| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Improvement in endothelium-dependent brachial artery flow-mediated vasodilation with low-density lipoprotein cholesterol levels <100 mg/dl Shechter, M., M. Sharir, et al. (2000), Am J Cardiol 86(11): 1256-9, A6. Abstract: To determine whether the current National Cholesterol Education Program cholesterol recommendations are consistent with beneficial endothelium-dependent vasodilation, we prospectively assessed endothelium-dependent brachial artery vasoreactivity in 50 patients with stable coronary artery disease. Our results showed that endothelial-dependent vasoreactivity was greater when low-density lipoprotein cholesterol was <100 mg/dl, suggesting that it may be beneficial to reach the National Cholesterol Education Program Adult Treatment Panel II target of low-density lipoprotein cholesterol of <100 mg/dl. |
| Improvement in Japanese clinical laboratory measurements of total cholesterol and HDL-cholesterol by the US Cholesterol Reference Method Laboratory Network Nakamura, M., S. Sato, et al. (2003), J Atheroscler Thromb 10(3): 145-53. Abstract: BACKGROUND: Accurate and precise measurements of total cholesterol (TC) and HDL-cholesterol (HDL-C) are necessary for effective diagnosis and treatment of lipid disorders. We studied the impact of TC certification and HDL-C evaluation in Japanese clinical laboratories to standardize their measurements. METHODS: We selected 78 laboratories participated at least twice for TC and 46 laboratories participated twice for HDL-C in the standardization protocols developed by the Cholesterol Reference Method Laboratory Network (CRMLN). We compared the initial and subsequent results using the performance guidelines established by US National Cholesterol Education Program (NCEP). RESULTS: For TC, mean percentage bias of all participants was -0.93% and -0.49% for the initial and second rounds, respectively. Mean within-sample CV was 0.72% and 0.69% for the initial and second rounds, respectively. For HDL-C, mean percentage bias of all participants was -1.86% and -0.06% for the initial and second events, respectively. Mean among-run CV was 1.56% and 1.58% for the initial and second events, respectively. CONCLUSIONS: TC accuracy in the second round than the initial round tended to improvement although statistically not significant, however in the five years follow-up, mean absolute percentage bias was reduced over time. HDL-C accuracy was statistically improved in the second event than the initial event. The precision for both TC and HDL-C did not change. This study shows CRMLN protocols contribute effectively to improvement of TC and HDL-C performance. |
| Improvement in the regulation of cellular cholesterologenesis in diabetes: the effect of reduction in serum cholesterol by simvastatin Owens, D., J. Stinson, et al. (1991), Diabet Med 8(2): 151-6. Abstract: Cellular cholesterol homeostasis was examined in 11 hypercholesterolaemic Type 2 diabetic patients prior to and following reduction of serum cholesterol using simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase. Following 12 weeks of treatment with simvastatin (10-40 mg day-1), serum cholesterol decreased by 30 +/- 3% from 7.8 +/- 0.2 mmol l-1 to 5.5 +/- 0.2 mmol l-1 (p less than 0.001) and LDL-cholesterol by 35 +/- 4% from 5.7 +/- 0.2 to 3.6 +/- 0.1 mmol l-1 (p less than 0.001). The esterified/free cholesterol ratio in LDL also decreased from 2.75 +/- 0.18 to 1.94 +/- 0.10 (p less than 0.01) after treatment. Cellular cholesterol synthesis, measured by 14C acetate incorporation into mononuclear leucocytes, decreased by 39 +/- 11% from 231 +/- 13 to 140 +/- 25 mumol g-protein-1 (p less than 0.01). The degree of suppression of 14Cacetate incorporation into cholesterol in normal mononuclear cells by diabetic patients' LDL increased from 32.1 +/- 4.0% to 48.8 +/- 2.5% (p less than 0.001) following simvastatin. The activity of acyl coenzyme A:cholesterol-0-acyltransferase (ACAT) increased significantly by 55 +/- 18% (p less than 0.05) after treatment. Cholesterol synthesis in patients' mononuclear cells correlated positively (r = 0.66, p less than 0.05) with the esterified/free cholesterol ratio of their LDL, while suppression of cholesterol synthesis by patients' LDL correlated negatively (r = -0.64, p less than 0.05) with the esterified/free cholesterol ratio of the LDL following treatment.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Improvement of coronary prognosis by reducing LDL-cholesterol Wolfram, G. (1990), Versicherungsmedizin 42(3): 88-91. Abstract: Elevated LDL-cholesterol levels mean increased risk for coronary heart disease. In different studies the indication for decreasing high LDL-cholesterol in patients with coronary heart disease was proven. This is also the case with patients suffering from high LDL-cholesterol but not yet coronary heart disease. It is supposed that with longer duration of studies the total mortality between verum and placebo groups will also reach significance. |
