Cholesterol Journal Articles

Record 1141 to 1160

Associations of the HDL2 and HDL3 cholesterol subfractions with the development of ischemic heart disease in British men. The Caerphilly and Speedwell Collaborative Heart Disease Studies
Sweetnam, P. M., C. H. Bolton, et al. (1994), Circulation 90(2): 769-74.
Abstract: BACKGROUND: The relative importance of HDL2 and HDL3 cholesterol as risk factors for ischemic heart disease (IHD) is still uncertain. Their associations with the incidence of IHD in the Caerphilly and Speedwell prospective studies are described. METHODS AND RESULTS: The two studies have a common core protocol and are based on a total of 4860 middle-aged men from the general population. The first follow-up was at a nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell: 251 major IHD events had occurred. Lipid levels were measured on fasting samples. Different laboratories were used by the two studies. Each laboratory used ultracentrifugation to separate HDL2 and HDL3. Both subfractions were inversely associated with risk of IHD. Standardized relative odds of developing major IHD were 0.95 (95% confidence interval CI, 0.80 to 1.14) for HDL2 cholesterol and 0.83 (95% CI, 0.68 to 1.00) for HDL3 cholesterol in Caerphilly and 0.76 (95% CI, 0.57 to 1.01) for HDL2 and 0.64 (95% CI, 0.49 to 0.83) for HDL3 in Speedwell. The association with incident IHD appeared to be stronger for HDL3 in both areas. No linear combination of the two subfractions was a better predictor of IHD than total HDL cholesterol alone. CONCLUSIONS: In British men, both HDL2 and HDL3 cholesterol are inversely associated with the incidence of IHD. However, the prediction of the risk of IHD from total HDL cholesterol alone could not be improved upon by measurement of the two HDL subfractions. The relative value of the two HDL subfractions as predictors of risk is still unresolved. The uncertainty may be due, at least in part, to problems associated with their measurement.

Astrocytosis, microgliosis, metallothionein-I-II and amyloid expression in high cholesterol-fed rabbits
Zatta, P., P. Zambenedetti, et al. (2002), J Alzheimers Dis 4(1): 1-9.
Abstract: Cholesterol is considered a risk factor in vascular dementia as well as in Alzheimer's disease. Several biochemical, epidemiological and genetic aspects established a correlation between cholesterol concentration and Alzheimer's disease. Microglia activation, astrocytosis with metallothionein-I-II overexpression, amyloid beta intraneuronal accumulation and a rare formation of amyloid beta extracellular positive deposits were the major immunohistochemical features observed in the brain of high cholesterol-fed animals. The relevance on the cholesterol metabolism in Alzheimer's disease pathogenesis is also discussed.

Asymmetric requirement for cholesterol in receptor-bearing but not envelope-bearing membranes for fusion mediated by ecotropic murine leukemia virus
Lu, X., Y. Xiong, et al. (2002), J Virol 76(13): 6701-9.
Abstract: We show that fusion mediated by ecotropic murine leukemia virus envelope is dependent on cholesterol in receptor-bearing membranes. The effect is >10 times larger in insect cells than mammalian cells, probably because the former can be more extensively depleted of cholesterol. The fact that cholesterol is apparently not needed in envelope-bearing membranes suggests that it plays a role in an asymmetric step in membrane fusion and argues against a class of models in which cholesterol is important in symmetric fusion intermediates. The insect cell system has promise for clarifying the role of membrane rafts in other aspects of cell physiology.

Asymptomatic and manifest types of hypertriglyceridemia with normal and elevated blood cholesterol
Lipovetskii, B. M. (2003), Kardiologiia 43(8): 58-9.

