| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients: relation to basal serum cholestanol Miettinen, T. A., T. E. Strandberg, et al. (2000), Arterioscler Thromb Vasc Biol 20(5): 1340-6. Abstract: Coronary patients with low baseline ratios of serum cholestanol and plant sterols to cholesterol (indicating low cholesterol absorption) but not those with high ratios (high absorption) experienced reduced recurrences of coronary events during simvastatin treatment in the Scandinavian Simvastatin Survival Study. Thus, in the present study, serum cholesterol, its precursor sterols (reflecting cholesterol synthesis), plant sterols (campesterol and sitosterol), and cholestanol were measured before and during a 5-year period of placebo treatment (n=433) and simvastatin treatment (n=434) in patients from a subgroup of the Scandinavian Simvastatin Survival Study to determine whether changes in cholesterol synthesis and serum levels were related to cholesterol absorption. Serum cholesterol level was unchanged, the ratios of cholesterol precursor sterols to cholesterol were decreased, and the ratios of plant sterols to cholesterol were increased in relation to increasing baseline ratios of cholestanol quartiles. The latter predicted 5-year ratios and simvastatin-induced reductions of the precursor sterols, with the lowering of the ratios (cholesterol synthesis reduction) being almost twice higher in the lowest versus the highest quartile. The ratios of plant sterols, especially campesterol, to cholesterol were markedly increased during simvastatin treatment, mostly in subjects with the highest baseline cholestanol quartiles. Simvastatin reduced serum cholesterol more (P=0.003) in the lowest versus the highest cholestanol quartile during the 5-year treatment period. The results show for the first time that baseline cholesterol metabolism, measured by serum noncholesterol sterols, predicts the effectiveness of simvastatin in reducing cholesterol synthesis and serum levels of cholesterol. The drug suppresses the synthesis of cholesterol markedly more effectively in subjects with high than with low baseline synthesis but reduces respective serum cholesterol levels less markedly than synthesis. Subjects with high cholesterol absorption and low synthesis may need a combination therapy to lower more effectively their serum cholesterol levels and prevent an increase in the levels of plant sterols. |
| Noncholesterol sterols in bile and stones of patients with cholesterol and pigment stones Miettinen, T. E., Y. A. Kesaniemi, et al. (1996), Hepatology 23(2): 274-80. Abstract: Human bile and cholesterol gallstones contain sterols including methylated (lanosterol and other dimethyl and monomethyl sterols), and demethylated cholesterol precursor sterols (delta 8-lathosterol, lathosterol, and desmosterol), plant sterols (campesterol and sitosterol), and cholestanol. The aim of the study was to analyze the noncholesterol sterols in gallbladder bile and stones from female and male patients with cholesterol stones (CS) and pigment stones (PS) to ascertain whether any sterol fraction contributes to the gallstone formation. Classification of gallstones to CS and PS was performed on the basis of the stone cholesterol content. The study group consisted of 165 consecutive cholecystectomized patients, 150 with CS and 15 with PS. Bile acids and sterols were quantitated using gas-liquid chromatography (GLC). The biliary lipid and noncholesterol sterol/cholesterol proportions were similar in the CS and PS patients. The proportions of methylated and plant sterols were significantly lower in the CS than in bile, whereas those of delta 8-lathosterol, lathosterol, and cholestanol were significantly higher. The PS, in contrast to the CS, were neither sex nor weight related. The bile acid and phospholipid concentrations and the proportions of lanosterol, delta 8,24-dimethylsterol, and sitosterol were up to 50 times higher and those of delta 8-lathosterol and lathosterol twice lower in the PS than in the CS. The results suggest that, in general, the stones with low cholesterol content are proportionately richer in nonpolar precursor and plant sterols and lower in demethylated precursors, the situation being opposite for the CS. The stone/bile ratios suggest that in both stone groups, but especially in the CS, levels of the polar precursor sterols and cholestanol were enriched in the stone, whereas levels of the nonpolar precursor sterols, and to a lesser extent plant sterols, were not enriched in the stone despite their high biliary proportions. |