| Improvement of erythrocyte deformability by cholesterol-lowering therapy with pravastatin in hypercholesterolemic patients Kohno, M., K. Murakawa, et al. (1997), Metabolism 46(3): 287-91. Abstract: Erythrocyte deformation is an important regulatory factor of the microcirculation. The present study was designed to examine whether erythrocyte deformability is altered in hypercholesterolemic patients and, if so, whether cholesterol-lowering therapy affects this parameter in these patients. The erythrocyte deformability of 37 hypercholesterolemic patients was evaluated before and after 1 year of therapy with pravastatin, an inhibitor of hepatic hydroxymethyl glutaryl coenzyme A reductase, under various shear stresses (4.7, 9.5, 23.6, 47.3, 118.1, and 236.2 dyne/cm2) using laser diffractometry. At study entry, erythrocyte deformability under 4.7 and 9.5 dyne/cm2 shear stress, which is actually observed in human vessels, was reduced compared with that in 20 age-matched normocholesterolemic subjects and was inversely correlated with serum cholesterol and low-density lipoprotein (LDL) cholesterol. Pravastatin therapy for 1 year, which reduced serum cholesterol from 288 +/- 28 to 223 +/- 20 mg/dL, significantly improved erythrocyte deformability by approximately 20%. There was a significant relation between the improvement of erythrocyte deformability and the reduction of serum cholesterol or LDL cholesterol. The results suggest that erythrocyte deformability is reduced in hypercholesterolemic patients, and that long-term cholesterol-lowering therapy can improve reduced erythrocyte deformability, which may contribute to the improvement of organ perfusion. |
| Improvement of glycaemic control in type 2 diabetes: favourable changes in blood pressure, total cholesterol and triglycerides, but not in HDL cholesterol, fibrinogen, Von Willebrand factor and (pro)insulin Becker, A., F. E. van der Does, et al. (2003), Neth J Med 61(4): 129-36. Abstract: BACKGROUND: Diabetes mellitus causes a substantial increase in cardiovascular risk, which can only partly be reduced by antihyperglycaemic treatment. We were interested in whether improvement in glycaemic control is associated with improvement of other cardiovascular risk factors. Therefore, we studied among type 2 diabetic patients the association between on the one hand changes in glycaemic control and on the other hand within-subject changes of both classic cardiovascular risk factors and less conventional cardiovascular risk indicators that are typically associated with type 2 diabetes (proinsulin, insulin, fibrinogen, von Willebrand factor and the urinary albumin-creatinine ratio). METHODS: The 214 type 2 diabetic patients were randomly assigned to either a strict fasting capillary glucose target level (< 6.5 mmol/l) or a less strict target (< 8.5 mmol/l). Duration of follow-up was two years. Since the interventions did not yield statistically significant differences between the treatment arms, we reanalysed the data focusing on within-subject changes of cardiovascular risk factors and indicators across tertiles of average HbA(1c). RESULTS: Individuals in whom HbA(1c) decreased had significant favourable concurrent changes in triglycerides, total cholesterol, blood pressure, and in the albumin-creatinine ratio in those who were normoalbuminuric at baseline. In contrast, these individuals had unfavourable, although not statistically significant, changes in HDL cholesterol, proinsulin, insulin, fibrinogen and von Willebrand factor. In the whole group, fibrinogen increased more than could be expected on the basis of the relationship between fibrinogen and age, namely from 3.5 +/- 0.8 to 3.9 +/- 0.9 g/l (p value < 0.01). CONCLUSIONS: Our results suggest that improvement in glycaemia in type 2 diabetes is associated with significant favourable changes in triglycerides, total cholesterol, blood pressure and, in normoalbuminuric individuals, albumin-creatinine ratio. In contrast, it is not consistently associated with favourable changes in some cardiovascular risk indicators typically associated with diabetes, which may in part explain why antihyperglycaemic treatment does not clearly lower atherothrombotic disease risk. |
