| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| High K diets markedly reduce atherosclerotic cholesterol ester deposition in aortas of rats with hypercholesterolemia and hypertension Tobian, L., T. M. Jahner, et al. (1990), Am J Hypertens 3(2): 133-5. Abstract: High K diets prevent hypertensive endothelial injury and intimal thickening. Cholesterol esters often deposit during hypercholesterolemia. Would a high K diet influence cholesterol ester deposits? In a normal rat on a normal diet, no cholesterol esters are detected in the aorta. Stroke prone SHR rats were fed for 3 months a basic diet containing 4% cholesterol, 14% coconut oil and 7% NaCl. One group of 13 rats had normal (5%) K in the diet. Another group of 10 rats ate high (2.1%) K. Mean intraarterial blood pressures averaged 165 mm Hg in the normal K group and 161 mm Hg in the high K group (P = NS). The serum cholesterol averaged 229 mg/dL in the normal K group and 214 in the high K group (P = NS). Total aortic cholesterol esters per rat involving 16 and 18 carbon chain fatty acids averaged 187 micrograms in normal K v 68 micrograms in high K, measured by gas chromatography. These were the main esters; other esters were negligible. Thus high K reduced cholesterol ester deposits by 64% (P less than.0003), even though blood pressure and cholesterol levels were quite similar in the two groups. Both high cholesterol and high BP injure endothelial cells and increase invasion of macrophages and vascular smooth muscle cells into the intima and increase endothelial permeability to proteins. With high plasma cholesterol, these processes lead to atherosclerosis with cholesterol ester deposition. The high K diet, by protecting endothelial cells, can greatly decrease this cholesterol ester deposition. This effect could possible be useful for preventing atherosclerotic complications such as heart attacks in human hypertension. |
| High level expression of human apolipoprotein A-I in transgenic rats raises total serum high density lipoprotein cholesterol and lowers rat apolipoprotein A-I Swanson, M. E., T. E. Hughes, et al. (1992), Transgenic Res 1(3): 142-7. Abstract: To examine the consequences of increased apolipoprotein A-I production on cholesterol and lipoprotein metabolism, we have produced two lines of transgenic rats; one expressing moderate and one very high levels of human apolipoprotein A-I. The rats were produced by microinjection of a 13 kbp DNA fragment containing the human apolipoprotein A-I gene plus 10 kbp of its 5' flanking sequence and 1 kbp of its 3' flanking sequence. Both lines of transgenic rats express human apolipoprotein A-I mRNA in liver and human apolipoprotein A-I in plasma. Sera from these rats contain significantly higher levels of total apolipoprotein A-I, high density lipoprotein cholesterol and phospholipid than sera from non-transgenic littermates. Transgenic rats expressing high levels of human apolipoprotein A-I have reduced levels of serum rat apolipoprotein A-I suggesting a mechanism exists to down-regulate apolipoprotein A-I production. These transgenic rats provide a unique animal model to examine the effects of increased apolipoprotein A-I production on lipid and lipoprotein metabolism. |
| High level of cholesterol increases coronary vasomotor tone during exercise Kaufmann, P., C. Matter, et al. (2000), Coron Artery Dis 11(6): 459-66. Abstract: BACKGROUND: Coronary vasomotor tone plays an important role in the regulation of myocardial perfusion and influences ischemic threshold significantly. Endothelial dysfunction occurs in the presence of coronary risk factors and is closely linked to the development of atherosclerosis affecting myocardial perfusion and decreasing ischemic threshold. OBJECTIVE: To study the effect of hypercholesterolemia on coronary vasomotor tone in normal and stenotic coronary arteries at rest and during exercise. PATIENTS AND METHODS: In total 48 patients were included in the present analysis. Patients were divided into two groups according to the actual levels of serum cholesterol: 18 patients had normal (mean 181 +/- 28 mg%; group 1) and 30 had elevated (mean 263 +/- 46 mg%; group 2) levels of serum cholesterol according to the 4S