| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Association of high density lipoprotein cholesterol with plasma lipolytic activity and C-peptide concentration in type 2 diabetes Baynes, C., S. G. Rains, et al. (1991), Diabetes Res 16(2): 49-53. Abstract: In order to assess whether insulin concentration or plasma lipolytic activity has any role in the regulation of HDL cholesterol concentrations in type 2 diabetes, fasting plasma C-peptide and HDL2-cholesterol concentrations and the post-heparin plasma activities of lipoprotein lipase and hepatic endothelial lipase were measured in 148 patients with type 2 diabetes (76 male, 72 female). HDL2-cholesterol was related negatively to hepatic lipase activity in men (r = -0.49, p less than 0.001) and women (r = -0.43, p less than 0.001) and positively to lipoprotein lipase activity in men (r = -0.33, p less than 0.01) and women (r = 0.36, p less than 0.01). A significant inverse relationship was confirmed between C-peptide and the HDL2-cholesterol subfraction in both sexes (men, r = -0.40, p less than 0.001, women r = -0.51, p less than 0.001). This persisted after adjustment for the effects of alcohol intake, mode of hypoglycaemic treatment, plasma glucose and body mass index. The relationship was lost in men and greatly diminished in women when hepatic lipase activity was included in multiple linear regression analysis, whereas the inclusion of lipoprotein lipase activity in the analysis had little effect on the relationship between C-peptide and HDL2-cholesterol. We suggest that hepatic lipase may be partly responsible for the commonly observed inverse relationship between measures of insulin secretion and HDL-cholesterol concentrations. We speculate that this may occur through a direct stimulatory effect of insulin on the enzyme's activity. |
| Association of high-density-lipoprotein cholesterol with mortality and other risk factors for major chronic noncommunicable diseases in samples of US and Russian men Perova, N. V., R. G. Oganov, et al. (1995), Ann Epidemiol 5(3): 179-85. Abstract: Previous reports from the Russian Lipid Research Clinics (LRC) study showed no association between the level of high-density-lipoprotein (HDL) cholesterol and mortality from coronary heart disease (CHD), while US LRC data indicated a strong negative association between HDL cholesterol and CHD mortality. This report investigated the association of HDL cholesterol and mortality in these same population samples with follow-up extended to 12 years. The association between HDL cholesterol and mortality remained inverse and significant in the US sample. In the Russian sample, high levels of HDL cholesterol were associated with higher risk of all-cause and cancer mortality, although adjustment for known risk factors reduced the strength of the association. The association between HDL cholesterol and CHD mortality was negative in the Russian sample, although the strength of the association was less than that for the US sample. Extended follow-up reduced the difference in the association between HDL cholesterol and mortality between the two countries; however, important differences remained. Further research will be required to clearly determine the cause for their differences. |
| Association of human cholesteryl ester transfer protein-TaqI polymorphisms with serum HDL cholesterol levels in a normolipemic Japanese rural population Chen, J., T. Yokoyama, et al. (2002), J Epidemiol 12(2): 77-84. Abstract: We examined allele frequencies for the common cholesteryl ester transfer protein (CETP) TaqI polymorphisms and the associations of CETP-TaqI polymorphisms with serum lipid and lipoprotein levels taking into account for selected lifestyle factors in a well-characterized random sample of 527 healthy subjects living a rural community in Japan (256 men and 271 women aged 40-69 years). B2 allele frequency was 0.39 in men and 0.41 in women, and its presence was significantly associated with increased levels of HDL cholesterol (HDL-C) in men (P=0.003 for linear trend). A similar tendency in women was observed, although P value for trend did not reach 0.05. There were not significant interactions between TaqIB genotype and smoking and alcohol drinking or daily physical activity in HDL-C. There were no statistically significant differences among TaqIA genotype in lipid and lipoprotein levels. Multiple linear regression analysis showed that B1B2 and B2B2 explained 1.7% and 2.2%, and 0.6% and 1.0% of variation in men and in women in HDL-C, respectively. We conclude that the CETP-TaqIB polymorphism has a quantitative influence, but appears to be stronger one in men, on HDL-C levels even after adjustment for important lifestyle factors (smoking, alcohol drinking, and daily physical activity). |