| Improvement of HDL- and LDL-cholesterol levels in diabetic subjects by feeding bread containing chitosan Ausar, S. F., M. Morcillo, et al. (2003), J Med Food 6(4): 397-9. Abstract: In this work we evaluated the efficacy and safety of a bread formulation containing chitosan in dyslipidemic type 2 diabetic subjects. For this purpose a total of 18 patients were allowed to incorporate to their habitual diets 120 g/day of bread containing 2% (wt/wt) chitosan (chitosan group, n= 9) or standard bread (control group, n= 9). Before the study and after 12 weeks on the modified diet, the following parameters were evaluated: body weight, plasma cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, and hemoglobin A(1c) (HbA(1c)). Compared with the control group, the patients receiving chitosan-containing bread decreased their mean levels of LDL-cholesterol and significantly increased their mean levels of HDL-cholesterol at the end of the study. There were no significant differences in the body weight, serum triglyceride, and HbA(1c). These results suggest that chitosan incorporated into bread formulations could improve the lipoprotein balance similar to typical biliary salts trappers, increasing the HDL- and lowering the LDL-cholesterol, without changing the triglyceride levels. These results warrant further studies over a longer period of time to evaluate if a persistent improvement in levels of lipoproteins can be attained with this strategy. |
| Improvement of paclitaxel therapeutic index by derivatization and association to a cholesterol-rich microemulsion: in vitro and in vivo studies Rodrigues, D. G., D. A. Maria, et al. (2005), Cancer Chemother Pharmacol 55(6): 565-76. Abstract: A cholesterol-rich microemulsion or nanoparticle termed LDE concentrates in cancer tissues after injection into the bloodstream. Here the cytotoxicity, pharmacokinetics, toxicity to animals and therapeutic action of a paclitaxel lipophilic derivative associated to LDE is compared with those of the commercial paclitaxel. Results show that LDE-paclitaxel oleate is stable. The cytostatic activity of the drug in the complex is diminished compared with the commercial paclitaxel due to the cytotoxicity of the vehicle Cremophor EL used in the commercial formulation. Competition experiments in neoplastic cultured cells show that paclitaxel oleate and LDE are internalized together by the LDL receptor pathway. LDE-paclitaxel oleate arrests the G(2)/M phase of cell cycle, similarly to commercial paclitaxel. Tolerability to mice is remarkable, such that the lethal dose (LD(50)) was ninefold greater than that of the commercial formulation (LD(50) = 326 microM and 37 microM, respectively). LDE concentrates paclitaxel oleate in the tumor roughly fourfold relative to the normal adjacent tissues. At equimolar doses, the association of paclitaxel oleate with LDE results in remarkable changes in the drug pharmacokinetic parameters when compared to commercial paclitaxel (t(1/2)=218 min and 184 min, AUC=1,334 microg h/ml and 707 microg h/ml and CL=0.125 ml/min and 0.236 ml/min, respectively). Finally, the therapeutic efficacy of the complex is pronouncedly greater than that of the commercial paclitaxel, as indicated by the reduction in tumor growth, increase in survival rates and % cure of treated mice. In conclusion, LDE-paclitaxel oleate is a stable complex and compared with paclitaxel toxicity is considerably reduced and activity is enhanced, which may lead to improved therapeutic index in clinical use. |
| Improvement of thermal stability of Streptomyces cholesterol oxidase by random mutagenesis and a structural interpretation Nishiya, Y., N. Harada, et al. (1997), Protein Eng 10(3): 231-5. Abstract: Random mutagenesis was used to enhance the thermal stability of Streptomyces cholesterol oxidase. Four thermostable mutants were isolated and the following amino acid substitutions were identified: Ser103 to Thr (mutant S103T), Val121 to Ala (mutant V121A), Arg135 to His (mutant R135H) and Val145 to Glu (mutant V145E). The wild-type and mutant enzymes were purified and characterized. The properties of mutants S103T, V121A and R135H were similar to those of the wild type but they showed improved thermal stability. When the V145E mutation was introduced, the thermal stability of the enzyme was markedly increased and the optimum pH was desirably changed to encompass a broad range from acid to alkali. Analysis of multiple mutants constructed by site-directed mutagenesis showed that all the mutations except that of R135H had an additive influence on the other mutations. These mutational effects are discussed in terms of a three-dimensional structural model of the enzyme constructed on the basis of homology modelling. |
