| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Applying the new cholesterol guidelines to your practice Geisler, S. L. (2001), Jaapa 14(11): 12-4, 17-8, 21-3. |
| Approach to lipoprotein management in 2001 National Cholesterol Guidelines Grundy, S. M. (2002), Am J Cardiol 90(8A): 11i-21i. Abstract: In 2001 the National Cholesterol Education Program (NCEP) released its Adult Treatment Panel (ATP) III report. This was an evidence-based report that upgraded cholesterol management guidelines. The update was made possible by a series of large, cholesterol-lowering clinical trials. These trials demonstrated strongly the efficacy and safety of cholesterol reduction in both primary and secondary prevention of coronary heart disease (CHD). The major recommendations of the report were several. Low-density lipoprotein (LDL) cholesterol continued to be identified as the major target of cholesterol-lowering therapy. However, more emphasis was given to HDL cholesterol and triglycerides as important targets for management. The concept of CHD risk equivalents was introduced. A CHD risk equivalent represents an absolute risk for future CHD events equal to that in persons with established CHD. Diabetes was identified as a CHD risk equivalent, requiring more intensive LDL-lowering therapy. Finally, the report placed more emphasis on the metabolic syndrome as a major, multiplex risk factor requiring increased clinical attention. |
| Approaches to measuring cholesterol absorption in humans Matthan, N. R. and A. H. Lichtenstein (2004), Atherosclerosis 174(2): 197-205. Abstract: Under optimal conditions, plasma cholesterol homeostasis is maintained by a variety of mechanisms, balancing input and output, thereby preventing the net accumulation of cholesterol in circulation and tissues. Among these mechanisms, intestinal cholesterol absorption has recently re-emerged as a potentially important contributor to cholesterol homeostasis. However, its regulation has been difficult to study in humans because of technical limitations in methodologies. In this review the major methods available for measuring cholesterol absorption including those that utilize cholesterol balance, single dose isotopic feeding, dual isotope plasma ratio, continuous isotope feeding, intestinal perfusion, stable isotopes and serum plant sterols or cholestanol to cholesterol ratios are reviewed and contrasted. Emphasis is placed on the strengths, technical and interpretational limitations and their applicability for use in metabolic, small-scale outpatient, population and large-scale intervention studies. |
| Appropriate days for measuring intake of dietary fat and cholesterol Brekke, M. J., M. L. Brekke, et al. (1992), Ann Nutr Metab 36(5-6): 318-27. Abstract: Seven consecutive day food records were assessed in 224 free-living adult volunteers to (1) identify the smallest number of days, and which days of the week, would provide most of the information about dietary fat and cholesterol intake (assessed by B score) and (2) whether a complex mathematical formula for weighting certain days was required to achieve reasonable validity. A factor analytic approach was used to identify 3- and 4-day sets. The correlations with the 7-day average B score ranged from 0.95 for the best 4-day (Saturday through Tuesday) average B score to 0.91 for the best 3-day (Sunday through Tuesday) average B score. Simple averaging (no weighting) was found to be adequate to achieve this level of validity. |
| Appropriateness of cholesterol and triglycerides reporting checked by External Quality Assessment programs Secchiero, S., L. Sciacovelli, et al. (2003), Clin Chim Acta 333(2): 221-30. Abstract: BACKGROUND: The recommendations of the Second Joint Task Force of European and Other Societies on Coronary Prevention and the third Adult Treatment Panel report (ATPIII) released by the National Cholesterol Education Program are based on accumulating evidence concerning the contribution of lipoproteins and other risk factors in the development of coronary heart disease (CHD). The laboratories play an important role in the successful adoption of these guidelines. METHODS: In External Quality Assessment (EQA) programs managed by the Center of Biomedical Research, results and respective reference intervals (RI) are sent as laboratory's medical form. We assessed how well the 200 participants to EQA scheme 2002 for clinical biochemistry reported total cholesterol (TC) and triglycerides (TGs) results according to either European or National Cholesterol Education Program (NCEP) guidelines. RESULTS: Only 18% of laboratories reported