT genotypes) had significantly lower plasma total cholesterol (P = 0.04) and low density lipoprotein (LDL)-cholesterol (P = 0.02) levels than individuals homozygous for the A allele (AA genotype). The codon 347 polymorphism explained 2.2 and 2.6% of the phenotypic variation in total cholesterol and LDL-cholesterol, respectively. The 2 allele at codon 360 was associated with marginally reduced plasma LDL-cholesterol (P = 0.09) and increased triglyceride (P = 0.05) levels compared to the 1 allele. To further elucidate the combined effects of the two polymorphism we constructed two-site haplotypes. The haplotype data showed a stronger influence and explained 3.0 and 5.2% of the phenotypic variation in total cholesterol and LDL-cholesterol, respectively. The two uncommon haplotypes, T1 and A2, were associated with 24.2 and 23.5 mg/dl lower total cholesterol and 22.5 and 42.0 mg/dl lower LDL-cholesterol levels, respectively. The accentuated effect of apo A4 polymorphisms on non-fasting plasma cholesterol suggest that apo A-IV may play an important role in regulating the postprandial metabolism of lipoproteins.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9199279&dopt=Abstract cholesterol




Consumption of buckwheat protein lowers plasma cholesterol and raises fecal neutral sterols in cholesterol-Fed rats because of its low digestibility.

Kayashita J, Shimaoka I, Nakajoh M, Yamazaki M, Kato N.

Development, Health Care, Kissei Pharmaceutical Co., Ltd., Yoshino, Matsumoto 399, Japan.

Buckwheat protein product (BWP) has a strong hypocholesterolemic activity in rats fed a cholesterol-enriched diet. In this study, we examined the influence of BWP on fecal excretion of sterols and nitrogen in rats fed a diet containing 5 g/kg cholesterol and 1.25 g/kg sodium cholate, and we examined whether the cholesterol-lowering activity of BWP is due to its low digestibility. In Experiment 1, rats fed BWP for 3 wk had significantly lower concentrations of plasma cholesterol and enhanced excretion of fecal total neutral sterols and nitrogen compared with rats fed casein. There was a significant correlation between fecal total neutral sterols and nitrogen (r = 0.89, P < 0.01). Fecal excretion of acidic sterols was unaffected by BWP. In Experiment 2, plasma cholesterol in rats fed trypsin-digested BWP for 2 wk was significantly higher than that in rats fed intact BWP. In Experiment 3, rats were fed BWP, low-molecular-weight fraction of the digest of BWP (LMF ) or high-molecular-weight fraction of the digest of BWP (HMF ) for 3 wk. Plasma cholesterol was lower in the BWP group than in the LMF group (P < 0.05), whereas that in the HMF group was intermediate. The in vitro digestibility of BWP with pepsin and pancreatin was significantly lower than that of casein. The results suggest that the cholesterol-lowering effect of BWP is mediated by higher fecal excretion of neutral sterols and that lower digestibility of BWP is at least partially responsible for the effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9202097&dopt=Abstract cholesterol




Effects of cabbage leaf protein concentrate on the serum and liver lipid concentrations in rats.

Igarashi K, Satoh A, Numazawa S, Takahashi E.

Department of Bioproduction, Faculty of Agriculture, Yamagata University, Japan.

The effects of cabbage leaf protein concentrate (CLPC) on serum and liver lipid concentrations were determined in rats fed cholesterol-enriched and cholesterol-free diets. In rats fed the cholesterol-enriched diet with CLPC, total cholesterol, triacylglycerol and phospholipid concentrations in both the serum and liver, as well as the atherogenic index diet were significantly lower than those of the rats fed a casein diet. A supplement of methionine to the CLPC diet raised serum HDL-cholesterol and body weight gain, indicating that the addition of methionine to the CLPC diet is not only available to improve the nutritive value of CLPC but also to lower the atherogenic index. In rats fed the cholesterol-free diet, the liver total cholesterol and triacylglycerol concentrations of the CLPC-fed rats also showed lower values than those of the casein-fed rats, however, the serum total cholesterol concentration of the CLPC-fed rats did not differ from that of the casein-fed rats.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9219099&dopt=Abstract cholesterol




Increased levels of cholesterol esters in glioma tissue and surrounding areas of human brain.

Nygren C, von Holst H, Mansson JE, Fredman P.

Department of Neurosurgery, Karolinska Hospital, Stockholm, Sweden.

The proliferation of glioma cells requires cholesterol, which could be provided by synthesis within the cells or by uptake of cholesterol esters in particles of Low Density Lipoprotein (LDL). Cholesterol esters and cholesterol were therefore analysed in human glioma tissue, its surrounding areas and serum from 40 patients. The analyses revealed an increased concentration of cholesterol esters up to 100 times (0.1-10 mumol/g) in both tumour-tissue and surrounding areas compared with control material (< 0.1 mumol/g). The analyses also demonstrated that cholesterol esters in tumour tissue eminated mainly from serum. The cholesterol concentrations were significantly lower in tumour tissue compared with surrounding areas as expected. These results indicate that tumour cell proliferation utilises serum derived cholesterol esters presumably carried by LDL particles.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9231009&dopt=Abstract cholesterol