Cholesterol Articles and Abstracts

For medical practitioners and the general public - Cholesterol Journal Article Catalog.

Cholesterol Journal Articles



Record 5681 to 5700
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Effects of vitamin C on high-density lipoprotein cholesterol and blood pressure
Jacques, P. F. (1992), J Am Coll Nutr 11(2): 139-44.
Abstract: Diet has been linked to cardiovascular disease risk by its influence on low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and blood pressure (BP). Recent evidence suggests that vitamin C may play a role in regulation of cholesterol and BP. The cross-sectional relationships of plasma ascorbic acid (PAA) with cholesterol and BP are described in three Boston area samples: 1) 249 males and 447 females (aged 60-100 years), 2) 100 Chinese-American males and 159 Chinese-American females (aged 60-96 years), and 3) 225 male and 192 female participants (aged 20-60 years) in a randomized field trial of vitamin C supplementation. Results indicate 3.7-9.5% higher levels of HDL-C, 4.1% lower levels of LDL-C, and 1.9-5.5% lower levels of BP with each 30 mumol/L increment in PAA. These relationships may be stronger at lower levels of PAA.

Effects of work overload and burnout on cholesterol and triglycerides levels: the moderating effects of emotional reactivity among male and female employees
Shirom, A., M. Westman, et al. (1997), J Occup Health Psychol 2(4): 275-88.
Abstract: The effects of objective and subjective overload, and of physical and emotional burnout, on cholesterol and triglycerides levels were studied in a quasiprospective design. The possible moderating effects of emotional reactivity on these relationships were also investigated. The study's hypotheses were tested separately for male and female employees. Time 1 (T1) data were collected from 665 healthy employees (30% women) while they were undergoing periodic health examinations in a health-screening center. Time 2 (T2) measures of cholesterol and triglycerides were collected 2 to 3 years after T1. The hypotheses were tested by regressing each T2 criterion on its T1 level; the control variables of age, obesity, diet, alcohol consumption, and smoking; and the other predictors. For female employees, the T2-T1 changes in the serum lipids were positively predicted by emotional burnout, as expected, but negatively predicted by physical fatigue. For male employees, both types of T1 burnout were positive predictors of the T2-T1 change in total cholesterol.

Effects of zinc and vitamin A supplements on plasma levels of thyroid hormones, cholesterol, glucose and egg yolk cholesterol of laying hens
Kaya, S., T. Kececi, et al. (2001), Res Vet Sci 71(2): 135-9.
Abstract: The effects of zinc and vitamin A supplementation to the diet on some blood metabolites were evaluated in Hisex brown laying hens from 56 weeks to 68 weeks of age. A total of 130 birds were divided into two main groups according to vitamin A treatment (0 and 3.44 mg retinyl acetate kg(-1) feed, respectively), each consisting of 65 hens. Hens in both of the main groups were then divided into five zinc treatment groups (0, 25, 50, 100 and 200 mg zinc kg diet(-1) respectively) of 13 hens each. It was observed that plasma T4, T3 and total cholesterol levels were affected by only zinc supplementation. While 100 and 200 mg Zn kg(-1) decreased plasma T4 level compared to control value, plasma T3 level was reduced by 100 mg Zn kg(-1) compared to groups fed less Zn. Adding 50 and 200 mg Zn kg(-1) to the diet increased plasma total cholesterol level in the birds compared to other groups. Vitamin A, zinc, and their interaction did not influence the concentration of plasma high-density lipoprotein (HDL)-cholesterol, glucose and egg yolk cholesterol in laying hens.