total cholesterol concentrations correctly in terms of desirable, borderline-high, and high risk for the CHD development, 12% reported a single desirable value (180, 190, or 200 mg/dl), and 70% reported the RI (85 laboratories in the whole interval, 34 are the only upper reference limit and 15 are the desirable value in addition to RI). The upper reference limit was 200 mg/dl in 65% of cases, but 32% of laboratories presented higher limits, reaching values as high as 250-260 mg/dl. Only the 3.7% of laboratories reported triglyceride concentrations in terms of risk-oriented ranges for the CHD development, 6.8% the single desirable value, and 89.5% the RI. CONCLUSION: Our study demonstrates that the current practice of reporting results for cholesterol and triglycerides does not follow the guidelines, and appropriate changes are required to be made. |
| Arachidonic acid concentrations in plasma and liver phospholipid and cholesterol esters of piglets raised on formulas with different linoleic and linolenic acid contents Rioux, F. M. and S. M. Innis (1992), Am J Clin Nutr 56(1): 106-12. Abstract: The influence of sow milk or infant formulas containing 18:2n-6 and 18:3n-3 (% fatty acids) at 30/1, 16/1, 35/4, or 16/4 on plasma and liver phospholipid (PL) and cholesterol ester (CE) arachidonic acid (20:4n-6) was studied in piglets fed from birth for 15 d. Piglets fed the 35/4, 16/1, and 16/4 formulas had a significantly lower percentage of plasma 20:4n-6 in PL than did piglets fed sow milk or the 30/1 formula. The lowest plasma PL 20:4n-6 was in the 16/4 group, the only group in which liver PL 20:4n-6 was significantly reduced. This suggests competitive inhibition of synthesis or acylation of 20:4n-6 when formula with a high content of 18:3n-3 is fed in conjunction with a low content of 18:2n-6. The percentage of plasma CE 20:4n-6 was not altered by formula feeding. In contrast, the liver CE 20:4n-6 was significantly lower in all formula-fed animals than it was in sow-milk-fed animals. These studies confirm that 20:4n-6 metabolism is altered in artificially fed neonates. Liver and plasma cholesterol concentrations were also significantly lower in all formula-fed than in milk-fed piglets. The potential relationship of the decrease in cholesterol to n-6 fatty acids in CE is unknown. |
| Arachidyl amido cholanoic acid (Aramchol) is a cholesterol solubilizer and prevents the formation of cholesterol gallstones in inbred mice Gilat, T., A. Leikin-Frenkel, et al. (2001), Lipids 36(10): 1135-40. Abstract: We have recently synthesized fatty acid bile acid conjugates (FABAC) that were able to reduce and retard cholesterol crystallization in model and human biles. When given orally, they prevented the formation of cholesterol crystals in the bile of hamsters. The aim of the present study was to determine whether the FABAC are cholesterol solubilizers, whether they can dissolve pre-existing crystals, whether they can prevent the formation of cholesterol gallstones, and to investigate the optimal type of bond between the fatty acid and bile acid. The presence of cholesterol crystals was determined by light microscopy, and the total crystal mass of precipitated crystals was measured by chemical means. Inbred (C57J/L) mice on a lithogenic diet were used to evaluate cholesterol crystal formation, dissolution, and gallstone formation in vivo. Arachidyl amido cholanoic acid (Aramchol) was the FABAC used in the present experiments. At equimolar amounts, the cholesterol-solubilizing capacity of Aramchol was higher than that of taurocholate and similar to that of phosphatidylcholine. The addition of Aramchol dissolved approximately 50% of pre-existing crystals in model bile solutions. The same phenomenon was demonstrated in human bile ex vivo, with a dose-response effect. All inbred mice developed cholesterol crystals in bile after 10-14 d on the lithogenic diet. Thereafter, supplementation of the diet with Aramchol progressively reduced the proportion of mice with crystals to 25% after 28 d. On the lithogenic diet, 100% of inbred mice developed cholesterol gallstones in the gallbladder by day 21. None of the mice whose diet was supplemented with 0.5 mg or 1.0 mg of Aramchol/d developed stones or crystals. FABAC are a new class of molecules that are cholesterol solubilizers and which are able to dissolve cholesterol crystals in bile. Upon oral administration, they dissolve pre-existing cholesterol crystals and prevent the formation of gallstones in gallstone-susceptible mice. |