| Non-cholesterol sterols, absorption and synthesis of cholesterol and apolipoprotein A-I kinetics in a Finnish lecithin-cholesterol acyltransferase deficient family Gylling, H. and T. A. Miettinen (1992), Atherosclerosis 95(1): 25-33. Abstract: We describe the first Finnish LCAT-deficient family with two affected, one questionably affected and one healthy family member. The affected family members presented stomatocytes in the peripheral blood, exhibited low serum levels of total, LDL and HDL cholesterol, triglycerides, phospholipids and apolipoprotein A-I and especially A-II. Apolipoprotein A-I catabolism was accelerated to moderately high and very high levels in the two affected subjects. Cholesterol esterification percentage was low in all lipoprotein fractions. The intestinal cholesterol absorption efficiency and cholesterol and bile acid synthesis were within normal limits. The esterification percentage of demethylated cholesterol precursor sterols, cholestanol and plant sterols resembled mostly that of cholesterol, while those of VLDL and LDL methostenols, precursor sterols esterified by acyl-CoA:cholesterol acyltransferase (ACAT), suggested normal ACAT activity. In HDL all sterols were poorly esterified. The observations on stomatocytes, normal absorption and synthesis of cholesterol and bile acids, abnormal kinetics of apolipoprotein A-I, evidence of normal ACAT activity and abnormal esterification of non-cholesterol sterols are findings presented for the first time in LCAT deficiency. |
| Nonenzymatic glycosylation of HDL and impaired HDL-receptor-mediated cholesterol efflux Duell, P. B., J. F. Oram, et al. (1991), Diabetes 40(3): 377-84. Abstract: Previous studies have shown that nonenzymatic glycosylation of high-density lipoprotein (HDL) inhibits high-affinity binding to cultured cells and the candidate HDL-receptor protein. Because binding of HDL to its receptor is required for HDL-receptor-mediated cholesterol efflux from cells, we hypothesized that glycosylated HDL3 would have reduced ability to remove cholesterol from cells. HDL3 was glycosylated in vitro to achieve up to 40-50% reductions in free-lysine residues. Glycosylated HDL3 had a slightly greater ability than control HDL3 to sequester cholesterol directly from the plasma membrane, as predicted by changes in lipid composition. This process is independent of HDL-receptor binding and should not be influenced by reduced binding of HDL3. In contrast, efflux of intracellular cholesterol from cells, which is HDL-receptor dependent, was reduced 25-40%. The ability of glycosylated HDL3 to diminish cholesterol esterification was significantly reduced, indicating reduced net cholesterol efflux. Steady-state efflux of LDL-derived cholesterol was also markedly reduced. These findings suggest that nonenzymatically glycosylated HDL is functionally abnormal and might contribute to the accelerated development of atherosclerosis in patients with diabetes mellitus. |
| Nonequilibrium behavior in supported lipid membranes containing cholesterol Stottrup, B. L., S. L. Veatch, et al. (2004), Biophys J 86(5): 2942-50. Abstract: We investigate lateral organization of lipid domains in vesicles versus supported membranes and monolayers. The lipid mixtures used are predominantly DOPC/DPPC/Chol and DOPC/BSM/Chol, which have been previously shown to produce coexisting liquid phases in vesicles and monolayers. In a monolayer at an air-water interface, these lipids have miscibility transition pressures of approximately 12-15 mN/m, which can rise to 32 mN/m if the monolayer is exposed to air. Lipid monolayers can be transferred by Langmuir-Schafer deposition onto either silanized glass or