| Association of I27L polymorphism of hepatocyte nuclear factor-1 alpha gene with high-density lipoprotein cholesterol level Babaya, N., H. Ikegami, et al. (2003), J Clin Endocrinol Metab 88(6): 2548-51. Abstract: The serum level of high-density lipoprotein cholesterol (HDL-c), which protects against the development of atherosclerosis, is under genetic control. However, the genetic components responsible for the serum HDL-c level are yet to be determined. A recent knockout mouse study demonstrated that hepatocyte nuclear factor-1 alpha (HNF-1 alpha) is an essential transcriptional regulator of HDL-c metabolism. In this study, the association of an HNF-1 alpha gene polymorphism, isoleucine (Ile) 27 leucine (Leu), with lipid parameters, in particular with serum HDL-c level, was studied in 356 unrelated Japanese men. Though no significant difference was observed in total cholesterol and triglyceride levels among the three genotypes, the serum HDL-c level was significantly associated with the genotype (P < 0.01, trend test). Subjects with the Ile/Ile genotype had low serum HDL-c levels, and those with the Leu/Leu genotype had high serum HDL-c levels. These results demonstrate that the HNF-1 alpha gene locus is associated with serum HDL-c level and suggest that the Ile27 allele is a risk marker for atherosclerosis. |
| Association of lipid accumulation in small intestinal mucosa with decreased serum triglyceride and cholesterol levels in AIDS Benhamou, Y., I. Hilmarsdottir, et al. (1994), Dig Dis Sci 39(10): 2163-9. Abstract: Lipid accumulation has been described in the duodenal lamina propria of human immunodeficiency virus (HIV)-infected patients with diarrhea and malabsorption. Using light and electron microscopy, we studied duodenal biopsies obtained from 54 consecutive HIV-infected patients by means of upper gastrointestinal endoscopy after an overnight fast. The presence of diarrhea and weight loss were recorded, and all the patients had standard stool study for ova, parasites, and bacteria. Serum levels of albumin, triglycerides, and cholesterol were obtained within one week of the endoscopy. Fecal fat and fecal alpha 1-antitrypsin clearance were measured in 11 patients. Lipid accumulation was observed in nine patients (16.6%). Fat droplets were seen in enterocytes, in their basolateral membrane spaces, and in the lamina propria. The mean serum levels of triglycerides (1.85 +/- 0.20 mmol/liter) and cholesterol (2.81 +/- 0.30 mmol/liter) were significantly lower in the patients with enteric steatosis than in patients without this anomaly (respectively, 3.38 +/- 0.39 and 3.97 +/- 0.18 mmol/liter, P < 0.001 P < 0.01). The mean amount of fecal fat in the three patients with lipid accumulation (16 +/- 1.60 g/24 hr) was significantly larger than in the eight patients without lipid accumulation (4.50 +/- 0.62 g/24 hr, P < 0.01). These findings suggest that fat malabsorption in HIV-infected individuals is due to a blockage of transport through the duodenal mucosa. The frequency of diarrhea, weight loss, or identified enteric pathogens did not differ significantly between patients with and without enteric steatosis. Both the etiology and the pathophysiology of these alterations remain to be documented. |
| Association of lipoprotein cholesterol and triglycerides with the severity of coronary artery disease in men and women Korhonen, T., M. J. Savolainen, et al. (1996), Atherosclerosis 127(2): 213-20. Abstract: The differences between the lipid profiles of male and female patients and the effect of plasma lipids on the extent of coronary artery disease were evaluated in 122 angiographically assessed coronary artery disease patients (95 males and 27 females) and 60 controls. Both male and female patients had lower HDL-cholesterol and higher total cholesterol, LDL-cholesterol, triglyceride, VLDL-cholesterol and VLDL-triglyceride concentrations than the controls. The VLDL lipid values did not differ significantly between the male patients with different extent of CAD, whereas the VLDL lipid values of female patients tended to increase with an increasing severity of CAD. High Lp(a) (> or = 35 mg/dl) values were more prevalent in patients with > 50% coronary stenosis compared to patients with < 50% stenosis and the controls (29%, 17% and 12%, respectively). The apolipoprotein E phenotypes and epsilon allele frequencies were similar in the patients and the controls. Low HDL-cholesterol and high LDL-cholesterol are CAD risk factors for both sexes. For women, elevated VLDL-triglycerides seem to be an additional risk factor for CAD. |