| ARBITER: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol: a randomized trial comparing the effects of atorvastatin and pravastatin on carotid intima medial thickness Taylor, A. J., S. M. Kent, et al. (2002), Circulation 106(16): 2055-60. Abstract: BACKGROUND: Whether marked LDL reduction to levels well below 100 mg/dL would further reduce the burden of cardiovascular disease is controversial. We compared the effects of 2 statins with widely differing potencies for LDL reduction (pravastatin 40 mg/d and atorvastatin 80 mg/d) on carotid intima-media thickness (CIMT). METHODS AND RESULTS: This was a single-center, randomized, clinical trial of 161 patients (mean age, 60 years; 71.4% male; 46% with known cardiovascular disease) that met National Cholesterol Education Program (NCEP) II criteria for lipid-lowering therapy. The effects of atorvastatin (80 mg/d; n=79) and pravastatin (40 mg/d; n=82) on CIMT were compared using blinded, serial assessments of the far wall of the distal common carotid artery. Baseline CIMT and other characteristics were similar between study groups. As anticipated, atorvastatin was substantially more potent for LDL reduction after 12 months: in the atorvastatin group, LDL cholesterol was 76+/-23 mg/dL after 12 months (-48.5%); LDL cholesterol was 110+/-30 mg/dL in the pravastatin group (-27.2%; P<0.001). Atorvastatin induced progressive CIMT regression over 12 months (change in CIMT, -0.034+/-0.021 mm), whereas CIMT was stable in the pravastatin group (change of 0.025+/- 0.017 mm; P=0.03). CONCLUSIONS: Marked LDL reduction (<100 mg/dL) with a high-potency statin provides superior efficacy for atherosclerosis regression at 1 year. This early effect on CIMT, a surrogate for clinical benefit, suggests that marked LDL reduction with synthetic statins may provide enhanced reduction in clinical coronary event rates. |
| Are changes in blood pressure and total cholesterol related to changes in mood? An 18-month study of men and women Pollard, T. M. and J. E. Schwartz (2003), Health Psychol 22(1): 47-53. Abstract: The authors investigated the within-person association of reported mood with blood pressure and total cholesterol (TC) levels, each assessed 4 times over an 18-month period in 128 men and 154 women. Change over time in tense arousal was significantly positively associated with changes over time in systolic blood pressure (SBP) and diastolic blood pressure (DBP) but not TC. A change in hedonic tone was significantly associated with SBP (an increase in negative affect was associated with an increase in SBP) but not with DBP or TC. There were no sex differences in associations of mood with SBP or TC. However, increases in tense arousal and negative affect were significantly associated with an increase in DBP for women but not men. |
| Are early clinical effects of cholesterol lowering mediated through effects on inflammation? Olsson, A. G., G. G. Schwartz, et al. (2002), Acta Physiol Scand 176(2): 147-50. Abstract: In a randomized, double-blind trial in 3086 patients with unstable angina pectoris or non-Q wave myocardial infarction we investigated if 80 mg of atorvastatin daily could improve outcome of cardiovascular events during a short period of time (16 weeks) compared with placebo. Baseline LDL cholesterol was 3.2 mmol L-1 (124 mg dL-1) and decreased by 40% to 1.9 mmol L-1 (72 mg dL-1) during atorvastatin treatment. The primary endpoint, which was a composite of death, non-fatal acute myocardial infarction, cardiac arrest with resuscitation or recurrent symptomatic myocardial ischaemia with objective evidence and requiring emergency rehospitalization occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group. The relative risk was 0.84 and 95% confidence interval was 0.70-1.00 (P = 0.048). Thus for patients with acute coronary syndromes, lipid-lowering therapy with high dose atorvastatin reduces recurrent ischaemic events in the short-term. A possible mechanism behind this rapid clinical effect induced by statin treatment is on inflammatory processes. Recent studies strongly suggest that acute T-cell activation is involved in the pathogenesis of unstable angina. In another study we investigated whether circulating T cells showed signs of activation in patients with stable angina pectoris (SA). Systemic venous blood samples were taken from 38 men with SA and 42 healthy controls. The T-cell receptor expression was assessed by three-colour flow cytometry using monoclonal antibodies against CD3,CD4, CD8, CD25 and human leucocyte antigen (HLA)-DR. Soluble interleukin-2 receptor (sIL-2R) was measured as the circulating form in serum. Levels of circulating CD3+ and CD4+ T cells tended to be higher in patients