existing Langmuir-Blodgett supported monolayers. Micron-scale domains are present in the transferred lipids only if they were present in the original monolayer before deposition. This result is valid for transfers at 32 mN/m and also at lower pressures. Domains transferred to glass supports differ from liquid domains in vesicles because they are static, do not align in registration across leaflets, and do not reappear after temperature is cycled. Similar static domains are found for vesicles ruptured onto glass surfaces. Although supported membranes on glass capture some aspects of vesicles in equilibrium (e.g., gel-liquid transition temperatures and diffusion rates of individual lipids), the collective behavior of lipids in large liquid domains is poorly reproduced. |
| Nonesterified phytosterols dissolved and recrystallized in oil reduce plasma cholesterol in gerbils and humans Hayes, K. C., A. Pronczuk, et al. (2004), J Nutr 134(6): 1395-9. Abstract: When free phytosterols are adequately heated and then cooled in fat, they recrystallize and are rendered bioavailable for blocking cholesterol absorption. To extend the application of phytosterols to fried foods, the activity of these modified crystals was assessed in 2 experiments with 26 male gerbils fed purified diets containing 0.15 g/100 g cholesterol with or without 0.75 g/100 g free phytosterols. The heat-modified soybean sterols were added directly to the diet (Expt. 1) or as phytosterol-enriched potato chips (Expt. 2). In the gerbil experiments, only the diet containing phytosterols significantly reduced plasma cholesterol (35-48%) and the total cholesterol/HDL cholesterol (HDL-C) ratio (40%), as well as hepatic cholesterol esters (80%). In a subsequent human study, subjects (n = 7) consumed two 28-g servings of tortilla chips fried in oil with or without phytosterols that provided 0 or 1.5 g/d for 4-wk periods in a crossover design (Expt. 3). During consumption of the phytosterol-enriched chips, significant reductions in plasma cholesterol (10%) and LDL cholesterol (15%) were achieved without affecting HDL-C. This novel means of delivering free phytosterols proved to be both functionally efficient and effective. |
| Non-esterified plant sterols solubilized in low fat milks inhibit cholesterol absorption--a stable isotope double-blind crossover study Pouteau, E. B., I. E. Monnard, et al. (2003), Eur J Nutr 42(3): 154-64. Abstract: BACKGROUND: The cholesterol absorption inhibiting properties of plant sterols in milks are unknown. The milk fat globule membrane components may enhance the absorption of cholesterol and could make plant sterols less efficient in this complex matrix. AIM OF THE STUDY: To evaluate in hypercholesterolemic men the cholesterol absorption inhibiting properties of verified properly solubilized, non-esterified plant sterols in partly vegetable oil containing milks. METHODS: The plant sterols in milk were determined to be properly solubilized, and to have effective in vitro functionality. Sixteen hypercholesterolemic adult men (initial total cholesterol 5.8-8.6 mM) then consumed milk containing sterols (1.8 g of non-esterified pure plant sterols/d) and control milk, alternatively, during two 6-day periods in a double blind cross over design. During the trial, cholesterol absorption was evaluated from the ratio of plasma isotopic enrichment of 26, 26, 26, 27, 27, 27-(2)H(6)cholesterol from oral intake (35.6 +/- 0.2 micromol, +/- SEM) over enrichment of 23, 24, 25, 26, 27-(13)C(5)cholesterol from intravenous injection (77.9 +/- 0.5 micromol). RESULTS: Plant sterols in low fat milks contained very few crystals > 11 microm in the presence and absence of bile salts and lysophospholipids, and inhibited cholesterol uptake in Caco-2 cell. This assured that the sterols were properly solubilized prior to the clinical trial. In the clinical study, compliance of volunteers was excellent. After tracer injections (72 h), the plasma (2)H and (13)C isotopic enrichments changed from 0.024 +/- 0.001 and 0.072 +/- 0.003 MPE (control) to 0.015 +/- 0.001 and 0.074 +/- 0.002 MPE during sterol treatment, respectively. Cholesterol absorption was reduced from 70.1 +/- 4.2 % with control to 41.1 +/- 4.0 % with milks containing plant sterol (P < 0.001). CONCLUSIONS: These results demonstrate that properly solubilized non-esterified plant sterols in milks significantly inhibit cholesterol absorption in mildly hypercholesterolemic men. |