Effects on apoB-100 secretion and bile acid synthesis by redirecting cholesterol efflux from HepG2 cells
Sniderman, A. D., Z. Zhang, et al. (2003), J Lipid Res 44(3): 527-32.
Abstract: This study determined the effects of apoA-I, HDL3, or hydroxy-beta-cyclodextrin on apoB-100 secretion and bile acid synthesis by HepG2 cells. The principal observations were that: 1) ApoB-100 secretion into the medium was significantly less after the addition of any of the three agents. 2) Triglyceride mass was not significantly changed from control in the medium but was significantly, although modestly, reduced in the cells. 3) Neither free cholesterol (FC) nor cholesteryl ester (CE) mass in the medium was changed; by contrast, CE mass was reduced within the cells although FC was not. 4) Although the total mass of cholesterol in the medium was unaffected, the proportion associated with apoB-100 was reduced, whereas the proportion associated with the non-apoB-100 fraction was increased. 5) There was also an unanticipated, but substantial, increase in bile acid synthesis induced by apoA-I, HDL3, or hydroxy-beta-cyclodextrin, which was time and concentration dependent, and which was associated with marked increases in cholesterol 7 alpha-hydroxylase activity. There were no significant changes in ACAT activity and only modest increases in HMG-CoA reductase activity. These findings support previous clinical observations that an elevated apoB-100 can accompany a low HDL cholesterol in normotriglyceridemic subjects. They also point to physiologically important, although still only partially understood, metabolic relationships amongst hepatic apoB-100 secretion, cholesterol efflux, and bile acid synthesis.

Effects on cholesterol balance and LDL cholesterol in the rat of a soft-ripened cheese containing vegetable oils
During, A., N. Combe, et al. (2000), J Am Coll Nutr 19(4): 458-66.
Abstract: OBJECTIVE: The purpose of this study was to examine effects of a modified soft-ripened cheese containing vegetable oils on cholesterol status, using the rat as the experimental model and the traditional soft-ripened cheese as the control. METHODS: Adult male Wistar rats (approximately 370 g) were divided into two dietary groups (20 rats/group) and fed either the standard diet (STD, containing traditional cheeses made from whole milk) or the experimental diet (EXP, containing modified cheeses made from the combination of skim milk with the following fat mixture: milk fat/oleic acid-enriched sunflower oil/soybean oil mixture). Lipids of the diets came solely from cheeses (14 g/100 g diet); the EXP diet contained (3-fold) less saturated fat, (2-fold) less cholesterol, and (15-fold) more phytosterols than the STD diet. RESULTS: Although serum triglyceride and total cholesterol concentrations were not affected by the type of diet, the EXP diet resulted in a significant reduction of LDL-cholesterol (31%, p < 0.001) and a significant increase of HDL-cholesterol (11%, p < 0.05), compared to the STD diet. Thus, a marked reduction (39%) of serum LDL/HDL cholesterol ratio was observed in the EXP group (p < 0.001). In addition, the two quantitative balances (excreted/ingested) of cholesterol and total neutral sterols (for which phytosterols were excluded) were significantly higher by 183% and 174%, respectively for the EXP group, compared to the STD group (p < 0.05). On another hand, rats fed the EXP diet excreted more cholesterol than they ingested dietary cholesterol (cholesterol balance > 1), indicating that those animals eliminated some endogenous cholesterol in their feces, while the opposite was true for rats fed the STD diet (cholesterol balance < 1). Finally, fecal bile salt concentration was not significantly different between the two dietary groups. CONCLUSIONS: The partial substitution of milk fat by vegetable oils in soft-ripened cheese resulted in a decreased blood LDL/HDL cholesterol ratio and an increased fecal excretion of endogenous cholesterol and neutral sterols and, thus, markedly improved its nutritional qualities. Therefore, the consumption of the described modified cheese may meet the demand of subjects who wish to lower their risk for atherosclerosis and cardiovascular disease.

Effects on Walker 256 tumour of carmustine associated with a cholesterol-rich microemulsion (LDE)
Teixeira, R. S., R. Curi, et al. (2004), J Pharm Pharmacol 56(7): 909-14.
Abstract: A cholesterol-rich microemulsion that binds to low-density lipoprotein (LDL) receptors (LDE), after injection into the bloodstream, concentrates in neoplastic tissues that over-express those receptors. LDE can thus serve as a vehicle for drug targeting. It was shown that carmustine side effects are pronouncedly reduced when the drug is associated with LDE in cancer patients. In this study, the therapeutic action of LDE associated with carmustine was compared with that of the non-associated drug in rats implanted with Walker 256 tumour. The toxicity and anti-tumour activity in rats treated with either free carmustine or carmustine associated with LDE and in control rats treated with saline solution were determined after a single intraperitoneal injection. The LD90 (90% lethal dose) of LDE-carmustine was 77 mg kg(-1) and of free carmustine was 44 mg kg(-1), indicating that LDE decreases toxicity. LDE-carmustine was able to decrease tumour mass at a lower dose level than free carmustine. Tumour regression time was shorter in LDE-carmustine- than in free carmustine-treated animals. Therefore, this study shows that the association of carmustine with LDE increases the therapeutic index of carmustine.