compared with controls. Patients were also shown to have a significant increase in CD4+ T cells expressing the activation markers CD25 (P < 0.05) and HLA-DR (P < 0.01). Furthermore, serum levels of sIL-2R were significantly higher (P < 0.001) in patients than in controls. We also observed that the T-cell response was more pronounced in patients without simvastatin treatment (n = 18) compared with simvastatin-treated patients (n = 20). In conclusion, our findings indicate that a continuous immune system activation takes place in patients with chronic angina pectoris, predominantly involving proliferation of CD4+ T cells. Statin treatment seems to be able to decrease this inflammatory response. |
| Are low levels of HDL2-cholesterol a risk factor for atherosclerosis of cerebral vascular disease? Case report Cordova, C., C. Alessandri, et al. (1990), Int Angiol 9(4): 282-4. Abstract: A case of a 45 years old man with an atherosclerotic stenosis of right internal carotid and TIA event is reported. The patient showed an increase of total cholesterol and LDL-cholesterol serum levels and, in particular, a very low familiar HDL2-cholesterol serum value. The possibility that this last condition could represent an important co-factor of the extracranial cerebrovascular disease is discussed. The usefulness of a long-term follow-up of all family members, showing the same lipids pattern, is also suggested. |
| Are parents' self-reported total cholesterol levels useful in identifying children with hyperlipidemia? An examination of current guidelines Resnicow, K. and D. Cross (1993), Pediatrics 92(3): 347-53. Abstract: OBJECTIVE. Recently, the American Academy of Pediatrics (AAP) Committee on Nutrition adopted the recommendation of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents (NCEP) that children and adolescents with a family history of premature cardiovascular disease or parental hypercholesterolemia (> or = 240 mg/dL) be screened for hyperlipidemia. The rationale for using parental hypercholesterolemia as a screening trigger is based on sensitivity estimates using parents' actual lipid values. However, in clinical practice pediatricians may often have to rely on parents' self-reported cholesterol levels to determine a child's family risk history. This study examines the feasibility and utility of parental self-reported cholesterol levels as a means of identifying children with elevated total cholesterol levels. METHODS. As part of a school-based risk factor screening program that included total cholesterol measurement, conducted in nine elementary schools between 1989 and 1991, parents of participating children were asked if they had their cholesterol tested in the past year and if they had, to provide their total cholesterol values. RESULTS. If only the children who had one parent with a self-reported total cholesterol value > or = 240 mg/dL would have been screened, between 90% and 93% of children with elevated total cholesterol values, either > or = 170 mg/dL or > or = 200 mg/dL, would have been missed. CONCLUSIONS. These data suggest that parents' self-reported cholesterol values are an ineffective means of identifying children with elevated total cholesterol and modification of the current AAP, and NCEP guidelines for selective cholesterol screening in children may be warranted. |
| Are serum albumin and cholesterol reliable outcome markers in elderly dialysis patients? Piccoli, G. B., F. Quarello, et al. (1995), Nephrol Dial Transplant 10 Suppl 6: 72-7. Abstract: Albumin and cholesterol are considered reliable outcome markers in dialysis patients; their influence, however, may also be related to non-independent factors, such as age and presence of co-morbid conditions. The aim of the study was an analysis of four outcome markers, assessed at start of dialysis: age, high risk conditions, cholesterol and albumin levels. Data were obtained from the Piedmont Dialysis and Transplantation Registry (northern Italy, about 4,400,000 inhabitants, 21 dialysis centres, open acceptance since mid-1970s, 5661 patients on file at 31 December 1992). Prevalence of albumin and cholesterol in the normal range increases with age; in each age group prevalence in the range is higher in patients at high risk. However, influence of these biochemical parameters is evident also in no-risk cohorts, thus identifying a subgroup with poorer prognosis also in the population without any identified classic risk factor. The influence of albumin, more evident in the population studied compared with cholesterol, is reflected by impaired survival of low-albumin patients (age > or = 65 high risk at 1 year: 60.7% vs 76.6%, P = 0.0052; age > or = 65 non-high risk, at 1 year: 76.5% vs 90.7%, P = 0.0001). In conclusion, albumin and cholesterol, assessed at start of dialysis, are reliable outcome markers even in elderly patients, identifying, in this high mortality cohort, a subgroup with poorer prognosis. If and how their effect may be reversed by dialysis therapy remains to be assessed. |
