Gender differences in response to a hypercholesterolemic diet in hamsters: effects on plasma lipoprotein cholesterol concentrations and early aortic atherosclerosis.

Wilson TA, Nicolosi RJ, Lawton CW, Babiak J.

Department of Health and Clinical Science, Center for Chronic Disease Control, University of Massachusetts Lowell 01854, USA.

Gender is a strong predictor of coronary heart disease (CHD) susceptibility and reports indicate that males are more likely to develop CHD compared to age-matched premenopausal females. To test whether similar gender differences exist in hamsters, 16 male and 16 female F1B Golden Syrian hamsters, aged 10 weeks, were fed a hypercholesterolemic nonpurified diet (HCD) containing 10% coconut oil and 0.05% cholesterol for 12 weeks. Plasma lipid and lipoprotein cholesterol concentrations, LDL oxidative susceptibility, LDL tocopherol concentrations, LDL fatty acid composition, LDL particle size, plasma estradiol and testosterone concentrations, and early aortic atherosclerosis were analyzed. Female hamsters had significantly lower plasma total cholesterol and nonhigh-density lipoprotein cholesterol (nonHDL-C) and greater high-density lipoprotein cholesterol (HDL-C) concentrations compared to male hamsters (-15, -33, and 33%; respectively). Female hamsters had significantly greater LDL particle size (4%), LDL 22:6 (21%) fatty acid, and rate of LDL oxidation (34%) compared to male hamsters. Female hamsters had a significantly higher concentration of plasma estradiol (49%) compared to male hamsters. Female hamsters also had significantly less early aortic atherosclerosis compared to male hamsters (-77%). In female hamsters, aortic fatty streak formation was significantly associated with plasma nonHDL-C (r = 0.76, P<0.0007), LDL particle size (r = -0.66, P<0.005), plasma TC (r = 0.68. P<0.004), and lag phase of LDL oxidation (r = 0.84. P<0.02). In male hamsters, aortic fatty streak formation was significantly associated with plasma nonHDL-C (r = 0.52, P<0.04), plasma TC (r = 0.55, P<0.03), plasma TG (r = 0.79, P<0.0003), and LDL 22:6 (r = -0.78, P<0.03) with no association with any measures of LDL oxidation susceptibility. This study demonstrates that female hamsters have an improved plasma lipoprotein cholesterol profile, larger LDL particle size, and less early aortic atherosclerosis compared to male hamsters fed the same HCD.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10487490&dopt=Abstract cholesterol




Contribution of the cholesteryl ester transfer protein gene TaqIB polymorphism to the reduced plasma HDL-cholesterol levels found in abdominal obese men with the features of the insulin resistance syndrome.

Vohl MC, Lamarche B, Pascot A, Leroux G, Prud'homme D, Bouchard C, Nadeau A, Despres JP.

Lipid Research Center, Quebec, Canada.

OBJECTIVE: The aim of this study was to examine the relation between the CETP-TaqIB polymorphism and reduced plasma HDL-cholesterol levels commonly observed among men characterized by abdominal obesity and features of the insulin resistance syndrome. SUBJECTS: A total of 187 sedentary men, non-smokers and free from metabolic disorders were classified on the basis of their CETP-TaqIB genotype. RESULTS: Plasma HDL and HDL3-cholesterol concentrations as well as the CETP activity were significantly different between the three genotypes, B1B1 men having significantly lower HDL and HDL3-cholesterol levels and higher CETP activity than B2B2 homozygotes. A 2x3 ANOVA was used to determine the source of variation of plasma HDL and HDL2-cholesterol levels among the three genotypic groups of men divided on the basis of either a high (>/=27 kg/m2) or a low (<27 kg/m2) BMI, a high (>/=130 cm2) or a low (<130 cm2) accumulation of visceral adipose tissue assessed by computed tomography, or a low versus a high fasting plasma insulin concentration (using the median value as a cut-off point). The effect of the CETP genotype observed on plasma HDL-cholesterol concentrations was attenuated among men with features of the insulin resistance syndrome. It seems that the expected raising effect of the B2 allele on plasma HDL-cholesterol concentrations was blunted in the presence of a BMI>/=27 kg/m2, a high accumulation of visceral adipose tissue or hyperinsulinaemia. CONCLUSION: Our data indicate that the CETP gene TaqIB polymorphism influences plasma CETP activity on one hand and plasma HDL-cholesterol concentrations on the other hand among men. The association between the TaqIB polymorphism and plasma HDL-cholesterol concentrations is altered by the presence of abdominal obesity and some features of the insulin resistance syndrome.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10490796&dopt=Abstract cholesterol




[Recent determination of cholesterolemia in a healthy adult population from Pamplona]

[Article in Spanish]

Martinez-Gonzalez MA, Hernandez I, Villar J, Riverol M, Miranda P, de Irala Estevez J.