| Association of low cholesterol with aggression Peer, D. A. and C. A. Stoukides (1992), Ann Pharmacother 26(6): 785-6. |
| Association of low plasma cholesterol with mortality for cancer at various sites in men: 17-y follow-up of the prospective Basel study Eichholzer, M., H. B. Stahelin, et al. (2000), Am J Clin Nutr 71(2): 569-74. Abstract: BACKGROUND: Low serum cholesterol has been associated with an increased risk of cancer mortality in various studies, which has led to uncertainty regarding the benefit of lower blood cholesterol. OBJECTIVE: The aim of our study was to evaluate the association between low blood cholesterol (<5.16 mmol/L) and cancer at sites that have rarely been evaluated. We placed special emphasis on the potential confounding effect of antioxidant vitamins. DESIGN: Plasma concentrations of cholesterol and antioxidant vitamins were measured in 1971-1973 in 2974 men working in Basel, Switzerland. In 1990, the vital status of all participants was assessed. RESULTS: Two hundred ninety of the participants had died from cancer, 87 from lung, 30 from prostate, 28 from stomach, and 22 from colon cancer. Group means for plasma cholesterol concentrations did not differ significantly between survivors and those who died from cancer at any of the studied sites. With plasma cholesterol, vitamins C and E, retinol, carotene, smoking, and age accounted for in a Cox model, an increase in total cancer mortality in lung, prostate, and colon but not in stomach cancer mortality was observed in men >60 y of age with low plasma cholesterol. When data from the first 2 y of follow-up were excluded from the analysis, the relative risk estimates remained practically unchanged with regard to lung cancer but decreased for colon, prostate, and overall cancer. CONCLUSIONS: Increased cancer mortality risks associated with low plasma cholesterol were not explained by the confounding effect of antioxidant vitamins, but were attributed in part to the effect of preexisting cancer. |
| Association of low serum total cholesterol with major depression and suicide Partonen, T., J. Haukka, et al. (1999), Br J Psychiatry 175: 259-62. Abstract: BACKGROUND: It has been suggested that low serum total cholesterol is associated with an increased risk of suicide. AIMS: To study the association between serum total cholesterol, depression and suicide using versatile, prospective data. METHOD: A total of 29,133 men aged 50-69 years were followed up for 5-8 years. Baseline blood samples were analysed for serum total and high-density lipoprotein cholesterol concentrations. Self-reported depression was recorded, data on hospital treatments due to depressive disorders were derived from the National Hospital Discharge Register and deaths from suicide were identified from death certificates. RESULTS: Low serum total cholesterol was associated with low mood and subsequently a heightened risk of hospital treatment due to major depressive disorder and of death from suicide. CONCLUSIONS: Our results suggest that low serum total cholesterol appears to be associated with low mood and thus to predict its serious consequences. |
| Association of major histocompatibility complex II with cholesterol- and sphingolipid-rich membranes precedes peptide loading Karacsonyi, C., R. Knorr, et al. (2004), J Biol Chem 279(33): 34818-26. Abstract: Major histocompatibility complex class II protein (MHC II) molecules present antigenic peptides to CD4-positive T-cells. Efficient T cell stimulation requires association of MHC II with membrane microdomains organized by cholesterol and glycosphingolipids or by tetraspanins. Using detergent extraction at 37 degrees C combined with a modified flotation assay, we investigated the sequence of events leading to the association of MHC II with cholesterol- and glycosphingolipid-rich membranes (DRMs) that are distinct from tetraspanins. We find two stages of association of MHC II with DRMs. In stage one, complexes of MHC II and invariant chain, a chaperone involved in MHC II transport, enter DRMs in the Golgi stack. In early endosomes, these complexes are almost quantitatively associated