| Improvement of vascular function by chronic administration of a cyclo-oxygenase inhibitor in cholesterol-fed rabbits Srisawat, S., L. Phivthong-Ngam, et al. (2003), Clin Exp Pharmacol Physiol 30(5-6): 405-12. Abstract: 1. Atherosclerotic cardio- and cerebrovascular disease is a leading cause of mortality in Western countries. Aspirin-like drugs are widely used to prevent and treat these occlusive cardio- and cerebrovascular diseases. The beneficial effects of these drugs have been largely attributed to inhibition of platelet cyclo-oxygenase activity and thromboxane (TX) A2 production. We investigated the effect of an aspirin-like drug, namely indomethacin, on endothelial function, plaque and platelet aggregation and the formation of vasoactive substances during the development of atherosclerosis in cholesterol-fed rabbits. 2. Rabbits were fed 1% cholesterol (n = 8), 1% cholesterol plus 25 mg/day indomethacin (n = 8) or normal rabbit chow (control group; n = 8) for 12 weeks. Urinary excretion rates of 2,3-dinor-TXB2, 6-keto-prostaglandin (PG) F1alpha, 8-iso-PGF2alpha and nitrate were analysed at the beginning of dietary intervention and at 4 weekly intervals thereafter. At the end of the study period, platelet aggregation, aortic plaque formation and endothelium-dependent and -independent vascular functions of isolated aortic rings ex vivo were assessed. 3. Compared with control, in the cholesterol-fed group, urinary 2,3-dinor-TXB2, 6-keto-PGF1alpha and 8-iso-PGF2alpha excretion and platelet aggregation were significantly increased (P < 0.05), but urinary excretion of nitrate was decreased (P < 0.05). Treatment with indomethacin significantly reduced platelet aggregation, urinary 2,3-dinor-TXB2, 6-keto-PGF1alpha and 8-iso-PGF2alpha excretion (P < 0.05 vs the cholesterol-fed group) and attenuated the reduction in urinary nitrate excretion. 4. Cholesterol feeding progressively increased aortic intimal thickening and impaired endothelium-dependent vasodilator function (P < 0.05 vs control), whereas indomethacin partially prevented aortic plaque formation and restored endothelium-dependent vasodilation (P < 0.05 vs the cholesterol-fed group). 5. The present study demonstrates that indomethacin reduces the progression of atherosclerotic lesions and improves endothelium-mediated vascular responses ex vivo in cholesterol-fed rabbits. The beneficial effects of indomethacin may be due to its ability to prevent the elevation of platelet aggregation, TXA2 (measured as urinary 2,3-dinor-TXB2 excretion) and 8-iso-PGF2alpha formation and to retard the decrease in endogenous nitric oxide synthesis (assessed as urinary excretion of nitrate). Despite indomethacin treatment leading to the suppression of prostacyclin biosynthesis (assessed as urinary 6-keto-PGF1alpha excretion), according to our data, indomethacin appears to preserve endothelial function. |
| Improvements in cholesterol-related knowledge and behavior and plasma cholesterol levels in youths during the 1980s Frank, E., M. Winkleby, et al. (1993), Am J Prev Med 9(3): 168-74. Abstract: This article examines cholesterol-related knowledge, cholesterol-related behaviors, and plasma cholesterol levels in 12-24-year-olds, using data collected from four community-based cross-sectional surveys conducted 1979-1980, 1981-1982, 1985-1986, and 1989-1990. Participants included 1,552 individuals from randomly sampled households in two control cities (San Luis Obispo and Modesto, California) of the Stanford Five-City Project. Over the eleven-year study period, cholesterol-related knowledge improved in both control cities (P <.0002). Cholesterol-related behavior (P <.0003) and plasma cholesterol levels (P <.002) significantly improved only in San Luis Obispo (a college city with more 19-24-year-olds and a better-educated population than Modesto). In general, knowledge and behavior scores and plasma cholesterol levels were lower in these 12-24-year-olds than in 25-74-year-olds, although trends at all ages were similar over time and by demographic variables. Although the cholesterol-related interventions that began in the mid-1980s primarily targeted adults, these 12-24-year-olds' cholesterol-related knowledge improved (as did, to a lesser extent, their cholesterol-related behavior and plasma cholesterol levels). These findings have implications for upcoming youth-related cholesterol interventions. |