At what levels of total low- or high-density lipoprotein cholesterol should diet/drug therapy be initiated? European guidelines
Assmann, G. (1990), Am J Cardiol 65(12): 11F-15F.
Abstract: The control of coronary artery disease depends primarily on its prevention at an early stage. Researchers generally agree that early prevention depends on the elimination or treatment of known risk factors, among which hyperlipidemia occupies a central position. Two European Consensus Conferences have concluded that therapy of hyperlipidemia should always start with dietary counseling. First, subjects with body mass indexes (weight/height) greater than 27 should lose weight. Second, the lipid-lowering diet should provide 55% of calories from carbohydrates; 10 to 15% from protein; and up to 30% from fat comprising 10% each of saturated, monounsaturated and polyunsaturated fatty acids; less than 300 mg/day cholesterol; 35 g/day of fiber derived largely from legumes and other vegetables; and fruit. Further reduction of fat consumption (to 20 to 25% of total energy) and of cholesterol (to less than 150 mg/day) may be attempted when patients respond inadequately to the standard diet. The goal of treatment is to minimize the risk of coronary artery disease and of pancreatitis. Where possible, a low-density lipoprotein cholesterol level of 135 mg/dl (3.5 mmol/liter) should be the goal in hypercholesterolemic patients with multiple or severe risk factors and a level of 155 mg/dl (4 mmol/liter) in the absence of other risk factors. Also, high-density lipoprotein cholesterol greater than 35 mg/dl and triglycerides less than 200 mg/dl are considered important goals of treatment. Some patients with hyperlipidemia do not respond adequately to diet and correction of underlying causes; drug treatment should then be instituted, but careful attention to diet should be continued.

At what levels of total low- or high-density lipoprotein cholesterol should diet/drug therapy be initiated? United States guidelines
LaRosa, J. C. (1990), Am J Cardiol 65(12): 7F-10F.
Abstract: Guidelines for the detection, evaluation and treatment of hypercholesterolemia in adults have been established in the United States. These guidelines recommend that total cholesterol levels be used for screening purposes. Total cholesterol levels greater than 240 mg/dl are considered "high," those from 200 to 239 mg/dl "borderline," and those less than 200 mg/dl "normal," regardless of the person's age or gender. All persons in the high category, as well as those in the borderline category who have other risk factors or established vascular disease, require measurements of low-density lipoprotein (LDL) cholesterol levels. LDL cholesterol levels are used to guide the selection of treatment. Patients with LDL cholesterol levels greater than 130 mg/dl are candidates for active diet therapy. Those whose LDL cholesterol levels are 160 to 190 mg/dl after 3 to 6 months of diet therapy are candidates for drug therapy. A high-density lipoprotein (HDL) level less than 35 mg/dl is considered a risk factor and may influence the level of LDL at which drug therapy is initiated. Some observers have expressed concern that these guidelines overemphasize LDL cholesterol at the expense of total cholesterol, HDL cholesterol and triglyceride levels. Nevertheless, the guidelines have been broadly accepted and currently serve as the basis for a widespread public-health education program.

Atherogenesis in diabetic cholesterol-fed rabbits
Nordestgaard, B. G. (1991), Dan Med Bull 38(1): 1-8.

Atherogenic cholesterol-containing circulating immune complexes--one of the components of the serum in patients with systemic lupus erythematosus
Gerasimova, E. V., Z. S. Alekberova, et al. (2003), Klin Med (Mosk) 81(9): 39-41.
Abstract: To estimate concentrations of cholesterol (CS) and immune complexes (IC) in patients with systemic lupus erythematosus (SLE), we examined 20 new SLE cases (all women, mean age 30.2 +/- 6.6 years, duration of the disease 2.6 +/- 1.5 years) with no history of corticosteroids treatment. The control group of 20 healthy patients was matched by age, body mass index and absence of risk factors. CS in IC precipitates was estimated by enzyme assays (kits by Boehrinnger Mannheim GmbH, Germany). The level of CS-containing IC (CS-IC) was significantly higher in SLE patients (11.9 +/- 2.7 mcg/ml) versus controls (6.0 +/- 2.2 mcg/ml, p < 0.05). The lipid spectrum was similar in the patients and controls. A significant positive correlation was registered between LDP CS and CS-IC levels (r = 0.774; p = 0.041). Association with other indices of blood lipid spectrum (total CS, triglycerides, HDP CS) was not observed. Thus, elevated level of CS-IC and association with LDP CS may be involved in atherogenesis of SLE patients.

Atherogenic index of plasma log(triglycerides/HDL-cholesterol): theoretical and practical implications
Dobiasova, M. (2004), Clin Chem 50(7): 1113-5.

