| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Treatment with drugs to lower blood pressure and blood cholesterol based on an individual's absolute cardiovascular risk Jackson, R., C. M. Lawes, et al. (2005), Lancet 365(9457): 434-41. Abstract: In this review, we outline the rationale for targeting blood pressure and blood cholesterol lowering drug treatments to patients at high absolute cardiovascular risk, irrespective of their blood pressure or blood cholesterol levels. Because the specific levels of blood pressure and cholesterol are of little clinical relevance when considered in isolation from other risk factors, terms such as hypertension or hypercholesterolaemia have limited value. Separate management guidelines for raised blood pressure and blood cholesterol need to be replaced by integrated cardiovascular risk management guidelines, and absolute cardiovascular risk prediction scores should be used routinely. Since cardiovascular risk factors interact with each other, moderate reductions in several risk factors can be more effective than major reductions in one. An affordable daily pill combining low doses of various drugs could be useful for the many individuals with slightly abnormal cardiovascular risk factors. |
| Treatment with simvastatin and low-dose aspirin depresses thrombin generation in patients with coronary heart disease and borderline-high cholesterol levels Musial, J., A. Undas, et al. (2001), Thromb Haemost 85(2): 221-5. Abstract: Aspirin and statins are beneficial in coronary heart disease across a broad range of cholesterol levels. We assessed the effects of low-dose aspirin (75 mg daily) on thrombin generation in patients with coronary heart disease and average blood cholesterol levels. We also investigated whether in patients with borderline-high cholesterol level who have been already taking aspirin, additional treatment with simvastatin would affect thrombin generation. Seven-day treatment with low-dose aspirin decreased thrombin generation ex vivo only in patients with total cholesterol < or = 5.2 mmol/L. In patients with higher cholesterol levels aspirin had no effect. In these patients, already taking low-dose aspirin, additional three-month simvastatin treatment resulted in a reduction of thrombin generation. This demonstrates that low-dose aspirin depresses thrombin generation only in subjects with desirable blood cholesterol levels, while in others, with borderline-high cholesterol, thrombin formation is being reduced following the addition of simvastatin. |
| Trend in serum total cholesterol level in 110,000 young adults in The Netherlands, 1974 to 1986 Verschuren, W. M., M. Al, et al. (1991), Am J Epidemiol 134(11): 1290-302. Abstract: Data from two screening projects on cardiovascular risk factors were used to analyze the trend in serum total cholesterol level in the Netherlands between 1974 and 1986. Cholesterol levels were measured in a single reference laboratory of the World Health Organization throughout the entire study period. Between 1974 and 1980, about 30,000 men and women aged 37 to 43 years (mean age, approximately 40 years) were screened. A decrease in mean serum total cholesterol level was observed until the end of 1977, when it was followed by an increase. This resulted in a net change over the entire study period of -0.07 mmol/liter (3 mg/dl) in men and -0.03 mmol/liter (1 mg/dl) in women. Between 1981 and 1986, about 80,000 men aged 33 to 37 years (mean age, 35 years) were screened. During this period, a decrease of 0.20 mmol/liter (8 mg/dl) in the mean total cholesterol level was observed. In spite of the decline in the mean total cholesterol level, the prevalence of cholesterol values of greater than or equal to 6.5 mmol/liter (greater than or equal to 251 mg/dl) in young adult men was still high in 1986 (16 percent). A further reduction is therefore desirable. The decline in the mean total cholesterol level in young adults might indicate that a further decline in mortality from coronary heart disease can be expected. |