criteria with a cutoff level of 213 mg% (5.5 mmol/l). Coronary vasomotor tone at rest and during supine bicycle exercise was calculated by dividing mean aortic pressure by radius of coronary vessel obtained using biplanar quantitative coronary angiography. A normal as well as a stenotic vessel segment in each patient were studied. RESULTS: Normal vessel segments in patients with normal levels of cholesterol (group 1) exhibited no exercise-induced change in coronary vascular tone (+3%, NS), whereas a significant increase in tone (+24%, P < 0.01 versus rest) occurred in those with high levels of cholesterol (group 2). In contrast, stenotic segments in members of both groups exhibited an increase in vascular tone irrespective of the actual level of serum cholesterol. CONCLUSIONS: Hypercholesterolemia causes a pathologic increase in coronary vasomotor tone of angiographically normal vessel segments during exercise. A similar pathologic response occurs in stenotic arteries, but this is independent of the actual level of serum cholesterol. These findings suggest that hypercholesterolemia influences vasomotor tone of the nonstenosed coronary arteries in patients with coronary artery disease probably through the occurrence of endothelial dysfunction. |
| High level of deoxycholic acid in human bile does not promote cholesterol gallstone formation Gustafsson, U., S. Sahlin, et al. (2003), World J Gastroenterol 9(7): 1576-9. Abstract: AIM: To study whether patients with excess deoxycholic acid (DCA) differ from those with normal percentage of DCA with respect to biliary lipid composition and cholesterol saturation of gallbladder bile. METHODS: Bile was collected during operation through puncturing into the gallbladder from 122 cholesterol gallstone patients and 46 gallstone-free subjects undergoing cholecystectomy. Clinical data, biliary lipids, bile acid composition, presence of crystals and nucleation time were analyzed. RESULTS: A subgroup of gallstone patients displayed a higher proportion of DCA in bile than gallstone free subjects. By choosing a cut-off level of the 90th percentile, a group of 13 gallstone patients with high DCA levels (mean 50 percent of total bile acids) and a large group of 109 patients with normal DCA levels (mean 21 percent of total bile acids) were obtained. The mean age of the patients with high DCA levels was higher than that of the group with normal levels (mean age: 62 years vs 45 years) and so was the mean BMI (28.3 vs. 24.7). Plasma levels of cholesterol and triglycerides were slightly higher in the DCA excess groups compared with those in the normal DCA group. There was no difference in biliary lipid composition, cholesterol saturation, nucleation time or occurrence of cholesterol crystals in bile between patients with high and normal levels of DCA. CONCLUSION: Gallstone patients with excess DCA were of older age and had higher BMI than patients with normal DCA. The two groups of patients did not differ with respect to biliary lipid composition, cholesterol saturation, nucleation time or occurrence of cholesterol crystals. It is concluded that DCA in bile does not seem to contribute to gallstone formation in cholesterol gallstone patients. |
| High level of high-density lipoprotein cholesterol (HDL-C) does not attenuate increased risk of elevated triglycerides Williams, C. (2001), Arch Intern Med 161(19): 2385. |
| High levels of cholesterol and lipoprotein (A) in serum decreases the inhibitory effect of aspirin on generation of thrombin Szczeklik, A., J. Musial, et al. (1995), Pol Arch Med Wewn 93(6): 483-9. Abstract: Aspirin (ASA) is widely used in the treatment of cardiovascular diseases. Recently, we have found that aspirin decreases not only platelet aggregation but also thrombin generation. This effect, however, was seen only in certain subjects. Therefore we decided to examine influence of a single dose of aspirin (500 mg) on thrombin generation in healthy volunteers. Thrombin genesis was assessed by serial measurements of fibrinopeptide A concentration in blood emerging from standardised forearm skin incisions. Aspirin reduced thrombin generation in persons with normal serum level of lipids. This effect was lost, however, in subjects with high level of cholesterol and lipoprotein (a)--well known risk factors of ischaemic heart disease. While the mechanism by which aspirin affects thrombin generation remains to be elucidated, our data indicate that hypercholesterolemic subjects might benefit less than others from preventive aspirin treatment. |