with DRMs. Upon transport to late endocytic compartments, MHC II-bound invariant chain is stepwise proteolyzed to the MHC class II-associated invariant chain peptide (CLIP) that remains MHC II-bound and retains a preference for DRMs. At the transition between the two stages, CLIP is exchanged against processed antigens, and the resulting MHC II-peptide complexes are transported to the cell surface. In the second stage, MHC II shows a lower overall association with DRMs. However, surface MHC II molecules occupied with peptides that induce resistance to denaturation by SDS are enriched in DRMs relative to SDS-sensitive MHC II-peptide complexes. Likewise, MHC II molecules loaded with long-lived processing products of hen-egg lysozyme containing the immunodominant epitope 48-61 show a very high preference for DRMs. Thus after an initial mainly intracellular stage of high DRM association, MHC II moves to a second stage in which its preference for DRMs is modulated by bound peptides. |
| Association of N-glycosylation of apolipoprotein B-100 with plasma cholesterol levels in Watanabe heritable hyperlipidemic rabbits Tsunemitsu, M., Y. Ishikawa, et al. (1992), Atherosclerosis 93(3): 229-35. Abstract: We have previously demonstrated the heterogeneity of N-linked sugar chains of apolipoprotein (apo) B-100 in Watanabe heritable hyperlipidemic (WHHL) rabbit and fasting Japanese White rabbits (Arteriosclerosis, 10 (1990) 386-393). To investigate further the role of N-linked sugar chains of apo B-100 in lipid metabolism, we examined the correlation between the N-glycosylation of apo B-100 and serum cholesterol levels in WHHL rabbits. The N-linked sugar chains of apo B-100 were liberated by hydrazinolysis, followed by NaB3H4 reduction and were fractionated by paper electrophoresis and BioGel P-4 column chromatography. These were found to consist of one neutral (N) and two acidic fractions (A1 and A2). N contained a high mannose type oligosaccharide consisting of Man5.GlcNAc2 to Man9.GlcNAc2, while A1 and A2 contained monosialylated and disialylated complex type oligosaccharides, respectively. The molar ratio varied among the 5 WHHL rabbits. There was an inverse correlation between the ratio of acidic oligosaccharide fractions (A1 + A2) and serum cholesterol levels (r = -0.971, P less than 0.01) in the 5 WHHL rabbits. These results indicate that the N-glycosylation of apo B-100 is closely related to cholesterol metabolism in WHHL rabbits. |
| Association of personal and familial suicide risk with low serum cholesterol concentration in male lithium patients Bocchetta, A., C. Chillotti, et al. (2001), Acta Psychiatr Scand 104(1): 37-41. Abstract: OBJECTIVE: We sought to establish whether low cholesterol concentration may be associated with a personal history of attempted suicide or a family history of completed suicide in psychiatric out-patients on maintenance lithium treatment, who represent a population at risk for suicide. METHOD: We retrospectively reviewed charts regarding 783 out-patients consecutively admitted to a lithium clinic from 1976 to 1999. Individual age- and gender-specific quartile of serum cholesterol concentration were correlated against personal lifetime suicide attempts and completed suicide in first-degree relatives. RESULTS: The proportion of men with a personal lifetime history of attempted suicide, especially if violent, and that of men with history of completed suicide in a first-degree relative were significantly higher among the group with cholesterol concentration in the lowest quartile compared to the group with cholesterol levels above the 25th percentile. CONCLUSION: Low cholesterol concentration should be studied further as a potential biological/genetic marker of suicide risk. |
| Association of polymorphisms of apolipoprotein B gene with cholesterol gallstone disease Suo, G., T. Han, et al. (1999), Zhonghua Yi Xue Za Zhi 79(9): 673-5. Abstract: OBJECTIVE: To investigate the association between the apolipoprotein B (apoB) gene polymorphic sites Ins/Del and Xbal, and cholesterol gallstone disease. METHODS: The two polymorphic sites of apoB gene were examed in 101 cholesterol gallstone patients and 50 controls by polymerase chain reaction and restriction fragment length polymorphism methods. RESULTS: For Xbal polymorphic site, the frequency of the rare allele X+ and the distribution of X+X- genotype were significantly higher in the patient group than in the control group (P < 0.05). For Ins/Del polymorphic site, no significant difference was found in allele frequency and genotype distribution between the patient group and the control group. CONCLUSIONS: Xba1 polymorphism of apoB gene may be associated with cholesterol gallstone disease. The association, however, is not present for Ins/De1 polymorphism of apoB gene with cholesterol gallstone disease. |