Efficacy and safety of a new cholesterol synthesis inhibitor, atorvastatin, in comparison with simvastatin and pravastatin, in subjects with hypercholesterolemia
Wolffenbuttel, B. H., G. Mahla, et al. (1998), Neth J Med 52(4): 131-7.
Abstract: BACKGROUND: High levels of total and LDL-cholesterol are associated with an increased risk of atherosclerotic vascular disease. Lowering of serum cholesterol levels by pharmacologic intervention with inhibitors of cholesterol synthesis, the so-called statins, reduces the incidence of cardiovascular events in subjects with and without atherosclerotic manifestations. In a 16-week, multicenter, randomized, open-label cross-over study we compared the efficacy and safety of the new compound atorvastatin for reducing LDL-cholesterol with simvastatin or pravastatin. METHODS: Following a 4-week placebo-controlled baseline period patients with LDL-cholesterol between 4.1 and 6.2 mmol/l and serum triglycerides below 3.4 mmol/l were randomly assigned to treatment either with 5 or 20 mg atorvastatin, or with 10 mg simvastatin or 20 mg pravastatin once daily for 4 weeks. After a placebo-washout period of 4-6 weeks, patients switched to the alternate treatment. At the end of weeks 3 and 4 of each study phase the serum concentrations of lipid parameters and apolipoproteins as well as safety parameters were determined. RESULTS: A total of 78 subjects entered the study. Treatment with 5 mg atorvastatin reduced total and LDL-cholesterol by 21 and 27%, respectively, which was similar to 10 mg simvastatin (total cholesterol -20%, LDL-cholesterol -28%) and 20 mg pravastatin (-18 and -24%, respectively). The effects of this low dose of atorvastatin on triglyceride levels (-16%) was not different from that of simvastatin and pravastatin (-8 and -11%, respectively). Treatment with 20 mg atorvastatin caused significantly larger reductions in total cholesterol (-33%) and LDL-cholesterol (-44%), serum triglycerides (-23%), and apo B (-40%) compared to simvastatin and pravastatin. Atorvastatin was well-tolerated, and no serious or medically important adverse events were observed. CONCLUSIONS: We conclude that atorvastatin is a safe and very efficacious cholesterol-lowering agent, which also possesses significant triglyceride-lowering properties.

Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia
Dujovne, C. A., M. P. Ettinger, et al. (2002), Am J Cardiol 90(10): 1092-7.
Abstract: The efficacy and safety of ezetimibe, a new cholesterol absorption inhibitor, was evaluated in this randomized, double-blind, placebo-controlled trial of 892 patients with primary hypercholesterolemia. After > or =2 weeks on the National Cholesterol Education Program (NCEP) Step I or a stricter diet and a 4- to 8-week single-blind placebo lead-in, patients with low-density lipoprotein (LDL) cholesterol 130 to 250 mg/dl and triglycerides < or =350 mg/dl were randomized 3:1 to receive ezetimibe 10 mg or placebo orally each morning for 12 weeks. The primary efficacy end point was the percent reduction in direct plasma LDL cholesterol from baseline to end point. A total of 434 men and 458 women (ages 18 to 85 years) received randomized treatment (666 ezetimibe 10 mg, 226 placebo). Demographics and baseline characteristics were similar between treatment groups. Ezetimibe significantly reduced direct LDL cholesterol by a mean of 16.9%, compared with an increase of 0.4% with placebo (p <0.01). Subgroup analysis indicated that response to ezetimibe was generally consistent across all subgroups, regardless of risk-factor status, gender, age, race, or baseline lipid profile. Ezetimibe effects on LDL cholesterol occurred early (2 weeks) and persisted throughout the 12-week treatment period. Compared with placebo, ezetimibe 10 mg also significantly improved calculated LDL cholesterol, apolipoprotein B, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and HDL(3) cholesterol (p <0.01). Ezetimibe was well tolerated. There were no differences in laboratory or clinical safety parameters, or gastrointestinal, liver, or muscle side effects from that of placebo. Ezetimibe 10 mg/day is well tolerated, reduces LDL cholesterol approximately 17%, and improves other key lipid parameters.