| High levels of C-reactive protein with low total cholesterol concentrations additively predict all-cause mortality in patients with coronary artery disease Janoskuti, L., Z. Forhecz, et al. (2005), Eur J Clin Invest 35(2): 104-11. Abstract: BACKGROUND: This study aimed to investigate independent and additive predictive effects of raised C-reactive protein (CRP) levels and decreased total cholesterol levels on mortality in patients with chronic coronary artery disease (CAD). Low total cholesterol (TC) levels are associated with worsened survival in chronic and acute diseases. Elevated CRP level is an important predictor of vascular events and mortality in patients with CAD. Potential inhibition of immune activation by circulating lipoproteins could be a link between cholesterol and inflammatory markers. MATERIALS AND METHODS: A group of 387 patients (median age 59 years) with CAD and with or without severe heart failure (HF) were followed for a median of 5.06 years. Serum total cholesterol and CRP concentrations were measured at enrollment. RESULTS: The relationship between lipoproteins, CRP and survival was explored. High CRP concentrations were in significant association with severity of HF and predicted worsened survival in patients with CAD (hazard ratio 5.214, 95% CI 1.762-15.427). The association between CRP levels and mortality was independent of potential confounding factors such as age, body-mass index, severity of HF, smoking habits, hypertension and TC levels. The prediction of mortality by low TC levels was significant (hazard ratio 2.932, 95% CI 1.021-8.422). Furthermore, patients with increased CRP and decreased TC (additive predictive effect) phenotype had 11.714-times higher risk (95% CI 2.619-52.385) of being nonsurvivors than patients with low CRP/high TC. CONCLUSIONS: High CRP levels and low TC concentrations are independent and additive predictors of mortality in patients with CAD. Our data indicate that joint analysis of circulating lipoproteins and inflammatory biomarkers may improve prediction of survival in patients with CAD. |
| High levels of endogenous DNA adducts (I-compounds) in pig liver. Modulation by high cholesterol/high fat diet Vulimiri, S. V., G. D. Zhou, et al. (1998), Mutat Res 422(2): 297-311. Abstract: I (indigenous)-compounds are bulky endogenous DNA adducts which are detected by 32P-postlabeling in unexposed animals. I-compound levels in rodents depend on age, species, strain, gender, tissue, diet, and chemical exposure. There are two classes of I-compounds, type I and type II. While many type I I-compounds may not reflect DNA damage, type II I-compounds have been identified as oxidative DNA lesions some of which can be produced in vitro under Fenton reaction conditions. In rats, caloric restriction (CR) increases the levels of many type I I-compounds compared with ad libitum fed animals, while high fat diet has the opposite effect. Here, we have tested whether hepatic DNA of a non-rodent mammal, the pig, contains I-compounds and whether feeding a high cholesterol/high fat (HC/HF) diet modulates their levels, assuming this would affect the formation of lipid-related precursors and cause oxidative stress. Male Yorkshire pigs aged 2 months old, were fed either control or HC/HF diet (control diet supplemented with 2% cholesterol and 19% lard) for 2 months. Pig liver DNA contained at least 19 type I and five type II I-compounds. Among the former, only five matched corresponding spots in rat liver DNA, while all the latter DNA lesions were detected in both species. The levels of both types of DNA modifications were six to eight-fold higher in pig DNA. HC/HF diet reduced levels of many type I I-compounds up to several fold but had little effect on the oxidative lesions. Several type I I-compounds showed negative linear correlations with serum cholesterol levels, while this association was positive for total type II I-compounds. The substantially elevated steady-state levels of bulky endogenous DNA adducts in the species with the longer life expectancy were surprising. Thus, for the first time, an intimate link between nutritional status and endogenous DNA modifications has been established in a non-rodent system. We propose that in order to explain our observations, differences in diet composition, antioxidant defenses, and DNA repair, as well as cytochrome P450 modulation of precursor levels and hormonal effects need to be considered. |
