Average Serum Cholesterol Concentrations Research Articles

Influence of genetic polymorphisms on responsiveness to dietary fat and cholesterol

Genes influence quantitative variations in plasma lipoprotein concentrations. For example, intake of dietary saturated fat and cholesterol raises the average serum cholesterol concentration, leading to a higher risk of coronary artery disease in populations. However, not all individuals within the population are susceptible: genetic factors appear to render individuals either "dietary responsive" or "dietary nonresponsive." In this review, we focus on current knowledge about the influence of genetic polymorphisms in certain genes on the lipoprotein response to dietary fat and cholesterol. Our preliminary studies in the Dietary Intervention Study in Children suggest a significant dose-response relation between the decrease in LDL cholesterol from baseline to 36 mo of follow-up in both the intervention group (who consumed a low-fat, low-cholesterol diet) and the usual care group (who consumed a regular diet) and the presence of the APOA1*A allele at the M1 site and the + site at the M2 site of the gene encoding apolipoprotein (apo) A-I. The DNA polymorphisms on the genes encoding apo A-IV, apo B, apo C-III, apo E, lipoprotein lipase, cholesteryl ester transfer protein, lecithin:cholesterol acyltransferase (phosphatidylcholine-sterol O:-acyltransferase), and LDL receptor were found by others to be associated with the plasma lipoprotein response to dietary intervention. Possible mechanisms involved in these effects are discussed and certain discrepancies in the literature about some genetic effects on responsiveness are analyzed. An improved understanding of the influence of specific genes on lipoprotein responsiveness to dietary fat and cholesterol may allow us to identify and counsel certain individuals to avoid high-fat diets so that they may reduce their risk of developing hyperlipidemia and coronary artery disease.

Serum cholesterol and coronary artery disease in populations with low cholesterol levels: The Indian paradox

Objective: To examine the relation between serum cholesterol and coronary artery disease prevalence below the range of cholesterol values generally observed in developed countries. Design and Setting: Cross-sectional survey of two randomly selected villages from Moradabad district and 20 randomly selected streets in the city of Moradabad. Subjects and methods: 3575 Indians, aged 25–64 years including 1769 rural (894 men, 875 women) and 1806 urban (904 men, 902 women) subjects. The survey methods were questionnaires, physical examination and electrocardiography. Results: The overall prevalences of coronary artery disease were 9.0% in urban and 3.3% in rural subjects and the prevalences were significantly ( P<0.001) higher in men compared to women in both urban (11.0 vs. 6.9%) and rural subjects (3.9 vs. 2.6%). The average serum cholesterol concentrations were 4.91 mmol/l in urban and 4.22 mmol/l in rural subjects without any sex differences. The prevalences of coronary artery disease were significantly higher among subjects with low and high serum cholesterol concentration compared to subjects with very low cholesterol and showed a positive relation with serum cholesterol within the range of serum cholesterol level studied in both rural and urban in both sexes. Among subjects with low serum cholesterol, there was a higher prevalence of coronary risk factors, hypertension, diabetes, obesity and sedentary lifestyle. Serum cholesterol level showed a significant positive relation with low density lipoprotein cholesterol and triglycerides in all the four subgroups. Logistic regression analysis after pooling of data from both rural and urban, with adjustment of age showed that low serum cholesterol level (odds ratio: men 0.96, women 0.91) had a positive strong relation with coronary artery disease and there was no evidence of any threshold. Diabetes mellitus (men 0.73, women 0.74) and sedentary lifestyle (men 0.86, women 0.74) were significant risk factors of coronary disease in both sexes. Hypertension (men 0.82, women 0.64) and smoking (men 0.81, women 0.52) were weakly associated with coronary disease in men but not in women. Conclusion: Serum cholesterol level was directly related to prevalence of coronary artery disease even in those with low cholesterol concentration (<5.18 mmol/l). It is possible that some Indian populations may benefit by increased physical activity and decline in serum cholesterol below the range of desired serum cholesterol in developed countries.

Supplementation with Isoflavonoid Phytoestrogens Does Not Alter Serum Lipid Concentrations: A Randomized Controlled Trial in Humans ,

Isoflavonoids are a class of flavonoids that are derived in the human diet mainly from soybean-based foods. The major dietary isoflavonoids, genistein and daidzein, have estrogen-like activity and are classed as phytoestrogens. Because estrogens can lower serum LDL cholesterol and raise HDL cholesterol, the objective of this study was to determine if isoflavonoids could improve serum lipids in healthy subjects. Forty-six men and 13 postmenopausal women not receiving hormone replacement therapy completed a randomized, double-blind, placebo-controlled trial of two-way parallel design and 8 wk duration. One tablet containing 55 mg of isoflavonoids (predominantly in the form of genistein) or one placebo tablet was taken daily with the evening meal. Subjects maintained their usual diet and physical activity, which were unchanged throughout the intervention. Measurement of isoflavonoids and their metabolites in 24-h urine samples provided an assessment of compliance and of isoflavonoid metabolism. Serum total, LDL, HDL and HDL subclass cholesterol, triglycerides and lipoprotein (a) were assessed at baseline and during the last week of intervention. After adjustment for baseline values, no significant differences in postintervention serum lipid and lipoprotein (a) concentrations between groups were identified. Further adjustment for age, gender and weight change did not alter the results. In addition, changes in urinary isoflavonoids were not significantly correlated with changes in serum lipids and lipoprotein (a). Therefore, this study does not support the hypothesis that isoflavonoid phytoestrogens can improve the serum lipids, at least in subjects with average serum cholesterol concentrations.