| Non-genetic leuko-neutropenia is related to dietary cholesterol: an experimental model with the rat Ogunranti, J. O. (1994), Acta Haematol 92(2): 61-5. Abstract: A dietary factor is thought to be responsible for constant non-genetic neutropenia in Africans. The identify of this factor is unknown. The effect of diet on the differential white cell count in rat is studied. Twenty rats were divided into four dietary groups: (1) control rats on pellets, (2) millet, (3) peanut and (4) a special diet containing high cholesterol and saturated fatty acids from coconut, egg yolk, milk and Danish butter. After 3 months, group 4 rats had significantly higher total white cell counts and percentages of neutrophils in addition to higher serum cholesterol levels and higher weights. In the second experiment, pure cholesterol was injected intraperitoneally to rats while control rats received saline. Neutrophil counts increased 6 h after injection and peaked only in the test rats. It is concluded that low-cholesterol diet decreases neutrophil count. |
| Non-HDL cholesterol and apolipoprotein B in the dyslipidemic classification of type 2 diabetic patients Wagner, A. M., A. Perez, et al. (2003), Diabetes Care 26(7): 2048-51. Abstract: OBJECTIVE: To compare non-HDL cholesterol (HDLc) and apolipoprotein B (apoB) in the identification of nonconventional high-risk dyslipidemic phenotypes in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Total cholesterol and triglycerides, HDLc, LDL cholesterol, non-HDLc, apolipoprotein B (apoB), and LDL size were determined in 122 type 2 diabetic patients (68% male, aged 59.6 +/- 9.7 years, and HbA(1c) 7.5% range 5.2-16.0). They were then classified as normo- and hypertriglyceridemic if their triglyceride concentrations were below/above 2.25 mmol/l, as normo/hyper-non-HDLc if non-HDLc concentrations were below/above 4.13 mmol/l, and as normo- and hyperapoB if apoB concentrations were below/above 0.97 g/l. Both classifications were compared (concordance assessed with the kappa index), and low HDLc and LDL phenotype B were identified in each category. RESULTS: A total of 26 patients were hypertriglyceridemic and 96 were normotriglyceridemic. All hypertriglyceridemic subjects had increased non-HDLc, whereas 24 had increased apoB (kappa= 0.95). In the normotriglyceridemic group, 44 had increased non-HDLc, 68 had increased apoB, and 25 of the 52 patients with normal non-HDLc had increased apoB (kappa= 0.587). Low HDLc and LDL phenotype B were similarly distributed into the equivalent categories. CONCLUSIONS: Non-HDLc and apoB are equivalent risk markers in hypertriglyceridemic patients, but apoB identifies additional patients with high-risk dyslipidemic phenotypes in normotriglyceridemic type 2 diabetic patients. |
| Non-HDL cholesterol and apolipoprotein B predict cardiovascular disease events among men with type 2 diabetes Jiang, R., M. B. Schulze, et al. (2004), Diabetes Care 27(8): 1991-7. Abstract: OBJECTIVE: To evaluate the role of non-HDL cholesterol and apolipoprotein (apo)B, markers of all potentially atherogenic lipoproteins, as predictors of cardiovascular disease (CVD) in comparison with LDL cholesterol in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We prospectively followed 746 diabetic men in the Health Professionals' Follow-up Study who were aged 46-81 years and free of CVD or cancer at the time of blood draw in 1993-1994. During 6 years of follow-up, we ascertained 103 incident CVD cases. RESULTS: We used Cox proportional hazard modeling to estimate the relative risk (RR) of CVD. After adjustment for age, BMI, and other lifestyle risk factors, the multivariate RR of CVD (the highest versus the lowest quartile) was 2.34 (95% CI 1.26-4.32) for non-HDL cholesterol, 2.31 (1.23-4.35) for apoB, and 1.74 (0.99-3.06) for LDL