| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Cholesterol lowering in older patients Bannerman, K. S. (1999), Ann Intern Med 131(2): 155-6. |
| Cholesterol lowering in pigs through enhanced bacterial bile salt hydrolase activity De Smet, I., P. De Boever, et al. (1998), Br J Nutr 79(2): 185-94. Abstract: The effect of feeding live Lactobacillus reuteri cells containing active bile salt hydrolase (BSH) on plasma cholesterol levels was studied in pigs. During an experiment lasting 13 weeks, twenty pigs were fed on a high-fat, high-cholesterol, low-fibre for the first 10 weeks, and a regular pig diet for the last 3 weeks. One group of animals received, twice daily, 11.25 (SD 0.16) log10 colony forming units of the potential probiotic bacteria for 4 weeks (from week 3 until week 7). From week 8 onwards, the treated group was again fed on the same diet as the control group without additions. The total faecal Lactobacillus counts were only significantly higher in the treated pigs during the first 2 weeks of L reuteri feeding. Based on limited data, it was suggested that the administered Lactobacillus species had caused a temporary shift within the indigenous Lactobacillus population rather than permanently colonizing the intestinal tract. The probiotic feeding brought about significant lowering (P < or = 0.05) of total and LDL-cholesterol concentrations in the treated pigs compared with the control pigs, while no change in HDL-cholesterol concentration was observed. The data for faecal output of neutral sterols and bile salts were highly variable between the animals of each group, yet they indicated an increased output in the treated pigs. Although the blood cholesterol levels went up in both groups during the 3 weeks following the Lactobacillus administration period, significantly lower serum total and LDL-cholesterol levels were observed in the treated pigs. During the final 3 weeks of normalization to the regular diet, cholesterol concentrations significantly decreased in both animal groups and the differences in total and LDL-cholesterol concentrations between the groups largely disappeared. |
| Cholesterol lowering in the elderly population. Coordinating Committee of the National Cholesterol Education Program Grundy, S. M., J. I. Cleeman, et al. (1999), Arch Intern Med 159(15): 1670-8. Abstract: The incidence of coronary heart disease (CHD) peaks in the elderly population. In secondary and primary prevention trials, cholesterol-lowering therapy reduces risk for CHD in both older and younger participants. This benefit, therefore, can be extended to the elderly. |
| Cholesterol lowering in the management of coronary artery disease: the clinical implications of recent trials Eisenberg, D. A. (1998), Am J Med 104(2A): 2S-5S. Abstract: Atherosclerotic vascular disease is the major cause of death and disability in adult men and women living in the United States, where 13-14 million adults have a history of coronary artery disease (CAD). One-third of the 1.5 million individuals who experience a myocardial infarction (MI) each year will die and one half of these deaths will occur within 60 minutes of the event. The relation between elevated serum lipids and CAD has been corroborated by epidemiologic as well as pathologic evidence. Approximately 96 million people have total cholesterol levels > 200 mg/dL, with 38 million of these individuals having values > 240 mg/ dL. The National Cholesterol Education Program (NCEP) identified elevated low-density lipoprotein (LDL) cholesterol as a primary risk factor for CAD in 1988. This conclusion, along with recommendations for assessment and treatment, was reaffirmed in 1993. The NCEP also recommended that high-risk patients, with or without clinical manifestations of coronary atherosclerosis, should substantially lower their serum cholesterol levels. Specifically, the NCEP recommends that patients with CAD need to maintain serum LDL cholesterol levels of < or = 100 mg/dL; this means that the vast majority of patients need to decrease LDL cholesterol levels by > or = 30%. Aggressive dietary and/or drug therapy are recommended to achieve these reductions. In recent years, clinical trials have demonstrated the efficacy of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins") in lowering elevated levels of LDL cholesterol and decreasing the risk for clinical coronary events. |