Serum cholesterol concentration and death from suicide in men: Paris prospective study I.

To investigate whether low serum cholesterol concentration or changing serum cholesterol concentration is associated with risk of suicide in men. Cohort study with annual repeat measurements of serum cholesterol concentration (for up to four years). Paris, France. 6393 working men, aged 43-52 in 1967-72, who had at least three measurements of serum cholesterol concentration. Individual change over time in serum cholesterol concentration (estimated using within person linear regression method); death from suicide during average of 17 years' follow up after last examination. 32 men committed suicide during follow up. After adjustment for age and other factors, relative risk of suicide for men with low average serum cholesterol concentration (< 4.78 mmol/l) compared with those with average serum cholesterol concentration of 4.78-6.21 mmol/l was 3.16 (95% confidence interval 1.38 to 7.22, P = 0.007). Men whose serum cholesterol concentration decreased by more than 0.13 mmol/l a year had multivariate adjusted relative risk of 2.17 (0.97 to 4.84, P = 0.056) compared with those whose cholesterol remained stable (change of < or = 0.13 mmol/l a year). Both low serum cholesterol concentration and declining cholesterol concentration were associated with increased risk of death from suicide in men. Although there is some evidence in favour of a concomitant rather than a causal effect for interpreting these associations, long term surveillance of subjects included in trials of lipid lowering treatments seems warranted.

Two-Compartment Model of Cholesterol Kinetics for Establishment of Treatment Strategy of LDL Apheresis in Nephrotic Hypercholesterolemia

Cholesterol kinetics in the time course after LDL apheresis using a dextran sulfate cellulose column was analyzed by adapting a two-compartment cholesterol kinetic model. Fifteen sets of serial serum cholesterol concentrations after LDL apheresis from 4 patients with drug-resistant nephrotic hypercholesterolemia due to focal glomerulosclerosis (FGS) were analyzed and cholesterol kinetic parameters were estimated with the nonlinear least-squares method. The fractional cholesterol catabolic rates (Kc; 0.171 +/- 0.073/day, mean +/- SD) were markedly decreased as reported in familial hypercholesterolemia (homo: 0.101/day, hetero: 0.280/day). Cholesterol generation rates (G; 68.0 +/- 28.7 mg/dl/day, mean +/- SD) considerably overlapped the normal range (39.2-77.5 mg/dl/day). This result was compatible with an earlier report that Kc was reduced earlier than G in nephrotic hypercholesterolemia. The time average serum cholesterol concentrations (TAC) in the rebound phase after LDL apheresis can be simulated using these kinetic parameters by the Runge-Kutta-Gill method. According to our previous report, TAC must be reduced to under a near-normal level in order to obtain a beneficial effect on nephrotic syndrome due to FGS. In 10 sets out of the 15, once-weekly treatment of LDL apheresis was sufficient to achieve this aim, but in the remaining 5 cases, more frequent LDL apheresis up to twice a week was necessary in the early phase of treatment. In conclusion, the two-compartment cholesterol kinetic model is useful in clarifying the abnormal cholesterol kinetics in nephrotic syndrome and may be helpful in establishing a more rational strategy of LDL apheresis for nephrotic hypercholesterolemia.

Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations.

To examine the relation between serum cholesterol concentration and mortality (from coronary heart disease and from other causes) below the range of cholesterol values generally seen in Western populations. Prospective observational study based on 8-13 years of follow up of subjects in a population with low cholesterol concentrations. Urban Shanghai, China. 9021 Chinese men and women aged 35-64 at baseline. Death from coronary heart disease and other causes. The average serum cholesterol concentration was 4.2 mmol/l at baseline examination, and only 43 (7%) of the deaths that occurred during 8-13 years of follow up were attributed to coronary heart disease. There was a strongly positive, and apparently independent, relation between serum cholesterol concentration and death from coronary heart disease (z = 3.47, p less than 0.001), and within the range of usual serum cholesterol concentration studied (3.8-4.7 mmol/l) there was no evidence of any threshold. After appropriate adjustment for the regression dilution bias, a 4 (SD 1)% difference in usual cholesterol concentration was associated with a 21 (SD 6)% (95% confidence interval 9% to 35%) difference in mortality from coronary heart disease. There was no significant relation between serum cholesterol concentration and death from stroke or all types of cancer. The 79 deaths due to liver cancer or other chronic liver disease were inversely related to cholesterol concentration at baseline. Blood cholesterol concentration was directly related to mortality from coronary heart disease even in those with what was, by Western standards, a "low" cholesterol concentration. There was no good evidence of an adverse effect of cholesterol on other causes of death.