| Trends in cholesterol levels in the adult population of Sao Jose do Rio Preto Nicolau, J. C., C. Nogueira, et al. (1998), Arq Bras Cardiol 71(5): 699-704. Abstract: PURPOSE: To develop a survey about risk factors for atherosclerosis in a > or = 20-year-old population from Sao Jose do Rio Preto, and compare the results with those obtained in a similar survey in 1991. METHODS: Quantitative survey with sample stratified by sex and age. The individuals (a total of 646, 303 men) where contacted in outpatient facilities from the Health Secretary and other populated sites, distributed by geographic zone and social class of different neighborhoods. The standard error of the survey was 4%, and the confidence interval was 95%. RESULTS: A) Mean HDL-cholesterol (only in 1997): male gender 43.7 +/- 15 mg/dL, female gender 49.6 +/- 13.5 mg/dL (p < 0.001, 95% CI 3.7 a 8.1). B) Mean total cholesterol in 1991 vs 1997: for the global population 192.5 +/- 48.9 mg/dL vs 190.5 +/- 42.5 mg/dL (p = NS); for men 187.6 +/- 53.3 mg/dL vs 190.5 +/- 42.5 mg/dL (p = NS); for women 196.8 +/- 40 mg/dL vs 187.6 +/- 37.8 mg/dL (p = 0.008, 95% CI 2.4 a 15.9). C) By regression analysis, the variables that correlated significantly with cholesterol levels, in both surveys, were: age (p < 0.001), systolic (p < 0.001) and diastolic (p < 0.001) arterial pressure, diet (p < 0.001). Female gender showed correlation only in the 1991 survey (p = 0.011), and sedentarism only in 1997 (p = 0.014). CONCLUSION: The mean cholesterol levels in the adult population of Sao Jose do Rio Preto are very favorable and, in female gender, showed a significant decrease in the 1997 survey, relatively to the 1991 survey. |
| Trends in levels of cholesterol in Japanese children from 1993 through 2001 Kouda, K., H. Nakamura, et al. (2004), J Epidemiol 14(3): 78-82. Abstract: BACKGROUND: Cardiovascular risk factors in children raise the possibility of cardiovascular disease later in life. We attempted to determine the current trends in cardiovascular risk factors among Japanese children. METHODS: We examined fifth-graders at all the elementary schools in Iwata city in Japan every year from 1993 through 2001. We examined 4,673 boys and 4,484 girls, aged 10-11 years. Height, body weight, body mass index, and serum total cholesterol concentrations were measured. Regression analysis was used to evaluate the trends. The independent variable was the calendar year of the examination. The dependent variables were the anthropometric values and the serum total cholesterol concentration in each individual. The relationships between the year and the prevalence of hyperlipidemia and the prevalence of obesity were also examined. RESULTS: Both the heights of the girls and the body weights of the both sexes were positively associated with the year. The body mass index in both girls and boys also showed positive relationships with the calendar year. In addition, there was an increase in the prevalence of obesity. Concerning the levels of cholesterol, positive regression coefficients were shown between the total cholesterol concentration and the year in both sexes. Furthermore, there was an increase in prevalence of hyperlipidemia. CONCLUSION: These results indicate that during the past decade among Japanese children involved in the study, both the body mass index and the serum total cholesterol concentrations increased. |
| Trends in nutritional intake and serum cholesterol levels over 40 years in Tanushimaru, Japanese men Adachi, H. and A. Hino (2005), J Epidemiol 15(3): 85-9. Abstract: BACKGROUND: Rapid socioeconomic development in Japan since the beginning of the Seven Countries Study in 1958 has brought remarkable changes in lifestyle and dietary patterns. We investigated the relationship between time trends in nutrient intake and serum cholesterol levels in a Japanese cohort of the Seven Countries Study, in Tanushimaru, a typical farming town on Kyushu Island. METHODS: Subjects totaled 628 in 1958, 539 in 1977, 602 in 1982, 752 in 1989, and 402 in 1999, and all of the subjects were men aged 40-64 years. Eating patterns were evaluated by 24-hour dietary recall from 1958 through 1989, and by a food frequency questionnaire in 1999. We also measured serum cholesterol levels in each health examination. RESULTS: The total daily energy intake decreased from 2837 kcal in 1958 to 2202 kcal in 1999. The carbohydrate intake in percentage of total daily energy intake decreased markedly, from 84% in 1958 to 62% in 1999, in contrast to large increases during this period in protein intake (from 11% to 18%) and fat intake (from 5% to 20%). In proportion to the dramatic change in protein and fat intake, serum cholesterol levels showed large increases (from 152.5mg/dl to 194.2 mg/ dL). CONCLUSIONS: In spite of such big dietary changes toward a westernized diet, the incidence of coronary artery disease in a rural Japanese area remains low. However, careful surveillance is needed in the future because of the remarkably increasing intake of fats, especially saturated fatty acids. |