| Cholesterol lowering margarine is effective Thompson, G. R. (1999), Bmj 319(7218): 1200-1. |
| Cholesterol lowering margarine may not be useful in healthy fat modified diet van Heyningen, C. (1999), Bmj 319(7203): 186. |
| Cholesterol lowering treatment and mortality Schmidt, J. G. (1992), Bmj 305(6863): 1226-7. |
| Cholesterol lowering trials and the theory of atherosclerosis Beranek, J. T. (1993), N Z Med J 106(953): 143-4. |
| Cholesterol lowering trials in coronary heart disease: frequency of citation and outcome Ravnskov, U. (1992), Bmj 305(6844): 15-9. Abstract: OBJECTIVE--To see if the claim that lowering cholesterol values prevents coronary heart disease is true or if it is based on citation of supportive trials only. DESIGN--Comparison of frequency of citation with outcome of all controlled cholesterol lowering trials using coronary heart disease or death, or both, as end point. SUBJECTS--22 controlled cholesterol lowering trials. RESULTS--Trials considered by their directors as supportive of the contention were cited almost six times more often than others, according to Science Citation Index. Apart from trials discontinued because of alleged side effects of treatment, unsupportive trials were not cited after 1970, although their number almost equalled the number considered supportive. In three supportive reviews the outcome of the selected trials was more favourable than the outcome of the excluded and ignored trials. In the 22 controlled cholesterol lowering trials studied total and coronary heart disease mortality was not changed significantly either overall or in any subgroup. A statistically significant 0.32% reduction in non-fatal coronary heart disease seemed to be due to bias as event frequencies were unrelated to trial length and to mean net reduction in cholesterol value; individual changes in cholesterol values were unsystematically or not related to outcome; and after correction for a small but significant increase in non-medical deaths in the intervention groups total mortality remained unchanged (odds ratio 1.02). CONCLUSIONS--Lowering serum cholesterol concentrations does not reduce mortality and is unlikely to prevent coronary heart disease. Claims of the opposite are based on preferential citation of supportive trials. |
| Cholesterol lowering trials: advice for the British physician Rees, J. A. (1994), J R Coll Physicians Lond 28(1): 70-3. Abstract: In summary, there is considerable agreement as to the appropriate management of hyperlipidaemia in patients at high risk of CHD. As in all branches of medicine, there are contentious areas particularly with respect to the 'middle risk range', where a strong case can be made for further appropriate clinical trials to be performed. Several of the hitherto published guidelines for the treatment of hyperlipidaemia have been inconsistent and have overestimated the proportion of the population who would benefit from the therapeutic intervention. Nevertheless, the reality of the situation in contemporary British clinical practice is that a large proportion of high-risk patients are not adequately treated, and that the perfectly reasonable clinical aphorism of 'first do no harm' is erroneously extrapolated and used as a therapeutic nihilist's charter. As always, British clinicians will use their discretion in the treatment of individual patients, but where consensus clearly does exist, it would be an appropriate subject of clinical audit to review not only those patients who may be inappropriately receiving lipid lowering drugs but, equally if not more importantly, also to justify why large numbers of patients who would clearly benefit from such drug intervention are not currently receiving it. The cholesterol debate should no longer be the justification for therapeutic nihilism. |