Unidad de Epidemiologia y Salud Publica, Universidad de Navarra. mamartinez unav.es

BACKGROUND: The aims of the study were to assess the proportion of the healthy adult population from Pamplona who were aware of their blood cholesterol levels, and to identify factors associated with this awareness. METHODS: A cross-sectional study was implemented with personal interview to 1066 citizens from Pamplona selected by a random routes sampling procedure. The city was stratified in three urban districts according to the socioeconomic status (high, middle, low). The response rate was 91.8%. The crude odds ratios were computed and a multivariable logistic regression model was fitted using awareness of the blood cholesterol level as the dependent variable, and age, sex, socioeconomic status and smoking as independent variables. RESULTS: 71.2% of the sample (95% CI: 68.3-74.0) reported having some cholesterol determination during the last five years. The multivariate analysis disclosed that non-smokers were aware of their cholesterol levels more frequently than smokers (adjusted OR = 1.38; 95% CI 1.0-1.9), determination of cholesterolemia was also less frequent in individuals under 30 years old and in females (adjusted OR in males: 1.5; 95% CI 1.1-2.0). Regarding socioeconomic status, cholesterol measurement was more frequent in middle and high levels with adjusted OR = 3.2; 95% CI 2.2-4.71 and 1.59; 95% CI 1.11-2.27), respectively. CONCLUSIONS: Cholesterol awareness was more frequent in older individuals and among males. It is remarkable that blood cholesterol measurement was less likely in population groups with worse coronary risk profile (lower socioeconomic status, smokers). This study suggests that there is a need for improving the awareness and control of blood cholesterol levels in healthy adults from Pamplona.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11002898&dopt=Abstract cholesterol




Apolipoprotein A-I (R151C)Paris is defective in activation of lecithin: cholesterol acyltransferase but not in initial lipid binding, formation of reconstituted lipoproteins, or promotion of cholesterol efflux.

Daum U, Langer C, Duverger N, Emmanuel F, Benoit P, Denefle P, Chirazi A, Cullen P, Pritchard PH, Bruckert E, Assmann G, von Eckardstein A.

Institut fur Arterioskleroseforschung an der Universitat Munster, Germany.

ApoA-I(R151)Paris is a natural apolipoprotein (apo) A-I variant that is associated with low levels of high-density lipoprotein cholesterol (HDL-cholesterol) and the partial deficiency of lecithin:cholesterol acyl-transferase (LCAT) in the plasma of heterozygous carriers. We compared the abilities of recombinant normal apoA-I and recombinant apoA-I(R151C)Paris to clear an emulsion of dimyristoylphosphatidylcholine (DMPC), to form reconstituted lipoproteins with dipalmitoylphosphatidylcholine (DPPC), to activate LCAT, and to promote efflux of biosynthetic cholesterol from porcine aortic smooth muscle cells (SMCs) or of exogenous cholesterol from lipid-loaded mouse peritoneal macrophages. Recombinant apoA-I(R151C)Paris occurred in monomeric and dimeric forms at a ratio of 60:40. Normal apoA-I and apoA-I(R151C)Paris cleared DMPC emulsions at equal rates. Both isoforms associated completely with DPPC during cholate dialysis. Normal apoA-I formed one single particle with a mean diameter of 9.3 nm, whereas apoA-I(R151)Paris gave rise to three particles with mean diameters of 9.3 nm (containing 74% of apoA-I), 10.6 nm, and 12.1 nm, respectively. Compared to normal apoA-I, apoA-I(R151C)Paris had a reduced LCAT-cofactor activity with a 60% lower Vmax/Km ratio due to a 50% higher affinity constant, Km. During incubations for 10 min and 360 min, normal apoA-I/DPPC complexes and apoA-I(R151C)Paris/DPPC complexes were equally efficient in releasing biosynthetic cholesterol from SMCs. In the lipid-free form, apoA-I(R151C)Paris induced normal hydrolysis of cholesteryl esters and normal cholesterol efflux from lipid-loaded mouse-peritoneal macrophages. In conclusion, in addition to its ability to form homo- and heterodimers, apoA-I(R151C)Paris is characterized by defective LCAT-cofactor activity but by normal lipid binding and cholesterol-efflux-promoting abilities.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10543393&dopt=Abstract cholesterol




Cholesterol-lowering activity of naringenin via inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl coenzyme A:cholesterol acyltransferase in rats.