| Trends in plasma cholesterol levels in the atherosclerosis risk in communities (ARIC) study Szklo, M., L. E. Chambless, et al. (2000), Prev Med 30(3): 252-9. Abstract: BACKGROUND: Data from the Atherosclerosis Risk in Communities (ARIC) cohort study were examined both cross-sectionally and intraindividually to confirm recent findings from population-based studies showing a decline in total cholesterol (TC) levels in the United States. METHODS: For the cross-sectional analysis, mean plasma TC levels from 15,792 participants aged 45-64 at baseline visit, and who were selected randomly from four U.S. communities, were examined for each year covered by the first cohort visit (1987, 1988, and 1989). Ninety-three percent of the cohort participants returned for the follow-up visit (1990, 1991, and 1992), and were included in the assessment of intraindividual TC trends. RESULTS: Both mean TC and prevalence of hypercholesterolemia (defined as plasma cholesterol concentration >/=240 mg/dl) consistently declined over the 3 years covered by visit 1 for all age-gender-race groups. For 1987, 1988, and 1989, mean TC values (mg/dl) were, respectively, 220.3, 216.7, and 214.1 (annual average change, -1.4%, P < 0.001). For these same years, hypercholesterolemia prevalence rates were 30. 0, 27.8, and 25.3% (annual average change, -7.8%, P < 0.001). The mean plasma TC also decreased within individuals between the two visits across race, gender, and age decade categories. With the exception of black men, this decline was more marked for older than younger subjects, but no consistent differences were seen between the racial groups. However, in whites, decreases were greater for men than for women. Expected results were seen when these changes were correlated with changes in cardiovascular risk factors between the two visits. CONCLUSION: The current study results are consistent with those of previous studies, and confirm the notion that preventive programs appear to be effective in reducing mean population TC levels. |
| Trends in serum cholesterol and lifestyle indicators in Members of the Finnish Parliament Kohvakka, A., P. Palmroos, et al. (2003), Public Health 117(1): 11-4. Abstract: OBJECTIVE: To examine the extent that public health promotion activity is reflected in life styles of national decision makers, by analysing trends in coronary heart disease risk factors in Members of the Finnish Parliament (MPs). METHODS: The MPs were studied at the beginning of two subsequent 4-year parliamentary periods between 1991 and 1999. The studies included analyses of serum total cholesterol and high-density lipoprotein (HDL) cholesterol, and a questionnaire about alcohol, smoking and physical activity. RESULTS: Serum total cholesterol was above the national recommendation of 5.0 mmol/l in 85% of the male MPs and 62% of the female MPs. The mean level of serum total cholesterol increased in female MPs during the 4-year follow-up period (P < 0.05), and male MPs showed an increase in mean HDL cholesterol (P < 0.001). The mean body mass index increased in both male (P < 0.01) and female (P < 0.01) MPs during the same period. Alcohol consumption, smoking and physical activity were unchanged during follow-up. CONCLUSIONS: From the public health perspective, serum cholesterol is too high in most MPs, and the level in males is above the national average. Both males and females put on weight during the parliamentary period, and male MPs also showed an increase in HDL cholesterol, which may be explained by other lifestyle factors. |
| Trends in serum cholesterol levels from 1980 to 1987. The Minnesota Heart Survey Burke, G. L., J. M. Sprafka, et al. (1991), N Engl J Med 324(14): 941-6. Abstract: BACKGROUND AND METHODS. We assessed community trends in the awareness, treatment, and control of hypercholesterolemia (defined as a serum cholesterol level greater than 6.21 mmol per liter 240 mg per deciliter) during the 1980s in the Minneapolis-St. Paul (Twin Cities) metropolitan area. Twin Cities residents 25 to 74 years old participated in independent, cross-sectional, population-based surveys of risk factors for cardiovascular disease in 1980-1982 (n = 3365) and 1985-1987 (n = 4545). RESULTS. Mean serum total cholesterol levels, as adjusted for age, decreased significantly (P less than 0.01) from 1980-1982 to 1985-1987 in men (from 5.30 mmol per liter 205 mg per deciliter to 5.16 