Efficacy and safety of doxazosin in the treatment of patients with mild or moderate essential hypertension and elevated levels of cholesterol
Taylor, S. H. (1991), Am Heart J 121(1 Pt 2): 362-6.
Abstract: In hypertensive patients, elevated serum cholesterol is a frequent and sinister additional coronary risk factor. Selective alpha 1-adrenoreceptor inhibitors appear to have the unique ability to control both risk factors. Forty-two patients, ages 42 to 65 years, including 21 men with sustained hypertension and elevated serum cholesterol levels, were included in a trial of monotherapy with doxazosin administered once daily (range, 1 to 16 mg). The influence of the drug on high blood pressure and elevated serum cholesterol was evaluated over a 28-week period, which consisted of a 4-week, single-blind placebo lead-in period, an open 10-week dose-adjustment period, and finally a 14-week maintenance period. Of the 39 efficacy-evaluable patients, 25 (64%) achieved adequate blood pressure control (diastolic blood pressure less than 90 mm Hg or a decrease in diastolic blood pressure greater than 10 mm Hg) at a mean daily dose of 2 mg of doxazosin. No persistent changes occurred in heart rate. In the 32 patients with evaluable lipid data, there were nonsignificant trends to an increase in high-density lipoprotein cholesterol and a reduction in total cholesterol, together with a significant reduction in serum triglyceride concentration. The combined changes in blood pressure and blood lipid levels resulted in a reduction of 36% in the calculated risk of coronary heart disease. Eleven patients reported side effects and four were withdrawn from therapy. These results confirm the antihypertensive and anticholesterolemic efficacy of once-daily treatment with doxazosin.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: a meta-analysis of randomized controlled trials
Birjmohun, R. S., B. A. Hutten, et al. (2005), J Am Coll Cardiol 45(2): 185-97.
Abstract: OBJECTIVES: The aim of this research was to estimate the efficacy and safety of current high-density lipoprotein cholesterol (HDL-C)-increasing drugs. BACKGROUND: Epidemiologic evidence has shown that HDL-C is inversely related to coronary heart disease (CHD) risk. However, the evidence for reducing CHD risk by raising HDL-C is thin, predominantly due to the paucity of effective and safe HDL-increasing drugs. METHODS: Randomized controlled trials with fibrates and niacin, published between 1966 through February 2004 (MEDLINE), were retrieved. Information on treatment, baseline characteristics, serum lipids, end points, and side-effects were independently abstracted by two authors using a standardized protocol. RESULTS: Data from 53 trials (16,802 subjects) using fibrates and 30 trials (4,749 subjects) using niacin were included. Random-effects model showed 11% versus 10% reduction in total cholesterol, 36% versus 20% reduction in triglycerides, 8% versus 14% reduction in low-density lipoprotein cholesterol, and 10% versus 16% increase in HDL-C for fibrates and niacin, respectively. Apart from flushes in the niacin group, both fibrates and niacin were shown to be well-tolerated and safe. Fibrates reduced the risk for major coronary events by 25% (95% confidence interval 10% to 38%), whereas current available data for niacin indicate a 27% reduction. CONCLUSIONS: Fibrates reduce major coronary events and increase HDL-C levels without significant toxicity. Niacin has a more potent effect on HDL-C levels, whereas data on cardiovascular event rate reduction are limited. Future studies need to evaluate whether additional HDL increase by fibrates or particularly newer niacin formulations on top of statin therapy translates into further event reduction in high-risk subjects, without significant toxicity.