| Are the effects of cholesterol lowering drugs always equal? Vandenbroucke, J. P. and R. G. Westendorp (1996), Lancet 347(9010): 1267-8. |
| Are there differences in serum cholesterol and cortisol concentrations between violent and non-violent schizophrenic male suicide attempters? Marcinko, D., M. Martinac, et al. (2005), Coll Antropol 29(1): 153-7. Abstract: Previous studies have shown an association between low concentration of serum cholesterol, as well as high concentration of serum cortisol, in suicide behavior. The aim of this study was to evaluate whether men after a violent suicide attempts have different serum cholesterol and cortisol concentrations than those who attempted suicide by non-violent methods. Venous blood samples were collected within 24 hours of admission, to study concentrations of serum cholesterol and cortisol. The sample consisted of 31 male subjects suffering from schizophrenia, admitted in a general hospital after suicide attempt, and was compared with 15 schizophrenic nonsuicidal male controls. Patients with a violent suicidal attempt were found to have significantly lower cholesterol levels and significantly higher cortisol level than patients with non-violent attempts and the control subjects. Our findings suggest that suicide attempts should not be considered a homogenous group. The hypothesis of an association of violent suicidal attempts and peripheral biological markers (cholesterol and cortisol) was supported by our findings. |
| Are there good and bad carbohydrates for HDL cholesterol? Katan, M. B. (1999), Lancet 353(9158): 1029-30. |
| Are we aggressive enough in lowering cholesterol? Waters, D. D. (2001), Am J Cardiol 88(4A): 10F-5F. Abstract: To date, 5 major randomized, placebo-controlled statin trials--the Scandinavian Simvastatin Survival Study, West of Scotland Coronary Prevention Study, Cholesterol and Recurrent Events trial, Long-term Intervention with Pravastatin in Ischaemic Disease, and Air Force/Texas Coronary Atherosclerosis Prevention Study--have convincingly shown that total mortality and major coronary events can be significantly reduced by lowering levels of low-density lipoprotein cholesterol (LDL-C) with statin therapy. These results were achieved in a broad range of patients including those with and without a history of coronary artery disease and with elevated or average LDL-C levels. The results also support the large body of epidemiologic evidence demonstrating that the lower the cholesterol level, the lower the cardiovascular risk. Evidence now substantially supports the urgency of physicians to aggressively target the lowering of LDL-C levels for the primary and secondary prevention of coronary disease. |
| ARH missense polymorphisms and plasma cholesterol levels Hubacek, J. A. and T. Hyatt (2004), Clin Chem Lab Med 42(9): 989-90. Abstract: Mutations in a putative low-density lipoprotein (LDL) receptor adaptor protein called ARH have been recently described in patients with autosomal recessive hypercholesterolemia (ARH). ARH plays a tissue-specific role in determination of LDL receptor function. In the ARH gene three mismatched polymorphisms have been detected: Pro202Ser, Pro202His and Arg238Trp. These are of putative interest in plasma cholesterol level determination. To evaluate the effect of polymorphisms on plasma cholesterol levels, all polymorphisms were analyzed by PCR and restriction enzyme analysis by MnII, HpyCH4IV and SacII in 100 Caucasian males with high (>90%, 6.29 +/- 0.89 mmol/l), and 100 males with low (<10%, 3.60 +/- 0.57 mmol/l), total plasma cholesterol levels. No significant differences were observed in frequencies of ARH genotypes or alleles between these two extreme groups. These results suggest that ARH polymorphisms are unlikely to be important genetic determinants of plasma cholesterol levels. |
| Army targets a potential vaccine against cholesterol Travis, J. (1993), Science 262(5142): 1974-5. |
| Aronow's "Should the NCEP III guidelines be changed in elderly and younger persons at high risk for cardiovascular events?" Cholesterol and the aged.and the beat goes on Wilson, M. M. (2005), J Gerontol A Biol Sci Med Sci 60(5): 600-2; author reply 602. |