| Association of remnant-like particle cholesterol with coronary artery disease in patients with normal total cholesterol levels Masuoka, H., S. Kamei, et al. (2000), Am Heart J 139(2 Pt 1): 305-10. Abstract: BACKGROUND: Limited information is available as to whether there is a difference in the association of lipid and fibrinolytic variables with coronary artery disease according to the presence or absence of elevated serum total cholesterol. We examined the levels of various lipid and fibrinolytic variables including remnant-like particle cholesterol (RLP-C). RLP-C is a recently established simple assay method for the estimation of triglyceride-rich lipoprotein remnants. METHODS AND RESULTS: Levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), triglyceride, lipoprotein(a), RLP-C, uric acid, blood glucose, tissue plasminogen activator, tissue plasminogen activator inhibitor type 1, antithrombin III, and protein C were measured in 208 patients who underwent diagnostic coronary angiograms. Of these 208 patients, 57 were hypercholesterolemic (> or =220 mg/dL) and 151 were normocholesterolemic. HDL-C showed significant differences between patients with and those without angiographically determined coronary artery stenosis in both hypercholesterolemic and normocholesterolemic patients (P =.0025 and P =.0003, respectively). Both RLP-C and uric acid showed significant differences only in the normocholesterolemic subgroup (P =.0006 and P =.0060, respectively). This difference in uric acid was not significant by multivariable analysis. The ratio of RLP-C/HDL-C was demonstrated to be highly significantly (P <.0001) associated with coronary artery stenosis in patients with normal total cholesterol, whereas there was no statistically significant association in the hypercholesterolemic patient subgroup. CONCLUSIONS: Our current study disclosed that RLP-C levels are strongly associated with coronary artery disease, especially in patients with normal total cholesterol levels. Moreover, RLP-C/HDL-C ratio may be even more significantly associated with the presence of coronary artery stenosis in normocholesterolemic patients. |
| Association of serum apolipoprotein A-I (but not high-density lipoprotein cholesterol) with healed myocardial infarction in men independent of serum insulin and C-peptide von Eckardstein, A., F. Fischer, et al. (2001), Am J Cardiol 88(7): 723-6. Abstract: Low serum levels of high-density lipoprotein (HDL) cholesterol or apolipoprotein A-I and high serum levels of insulin increase the risk of coronary heart disease (CHD) and can indicate insulin resistance. We tested the strength, independence, and interactions of associations between HDL cholesterol (or apolipoprotein A-I), insulin (or C-peptide), glucose, and CHD in 95 male nondiabetic patients with CHD who were <60 years old, in 92 probands from the PROCAM study, and in 61 non-cardiologic patients; all subjects were matched by age, body mass index, and smoking habits. Systemic hypertension (odds radio OR 2.8, 95% confidence intervals CI 1.6 to 4.8), high serum levels of glucose (OR 2.3, 95% CI 1.6 to 4.8), insulin (OR 2.1, 95% CI 1.3 to 3.6), and C-peptide (OR 4.1, 95% CI 2.2 to 7.5) as well as low serum levels of HDL cholesterol (OR 2.0, 95% CI 1.1 to 3.5) or apolipoprotein A-I (OR 3.9, 95% CI 2.1 to 7.1) had significant associations with CHD. At multivariate analysis, systolic blood pressure, glucose, apolipoprotein A-I, and C-peptide, but not HDL cholesterol and insulin, had consistent independent associations with CHD. Thus, the combined measurement of apolipoprotein A-I and C-peptide may improve the identification of nondiabetic patients at increased risk for CHD. |