Efficacy and safety of lowering dietary intake of total fat, saturated fat, and cholesterol in children with elevated LDL cholesterol: the Dietary Intervention Study in Children
Lauer, R. M., E. Obarzanek, et al. (2000), Am J Clin Nutr 72(5 Suppl): 1332S-1342S.
Abstract: BACKGROUND: Few studies have shown the efficacy and safety of lower-fat diets in children. OBJECTIVE: Our objective was to assess the efficacy and safety of lowering dietary intake of total fat, saturated fat, and cholesterol to decrease LDL-cholesterol concentrations in children. DESIGN: A 6-center, randomized controlled clinical trial was carried out in 663 children aged 8-10 y with LDL-cholesterol concentrations greater than the 80th and less than the 98th percentiles for age and sex. The children were randomly assigned to either an intervention group or a usual care group. Behavioral intervention promoted adherence to a diet providing 28% of energy from total fat, <8% from saturated fat,

Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels
Katan, M. B., S. M. Grundy, et al. (2003), Mayo Clin Proc 78(8): 965-78.
Abstract: Foods with plant stanol or sterol esters lower serum cholesterol levels. We summarize the deliberations of 32 experts on the efficacy and safety of sterols and stanols. A meta-analysis of 41 trials showed that intake of 2 g/d of stanols or sterols reduced low-density lipoprotein (LDL) by 10%; higher intakes added little. Efficacy is similar for sterols and stanols, but the food form may substantially affect LDL reduction. Effects are additive with diet or drug interventions: eating foods low in saturated fat and cholesterol and high in stanols or sterols can reduce LDL by 20%; adding sterols or stanols to statin medication is more effective than doubling the statin dose. A meta-analysis of 10 to 15 trials per vitamin showed that plasma levels of vitamins A and D are not affected by stanols or sterols. Alpha carotene, lycopene, and vitamin E levels remained stable relative to their carrier molecule, LDL. Beta carotene levels declined, but adverse health outcomes were not expected. Sterol-enriched foods increased plasma sterol levels, and workshop participants discussed whether this would increase risk, in view of the marked increase of atherosclerosis in patients with homozygous phytosterolemia. This risk is believed to be largely hypothetical, and any increase due to the small increase in plasma plant sterols may be more than offset by the decrease in plasma LDL. There are insufficient data to suggest that plant stanols or sterols either prevent or promote colon carcinogenesis. Safety of sterols and stanols is being monitored by follow-up of samples from the general population; however, the power of such studies to pick up infrequent increases in common diseases, if any exist, is limited. A trial with clinical outcomes probably would not answer remaining questions about infrequent adverse effects. Trials with surrogate end points such as intima-media thickness might corroborate the expected efficacy in reducing atherosclerosis. However, present evidence is sufficient to promote use of sterols and stanols for lowering LDL cholesterol levels in persons at increased risk for coronary heart disease.

Efficacy and safety of sitosterol in the management of blood cholesterol levels
Fernandez, M. L. and S. Vega-Lopez (2005), Cardiovasc Drug Rev 23(1): 57-70.
Abstract: Elevated levels of plasma LDL cholesterol (LDL-C) represent a major risk factor for cardiovascular disease. Treatments aimed at reducing levels of circulating LDL are regarded, therefore, as cardioprotective. The cholesterol lowering properties of plant sterols have been known for some time and many clinical studies have confirmed the efficacy of sitosterol in lowering plasma LDL-C concentrations. Animal studies have also shown reductions in LDL by sitosterol. The use of animal models has been useful in facilitating the elucidation of specific mechanisms by which this sterol exerts its hypocholesterolemic action. It is well known that plant sterols compete with cholesterol for space within bile salt micelles in the intestinal lumen thereby reducing cholesterol absorption. The understanding of the function of plant sterols in impeding cholesterol absorption has been clarified with the discovery of the adenosine binding cassette transporters, ABCG5/8, involved in the regulation of sterol absorption and secretion into the enterocyte and hepatocyte. Compared to cholesterol and other sterols, sitosterol is preferentially pumped out to the intestinal lumen by the ABCG5/8 transporters. This selective binding of sitosterol to the transporters ultimately results in significant lowering of plasma cholesterol. However, some findings support the hypothesis that plant sterols might be an additional risk factor for coronary heart disease. From the review of these studies, it is apparent that sitosterol is a useful dietary supplement for the lowering of plasma cholesterol. Nevertheless, this plant sterol should be used with caution in certain individuals who have a higher absorption rate of sitosterol.