Atheroma formation: defective control in the intimal round-trip of cholesterol
Kovanen, P. T. (1990), Eur Heart J 11 Suppl E: 238-46.
Abstract: This article is based on the concluding remarks by the author at the Ninth Paavo Nurmi Symposium on 'Lipoproteins and the Pathobiology of the Arterial Intima'. Circulating cholesterol is carried into the arterial intima, the site of atherogenesis, in low-density lipoprotein (LDL) particles, and from the intima back into the circulation in high-density lipoprotein (HDL) particles. At affected sites in the intima, cholesterol accumulates in deposits known as atheromas. These local accumulations are due to disturbances in the cholesterol flow through the intima, resulting in imbalance between inflow and outflow of cholesterol. The rate of cholesterol accumulation depends ultimately on the severity of the imbalance. The factor primarily responsible for this cholesterol imbalance appears to be local modification of LDL particles. Hence, to prevent accumulation of cholesterol in the intima, the production of modified LDL particles must be prevented. This can best be achieved by reducing the inflow of LDL particles into the intima. This, in turn, can be achieved by lowering the concentration of circulating LDL particles. In addition, increasing the concentration of circulating HDL particles should accelerate the rate of removal of cholesterol from the intima, so further improving the disturbed cholesterol balance at the atheromatous sites.

Atheromatous plaque reflects serum total cholesterol levels: a comparative morphologic study of endarterectomy coronary atherosclerotic plaques removed from patients from the southern part of India and Caucasians from Ottawa, Canada
Varghese, P. J., S. B. Arumugam, et al. (1998), Clin Cardiol 21(5): 335-40.
Abstract: BACKGROUND: Natives of South India have a very high incidence of coronary artery disease, despite low calorie and fat intake. HYPOTHESIS: This study was undertaken to determine whether morphologic features of atheromatous plaque reflect the serum total cholesterol. METHODS: Fifty-three endarterectomy specimens from patients (mean age 47 +/- 9 years, mean cholesterol 203 +/- 47 mg/dl) obtained from one cardiac surgeon working in a single institution in South India were evaluated. Morphologic findings were compared with 40 endoarterectomy specimens obtained from age-matched Caucasians from Ottawa, Canada, with a reported mean cholesterol of 262 +/- 47 mg/dl. Morphometric measurements of the vessel size, percent stenosis, and the various components of the atherosclerotic plaque were determined by computerized planimetry. RESULTS: The vessel size was smaller in the Indian than in the Canadian population (4.6 +/- 2.9 vs. 5.6 +/- 3.0 mm2, p = 0.07), the plaque area was less (4.3 +/- 2.3 vs. 5.3 +/- 2.8 mm2, p = 0.055) and the calculated percent stenosis was significantly less (93 vs. 96%, p = 0.028). Of all the parameters evaluated, only necrotic core in the Indian population (7.1 +/- 10.9% vs. Canadian 16.7 +/- 19.7%, p < 0.001) and proteoglycan deposition (7.9 +/- 11.2% vs. Canadian 3.7 +/- 5.3%, p < 0.023) were significantly different. Despite the Indians having low total cholesterol, there was greater diffuse double and triple-vessel disease and at a younger age than in the Caucasians. CONCLUSIONS: From our data, it appears that the mechanism of development of atherosclerotic disease in the Indians may be different because they have smaller vessels, smaller necrotic core, and greater proteoglycan deposition. Other etiologies, especially those related to a high carbohydrate diet (which is typical for South Indians), should be considered.

Atherosclerosis and cholesterol. The end of the controversy?
Heller, F. R. (1996), Acta Clin Belg 51(1): 1-7.

Atherosclerosis and sterol 27-hydroxylase: evidence for a role of this enzyme in elimination of cholesterol from human macrophages
Bjorkhem, I., O. Andersson, et al. (1994), Proc Natl Acad Sci U S A 91(18): 8592-6.
Abstract: 27-Hydroxycholesterol was found in surprisingly high amounts in atherosclerotic human femoral arteries. When human macrophages were cultured in a medium containing serum, there was a significant transfer of 27-hydroxy-cholesterol and 3 beta-hydroxy-5-cholestenoic acid from the cells into the medium. Sterol 27-hydroxylase (EC 1.14.13.15) is likely to be responsible for formation of the two products as shown by use of immunoblotting, a specific inhibitor, and the 18O-labeling technique. Sterol 27-hydroxylase has the unusual ability to hydroxylate the same methyl group three times to give a carboxylic acid; thus, 3 beta-hydroxy-5-cholestenoic acid is likely to be a direct product of the enzyme. The production of these steroids increased after addition of cholesterol to the culture medium. By using deuterium-labeled cholesterol, it was ascertained that most of the oxidized products were formed from exogenous cholesterol taken up by the cells. 27-Hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid are present in the circulation and are efficiently converted into bile acids in human liver. It is suggested that conversion of cholesterol into 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid represents a general defence mechanism for macrophages and possibly also other peripheral cells exposed to cholesterol. Absence of this defence mechanism may contribute to the premature atherosclerosis known to occur in patients with sterol 27-hydroxylase deficiency (cerebrotendinous xanthomatosis).