| High levels of human apolipoprotein A-I and high density lipoproteins in transgenic mice do not enhance efflux of cholesterol from a depot of injected lipoproteins. Relevance to regression of atherosclerosis? Stein, O., Y. Dabach, et al. (1999), Atherosclerosis 144(2): 367-74. Abstract: The role of high density lipoprotein (HDL) and apolipoprotein A-I (apo A-I)in promoting cholesterol efflux from cultured cells and attenuation of development of atherosclerosis in transgenic (tg) animals has been well documented. The aim of the present study was to determine whether high levels of human (h) apo A-I will enhance cholesterol removal in vivo. h apo A-I in sera of tg mice was 429 +/- 18 and 308 +/- 10 mg/dl in male and female mice, the ratio of phospholipid (PL) to apo A-I was 0.94 in tg and 2.4 and 1.9 in male and female controls, taking mouse apo A-I as 100 mg/dl. The removal of lipoprotein cholesterol injected in the form of cationized low density lipoprotein (cat-LDL) into the rectus femoris muscle of h apo A-I tg is compared with control mice. After injection of cat-LDL labeled with 3Hcholesterol, the labeled cholesterol was cleared from the depot with a t 1/2 of about 4 days in both control and tg mice. The clearance of the exogenous cholesterol mass was initially much slower, it approached the t 1/2 of about 4 days between day 8 and 14 but there was no difference between tg and control mice. Cholesterol efflux from cultured macrophages exposed to media containing up to 10% serum was 56% higher with serum from tg mice than controls. In conclusion, the efflux of cholesterol from a localized depot of cat-LDL was not enhanced in h apo A-I tg mice. It appears, therefore, that while an increase above physiological levels of apo A-I or plasma HDL does play a pivotal role in the prevention of initiation and progression of early stages of atherosclerosis, the effectiveness of such an increase for the regression stage remains still to be demonstrated. |
| High levels of plant sterols and cholesterol precursors in cerebrotendinous xanthomatosis Kuriyama, M., J. Fujiyama, et al. (1991), J Lipid Res 32(2): 223-9. Abstract: We measured the cholestanol, cholesterol precursor (lathosterol), and plant sterol (campesterol and sitosterol) concentrations of serum and bile in 11 patients with cerebrotendinous xanthomatosis. The mean values of serum cholestanol, lathosterol, campesterol, and sitosterol were, respectively, 8.4-, 2.5-, 2.7-, and 1.4-times higher in the patients than in normal control subjects (n = 26). Cholestanol (6.7-fold) and campesterol (3.7-fold) levels in bile (n = 4) were also elevated in the patients. There was no significant difference of serum sterol levels between patients with coronary artery disease and those without it. Chenodeoxycholic acid treatment for periods ranging from 6 months to 3 years and 4 months lowered serum lathosterol (57.7% reduction) and campesterol (57.8%) levels in parallel with cholestanol (70.8%) level, but the sitosterol level (19.7%) decreased less. Thus, increased levels of cholesterol precursor (lathosterol), plant sterols (campesterol and sitosterol), and cholestanol were found in the serum and bile in cerebrotendinous xanthomatosis. Chenodeoxycholic acid treatment effectively reduced the levels of these sterols, except for sitosterol. |