cholesterol. Comparisons of nested models indicate that non-HDL cholesterol, but not apoB, adds significantly to the prediction of CVD risk beyond LDL cholesterol. The area under the receiver operating characteristic curve was 0.685, 0.691, 0.695, and 0.722 for the CVD risk-prediction model with LDL cholesterol, apoB, non-HDL cholesterol, and total cholesterol-to-HDL cholesterol ratio (or the non-HDL-to-HDL cholesterol ratio), respectively. CONCLUSIONS: Non-HDL cholesterol and apoB are more potent predictors of CVD incidence among diabetic men than LDL cholesterol. Statistically, the ratio of total to HDL cholesterol is the best predictor of CVD in this cohort of diabetic men. |
| Non-HDL cholesterol as a measure of atherosclerotic risk Packard, C. J. and Y. Saito (2004), J Atheroscler Thromb 11(1): 6-14. Abstract: Elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels, hallmarks of the atherogenic lipid profile found in the metabolic syndrome and type 2 diabetes, are commonly seen in Japanese patients with coronary heart disease (CHD). In the setting of mildly to moderately elevated plasma TG (150-500 mg/dl), very-low-density lipoprotein (VLDL) accumulates and so do high levels of atherogenic TG-rich, cholesterol-enriched remnant particles. Indeed, in hypertriglyceridemia, abnormalities are seen in the quantity and quality of all lipoprotein B-containing lipoproteins. Non-HDL-C (total cholesterol minus HDL-C) provides a convenient measure of the cholesterol content of all atherogenic lipoproteins, and thus incorporates the potential risk conferred by elevated levels of atherogenic TG-rich remnants that is additional to the risk associated with low-density lipoprotein cholesterol (LDL-C). Non-HDL-C level has been found to be a strong predictor of future cardiovascular risk among patients whether or not they exhibit symptoms of vascular disease, and was recently recommended as a secondary treatment target (after LDL-C) in patients with elevated TG by the National Cholesterol Education Program Adult Treatment Panel III. Adoption of this readily available measure to assess risk and response to treatment in patients with elevated TG would improve treatment of dyslipidemia in a substantial number at risk for CHD. |
| Non-HDL cholesterol as a predictor of cardiovascular disease in type 2 diabetes: the strong heart study Lu, W., H. E. Resnick, et al. (2003), Diabetes Care 26(1): 16-23. Abstract: OBJECTIVE: To determine whether non-HDL cholesterol, a measure of total cholesterol minus HDL cholesterol, is a predictor of CVD in patients with diabetes. RESEARCH DESIGN AND METHODS: The Strong Heart Study, a population-based study of CVD and its risk factors in 13 American Indian communities in three geographic areas in the U.S. The baseline examination, conducted between July 1989 and January 1992, consisted of a personal interview, a physical examination, and laboratory tests. Of the 4,549 women and men aged 45-74 years participating in the study, 2,108 had diabetes but no CVD at baseline. Data on fatal and nonfatal CVD were collected during the follow-up period through 31 December 1998 (average 9 years). RESULTS: Multivariable analyses indicated that non-HDL cholesterol is a strong predictor of CVD in men and women with diabetes and is particularly indicative of coronary events. Hazard ratios for the highest tertile of non-HDL cholesterol in men and women with diabetes (2.23 and 1.80, respectively) were higher than those for either LDL cholesterol or triglycerides alone in both men and women and were higher than the ratio of total/HDL cholesterol in women. The utility of non-HDL cholesterol in predicting CVD extended over a wide range of triglyceride concentrations. CONCLUSIONS: This study suggests that non-HDL cholesterol index may be particularly useful in predicting CVD risk in patients with diabetes. |