Efficacy of 2 cholesterol apheresis systems
Schooneman, F., O. Ziegler, et al. (1990), Ann Med Interne (Paris) 141(7): 600-3.
Abstract: A new generation of techniques can be applied to the selective removal of some well-defined molecules from plasma. This is the field of plasma treatment. We investigated the selective removal of LDL cholesterol, by double filtration and dextran sulfate cellulose column plasmapheresis, from 3 to 4 liters of plasma from 4 hypercholesterolemic patients. The extraction rate of Apo A1 lipoprotein in dextran sulfate was less than 25% and Apo B was between 50 and 90%. Cascade filtration gave an extraction rate for Apo A1 between 25 and 50%; the extraction rate for Apo B was about the same as that found using the dextran sulfate procedure. Both techniques decreased the concentrations of coagulation factors (V, VIII and fibrinogen). In conclusion, we obtained good removal of LDL cholesterol with both systems. Dextran sulfate (from Kaneka) was more selective but very expansive. However, we observed side effects with this product that probably result from the release of dextran sulfate from the column.

Efficacy of a National Cholesterol Education Program Step 2 diet in normolipidemic and hypercholesterolemic middle-aged and elderly men and women
Schaefer, E. J., A. H. Lichtenstein, et al. (1995), Arterioscler Thromb Vasc Biol 15(8): 1079-85.
Abstract: We tested the effects of a National Cholesterol Education Program (NCEP) Step 2 diet (30% of calories or less as total fat, less than 7% saturated fat, and less than 200 mg cholesterol per day) on plasma lipid levels in normocholesterolemic and hypercholesterolemic middle-aged and elderly men and women. Thirty-two subjects were studied. Eight normolipidemic subjects (6 men and 2 women, mean age 56 +/- 13 years) with LDL cholesterol levels of less than 4.14 mmol/L (160 mg/dL) were given a baseline diet similar in composition to the diet currently consumed in the United States (35% of calories as total fat and 14% as saturated fat, with 147 mg cholesterol per 1000 kcal) for 6 weeks. Subjects were then placed on an NCEP Step 2 diet (26% total fat, 4% saturated fat, 45 mg cholesterol per 1000 kcal) for 24 weeks. In addition, 24 subjects (12 men and 12 women, mean age 62 +/- 12 years) with moderate hypercholesterolemia (LDL cholesterol levels of 4.14 mmol/L or above) were given a baseline diet for 6 weeks and then the NCEP Step 2 diet for 6 weeks. Energy intakes were adjusted to keep body weight constant throughout the study. In both normolipidemic and hypercholesterolemic subjects, consumption of the NCEP Step 2 diet was associated with significant changes in levels of total cholesterol (-20% and -16%, respectively), LDL cholesterol (-21% and -18%, respectively), and HDL cholesterol (-16% and -15%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of atorvastatin in achieving National Cholesterol Education Program low-density lipoprotein targets in women with severe dyslipidemia and cardiovascular disease or risk factors for cardiovascular disease: The Women's Atorvastatin Trial on Cholesterol (WATCH)
McPherson, R., C. Angus, et al. (2001), Am Heart J 141(6): 949-56.
Abstract: BACKGROUND: Recent studies have demonstrated that women at high risk for cardiovascular disease (CVD) benefit from cholesterol lowering to an extent similar to that of men. The ability to achieve established treatment goals for low-density lipoprotein cholesterol (LDL-C) in women with clearly defined risk factors has not been examined in detail. METHODS AND RESULTS: We have determined the efficacy and frequency of achieving target levels for LDL-C with atorvastatin on the basis of National Cholesterol Education Program Adult Treatment Panel II recommendations in 318 women according to the presence of CVD (198 women) or risk factors for CVD (120 women) and the presence of mixed dyslipidemia with obesity with or without CVD (72 women). Mean baseline LDL-C concentrations for women with established CVD were in the upper 10% of the distribution for age-matched North American women and, for those without CVD, were also extremely elevated and were in the top 5% of the LDL-C distribution for age-matched women in this population. The majority of participants without CVD (63%) reached LDL-C targets (LDL-C or=2 CVD risk factors) with 10 mg atorvastatin and 79% reached targets with up to 20 mg of atorvastatin. For women with established CVD, 34% achieved an LDL-C