| High methionine and cholesterol diet abolishes endothelial relaxation Zulli, A., R. E. Widdop, et al. (2003), Arterioscler Thromb Vasc Biol 23(8): 1358-63. Abstract: OBJECTIVE: High plasma cholesterol or homocysteine is a risk factor for atherosclerosis. Cholesterol and methionine, the precursor of homocysteine, are rarely eaten separately. Thus, the aims of this study were to determine neointima formation, aortic reactivity, and factors involved in endothelial function in rabbits fed high dietary cholesterol, methionine, or a combination of the two for 12 weeks. METHODS AND RESULTS: Rabbit dietary groups were randomized into the following: control (Con), 0.5% cholesterol (Chol), 1% methionine (Meth), and 1% methionine+0.5% cholesterol (MethChol). Aortic reactivity was studied by isometric tension techniques, aortic volumetric analysis was determined by stereological techniques, and immunohistochemistry was used to localize endothelial and inducible NO synthases, superoxide dismutase, macrophages, and nitrotyrosine. Atherosclerosis was present in the Chol and MethChol groups. Endothelium-dependent relaxation was virtually abolished in the MethChol group compared with control. Such decrease in relaxation was not attributable to a vascular smooth muscle cell defect or to a decrease in endothelial NO synthase or superoxide dismutase content. Macrophages and inducible NO synthase immunoreactivity were present in Chol and MetChol groups. CONCLUSIONS: The combination of high dietary cholesterol plus methionine virtually abolishes endothelium-dependent relaxation, underscoring the importance of multiple risk factors in the development of cardiovascular disease. |
| High PAI activity with correlation to triglyceride and HDL cholesterol values in patients with coronary artery disease with no difference in survivors of myocardial infarction Ihnken, K., W. Speiser, et al. (1993), Ann Hematol 67(5): 237-44. Abstract: The fibrinolytic capacity of blood depends mainly on the amount of tissue-type plasminogen activator (t-PA) activity and plasminogen activator inhibitor type-1 (PAI-1) activity. Previous studies linked high PAI activity or low t-PA activity with the development of atherosclerosis and thromboembolic diseases. Yet, there are conflicting reports in the literature as to whether there is higher PAI activity in patients with myocardial infarction (MI) than in patients with coronary artery disease (CAD) without previous MI. In this retrospective study, t-PA activity, t-PA antigen, and PAI activity before and after a venous occlusion test (VOT) of 10 min were assessed in 109 patients with angiographically documented CAD, in two subgroups of CAD patients with (n = 66) or without (n = 43) previous MI, and in subgroups of CAD patients according to their triglyceride levels and other risk factors. The mean values of t-PA activity in the whole patient group showed a 100-fold increase and a 3.1-fold increase in t-PA antigen after VOT (0.03 +/- 0.03 to 3.0 +/- 6.8 U/ml and 16.5 +/- 6.9 to 51.0 +/- 25.4 ng/ml, p < 0.05). PAI activity was 24.4 +/- 11.0 before and 19.6 +/- 13.2 U/ml after VOT. Within the CAD group, no difference was found between patients without MI and survivors of previous MI in PAI activity before VOT (24.6 +/- 10.7 vs. 24.3 +/- 11.3 U/ml) and after VOT (19.0 +/- 12.1 vs 20.0 +/- 14.0 U/ml), or t-PA activity before (0.03 +/- 0.01 vs. 0.04 +/- 0.04 U/ml) and after VOT (2.8 +/- 7.0 vs. 3.2 +/- 6.7 U/ml). In 39.4% of CAD patients elevated plasma PAI activity before VOT (> 25 U/ml) was found. This subgroup of patients represented the highest PAI activity after VOT (p < 0.05), the lowest t-PA activity after VOT (p < 0.001), and the highest triglyceride levels (p < 0.05). In 11% of the patients, a small increase in t-PA activity (less than 0.5 U/ml) after VOT was seen. This group showed the lowest t-PA antigen after VOT (p < 0.001) and the highest fibrinogen level (p < 0.05). Both subgroups showed the same distribution among patients with and without MI. CAD patients with triglyceride levels over 200 mg/dl had the highest PAI activity values before VOT (28.3 +/- 11.8 U/ml; p < 0.01) and after VOT (24.9 +/- 13.2 U/ml; p < 0.01), resulting in low t-PA activity after VOT (p < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS) |