| Improvements in circulating cholesterol, antioxidants, and homocysteine after dietary intervention in an Australian Aboriginal community Rowley, K. G., Q. Su, et al. (2001), Am J Clin Nutr 74(4): 442-8. Abstract: BACKGROUND: Poor nutrition contributes to high rates of coronary heart disease among Australian Aboriginal populations. Since late 1993, the Aboriginal community described here has operated a healthy lifestyle program aimed at reducing the risk of chronic disease. OBJECTIVE: We evaluated the effectiveness of a community-directed intervention program to reduce coronary heart disease risk through dietary modification. DESIGN: Intervention processes included store management policy changes, health promotion activities, and nutrition education aimed at high-risk individuals. Dietary advice was focused on decreasing saturated fat and sugar intake and increasing fruit and vegetable intake. Evaluation of the program included conducting sequential, cross-sectional risk factor surveys at 2-y intervals; measuring fasting cholesterol, lipid-soluble antioxidants, and homocysteine concentrations; and assessing smoking status. Nutrient intakes were estimated from analysis of food turnover in the single community store. RESULTS: There was a significant reduction in the prevalence of hypercholesterolemia (age-adjusted prevalences were 31%, 21%, and 15% at baseline, 2 y, and 4 y, respectively; P < 0.001). There were significant increases in plasma concentrations of alpha-tocopherol, lutein and zeaxanthin, cryptoxanthin, and beta-carotene across the population. Retinol and lycopene concentrations did not change significantly. Mean plasma homocysteine concentrations decreased by 3 micromol/L. There was no significant change in smoking prevalence between the 2 follow-up surveys. There was an increase in the density of fresh fruit and vegetables and carotenoids in the food supply at the community store. CONCLUSION: This community-directed dietary intervention program reduced the prevalence of coronary heart disease risk factors related to diet. |
| Improvements in hostility and depression in relation to dietary change and cholesterol lowering. The Family Heart Study Weidner, G., S. L. Connor, et al. (1992), Ann Intern Med 117(10): 820-3. Abstract: OBJECTIVE: To describe changes in negative emotions among participants of a cholesterol-lowering study. DESIGN: Cohort study. Quantitative evaluation of changes in negative emotions in relation to diet and plasma cholesterol levels before and after a 5-year dietary intervention program aimed at reducing plasma cholesterol levels. SETTING: Community-dwelling families of the Family Heart Study, Portland, Oregon. PARTICIPANTS: One hundred forty-nine men and 156 women from 233 families (mean age, 37.7 years). MEASUREMENTS: Changes in negative emotions including depression and aggressive hostility as measured by the Hopkins Symptom Checklist (SCL-90). RESULTS: Improvement in overall emotional state was noted for the entire sample. Those who consumed a low-fat, high complex-carbohydrate diet at the end of the study showed significantly greater improvements in depression (P = 0.044; difference in improvement, 2.9 points) and aggressive hostility (P = 0.035; difference in improvement, 3.3 points) as well as a reduction in their plasma cholesterol levels (P = 0.024; difference in improvement, 2.7%) compared with those who ate a high-fat "American diet." CONCLUSIONS: Participation in a cholesterol-lowering program may not be associated with a worsening in emotional state. To the contrary, improvements in diet appear to be associated with reductions in depression and aggressive hostility as well as with lowered plasma cholesterol levels. |
| Improving adherence to a cholesterol-lowering diet: a behavioral intervention study Burke, L. E., J. Dunbar-Jacob, et al. (2005), Patient Educ Couns 57(1): 134-42. Abstract: Less than 50% of US adults follow dietary recommendations. Despite these figures, little research has focused on improving adherence to a therapeutic eating plan. The research utilizing self-efficacy theory has shown promise for improving behavior change and treatment adherence. This study evaluated the efficacy of a telephone-delivered, self-efficacy based intervention designed to improve adherence to a cholesterol-lowering diet among those self-reporting nonadherence. Sixty-five men and women diagnosed with hypercholesterolemia were randomized to usual care or treatment, which consisted of six