| Cholesterol lowering with high-viscosity hydroxypropylmethylcellulose Maki, K. C., M. H. Davidson, et al. (1999), Am J Cardiol 84(10): 1198-203. Abstract: Hydroxypropylmethylcellulose (HPMC) is a food gum having several structural and functional properties in common with hypocholesterolemic soluble fibers. The safety and cholestero-lowering efficacy of HPMC, incorporated into a National Cholesterol Education Program Step I diet, was compared with placebo in patients with mild to moderate hypercholesterolemia. After an 8-week National Cholesterol Education Program Step I dietary lead-in phase, 160 patients with low-density lipoprotein (LDL) cholesterol between 130 and 200 mg/dl and triglycerides <300 mg/dl were randomized to placebo, 2.5, 5.0, or 7.5 g/day of HPMC for a 6-week treatment period. Patients returned to the clinic every 2 weeks for lipid measurements and safety assessments. HPMC significantly lowered total, LDL, and non-high-density lipoprotein (HDL) cholesterol. LDL cholesterol concentrations (average of weeks 4 and 6) decreased by 3.0% (4.9 mg/dl), 5.9% (10.3 mg/dl), 12.1% (20.4 mg/dl), and 11.7% (20.3 mg/dl) from baseline levels in the placebo and 2.5, 5.0, and 7.5 g/day HPMC treatment groups, respectively. Statistically significant (p<0.05) reductions in LDL cholesterol were observed in the 5.0 and 7.5 g/day HPMC groups compared with placebo and 2.5 g/day HPMC treatment groups. Total and non-HDL cholesterol responses paralleled those of LDL cholesterol. There were no significant differences between the treatment groups in HDL cholesterol or triglyceride responses, incidence of adverse experiences, or gastrointestinal-related adverse experiences. These results suggest that HPMC is a well-tolerated and effective adjunct to diet for lowering LDL cholesterol in patients with mild to moderate hypercholesterolemia. |
| Cholesterol lowering with pravastatin improves resistance artery endothelial function: report of six subjects with normal coronary arteriograms Houghton, J. L., T. A. Pearson, et al. (2000), Chest 118(3): 756-60. Abstract: STUDY OBJECTIVES: Improvement in coronary artery endothelial function has been demonstrated after cholesterol lowering in hypercholesterolemic patients with significant atherosclerosis. However, to our knowledge, no previous study has shown improvement in resistance artery function in subjects with normal coronary arteries after cholesterol lowering. The purpose of our study was to investigate the effect of cholesterol lowering with pravastatin on coronary resistance artery endothelial function in the setting of angiographically normal coronary arteries. METHODS: Invasive testing of coronary endothelial and vasomotor function was performed at baseline and after 6 months of pravastatin treatment in six patients with normal coronary arteriograms. RESULTS: After 6 months of pravastatin treatment, low-density lipoprotein cholesterol level dropped from 157+/-11 to 117+/-8 mg/dL (p = 0.02) and percent increase in coronary blood flow after acetylcholine improved from 97+/-13% to 160+/-16% (p = 0.01). There was a trend (p = 0.17) toward enhanced epicardial dilation in response to acetylcholine after pravastatin treatment when compared with the baseline study. CONCLUSIONS: Our study demonstrates significant improvement in coronary resistance artery endothelial function after 6 months of cholesterol lowering with pravastatin in six subjects presenting with chest pain who were found to have normal coronary arteriograms. A trend toward improved epicardial vasomotion was also observed. |
| Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. A subgroup analysis of the Scandinavian Simvastatin Survival Study (4S) Pyorala, K., T. R. Pedersen, et al. (1997), Diabetes Care 20(4): 614-20. Abstract: OBJECTIVE: To assess in diabetic patients with coronary heart disease (CHD) the effect of cholesterol lowering with simvastatin on mortality and the risk of CHD and other atherosclerotic events. RESEARCH DESIGN AND METHODS: A post hoc subgroup analysis was carried out on data from 202 diabetic patients and 4,242 nondiabetic patients with previous myocardial infarction or angina pectoris, serum total cholesterol 5.5-8.0 mmol/l, and serum triglycerides < or = 2.5 mmol/l who were participating in the Scandinavian Simvastatin Survival Study (4S). Participants in the 4S were randomly assigned to double-blind treatment with simvastatin, 20 mg daily, with blinded dosage titration up to 40 mg daily, according to cholesterol response during the first 6-18 weeks, or placebo. Endpoints were 1) total mortality, 2) major CHD events (CHD death or nonfatal myocardial infarction), 3) other acute atherosclerotic events, 4) myocardial revascularization procedures. RESULTS: Over the 5.4-year median follow-up period, simvastatin treatment produced mean changes in serum lipids in diabetic patients similar to those observed in nondiabetic patients. The relative risks (RRs) of main endpoints in simvastatin-treated