mmol per liter 200 mg per deciliter) and women (from 5.19 mmol per liter 201 mg per deciliter to 5.04 mmol per liter 195 mg per deciliter). The prevalence of hypercholesterolemia as adjusted for age decreased significantly (P less than 0.05) in men (17.8 to 15.1 percent) and women (17.1 to 13.6 percent). The ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol was unchanged during this period, because of a concurrent decline in the level of HDL cholesterol. Participants with hypercholesterolemia in the 1985-1987 survey were more likely than those in the 1980-1982 survey to be aware of their condition (32.6 vs. 25.4 percent), to be treated with lipid-lowering agents (4.3 vs. 1.9 percent), and to have their condition controlled (1.9 vs. 0.3 percent). Among those who reported treatment by a physician for hyperlipidemia, changes were observed in the type of treatment recommended. A significant increase (P less than 0.05) was noted from 1980-1982 to 1985-1987 in the percentage of men being treated for hyperlipidemia with lipid-lowering medication (5.2 vs. 11.6 percent) and with exercise programs (10.3 vs. 20.1 percent). In women being treated for hyperlipidemia, a nonsignificant increase was noted in the use of lipid-lowering medication (8.2 vs. 13.9 percent), and a significant increase (P less than 0.05) was observed in the number of exercise prescriptions (4.1 vs. 12.0 percent). CONCLUSIONS. We found a substantial decline in the prevalence of hypercholesterolemia in the Twin Cities between 1980-1982 and 1985-1987 that may be attributed to changes in lifestyle, such as diet and exercise, and to a lesser extent to more aggressive intervention with lipid-lowering drugs by physicians. |
| Trends in total and high density lipoprotein cholesterol and their determinants in The Netherlands between 1993 and 1997 Houterman, S., W. M. Verschuren, et al. (2001), Int J Epidemiol 30(5): 1063-70. Abstract: BACKGROUND: The aim of this study is to describe trends in plasma total and high density lipoprotein (HDL) cholesterol in The Netherlands between 1993 and 1997 and to examine whether these trends in cholesterol could be explained by changes in body mass index, smoking, alcohol intake, use of cholesterol lowering medication, intake of saturated fat, trans fatty acids and dietary cholesterol. METHODS: Each year a random sample of men and women aged 20-59 years living in three towns in The Netherlands was invited to participate in the study. In total more than 21 000 people were examined. RESULTS: Between 1993 and 1997 plasma total cholesterol decreased significantly by 0.19 mmol/l in men and by 0.27 mmol/l in women. During this period HDL cholesterol remained stable in both men and women. Small decreases were observed in the intake of saturated fat, trans fatty acids and dietary cholesterol in both men and women. The use of cholesterol lowering medication and for women oral contraceptives and prescribed oestrogens increased significantly. After adjustment for these determinants in multivariate analyses the trend in total cholesterol remained highly significant. CONCLUSIONS: Between 1993 and 1997 the mean total cholesterol level decreased significantly while the mean HDL cholesterol remained stable in both men and women in The Netherlands. The observed trend in total cholesterol could only for a small part be explained by changes in the determinants studied. |
| Triacsin C blocks de novo synthesis of glycerolipids and cholesterol esters but not recycling of fatty acid into phospholipid: evidence for functionally separate pools of acyl-CoA Igal, R. A., P. Wang, et al. (1997), Biochem J 324 (Pt 2): 529-34. Abstract: The trafficking of acyl-CoAs within cells is poorly understood. In order to determine whether newly synthesized acyl-CoAs are equally available for the synthesis of all glycerolipids and cholesterol esters, we incubated human fibroblasts with 14Coleate, 3Harachidonate or 3Hglycerol in the presence or absence of triacsin C, a fungal metabolite that is a competitive inhibitor of acyl-CoA synthetase. Triacsin C inhibited de novo synthesis from glycerol of triacylglycerol, diacylglycerol and cholesterol esters by more than 93%, and the synthesis of phospholipid by 83%. However, the incorporation of oleate or arachidonate into phospholipids appeared to be relatively unimpaired when triacsin was present. Diacylglycerol acyltransferase and lysophosphatidylcholine acyltransferase had similar dependences on palmitoyl-CoA in both liver and fibroblasts; thus