| Non-HDL cholesterol as a predictor of carotid atherosclerosis in the elderly Kawamoto, R., Y. Oka, et al. (2005), J Atheroscler Thromb 12(3): 143-8. Abstract: The aim of the present study was to evaluate sclerotic lesions of the common carotid artery by ultrasonography in 921 in-patients aged 65 years and older (77 +/- 7 years) and investigate whether lipid levels were associated with carotid atherosclerosis. In men, an increased risk for carotid atherosclerosis was associated with increased levels of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). Compared to men with the lowest tertile of LDL-C levels (< 83.4 mg/dl), the adjusted odds ratio was 2.502 (95% confidence interval: 1.426-4.390) in those with the middle tertile (83.4-115.2 mg/dl), and 2.688 (1.509-4.790) in those with the highest tertile (> 115.2 mg/dl). Like the LDL-C level, the non-HDL-C level showed a positive and linear relationship with carotid atherosclerosis. Compared to men with the lowest tertile of non-HDL-C levels (< 101 mg/dl), the adjusted odds ratio was 2.881 (1.633-5.081) for those with the middle tertile (101-135 mg/dl), and 2.990 (1.651-5.415) for those with the highest tertile (> 135 mg/dl). Similarly, in women, an increased risk for carotid atherosclerosis was also positively and linearly associated with LDL-C and non-HDL-C. The Non-HDL-C level is a potential predictor of risk for carotid atherosclerosis in the elderly. |
| Non-HDL cholesterol contributes to the "hypertriglyceridemic waist" as a cardiovascular risk factor: the Hoorn study Bos, G., J. M. Dekker, et al. (2004), Diabetes Care 27(1): 283-4. |
| Non-HDL cholesterol is less informative than the total-to-HDL cholesterol ratio in predicting cardiovascular risk in type 2 diabetes Holman, R. R., R. L. Coleman, et al. (2005), Diabetes Care 28(7): 1796-7. |
| Non-HDL cholesterol level is reliable to be an early predictor for vascular inflammation in type 2 diabetes mellitus Wang, C. Y. and T. C. Chang (2004), J Clin Endocrinol Metab 89(9): 4762-7. Abstract: Although LDL is the primary target for lipid-lowering therapy and non-HDL cholesterol is a secondary target in patients with elevated triglyceride (TG) levels, non-HDL cholesterol is still an early, reliable, and practical predictor for vascular inflammation. However, in comparison with LDL, further evidence for superiority in non-HDL cholesterol as the primary therapeutic target is required. A total of 189 type 2 diabetic patients (88 men and 101 women; mean age 58.4 +/- 14.0 years; duration of diabetes 9.8 +/- 4.2 years) who had not used anti-inflammatory agents in the past two years were enrolled in this study. Levels of various lipid fractions and C-reactive protein (CRP) and the cholesterol retention fraction (CRF) were measured. Lipid levels and CRF in samples with CRP levels below or above different cutoffs were compared. Statistically significant differences were seen at all CRP cutoffs in the levels of TG, HDL, and non-HDL cholesterol and the CRF, but no differences were seen in total cholesterol and LDL cholesterol levels. CRP levels correlated with non-HDL cholesterol levels (r = 0.16, P = 0.0236) and the CRF (r = 0.18, P = 0.14), but not with levels of HDL or TG. Besides, non-HDL levels showed a marked correlation with CRF (r = 0.68, P < 0.0001). On the basis of CRP levels, non-HDL levels are reliable in predicting vascular inflammation, and CRF could be another important predictor for cardiovascular events. Our results suggest that the emphasis placed on non-HDL cholesterol should be reevaluated in comparison with that placed on LDL cholesterol. |
| Non-HDL cholesterol predicts coronary heart disease in primary prevention: findings from an Italian 40-69 year-old cohort in general practice Ciardullo, A. V., L. Azzolini, et al. (2004), Monaldi Arch Chest Dis 62(2): 69-72. Abstract: OBJECTS: Non-HDL cholesterol is now recommended as an index of risk associated with combined dyslipidemia, and it has also been found useful in predicting coronary heart disease (CHD) risk in patients with diabetes. We studied the association between known CHD risk factors, enclosed non-HDL cholesterol, and a "high CHD risk condition", i.e. a "5-years CHD risk >15%" in general practice. METHODS: We studied 4,085 40-69 year-old diabetic (no. 489) and non-diabetic (no. 3,596) individuals from an opportunistic cohort. Cross-sectional descriptive statistics, and