| High plasma cholesterol in drug-induced cholestasis is associated with enhanced hepatic cholesterol synthesis Chisholm, J. W., P. Nation, et al. (1999), Am J Physiol 276(5 Pt 1): G1165-73. Abstract: In alpha-naphthylisothiocyanate-treated mice, plasma phospholipid (PL) levels were elevated 10- and 13-fold at 48 and 168 h, respectively, whereas free cholesterol (FC) levels increased between 48 h (17-fold) and 168 h (39-fold). Nearly all of these lipids were localized to lipoprotein X-like particles in the low-density lipoprotein density range. The PL fatty acyl composition was indicative of biliary origin. Liver cholesterol and PL content were near normal at all time points. Hepatic hydroxymethylglutaryl CoA reductase activity was increased sixfold at 48 h, and cholesterol 7alpha-hydroxylase activity was decreased by approximately 70% between 24 and 72 h. These findings suggest a metabolic basis for the appearance of abnormal plasma lipoproteins during cholestasis. Initially, PL and bile acids appear in plasma where they serve to promote the efflux of cholesterol from hepatic cell membranes. Hepatic cholesterol synthesis is then likely stimulated in the response to the depletion of hepatic cell membranes of cholesterol. We speculate that the enhanced synthesis of cholesterol and impaired conversion to bile acids, particularly during the early phase of drug response, contribute to the accumulation of FC in the plasma. |
| High plasma cholesterol, but low triglycerides and plaque-free arteries, in Mexican free-tailed bats Widmaier, E. P., E. R. Gornstein, et al. (1996), Am J Physiol 271(5 Pt 2): R1101-6. Abstract: Female mammals typically become hyperphagic from mid- to late pregnancy and during lactation. Mexican free-tailed bats, Tadarida brasiliensis mexicana, double their nightly food intake from late pregnancy to peak lactation and consume an insect diet that is exceptionally high in fat. During late pregnancy and throughout lactation, fasting plasma levels of cholesterol in this insectivorous bat are high (215 +/- 8 mg/dl) and are nearly 10-fold higher than in three species of Old World frugivorous bats. Fasting triglycerides were unexpectedly low in T. brasiliensis (25 +/- 2 mg/dl), despite evidence of high fat intake during nightly feeding bouts (postprandial cholesterol and triglycerides, 268 +/- 18 and 122 +/- 20 mg/dl, respectively). High-density lipoprotein (HDL) cholesterol levels were extraordinarily high (124 +/- 5 mg/dl) and unaffected by feeding. Low-density lipoprotein cholesterol levels were correspondingly low (86 +/- 7 mg/dl). This unusual plasma lipid profile was not associated with coronary or aortic atherosclerosis, nor was there evidence of hyperglycemia or hyperinsulinemia. A high-fat diet and high levels of cholesterol in T. brasiliensis are not correlated with cardiovascular disease or (possibly) insulin resistance. Among several possible factors that might account for these observations, nightly bouts of powered flight (commuting and foraging for food) may contribute to elevated HDL cholesterol, which may protect this species from developing atherosclerosis. |
| High plasma insulin is associated with lower LDL cholesterol in elderly individuals Strandberg, T. E., R. S. Tilvis, et al. (1996), Atherosclerosis 121(2): 267-73. Abstract: To investigate possible relationships between plasma low density lipoprotein (LDL) cholesterol and fasting plasma insulin in the elderly, cross-sectional random samples of age cohorts (65, 75, 80 and 85 years, n = 1188, M/F 38/62 percent) were studied in the neighbouring cities of Helsinki and Vantaa, Finland. Plasma total and high density lipoprotein (HDL) cholesterol, plasma triglycerides, blood glucose and plasma insulin were measured after an overnight fast. LDL cholesterol was calculated using the Friedewald equation. Statistical analyses were performed separately in subjects with non-insulin-dependent diabetes mellitus (NIDDM, n = 219) and non-diabetic subjects (n = 969). Comparison of lipid levels by insulin quartile (I < 7.4 IU/1, II 7.4-10.0, III 10.1-15.0, IV > 15.0) showed that total and LDL cholesterol decreased in the highest insulin quartile (P = 0.003). This trend prevailed after adjustments for age, gender, body mass index, blood glucose and serum triglycerides, and it was significant also in normotriglyceridemic (serum triglycerides <2.3 mmol/l) subjects. Furthermore, the association between high insulin and lower cholesterol was seen in normoglycemic (fasting blood glucose <6.7 mmol/l) and diabetic subjects. Lower LDL cholesterol in elderly subjects with higher fasting insulin may reflect poor health or a 'harvesting' effect, but the results may also be due to effects of insulin on LDL catabolism and/or cholesterol absorption. |