diabetic patients were as follows: total mortality 0.57 (95% CI, 0.30-1.08; P = 0.087), major CHD events 0.45 (95% CI, 0.27-0.74; P = 0.002), and any atherosclerotic event 0.63 (95% CI, 0.43-0.92; P = 0.018). The corresponding RRs in nondiabetic patients were the following: 0.71 (95% CI, 0.58-0.87; P = 0.001), 0.68 (95% CI, 0.60-0.77; P < 0.0001), and 0.74 (95% CI, 0.68-0.82; P < 0.0001). CONCLUSIONS: The results strongly suggest that cholesterol lowering with simvastatin improves the prognosis of diabetic patients with CHD. The absolute clinical benefit achieved by cholesterol lowering may be greater in diabetic than in nondiabetic patients with CHD because diabetic patients have a higher absolute risk of recurrent CHD events and other atherosclerotic events. |
| Cholesterol lowering, low cholesterol, and mortality LaRosa, J. C. (1993), Am J Cardiol 72(11): 776-86. Abstract: Cholesterol lowering in both primary and secondary prevention has been clearly demonstrated to lower coronary morbidity and, in secondary prevention, to lower coronary mortality as well. Putative dangers of cholesterol lowering remain unproven. Population studies linking low cholesterol to noncoronary mortalities do not demonstrate cause-and-effect relations. In fact, based on current studies, the opposite is more likely to be the case. Neither gender nor age should automatically exclude persons from cholesterol screening. Drug intervention, however, should be used conservatively, particularly in young adults and the elderly. Drugs should be used only after diet and lifestyle interventions have failed. The evidence linking high blood cholesterol to coronary atherosclerosis and cholesterol lowering to its prevention is broad-based and definitive. Concerns about cholesterol lowering and spontaneously low cholesterols should be pursued but should not interfere with the implementation of current public policies to reduce the still heavy burden of atherosclerosis in Western society. |
| Cholesterol lowering. Should it continue to be the last thing we do? Waters, D. (1999), Circulation 99(25): 3215-7. |
| Cholesterol lowering: perspectives on the 4S and West of Scotland studies Olin, J. W. (1996), Cleve Clin J Med 63(2): 80-3. |
| Cholesterol malabsorption caused by sitostanol ester feeding and neomycin in pravastatin-treated hypercholesterolaemic patients Vanhanen, H. (1994), Eur J Clin Pharmacol 47(2): 169-76. Abstract: Serum cholesterol values were insufficiently reduced by pravastatin in two different patient populations. Therefore, we studied whether further cholesterol reduction could be achieved by inhibiting both cholesterol synthesis (by pravastatin) and absorption (by neomycin or sitostanol ester). Thus, we measured serum cholesterol, cholesterol precursors (reflecting cholesterol synthesis), cholestanol and plant sterols (reflecting cholesterol absorption and biliary secretion) for up to 6 weeks in pravastatin-treated patients with familial hypercholesterolaemia (FH, n = 13) and with and without ileal bypass during addition of neomycin (1.5 g per day) and in another patient population of non-FH (n = 14) subjects during addition of sitostanol ester (1.5 g per day). Addition of neomycin lowered serum total, LDL and HDL cholesterol by a further 20%, and increased the pravastatin-lowered precursor:cholesterol ratios by 20% (irrespective of ileal bypass). It also reduced by 20% the plant sterol:cholesterol ratio (irrespective of ileal bypass) which was markedly increased by pravastatin alone. Pravastatin and neomycin in combination lowered total, LDL and HDL cholesterol by 45%, 53% and 17%, respectively. This combined regimen reduced the serum lathosterol:cholesterol ratio to about half of the reduction caused by pravastatin, while the elevation of the plant sterols:cholesterol ratio was less with the combination than with pravastatin alone. Changes in serum cholesterol precursor:cholesterol and plant sterol:cholesterol ratios during the combined treatment were smaller in the subgroup with ileal bypass. Addition of sitostanol ester did not lower serum total or LDL cholesterol nor the precursor:cholesterol ratios significantly, while the reduction observed in the plant sterols:cholesterol ratios was similar to that achieved with neomycin addition.