age- and gender-adjusted multiple logistic exponential betas have been calculated. RESULTS: About 12% of the participants had diabetes. Age- and gender-adjusted comparison showed that all the study variables were significantly worse in diabetic vs. non-diabetic individuals (except cigarette smoking, total blood cholesterol and the ratio of total to HDL cholesterol). They had a mean "5-year CHD-risk" significantly higher than non-diabetic individuals (18.8+/-11.9% vs 7.5+/-6.9%, P<0.01), and a four-fold prevalence of "5-years CHD risk >15%" (55.4% vs 11.1%, P<0.01). As to diabetic individuals, the study variables associated to a "high CHD risk condition" were cigarette smoking, systolic blood pressure, and non-HDL blood cholesterol levels. As to non-diabetic individuals cigarette smoking, systolic blood pressure, and HDL (inversely) and non-HDL blood cholesterol levels were associated to a "high CHD risk condition". CONCLUSIONS: Non-HDL cholesterol--and cigarette smoking and systolic blood pressure--strongly predicted a "high CHD risk condition" both in diabetic and non-diabetic individuals. |
| Non-HDL cholesterol versus apolipoprotein B in diabetic dyslipoproteinemia: alternatives and surrogates versus the real thing Sniderman, A. D. (2003), Diabetes Care 26(7): 2207-8. |
| Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women Ridker, P. M., N. Rifai, et al. (2005), Jama 294(3): 326-33. Abstract: CONTEXT: Current guidelines for cardiovascular risk detection are controversial with regard to the clinical utility of different lipid measures, non-high-density lipoprotein cholesterol (non-HDL-C), lipid ratios, apolipoproteins, and C-reactive protein (CRP). OBJECTIVE: To directly compare the clinical utility of total cholesterol, low-density lipoprotein cholesterol (LDL-C), HDL-C, non-HDL-C, apolipoproteins A-I and B(100), high-sensitivity CRP, and the ratios of total cholesterol to HDL-C, LDL-C to HDL-C, apolipoprotein B(100) to apolipoprotein A-I, and apolipoprotein B(100) to HDL-C as predictors of future cardiovascular events in women. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 15,632 initially healthy US women aged 45 years or older (interquartile range, 48-59 years) who were enrolled between November 1992 and July 1995. All participants were followed up over a 10-year period for the occurrence of future cardiovascular events. MAIN OUTCOME MEASURE: Hazard ratios (HRs) and 95% confidence intervals (CIs) for first-ever major cardiovascular events (N = 464) according to baseline levels of each biomarker. RESULTS: After adjustment for age, smoking status, blood pressure, diabetes, and body mass index, the HRs for future cardiovascular events for those in the extreme quintiles were 1.62 (95% CI, 1.17-2.25) for LDL-C, 1.75 (95% CI, 1.30-2.38) for apolipoprotein A-I, 2.08 (95% CI, 1.45-2.97) for total cholesterol, 2.32 (95% CI, 1.64-3.33) for HDL-C, 2.50 (95% CI, 1.68-3.72) for apolipoprotein B(100), 2.51 (95% CI, 1.69-3.72) for non-HDL-C, and 2.98 (95% CI, 1.90-4.67) for high-sensitivity CRP (P<.001 for trend across all quintiles). The HRs for the lipid ratios were 3.01 (95% CI, 2.01-4.50) for apolipoprotein B(100) to apolipoprotein A-I, 3.18 (95% CI, 2.12-4.75) for LDL-C to HDL-C, 3.56 (95% CI, 2.31-5.47) for apolipoprotein B(100) to HDL-C, and 3.81 (95% CI, 2.47-5.86) for the total cholesterol to HDL-C (P<.001 for trend across all quintiles). The correlation coefficients between high-sensitivity CRP and the lipid parameters ranged from -0.33 to 0.15, and the clinical cut points for CRP of less than 1, 1 to 3, and higher than 3 mg/L provided prognostic information on risk across increasing levels of each lipid measure and lipid ratio. CONCLUSIONS: Non-HDL-C and the ratio of total cholesterol to HDL-C were as good as or better than apolipoprotein fractions in the prediction of future cardiovascular events. After adjustment for age, blood pressure, smoking, diabetes, and obesity, high-sensitivity CRP added prognostic information beyond that conveyed by all lipid measures. |
| Non-HDL cholesterol: into the spotlight Hsia, S. H. (2003), Diabetes Care 26(1): 240-2. |