it did not appear that acyl-CoAs, when present at low concentrations, would be preferentially used to acylate lysophospholipids. We interpret these data to mean that, when fatty acid is not limiting, triacsin blocks the acylation of glycerol 3-phosphate and diacylglycerol, but not the reacylation of lysophospholipids. Two explanations are possible: (1) different acyl-CoA synthetases exist that vary in their sensitivity to triacsin; (2) an independent mechanism channels acyl-CoA towards phospholipid synthesis when little acyl-CoA is available. In either case, the acyl-CoAs available to acylate cholesterol, glycerol 3-phosphate, lysophosphatidic acid and diacylglycerol and those acyl-CoAs that are used by lysophospholipid acyltransferases and by ceramide N-acyltransferase must reside in two non-mixing acyl-CoA pools or, when acyl-CoAs are limiting, they must be selectively channelled towards specific acyltransferase reactions. |
| Triacylglycerol and cholesterol transport during absorption of glycerol trioleate vs. glycerol trielaidate Kalogeris, T. J., L. Gray, et al. (1996), Am J Physiol 270(2 Pt 1): G268-76. Abstract: We used conscious, chronic lymph-fistula rats to compare intestinal lymphatic transport of glycerol trioleate (TO) vs. glycerol trielaidate (TE) and to determine the effect of TO vs. TE on absorption and transport of cholesterol. Rats were implanted with intestinal lymph fistulas and duodenal cannulas and then given intraduodenal infusions of lipid emulsions containing purified TO or TE (40 mumol/h) and cholesterol (7.8 mumol/h + 2 microCi 14Ccholesterol). Lymph samples were collected at 0, 2, 4, 5, 6, 7, and 8 h after the start of lipid infusion. Lymphatic output and luminal and gut wall recovery of radioactive lipid at 8 h were quantified. Triacylglycerol (TG) fatty acid isomers did not affect lymphatic output of TG; lymph TG fatty acid composition and output reflected infusate composition. Lymphatic output of cholesterol (mass and radioactivity) did not differ between groups; luminal and gut wall recovery of 14Ccholesterol was also similar between groups. Similar lymphatic transport of TG and cholesterol between triolein- and trielaidin-infused rats was maintained for up to 16 h after the cessation of an infused lipid load. These results indicate that TO and TE are transported into lymph similarly, and that cholesterol absorption and transport are similar irrespective of whether TO or TE is the TG source. The data suggest that trans fatty acid-induced hypercholesterolemia is not due to altered intestinal absorption and transport of cholesterol. |
| Triacylglycerol-rich lipoprotein cholesterol is derived from the plasma membrane in CaCo-2 cells Field, F. J., E. Born, et al. (1995), J Lipid Res 36(12): 2651-60. Abstract: The source for triacylglycerol-rich lipoprotein cholesterol was investigated in CaCo-2 cells grown on filters separating an upper and a lower well. Oleic acid, a fatty acid that promotes triacylglycerol-rich lipoprotein synthesis and secretion in CaCo-2 cells, increased the vesicular-mediated influx of plasma membrane cholesterol to the endoplasmic reticulum. Unesterified and esterified cholesterol derived from the plasma membrane were increased in triacylglycerol-rich lipoproteins secreted by cells incubated with oleic acid. Fatty acids, which increased the number of lipoprotein particles secreted (increased apoB secretion), increased plasma membrane cholesterol influx and secretion. Oleic acid caused a modest increase in the synthesis of cholesterol and a two-fold increase in cholesteryl esters. The amount of newly synthesized cholesterol secreted in lipoproteins of density < 1.006 g/ml represented a small fraction of that present within the cell; however, oleic acid did increase the amount of both newly synthesized cholesterol and cholesteryl esters in triacylglycerol-rich lipoproteins. Oleic acid did not affect the fraction of newly synthesized cholesterol trafficking to the plasma membrane. Compared to cholesterol delivered to cells in micelles, plasma membrane cholesterol was the much preferred substrate for acyl-CoA:cholesterol acyltransferase. Micellar cholesterol displaced cholesterol from the plasma membrane causing more of it to influx intracellularly for esterification and secretion. We propose that plasma membrane cholesterol is the major source for triacylglycerol-rich lipoprotein cholesterol in CaCo-2 cells. Micellar cholesterol and newly synthesized cholesterol replenish the plasma membrane cholesterol that is being used for the transport of lipids. |