intervention sessions delivered every 2 weeks by telephone and focused on how to manage eating behavior in challenging situations. There were significant between group differences post intervention in the consumption of saturated fat (P <.001) and cholesterol (P =.040) with the intervention group improving their dietary adherence. Significant change (P =.013) occurred over time in low-density lipoprotein-cholesterol (LDL-C) in the intervention group. No changes were observed in self-efficacy between groups, suggesting that self-efficacy was not a mediator of the improved adherence. The study's findings confirm that the telephone is a useful tool to deliver adherence-enhancing interventions. |
| Improving cholesterol control in managed care populations McKenney, J. M. (2000), Am J Manag Care 6(19 Suppl): S997-1007. Abstract: Cholesterol management has clearly emerged as a top priority for prevention-oriented management of coronary artery disease, and National Cholesterol Education Program (NCEP) guidelines provide the best treatment targets for these efforts. However, even in the highest risk patients, where managed care organizations naturally tend to focus their prevention budgets, the percentage of patients attaining NCEP targets is dismal. To improve success rates in patients requiring pharmacologic therapy, more effective use of new and existing drug therapies may be required. This article provides an update on current options for lipid-modifying drug therapy and offers examples of combination regimens that may assist practitioners in attaining target lipid levels. |
| Improving effect of dietary taurine on marked hypercholesterolemia induced by a high-cholesterol diet in streptozotocin-induced diabetic rats Mochizuki, H., J. Takido, et al. (1999), Biosci Biotechnol Biochem 63(11): 1984-7. Abstract: The effect of dietary taurine on hypercholesterolemia induced by a high-cholesterol diet in streptozotocin (STZ)-induced diabetic rats was investigated. The concentrations of serum and liver cholesterol were markedly elevated in STZ-diabetic rats fed on the cholesterol-containing diet, and dietary taurine significantly reduced this elevated level of cholesterol in the serum and liver. The gene expression of cholesterol 7 alpha-hydroxylase (CYP7A1), which is the rate-limiting enzyme for cholesterol degradation, was induced by the supplementation of taurine to the high-cholesterol diet. It is suggested that one of the reasons for this hypocholesterolemic action by taurine might have been the enhancement of cholesterol degradation. |
| Improving effect of dietary taurine supplementation on the oxidative stress and lipid levels in the plasma, liver and aorta of rabbits fed on a high-cholesterol diet Balkan, J., O. Kanbagli, et al. (2002), Biosci Biotechnol Biochem 66(8): 1755-8. Abstract: The effect of a high-cholesterol diet with or without taurine on lipids and oxidative stress in the plasma, liver and aorta of rabbits was investigated. The animals were maintained on a basal diet (control), a high-cholesterol diet (HC, 1% w/w), or a high- cholesterol diet supplemented with taurine (HCHT, 2.5% w/w) for two months. Taurine has an ameliorating effect on atherosclerosis together with a decreasing effect on the cholesterol and triglyceride levels in rabbits fed on an HC diet. The HCHT diet caused a significant decrease in the malondialdehyde (MDA) and diene conjugate (DC) levels in the plasma, liver and aorta of rabbits as compared to the HC group. This treatment did not alter the antioxidant system in the liver of rabbits in the HC group. Our findings indicate that taurine ameliorated oxidative stress and cholesterol accumulation in the aorta of rabbits fed on the HC diet and that this effect may be related to its antioxidative potential as well as its reducing effect on serum lipids. |
| Improving the prediction of cardiovascular risk: interaction between LDL and HDL cholesterol Grover, S. A., M. Dorais, et al. (2003), Epidemiology 14(3): 315-20. Abstract: BACKGROUND: The ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol (or the ratio of low-density lipoprotein LDL to HDL) is currently advocated to estimate the coronary risk associated with LDL and HDL cholesterol levels. METHODS: We analyzed the relation between LDL and HDL cholesterol levels to predict the risk of future coronary events. Using data from the Lipid Research Clinics Follow-up Cohort, we developed multivariate equations to predict coronary deaths among 4684 men and women followed for approximately 12 years. We used these equations to compare