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Cholesterol malabsorption in pancreatic insufficiency: effects of enzyme substitution Vuoristo, M., H. Vaananen, et al. (1992), Gastroenterology 102(2): 647-55. Abstract: Defective lipolysis, steatorrhea, and hypocholesterolemia characterize pancreatic insufficiency. Lipid metabolism in pancreatic insufficiency was studied by measuring serum lipoproteins, cholesterol absorption with double labels and serum plant sterols, and bile acid and cholesterol synthesis with fecal and dietary steroid analysis and cholesterol precursor sterols before and during exogenous pancreatic enzyme substitution. Baseline fecal fat, masses, bile acids and neutral steroids, and cholesterol synthesis were increased, whereas cholesterol absorption was markedly reduced. In fact, the present data suggest that sterol absorption may be disturbed more sensitively than fat absorption in pancreatic insufficiency. Enzyme substitution significantly reduced fecal fat, masses, bile acids and neutral steroids, and synthesis of cholesterol and improved cholesterol absorption in relation to serum cholesterol, although normal values were not obtained. Serum level of high-density lipoprotein cholesterol was significantly elevated by exogenous enzymes, whereas levels of cholesterol or triglycerides in other lipoproteins remained unchanged. Improved sterol absorption increased also serum levels of plant sterols and reduced levels of cholesterol precursors and cholesterol synthesis and precursor sterol-plant sterol ratios. Thus, reduced intestinal lipolysis with expanded oil phase appears to be a major reason for impaired cholesterol absorption, causing enhanced cholesterol and, consequently, bile acid synthesis and reduced serum cholesterol level. Exogenous enzyme substitution seems partly to correct these abnormalities, improvements of which can be monitored by the gas-liquid chromatographic determination of serum plant sterols or cholesterol precursor-plant sterol ratios. |
| Cholesterol management in Dutch general practice. A comparison with national guidelines. Dutch College of General Practitioners van der Weijden, T., J. B. Hutten, et al. (1994), Scand J Prim Health Care 12(4): 281-8. Abstract: OBJECTIVE--To examine cholesterol diagnosis and treatment by Dutch general practitioners (GPs) in the period before publication of national guidelines, in order to develop implementation strategies based on discrepancies found between daily practice and the guidelines. DESIGN--Data of the 'Dutch National Survey of General Practice', in which GPs were involved in extensive consultation registration, were used. Patients were included for analysis if serum cholesterol, or the ICPC-code lipid metabolism disorder, or cholesterol-lowering treatment was registered. SETTING--General practice. PARTICIPANTS--161 GPs, 177 practice-nurses. OUTCOME MEASURES--Reasons for consultation, diagnoses, therapy, inter-doctor variation. RESULTS--The main discrepancies between daily practice and the guidelines concerned indications for cholesterol measurement, repeated measurements to diagnose hypercholesterolaemia, and attention for diet advice. A remarkable inter-doctor variation in diagnosis, and less so in treatment, was also found. CONCLUSION--The inter-doctor variation justifies the publication of the standard guidelines. Implementation strategies should aim at indications for cholesterol testing, repeating measurements for diagnosis, and advice on diet. |
| Cholesterol management in general practice White, H. L. and D. H. Roberts (1997), Curr Med Res Opin 14(1): 53-62. Abstract: Ninety general practitioners from the Fylde coast of Lancashire responded to a questionnaire regarding lipid management, revealing that only 22% aim for a target total cholesterol of < or = 5.2 mmol/l in patients with established ischaemic heart disease. One third are reassessing the cholesterol in these patients at yearly intervals or less frequently, and 36% select 65 years or less as the upper age limit for screening. Approximately 50% of GPs screen for hypercholesterolaemia in patients with cerebral or peripheral vascular disease. Primary screening and treatment of hypercholesterolaemia within the 'at risk' asymptomatic population is well established with 72% of GPs screening hypertensives, 88% screening diabetics and almost all screening patients with an adverse family history, but the therapeutic cholesterol targets vary widely between individual practitioners. |