| Triacylglycerol-rich lipoproteins alter the secretion, and the cholesterol-effluxing function, of apolipoprotein E-containing lipoprotein particles from human (THP-1) macrophages Lindholm, E. M., A. M. Palmer, et al. (2001), Biochem J 356(Pt 2): 515-23. Abstract: Elevated plasma levels of triacylglycerol-rich lipoproteins (TGRLP) are associated with increased risk of atherogenesis and abnormal reverse cholesterol transport, as illustrated in Type II diabetes. Here we examine the effect of plasma triacylglycerol-rich or cholesteryl ester-rich lipoproteins on the secretion of nascent apolipoprotein E (apoE)-containing lipoprotein E (LpE) particles by human (THP-1) macrophages. As expected, preincubation with low-density lipoprotein (LDL) yielded small but significant increases in total cellular cholesterol content and also the secretion of apoE by macrophages. By contrast, preincubation with TGRLP resulted in higher, dose-dependent, increases in apoE secretion that reflected, but were not dependent on, cellular triacylglycerol accumulation. Secreted apoE was incorporated into a pre-beta migrating LpE fraction that differed in lipid composition and flotation density depending on preincubation conditions. Specifically, the LpE-containing lipoprotein fraction produced by macrophages preincubated with TGRLP was cholesterol-poor, markedly heterogeneous and of higher peak flotation density (d 1.14-1.18) when compared with particles produced after preincubation with LDL. Both the conditioned medium and the isolated (d<1.21) LpE-containing fraction, yielded by macrophages preincubated with TGRLP, seemed poorer at inducing cholesterol efflux than the equivalent fractions from cells preincubated with LDL, as judged by (3)Hcholesterol efflux from untreated 'naive' macrophages. Thus, although the interaction of TGRLP with macrophages can enhance apoE output from these cells, the LpE particles produced seem to be relatively inefficient mediators of cholesterol efflux. These factors might contribute to the increased risk of atherosclerosis in individuals with Type II diabetes. |
| Triggerlike stimulation of cholesterol accumulation and DNA and extracellular matrix synthesis induced by atherogenic serum or low density lipoprotein in cultured cells Orekhov, A. N., V. V. Tertov, et al. (1990), Circ Res 66(2): 311-20. Abstract: A 72-hour incubation of cultured cells with blood sera or plasma of patients suffering from coronary heart disease (CHD) with angiographically assessed coronary atherosclerosis caused a threefold to fourfold elevation of intracellular cholesterol. An elevated cholesterol level in the cells precultured with patients' sera was retained several days after the removal of the examined serum from culture. The accumulation of intracellular cholesterol was accompanied by enhanced synthesis of DNA, total protein, collagen, sulfated glycosaminoglycans, and hyaluronic acid. Enhanced DNA and total protein synthesis was retained for at least 9 days after the serum had been removed from culture. The obtained results suggest that the sera of CHD patients possess an atherogenic potential that manifests itself at the arterial cell level in the stable stimulation of atherosclerotic cellular processes: proliferation, lipidosis, and fibrosis. The examined sera of healthy donors were devoid of such an atherogenic potential. The low density lipoprotein (LDL) fraction (density, 1.030-1.050 g/cm3) obtained from an atherogenic serum had the same atherogenic potential as a whole serum. Atherosclerotic alterations in cultured intimal cells caused by atherogenic LDL were retained for at least 3 days after the removal of the lipoprotein from culture. Preincubation of intimal cells with LDL obtained from healthy donors had no effect on the intracellular cholesterol level or the synthesis of DNA and extracellular matrix. One may assume that the atherogenic potential of CHD patients' sera is related to the presence of LDLs that are qualitatively different from the LDL of healthy subjects. |
| Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin Hodis, H. N., W. J. Mack, et al. (1994), Circulation 90(1): 42-9. Abstract: BACKGROUND: The Monitored Atherosclerosis Regression Study, a randomized, double-blind, placebo-controlled, 2-year trial of lovastatin monotherapy, found that coronary lesions < 50% diameter stenosis (%S) and coronary lesions > or = 50% S at baseline had different responses to therapy. We now report on clinical, lipid, and nonlipid risk factors of treatment response in these lesion subsets. METHODS AND RESULTS: Two hundred seventy subjects, 37 to 67 years old, with plasma total cholesterol (TC) 190 to 295 mg/dL (4.91 to 7.63 mmol/L) and total triglyceride < 500 mg/dL (5.65 mmol/L) were randomized to low-fat, low-cholesterol diet and either lovastatin 80 mg/d or placebo. Logistic regression was used to model the association between risk factors and coronary lesion progression in mild/moderate (< 50% S) and severe (> or = 50% S) lesions in 220 angiogram pairs analyzed by computer quantitative coronary angiography. In the placebo group, risk factors (P <.05) for the progression of mild/moderate lesions were triglycerides and TC/high-density lipoprotein cholesterol (HDL-C). Risk factors for the progression of severe lesions were HDL-C (negative), low-density lipoprotein cholesterol (LDL-C)/HDL-C, and TC/HDL-C. TC/HDL-C was the predominant risk factor for both mild/moderate and severe lesions in the multivariate analysis. In the lovastatin group, with aggressive lowering of LDL-C and TC below 85 mg/dL and 156 mg/dL, respectively, risk factors for mild/moderate lesions included triglycerides and very-low-density lipoprotein-LDL-associated apolipoprotein C-III (apo C-III-heparin precipitate), a marker of triglyceride-rich lipoprotein particles. Apo C-III-heparin precipitate was the predominant risk factor in the multivariate analysis. Risk factors for severe lesions were LDL-C, LDL-C/HDL-C, TC/HDL-C, and apo B; LDL-C/HDL-C was the predominant risk factor. CONCLUSIONS: These results indicate that triglyceride-rich lipoproteins and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression, respectively. These results add to the growing evidence of the importance of triglyceride-rich lipoproteins as a risk factor for coronary artery disease and the need for treatment in the progression of atherosclerosis. |
| Triglyceride and high-density lipoprotein cholesterol: predicting disorders in parents from their children Polonsky, S. M., L. A. Simbartl, et al. (1994), Pediatrics 94(6 Pt 1): 824-31. Abstract: OBJECTIVE: To determine whether lipid disorders can be predicted in parents after such disorders are identified initially in their children. Although this relation has been well determined for children with high cholesterol or low-density lipoprotein cholesterol (LDL-C), it has not been as well described for disorders involving triglycerides (TG) or high-density lipoprotein cholesterol (HDL-C), or their interaction with LDL-C. METHODS. Serum lipid values were obtained from 232 families in the comparison population of a large genetics study. Subjects were classified into four groups based on their lipid status: 1) isolated LDL-C disorder, defined by a high LDL-C level and normal TG and HDL-C levels; 2) isolated TG/HDL-C disorder, defined by either high TG, low HDL-C, or both, and normal LDL-C; 3) combined disorder, defined by high LDL-C in addition to either high TG, low HDL-C, or both; and 4) normal, defined by the absence of any of the above disorders. The frequencies of these disorders were noted in both parents and children, and logistic regression analyses were conducted to determine whether the presence of these disorders in at least one child in the family could predict similar disorders in the parents. RESULTS. Children with isolated LDL-C or TG/HDL-C disorder were more likely to have parents with the same disorder as themselves (P =.002 and P =.04, respectively). Children with the combined disorder were more likely to have parents with any lipid disorder (P =.009), but especially isolated LDL-C (P =.002) and isolated TG/HDL-C (P =.05). CONCLUSION. A classification scheme defining disorders of TG and HDL-C, LDL-C, or a combination can be useful for predicting lipid disorders in parents after such disorders are identified initially in their children. |