Effects of dietary cholesterol and hypothyroidism on rat apolipoprotein mRNA metabolism.

The effects of dietary cholesterol and hypothyroidism on the mRNA levels of rat apolipoproteins A-I, A-IV, and E were measured in extracts of rat liver and rat intestine by hybridization to specific cDNA. Four groups, each comprised of six rats, were fed diets consisting of normal laboratory rat chow and either no supplements (control); 5% lard, 1% cholesterol, and 0.3% taurocholic acid (CF); 5% lard, 1% cholesterol, 0.3% taurocholic acid, and 0.1% propylthiouracil (CF-PTU); or 0.1% propylthiouracil (PTU) for 32 days. At the conclusion of the diets, serum cholesterol, triiodothyronine, and thyroxine levels were measured. The average serum cholesterol concentrations for the four groups were 50.4 +/- 3.7, 75.6 +/- 15.3, 135.3 +/- 41.5, and 73.3 +/- 16.4 mg/dl, respectively. The presence of propylthiouracil in the diets significantly lowered triiodothyronine and thyroxine levels in the serum. The mRNA levels for apolipoproteins A-I and A-IV in rat liver decreased significantly after the feeding of the CF-PTU diet (31 +/- 4% and 32 +/- 3% of normal, respectively) and the PTU diet (34 +/- 8% and 43 +/- 12% of normal, respectively), but showed little change after the CF diet (88 +/- 16% and 108 +/- 15% of normal, respectively). The effects of dietary propylthiouracil on the hepatic mRNA levels for apolipoproteins A-I and A-IV imply a role for thyroid hormones in regulating the mRNA levels for these apolipoproteins in rat liver. ApoE mRNA levels in the rat liver decreased slightly after the CF-PTU diet (74 +/- 12% of normal) and after the PTU diet (73 +/- 10% of normal).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative primate atherosclerosis: I. Tissue Cholesterol Concentration and Pathologic Anatomy

Stump-tailed macaques (Macaca arctoides), African green monkeys (Cercopithecus aethiops), squirrel monkeys (Saimiri sciureus), and woolly monkeys (Lagothrix lagothricha) were fed control, solid atherogenic (1 mg cholesterol/cal) or liquid diets containing 0, 0.5, or 1 mg cholesterol/cal.Stump-tailed macaques fed the solid atherogenic diet had the highest tissue and serum cholesterol concentration (about 700 mg/dl) and the most extensive atherosclerosis. These monkeys appeared to respond differently to diets containing 1 mg cholesterol/cal. Those animals fed the liquid diet had higher liver cholesterol concentration but lower serum cholesterol concentration than animals fed the solid diet. African green monkeys fed the solid atherogenic diet had serum cholesterol concentrations of about 450 mg/dl. A greater percentage of the abdominal aorta was covered by plaque than the thoracic aorta. Coronary artery atherosclerosis was focal with the largest plaques being found in the left main coronary artery. The microscopic appearance of these plaques was similar to that of plaques from people.Squirrel monkeys fed the atherogenic diet were the most variable group. The average serum cholesterol concentration averaged about 450 mg/dl (range: 291 to 716). The percentage of aorta covered by plaque ranged from 0 to 55% with more thoracic than abdominal aortic atherosclerosis. There were findings consistent with hemorrhage in plaques from two animals. These monkeys, like stump-tailed macaques but unlike African green monkeys had relatively high liver cholesterol concentrations.Woolly monkeys appeared to develop atherosclerosis when fed 1 mg cholesterol/cal but did not have greatly elevated serum cholesterol concentrations.

Concentration of cholesterol and of lipid phosphorus in blood serum in multiple sclerosis.

HYPERCHOLESTEREMIA in multiple sclerosis has been reported by several investigators. 1 In three of these studies 1a-c the number of patients was too small to permit full confidence in the findings, and in two 1a,b the range of control serum-cholesterol concentrations with which the data from patients were compared was considerably below that which is usually accepted as normal. In one of these investigations 1c no control values were cited. Only one recent report 1d includes data on an acceptably large number of patients with multiple sclerosis. Average serum-cholesterol concentrations of 271, 267, and 230 mg. per 100 ml. were found, respectively, for 25 patients in relapse, 38 patients in remission, and 30 control subjects. The higher values for the patients were statistically significant, even though the average control concentration would be regarded by many as abnormally high. We were not satisfied that the available evidence was sufficient to establish