Lee SH, Park YB, Bae KH, Bok SH, Kwon YK, Lee ES, Choi MS.

Department of Nutrition and Food Science, Kyungpook National University, Taegu, South Korea.

The effects of dietary supplementation of a citrus bioflavonoid, naringenin, on the cholesterol metabolism were studied. For 42 days male rats were fed a 1% (wt/wt) high-cholesterol diet with or without a naringenin supplementation (0.1%, wt/wt) to study its effect on plasma lipid levels, hepatic lipid contents, activities of hepatic acyl coenzyme A:cholesterol O-acyltransferase (ACAT) and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and the excretion of fecal neutral sterols. Naringenin did not significantly alter the concentration of plasma triglycerides, but lowered the plasma cholesterol (3.80 vs. 3.12 mmol/l) concentration and the hepatic cholesterol content (70.3 vs. 54.0 mg/g) significantly (p < 0.05) compared to those of the controls. HMG-CoA reductase (1,879.0 vs. 1,715.0 pmol/min/mg) and ACAT activities (806.0 vs. 563.0 pmol/min/mg) were significantly lower in the naringenin-supplemented group than in controls. Naringenin supplementation caused a marked decrease in the excretion of fecal neutral sterols (242.9 mg/day) compared to the controls (521.9 mg/day). These results show that naringenin lowers the plasma and hepatic cholesterol concentrations by suppressing HMG-CoA reductase and ACAT in rats fed a high-cholesterol diet.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10545673&dopt=Abstract cholesterol




Leisure-time physical activity and coronary risk factors in women.

Ashton WD, Nanchahal K, Wood DA.

Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK. wdashton compuserve.com

BACKGROUND: Evidence that physical activity is cardioprotective in women is not as strong as that observed in men. Furthermore, the extent to which exercise protects against coronary heart disease via its influence on classical risk factors remains unclear. This study examines the relationship between reported physical activity, a range of coronary heart disease risk factors and a 10-year predicted coronary heart disease risk score. METHODS: A cross-sectional study of 14,077 female employees aged 30-64 years who were screened between 1988 and 1991 was employed. Measurements included systolic and diastolic blood pressure, body mass index, serum total cholesterol, high-density lipoprotein cholesterol, total cholesterol:high-density lipoprotein cholesterol ratio, low-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein a and fasting blood glucose. Participants were divided into three groups according to reported average frequency of vigorous leisure-time physical activity, that is zero, one to two, or three or more episodes per week. RESULTS: Increasing activity frequency was associated with lower systolic and diastolic blood pressure, total cholesterol, total cholesterol:high-density lipoprotein cholesterol ratio, triglycerides and body mass index (all P < 0.001), low-density lipoprotein cholesterol (P = 0.003), apolipoprotein B (P = 0.04) and blood glucose (P = 0.01) and higher high-density lipoprotein cholesterol (P < 0.001) and apolipoprotein A1 (P = 0.03). There was no association with lipoprotein a. After controlling for possible confounders, these relationships remained statistically significant except for apolipoprotein B and glucose. The odds ratios for being in the top quintile of predicted 10-year coronary heart disease risk for individuals in each category of activity were 1.0 (inactive), 0.70 (one to two episodes of activity per week) and 0.77 (three or more episodes of activity per week). CONCLUSION: Women engaging in vigorous, leisure-time physical activity have a less atherogenic coronary heart disease risk factor profile than those who do not, which translates into a potential reduction of approximately 30% in coronary heart disease risk.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11006896&dopt=Abstract cholesterol




The association of hyperlipidemia with retinopathy in diabetic patients aged 15-50 years in the county of Umea.

Larsson LI, Alm A, Lithner F, Dahlen G, Bergstrom R.

Department of Ophthalmology, Uppsala University Hospital, Sweden.