Atherosclerosis in Japanese Quail males selected for high or low plasma cholesterol
Siegel, H. S., S. M. Hammad, et al. (1995), Poult Sci 74(10): 1712-6.
Abstract: Three lines of Japanese quail males, unselected controls (CL), high response (HL), and low response (LL) lines, selected for plasma total cholesterol for 18 generations, were fed all-plant source, nonatherogenic diets to which 0 or.5% cholesterol were added from 6 to 18 wk of age. Atherosclerotic scores (AS) of aorta of HL birds fed cholesterol were significantly higher than those of LL birds fed cholesterol. Scores of LL fed cholesterol were not higher than LL not fed cholesterol. Fatty infiltration of muscularis and foam cell disruption of elastic fibers were observed in HL males fed cholesterol. In a second experiment, males of the three lines were fed from 6 to 14 wk of age four plant source diets to which were added: 1) 10% glucose monohydrate (cerelose); 2) 10% cerelose +.1% cholesterol; 3) 4% corn oil; or 4) 4% coconut oil. All diets were calculated to be isocaloric and isonitrogenous. Overall, AS of HL and CL males were significantly higher than LL males, but there were no effects of diet for the 56-d feeding period.

Atherosclerosis in young white males: arterial collagen and cholesterol
Miller, E. J., G. T. Malcom, et al. (1993), Matrix 13(4): 289-96.
Abstract: As part of a multicenter study on atherosclerosis, we examined defined segments of thoracic and abdominal aortas from 118 white males, age 15-34 years, who died from external causes. One half of each aorta specimen was graded for lesions. Intima-media preparations were assayed for collagen and cholesterol in two standardized regions (dorsal and ventral) derived from the alternate half of each segment. Even though the mean extent of intimal surface involvement with raised lesions remained minimal (0-6%), the data revealed a remarkable transition in vessel wall chemistry over this time span. For example, the amount of collagen per unit surface area increases with age in all vessel segments except the ventral domain of the thoracic aorta. The amount of collagen as a percent of total vessel protein rises with age only in the ventral and dorsal regions of the abdominal aorta. Free and esterified cholesterol levels per unit surface area increase with age in all vessel segments. There is a significant correlation between collagen and esterified cholesterol per unit surface area in all vessel regions with the exception of the abdominal ventral segment. In the latter segment increases in collagen per unit surface area occur without a corresponding increase in cholesterol level suggesting that connective tissue proliferation may actually precede lipid deposition in the genesis of atherosclerosis. Esterified cholesterol is present at higher levels in the dorsal domains of the thoracic and abdominal aortas than in the ventral domains. These findings provide chemical data confirming that the dorsal domains is the most lesion-prone region of these vessel segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Atherosclerosis mouse model induced by a high-cholesterol diet supplemented with beta-aminopropionitrile: effects of various anti-atherosclerotic agents on the biochemical parameters
Yamaguchi, Y., K. Yamada, et al. (1990), Jpn J Pharmacol 54(2): 187-96.
Abstract: A mouse model of atherosclerosis was produced by feeding a 1.5% cholesterol diet with 0.4% beta-aminopropionitrile (BAPN) fumarate, a chemical lathyrogen, for 10 weeks, and the pharmacological sensitivity and specificity of this model were evaluated biochemically with various hypolipidemic drugs and calcium antagonists. Histological findings on this model showed typical angiolathyrism with foam cells in the media of the thoracic aorta. Uniform and marked accumulation of cholesterol, notably esterified cholesterol, in the aorta was observed, although it was much less in mice receiving a high-cholesterol diet or BAPN alone. The reduction in elastin contents in the aorta was a characteristic feature of this model. Clofibrate, cetaben and elastase tended to prevent the increase of cholesterol contents in the aorta, together with their significant hypocholesterolemic effects. Nifedipine, diltiazem and verapamil showed a slight preventive effect on the cholesterol accumulation and on the reduction of elastin content in the aorta without a cholesterol lowering effect in the serum. MgCl2 was more effective than other calcium antagonists and even had a hypocholesterolemic effect. The results indicate that this mouse atherosclerosis model may be usable for primary drug evaluation.