| Association of serum cholesterol and history of school suspension among school-age children and adolescents in the United States Zhang, J., M. F. Muldoon, et al. (2005), Am J Epidemiol 161(7): 691-9. Abstract: The dietary guidelines developed for adults have been extended to children, but the role of serum cholesterol in the neurodevelopment of children is poorly understood. In the Third National Health and Nutrition Examination Survey (1988-1994), serum total cholesterol was measured in 4,852 children aged 6-16 years. Psychosocial development was evaluated by interviewing the mother regarding the child's history of school suspension or expulsion and difficulty in getting along with others. After adjustment for family socioeconomic status, maternal marital status and education, children's nutrition, and academic performance, the odds ratios of children with various concentrations of total cholesterol showed the children to be equally comfortable in their own peer subculture and not to be different in the proportion that had seen a mental health professional. However, non-African-American children with a serum total cholesterol concentration below the 25th percentile (<145 mg/dl) were almost threefold more likely to have been suspended or expelled from schools than their peers with total cholesterol at or above the 25th percentile (odds ratio = 2.96, 95% confidence interval: 1.55, 5.64). The authors concluded that, among non-African-American children, low total cholesterol is associated with school suspension or expulsion and that low total cholesterol may be a risk factor for aggression or a risk marker for other biologic variables that predispose to aggression. |
| Association of serum cholesterol and triglyceride levels with agitation and cognitive function in a geropsychiatry unit Orengo, C. A., M. E. Kunik, et al. (1996), J Geriatr Psychiatry Neurol 9(2): 53-6. Abstract: Several studies have reported an association between aggression and cholesterol levels. The purpose of this study was to investigate the relationship of serum cholesterol and triglyceride levels with aggression and cognitive function in elderly inpatients. One hundred ten patients consecutively admitted to the Geriatric Psychiatry inpatient unit at Houston's Veterans Affairs Hospital received comprehensive evaluations by a multidisciplinary team. Fasting serum cholesterol and triglyceride levels were obtained within 3 days of admission. In addition, two geriatric psychiatrists administered the Mini-Mental State Examination (MMSE) and the Cohen-Mansfield Agitation Inventory (CMAI). Correlation coefficients were calculated between lipid levels, CMAI total and subscale scores, and MMSE scores. Multiple linear-regression analyses were done to further investigate the relation between lipid concentrations and various confounders. We found no significant correlation between serum triglyceride levels and MMSE, CMAI total, and CMAI factor scores. In addition, we found a significant positive correlation between serum cholesterol levels and physical nonaggressive behavior, and a significant negative correlation between serum cholesterol levels and MMSE scores. We found no relationship between aggressive behavior and serum cholesterol or triglyceride levels. However, an association between high cholesterol levels and agitation exists, which may be mediated by the association between high cholesterol levels and impaired cognition. |
| Association of serum low density lipoprotein cholesterol, smoking and hypertension with different manifestations of atherosclerosis Salonen, J. T. and R. Salonen (1990), Int J Epidemiol 19(4): 911-7. Abstract: We investigated the association of elevated serum low density lipoprotein (LDL) cholesterol levels, smoking and hypertension with different manifestations of carotid atherosclerosis in a population-based sample of 720 Eastern Finnish men aged 42, 48, 54 or 60 years, examined in the Kuopio Ischaemic Heart Disease Risk Factor Study. Carotid atherosclerosis was assessed with high-resolution B-mode ultrasonography. Men who had neither a history nor symptoms of cardiovascular disease with serum LDL cholesterol concentration in the highest tertile (4.17 mM or more) had 3.40-fold (95% confidence interval (CI) 1.98-5.84) age-, smoking- and hypertension-adjusted probability of intimal-medial thickening as compared to men in the lowest serum LDL cholesterol tertile. The odds ratio for carotid plaque versus intimal-medial thickening was only 1.03 (95% CI 0.47-2.28). The respective odds ratios for smoking (28 pack-years or more) were 1.62 (95% CI 0.79-3.32) and 3.02 (95% CI 1.41-6.47) and those for hypertension were 1.10 (95% CI 0.70-1.73) and 0.99 (95% CI 0.53-1.84). Our findings suggest that elevated serum LDL cholesterol concentration associates with an increased risk of common carotid arterial wall thickening, whereas smoking is associated more strongly with carotid plaques than intimal-medial thickening. Our cross-sectional data do not support association between hypertension and either manifestation of carotid atherosclerosis. |