| Triglyceride depletion in THP-1 cells alters cholesteryl ester physical state and cholesterol efflux Lada, A. T., M. C. Willingham, et al. (2002), J Lipid Res 43(4): 618-28. Abstract: To study macrophage lipid droplet composition and the effects of TG on cholesteryl ester (CE) physical state, hydrolysis, and cholesterol efflux, a technique was developed to remove the majority of accumulated TG with minimal effect on CE content. THP-1 macrophages were incubated with acetylated LDL, and the accumulated TG was depleted by incubation with the acyl-CoA synthetase inhibitor triacsin D in the presence of albumin. Before TG removal, all cellular lipid droplets were isotropic as determined by polarizing light microscopy. When the TG concentration was reduced, anisotropic lipid droplets were visible, indicating a change in physical state, and suggesting that TG and CE originally accumulated in mixed lipid droplets. This change in physical state of lipid droplets was associated with slower rates of CE hydrolysis and cholesterol efflux. Although lipid droplets within the same cell had a similar physical state after TG depletion, there was considerable variability among cells in the physical state of their lipid droplets.In conclusion, THP-1 macrophages store accumulated CE and TG in mixed droplets, and the proportion of CE to TG varies among cells. Reducing accumulated TG altered CE physical state, which in turn affected hydrolysis of CE and cholesterol efflux. |
| Triglyceride, but not total cholesterol or low-density lipoprotein cholesterol levels, predict development of proteinuria Tozawa, M., K. Iseki, et al. (2002), Kidney Int 62(5): 1743-9. Abstract: BACKGROUND: Epidemiological data about the relationship between dyslipidemia and proteinuria are sparse. We conducted a retrospective and longitudinal study in a large screened cohort to evaluate whether triglyceride, high-density lipoprotein (HDL) cholesterol, total cholesterol, and low-density lipoprotein (LDL) cholesterol levels increase the risk of development of proteinuria and loss of renal function. METHODS: Post hoc analysis was performed for 4326 subjects who were free from proteinuria (dipstick 1+ or higher) at baseline (1997) with a follow-up period through 2000. Outcome measures were the development of proteinuria (1+ or higher) and change in glomerular filtration rate (GFR). Multiple logistic analysis and multiple regression analysis were used to analyze baseline characteristics related to the outcome measures. RESULTS: During the observational period, 505 (11.7%) of subjects had one or more episodes of proteinuria (>/=1+). Adjusted relative risk of triglycerides for one or more incidences of proteinuria was 1.007 (95% CI 1.000 to 1.105, P = 0.04) in men and 1.032 (95% CI 1.004 to 1.061, P = 0.02) in women. Total cholesterol, HDL cholesterol, and LDL cholesterol were not significant predictors of proteinuria. The mean change in GFR between 1997 and 2000 was -6.3 (SD = 9.0) mL/min/1.73 m2 in men, and -7.8 (SD = 10.7) mL/min/1.73 m2 in women. HDL cholesterol (beta = 0.04, t = 3.7, P = 0.0002) in men and triglycerides (per 10 mg/dL, beta = -0.09, t = -2.2, P = 0.02) in women were correlated with the change in GFR. CONCLUSIONS: High triglyceride levels predicted a risk of developing proteinuria in both men and women, but not total cholesterol nor LDL cholesterol. High triglyceride in women and low HDL cholesterol in men predicted the decline of renal function. It remains to be determined whether prospective treatment of dyslipidemia will protect against renal injury. |
| Triglyceride, cholesterol and weight changes among risperidone-treated youths. A retrospective study Martin, A. and S. L'Ecuyer (2002), Eur Child Adolesc Psychiatry 11(3): 129-33. Abstract: The purpose of this retrospective chart review was to assess triglyceride, cholesterol and weight changes among risperidone-treated youths. The charts of 22 child and adolescent inpatients were abstracted. The sample's mean (+/- SD) age was 12.8 (+/- 2.6) years, daily risperidone dose 2.7 (+/- 2.2) mg, and average length of exposure 4.9 (+/- 1.0) months. Repeated measures analysis of variance revealed statistically and clinically significant weight gain averaging 7.0 (+/- 4.7) kg (95% confidence interval CI for the mean = 4.9,9.1; F = 49.421, df = 1,21, p < 0.001). No significant changes in serum triglyceride or cholesterol levels were seen in the group as a whole. Triglyceride levels and weight were strongly correlated with each other: almost 25% of the variance in triglyceride level changes could be explained by weight gain alone (R2 = 0.22, F = 5.526, p = 0.029), although such association weakened when excluding subjects (N=5) concurrently treated with lithium or divalproex (R2 = 0.06, p > 0.05). On the basis of this preliminary report it seems prudent to be clinically vigilant and conservative, recommending regular laboratory monitoring until a clearer picture emerges regarding lipid dysregulation associated with risperidone and other atypical antipsychotic use in children and adolescents. |