Atherosclerosis prevention for the next decade: risk assessment beyond low density lipoprotein cholesterol
Lamarche, B. and G. F. Lewis (1998), Can J Cardiol 14(6): 841-51.
Abstract: Several lines of evidence have demonstrated that increased plasma cholesterol plays a primary role in the etiology of atherosclerosis and ischemic heart disease (IHD). Our ability to manage IHD adequately based on plasma cholesterol or low density lipoprotein (LDL) cholesterol concentrations is challenged, however, by evidence suggesting that a significant proportion of individuals with IHD or who will eventually develop IHD have desirable cholesterol concentrations. These observations have generated much interest in the scientific community, with the resultant identification of new metabolic risk factors that may help, in the future, to improve our ability to reduce the risk of IHD adequately. This review presents evidence that hypertriglyceridemia, particularly when associated with reduced high density lipoprotein (HDL) cholesterol concentrations and abdominal or visceral obesity, is a highly atherogenic phenotype, one that requires aggressive risk reduction management. Hypertriglyceridemia is frequently associated with elevated plasma apolipoprotein B concentrations, with states of hyperinsulinemia or insulin resistance and with small, dense LDL particles, which may all contribute to increase the risk of IHD further. This evidence suggests that a therapeutic strategy based on the assessment of plasma triglyceride concentrations, along with HDL cholesterol levels and abdominal obesity, may be a cost effective approach to assessing the high atherogenic risk of visceral obesity and insulin resistance. We can no longer afford to focus our attention exclusively on the detection and management of elevated LDL cholesterol concentrations, and need to adopt comprehensive risk reduction strategies in order to lower the incidence of IHD.

Atherosclerosis target of lipid-lowering therapy: is lower LDL cholesterol better?
Jones, P. H. (2003), Am J Manag Care Suppl: 1, 4-5.

Atherosclerosis, serum cholesterol and the homocysteine theory: a study of 194 consecutive autopsies
McCully, K. S. (1990), Am J Med Sci 299(4): 217-21.
Abstract: A retrospective study examined 194 consecutive autopsies to determine the proportion of cases of atherosclerosis without elevated serum cholesterol, diabetes mellitus, or hypertension. The study cases were classified into four groups, according to the cause of death and the degree of atherosclerosis. Cases in Group 1, in which death resulted from complications of severe atherosclerosis, have a mean serum cholesterol of 186.7 +/- 41.8 mg/dL, and the cholesterol is less than 200 in 65% and less than 250 in 92% of cases. Cases in Group 2, with severe atherosclerosis dying of other diseases, have a mean serum cholesterol of 174.6 +/- 60.4 mg/dL, and the cholesterol is less than 200 in 79% of cases and less than 250 in 89% of cases. Cases in Groups 3 and 4, with moderate and minimal atherosclerosis, respectively, have mean serum cholesterol values of 172.3 +/- 54.8 and 143.5 +/- 47.8 mg/dL, and the cholesterol is less than 200 in 71% and 92% and less than 250 in 92% and 96% of cases, respectively. Serum cholesterol is significantly associated with severity of atherosclerosis in the total sample (P = 0.01). Three fourths of all cases (147/194) have neither diabetes nor hypertension, and in 74% of these cases (109/147) the cholesterol is less than 200 and in 92% (135/147) the cholesterol is less than 250. In 66% (80/122) of the cases with severe atherosclerosis, the disease developed without evidence of elevated serum cholesterol, diabetes, or hypertension. Blood homocysteine, which has been shown by other studies to be an independent risk factor for atherosclerosis, is recommended for assessing prognosis in these cases.

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