PURPOSE: To study possible associations between serum lipid levels and degree of retinopathy in a population-based study on a specific age-group of patients with diabetes mellitus in the county of Umea, Sweden. METHODS: All patients with diabetes mellitus aged 15-50 years living in the county of Umea were invited to the study. The participating subjects had a standard clinical examination and an eye examination performed. Seven-field stereoscopic photographs were taken of each eye, and the photos were sent to Grading Center, Hammersmith Hospital, London, U.K. for grading of the retinopathy. Blood samples were drawn for analysis of lipoprotein(a), high density lipoprotein (HDL) cholesterol, cholesterol and triglycerides. Univariate and multivariate statistical analyses were performed. RESULTS: In the present study only patients with type 1 diabetes mellitus were included, and 285 of the invited 308 diabetic subjects (93%) took part. When univariate analysis was applied we found statistically significant associations between higher lipoprotein(a) levels, higher triglyceride levels, higher cholesterol levels, lower HDL cholesterol/total cholesterol ratios and increasing severeness of retinopathy. However, in the multivariate analysis triglyceride levels lost their importance while all other significant associations were still present. CONCLUSION: Associations were found between higher levels of serum total cholesterol, declining ratios of high density lipoprotein (HDL) cholesterol/total cholesterol, higher levels of serum lipoprotein(a) and more severe retinopathy in diabetes mellitus type 1. No such association was found between serum triglycerides and degree of retinopathy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10551307&dopt=Abstract cholesterol




Enhanced cholesterol reduction by simvastatin in diltiazem-treated patients.

Yeo KR, Yeo WW, Wallis EJ, Ramsay LE.

University Section of Clinical Pharmacology and Therapeutics, Royal Hallamshire Hospital, Sheffield, UK. k.r.yeo sheffield.ac.uk

AIMS: To investigate whether an interaction between diltiazem and the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin may enhance the cholesterol-lowering response to simvastatin in diltiazem-treated patients. METHODS: One hundred and thirty-five patients attending the Sheffield hypertension clinic who started consecutively on simvastatin for primary or secondary prevention of coronary heart disease (CHD) during the 2 years June, 1996-May 1998 were surveyed. From the clinic records we extracted and recorded absolute and percentage cholesterol responses to the starting dose of simvastatin and coprescription of diltiazem. RESULTS: The cholesterol reduction for the 19 patients on diltiazem was 33.3% compared with 24.7% in the remaining 116 patients (median difference 8.6%, 95% CI 1.1-12.2%, P<0.02). The interindividual variability of cholesterol response to simvastatin was greater for patients not taking diltiazem than for those patients taking diltiazem. The ratio of the variances in response for the nondiltiazem group relative to the diltiazem group was 1.34 at 10 mg simvastatin daily (not significant, 95% CI 0.16-4.11), and 3.42 at 20 mg daily (P<0.01, 95% CI 1.26-7.18). Concurrent diltiazem therapy (P<0.04), age (P=0.001) and starting dose of simvastatin (P=0.002) were found to be significant independent predictors of percentage cholesterol response. CONCLUSIONS: Patients who take both simvastatin and diltiazem may need lower doses of simvastatin to achieve the recommended reduction in cholesterol. The pharmacokinetic and pharmacodynamic aspects of this interaction need further study to confirm an enhanced effect on cholesterol reduction, and exclude an increased risk of adverse events.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10583033&dopt=Abstract cholesterol




Serum cholesterol levels in college students: opportunities for education and intervention.

Sparling PB, Snow TK, Beavers BD.

Department of Health and Performance Sciences, College of Sciences, Georgia Institute of Technology, Atlanta, USA. phil.sparling sac.gatech.edu

Elevated serum cholesterol levels have been shown to be associated with premature atherosclerosis in adolescents and young adults. The National Cholesterol Education Program recommends cholesterol screening for all adults aged 20 years or older, but normative data on the college-age population are limited. At a university where lipid profiles are made available to students in selected health/wellness courses, the authors analyzed and summarized lipid profiles on 1,088 undergraduates. Mean total cholesterol levels were similar for men (165 +/- 33 mg/dL) and women (168 +/- 27 mg/dL). The men, however, had significantly lower high-density lipoprotein (HDL) cholesterol and higher low-density lipoprotein (LDL) cholesterol than the women. One hundred twenty-one students (11.1% of the sample) had elevated serum cholesterol levels (LDL-C > or = 130 mg/dL). Cholesterol screening can be used as an educational tool for college students to reinforce the link between lipid levels and health habits.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10584446&dopt=Abstract cholesterol