| High plasma vitamin C associated with high plasma HDL- and HDL2 cholesterol Hallfrisch, J., V. N. Singh, et al. (1994), Am J Clin Nutr 60(1): 100-5. Abstract: High plasma vitamin C may lower risk of cardiovascular disease as indicated by direct association with plasma high-density-lipoprotein (HDL) cholesterol and HDL2 cholesterol. Plasma lipids and vitamin C were determined in 316 women and 511 men (aged 19-95 y). After adjustment for age, sex, obesity, and smoking, plasma vitamin C was directly associated with HDL- (P = 0.01) and HDL2 cholesterol (P = 0.0002). When men and women with diseases that might affect lipids were excluded, associations between plasma vitamin C and HDL- and HDL2 cholesterol persisted, though the relationships were strongest in older men. Comparisons of diets in a subset (n = 485) who completed 7-d diet records were made. Total fat, saturated fatty acids, energy from fat, and cholesterol intakes were not associated with plasma vitamin C. Mean intakes of vitamin C were well above recommended dietary allowances. These findings suggest that high plasma concentrations of vitamin C may lower atherogenic risk. |
| High postprandial plasma remnant-like particles-cholesterol in patients with coronary artery diseases on chronic maintenance hemodialysis Sekihara, T., T. Nakano, et al. (1996), Nippon Jinzo Gakkai Shi 38(5): 220-8. Abstract: The aim of this study was to determine the levels of postprandial plasma remnant-like particles-cholesterol (RLP-C) in patients with coronary artery disease (CAD) on chronic maintenance hemodialysis (HD). Forty-two patients on chronic maintenance HD with and without CAD were studied. The subjects took a meal within 1 hr before HD then underwent HD for 4 hr with heparin infusion. The plasma level of RLP-C was monitored before and during HD and its biochemical characteristics were analysed. In the CAD group, the RLP-C level was 5.9 +/- 3.5 mg/dl before HD and 6.9 +/- 4.6 mg/dl after HD. In patients without CAD, RLP-C levels before and after HD were 2.1 +/- 0.8 mg/ dl and 2.7 +/- 1.2 mg/dl respectively (within the normal range). The RLP-C levels between CAD and non-CAD were highly significant (p < 0.001). HPLC analysis of RLP revealed that VLDL remnants were reduced to smaller size, cholesterol rich particles within 1 hr of HD and a marked increase in chylomicron (CM) remnants was observed at the end of HD. These observations suggest that a latent metabolic disorder of chylomicrons and VLDL during HD after a meal can be detected by plasma RLP-C assay. The association between the frequency of latent metabolic lipoprotein disorders and CAD found in HD patients may require appropriate dietary intervention together with drugy therapy for the control of CAD. |
| High prebeta1-HDL levels in hypercholesterolemia are maintained by probucol but reduced by a low-cholesterol diet Miida, T., T. Yamaguchi, et al. (1998), Atherosclerosis 138(1): 129-34. Abstract: Previous study has shown that prebeta1-HDL levels increase in hypercholesterolemia, or high cholesteryl ester transfer protein (CETP) activity. To determine how prebeta1-HDL levels change after treatment with probucol or by following a low-cholesterol diet, we randomly assigned 24 hypercholesterolemic patients to either the probucol (P), or low-cholesterol diet group (D), and measured prebeta1-HDL levels before and after treatments using native two-dimensional gel electrophoresis. We also examined 12 subjects with normolipidemia (N). At baseline, prebeta1-HDL levels were higher in P (P < 0.05) and D (P < 0.05) than in N (9.2 +/- 4.3, 10.4 +/- 5.5, and 5.9 +/- 2.3 mg/dl apo A-I). After a 4-week treatment, prebeta1-HDL levels were still high in P (10.5 +/- 4.2 mg/dl apo A-I, N.S.), but reduced in D (7.7 +/- 3.0 mg/dl apo A-I, P < 0.001). Delta prebeta1-HDL (Y) was positively correlated with deltaCETP mass (X) in P (y = 7.83x - 1.93; r = 0.584, P < 0.05). In summary, high prebeta1-HDL levels in hypercholesterolemia are maintained by probucol but reduced by a low-cholesterol diet. These findings suggest that prebeta1-HDL levels may be regulated by cholesterol and CETP levels. |