the predictive power of the LDL/HDL ratio with the independent effects of LDL and HDL and an LDL-HDL interaction term. We then used each model to forecast the 10-year risk of coronary death based on various lipid levels after adjustment for conventional risk factors (eg, blood pressure, gender, cigarette smoking). RESULTS: Levels of LDL and HDL and the interaction between them are all independent risk factors for coronary death. The benefits of increasing HDL are strongest among persons with high LDL. Conversely, the benefits of decreasing LDL are greatest among those with low HDL. We confirmed these observations in a published dataset showing the effects of treatment of hyperlipidemia. Predictions of benefits of treatment that were based on interaction of LDL and HDL were more accurate than predictions without interaction. CONCLUSIONS: The LDL/HDL ratio alone may not fully capture the complex interaction between LDL and HDL and the relation of each to coronary risk. |
| Improving the prediction of coronary heart disease to aid in the management of high cholesterol levels: what a difference a decade makes Avins, A. L. and W. S. Browner (1998), Jama 279(6): 445-9. Abstract: CONTEXT: A patient's coronary heart disease (CHD) risk must be correctly classified to successfully apply risk-based guidelines for treatment of hypercholesterolemia. OBJECTIVE: To determine the classification accuracy of the National Cholesterol Education Program (NCEP) CHD risk-stratification system and compare it with a simple revised system that gives greater weight to age as a CHD risk factor. DESIGN: Modeling of 10-year CHD risk, using equations from the Framingham Heart Study applied to a cross-sectional survey of the US population. SUBJECTS: The 3284 subjects aged 20 to 74 years surveyed in the Second National Health and Nutrition Examination Survey (1978-1982) who had fasting lipid levels measured. MAIN OUTCOME MEASURES: The area under the receiver operating characteristic curve (AUC) for 10-year CHD risk for the NCEP and revised scales. RESULTS: Among all adults with a low-density lipoprotein cholesterol value of at least 4.1 mmol/L (160 mg/dL), the NCEP system showed fairly good discrimination (AUC=0.90), though there was a substantial decline among men 35 to 74 years old and women 55 to 74 years old (AUC=0.81). By contrast, the revised system showed superior performance in all hypercholesterolemic adults (AUC=0.94-0.97) as well as in the subgroup of men 35 to 74 years old and women 55 to 74 years old (AUC=0.94-0.96). CONCLUSIONS: Simple modifications of the NCEP treatment criteria result in a substantially improved ability to discriminate between higher and lower CHD risk groups. Unlike the NCEP system, this revised system retains its classification ability in all age groups studied. |
| Improving the quality of plasma cholesterol measurements in primary care Broughton, P. M., D. G. Bullock, et al. (1990), Scand J Clin Lab Invest Suppl 198: 43-8. Abstract: During the last 2 years an external quality assessment (EQA) scheme has been developed for plasma cholesterol measurements made in primary care. The scheme, which is supported by the UK Department of Health and by the instrument manufacturers, now has over 300 participants, most of whom use the Boehringer Reflotron. Operators are mostly nurses, with little or no laboratory experience. To avoid matrix effects, fresh plasma specimens collected from normal volunteers and those attending a hospital lipid clinic are used. Three specimens, mostly with cholesterol concentrations in the range 5-9 mmol/L, are distributed every 2 months. The mean plasma cholesterol results show good agreement with those from 'reference' laboratories, and efforts are now being made to link these laboratories with the CDC-based reference system. The scheme uses a predominantly graphical presentation of results, with a greater element of interpretation by the organisers than is usually provided for laboratory-based participants. The distribution of results shows a higher proportion of outliers than in the UK national EQA scheme for laboratory cholesterol measurements. At present about 10% of participants in primary care obtain results which could be clinically misleading, and new approaches are needed in dealing with these 'poor performers'. This scheme could serve as a model for other assays in primary care. It illustrates the importance of training, quality assurance and education, and the need for laboratory staff to become more involved in this growing and important area of laboratory medicine. |