| Association of serum total cholesterol with coronary disease and all-cause mortality: multivariate correction for bias due to measurement error Iribarren, C., D. Sharp, et al. (1996), Am J Epidemiol 143(5): 463-71. Abstract: Measurement error in the exposure under investigation is an important but often ignored source of bias in observational studies. The authors examined the impact of measurement error in the association between total serum cholesterol and 16-year coronary heart disease and all-cause mortality in a cohort of 6,137 middle-aged men of Japanese descent in the Honolulu Heart Program (1973-1988). A Cox regression model that enables modeling of survival time with correction for measurement errors in multiple covariates was employed. After controlling for age, body mass index, systolic blood pressure, smoking status, alcohol consumption, dietary cholesterol, and total calorie intake, a difference of one standard deviation (38 mg/dL) in total cholesterol was associated with a significant increase in the risk of coronary disease death (uncorrected hazard ratio = 1.35). After correction for measurement errors in total cholesterol and covariates (except smoking and age), the estimated hazard ratio increased to 1.65 (a 22% increase). A U-shaped relation was observed between total cholesterol levels and the risk of all-cause mortality. This association was then examined with a quadratic model and with a two-slope or V-shaped regression model. In the quadratic fit, the magnitude of the quadratic total cholesterol term increased threefold after the adjustment for measurement error. In the V fit, the hazard ratio of all-cause death corresponding to a change in one standard deviation above 214 mg/dL (the nadir of the V) was 1.15, and increased to 1.49 (by 29%) after the correction. The corresponding hazard ratio of a change in one standard deviation below 214 mg/dL was 1.11, and increased to 1.37 (by 23%) after the correction. The authors conclude that the impact of elevated total cholesterol on the risk of coronary disease and all-cause mortality may be greater than previously estimated with standard methods of analysis. In addition, the correction for measurement error in total cholesterol and covariates did not explain the excess mortality associated with low total cholesterol. More research is needed to elucidate the fundamental issues underlying the U-shaped association, i.e., confounding versus causal implications. |
| Association of serum tumor necrosis factor levels with decrease of cholesterol during septic shock Fraunberger, P., G. Pilz, et al. (1998), Shock 10(5): 359-63. Abstract: Recent studies suggest that release of cytokines during inflammatory states such as septic shock leads to hypocholesterolemia. To examine whether tumor necrosis factor alpha (TNF), which is the major cytokine in inflammatory disease, causes hypocholesterolemia, we measured serum levels of total (bioactive and receptor-bound) TNF, cholesterol, Apo B, and Apo A1 in seven patients with septic shock over a period of 8 days. Since elevated serum TNF levels are accompanied by the release of soluble TNF receptors, levels of TNF receptors p55 and p75 were also measured. Patients with septic shock had significantly higher serum TNF and TNF receptor levels compared with healthy controls. Increased cytokine levels were accompanied by a significant decline in total serum cholesterol apolipoprotein A1 and B. In vitro studies with cultured human skin fibroblasts, human umbilical vein endothelial cells, and HepG2 hepatoma cells showed that TNF increased the degradation of 125I-labeled low-density lipoprotein in all the cell lines tested. Recombinant soluble TNF receptors inhibited the TNF-induced stimulation of low-density lipoprotein receptor in a concentration-dependent manner. However, the calculated ratio of TNF receptors to total TNF measured in serum of these patients was not able to counteract the stimulatory effect of TNF, possibly due to the higher molar excess of TNF receptors required to achieve this effect in vitro. Our data strengthen the hypothesis that serum values of total TNF determine the extent of hypocholesterolemia during sepsis and septic shock despite the presence of a high concentration of TNF receptors. Studies with recombinant TNF also confirm the role of TNF in hypocholesterolemia in inflammation. |