| High preprocedural non-HDL cholesterol is associated with enhanced oxidative stress and monocyte activation after coronary angioplasty: possible implications in restenosis Cipollone, F., M. Fazia, et al. (2003), Heart 89(7): 773-9. Abstract: OBJECTIVE: To investigate whether enhanced oxidant stress in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) is associated with a higher concentration of non-high density lipoprotein (HDL) cholesterol at baseline, and whether this contributes to the inflammatory reaction and luminal renarrowing after PTCA. DESIGN: An ex vivo and in vitro study of 46 patients who underwent PTCA and who had repeat angiograms after six months. Blood samples were collected immediately before PTCA, and at 24 hours, 48 hours, and 15 days after. SETTING: Tertiary referral centre. SUBJECTS: 46 patients (30 male, 16 female; mean (SD) age, 62 (5) years) with stable or unstable angina who underwent elective PTCA. MAIN OUTCOME MEASURES: Continuous variable luminal loss as defined by change in minimum lumen diameter during follow up, normalised for vessel size; lag phase of low density lipoprotein to in vitro oxidation; plasma fluorescent products of lipid peroxidation (FPLP); plasma vitamin C and E; interleukin (IL) 1beta secretion from unstimulated monocytes; plasma C reactive protein (CRP). RESULTS: Restenosis occurred in 12 patients (26%). Oxidant stress after PTCA was greater (p < 0.0001 at 15 days) in the patients with restenosis and showed a significant correlation with the preprocedural concentration of non-HDL cholesterol (p < 0.001). Inflammatory reaction (as reflected by IL-1beta production and CRP) and late lumen loss were linearly correlated (p < 0.001) with lag phase and FPLP throughout the study, and inversely (p < 0.05) with vitamin C and E measured at two and 15 days after PTCA. CONCLUSIONS: This study provides evidence for the critical role of cholesterol dependent oxidant stress in the pathophysiology of restenosis after PTCA. The findings raise the possibility that drugs capable of modulating oxidant status might provide a novel form of adjuvant treatment in patients with hypercholesterolaemia undergoing PTCA. |
| High prevalence of diabetes in Bahrainis. Associations with ethnicity and raised plasma cholesterol al-Mahroos, F. and P. M. McKeigue (1998), Diabetes Care 21(6): 936-42. Abstract: OBJECTIVE: To determine prevalence of diabetes and associated risk factors in the population of Bahrain. RESEARCH DESIGN AND METHODS: A cross-sectional study of 2,128 Bahrainis aged 40-69 years was conducted. RESULTS: Age-standardized prevalence of diabetes was 25% in Jaafari Arabs, 48% in Sunni Arabs, and 23% in Iranians. In multivariate analyses, positive family history of diabetes, low educational status, waist girth, plasma cholesterol, and, in women, postmenopausal status were independently associated with diabetes. Adjusting for these factors did not account for the difference in prevalence between Jaafari and Sunni Arabs. There was no association between diabetes and parental consanguinity. Mean plasma cholesterol was 0.5 mmol/l higher in diabetic than in normoglycemic participants, 0.5 mmol/l higher in Sunni than in Jaafari Arabs, and, excluding diabetic individuals, 0.2 mmol/l higher in those with a positive family history of diabetes than in those with a negative family history. Although 28% of participants had BMI > or = 30 kg/m2, only 42% of these obese individuals rated themselves as overweight. In men, obesity was inversely related to physical activity at work. In women, obesity was associated with high parity and inversely associated with employment outside the home. CONCLUSIONS: The high rates of diabetes in Bahrain and other Arabian Peninsula populations appear to be part of a familial syndrome that includes raised plasma cholesterol levels. Risk is related to ethnic origin but not to parental consanguinity. Despite the high rates of diabetes, obesity is still perceived as a desirable attribute in this population. |