Efficacy of atorvastatin in treating high risk patients to reach low density lipoprotein-cholesterol goals: the Treat to Target (TTT-Israel) Study
Leibovitz, E., D. Harats, et al. (2002), Isr Med Assoc J 4(6): 407-10.
Abstract: BACKGROUND: Hyperlipidemia is a major risk factor for coronary heart disease. Reducing low density lipoprotein-cholesterol can significantly reduce the risk of CHD, but many patients fail to reach the target LDL-C goals due to low doses of statins or low compliance. OBJECTIVES: To treat high risk patients with atorvastatin in order to reach LDL-C goals (either primary or secondary prevention) of the Israel Atherosclerosis Society. METHODS: In this open-label study of 3,276 patients (1,698 of whom were males, 52%), atorvastatin 10 mg was given as a first dose, with follow-up and adjustment of the dose every 6 weeks. While 1,670 patients did not receive prior hypolipidemic treatment, 1,606 were treated with other statins, fibrates or the combination of both. RESULTS: After 6 weeks of treatment, 70% of the patients who did not receive prior hypolipidemic medications and who needed primary prevention reached target LDL-C levels. Interestingly, a similar number of patients who received prior hypolipidemic treatment (other statins, fibrates or both) and who did not reach the LDL-C treatment goals reached the LDL-C goals for primary prevention with atorvastatin. Only 34% of all patients who needed secondary prevention reached the ISA LDL-C target of 100 mg/dl. Atorvastatin proved to be completely safe, only two patients had creatine kinase elevation above 500 U/L, and another six had mild CK elevation (< 500 U/L). None of the patients had clinical myopathy, and only one had to be withdrawn from the study. CONCLUSION: Atorvastatin is a safe and effective drug that enables most patients requiring primary prevention to reach LDL-C goal levels, even with a low dose of 10 mg. Patients in need of secondary prevention usually require higher doses of statins.

Efficacy of cholesterol ester transfer protein inhibitors in prevention of atherosclerosis
Kinoshita, M. (2004), Curr Atheroscler Rep 6(2): 79-80.

Efficacy of cholesterol levels and ratios in predicting future coronary heart disease in a Chinese population
Wang, T. D., W. J. Chen, et al. (2001), Am J Cardiol 88(7): 737-43.
Abstract: In this study, we assessed the efficacy of various lipid and lipoprotein measurements at baseline for predicting the risk for coronary heart disease (CHD) and determined the associated risk of CHD in subgroups stratified by different lipid and lipoprotein screening strategies to evaluate the adequacy of current total and low-density lipoprotein (LDL) cholesterol-based approaches in lipid management. We analyzed data from the Chin-Shan Community Cardiovascular Cohort study, a Chinese population-based prospective cohort study that began in 1990. During an 8-year follow-up period, 213 of 3,159 participants (6.7%) without CHD (aged > or =35 years) developed CHD. The total cholesterol/high-density lipoprotein (HDL) cholesterol ratio was the most powerful lipoprotein predictor of future CHD (hazard ratio 1.21 for a 1.0 increment in ratio; p <0.001). Subjects with "high-risk" LDL cholesterol levels (>160 mg/dl) and low total cholesterol/HDL cholesterol ratios (< or =5) had an incidence of CHD similar to those with low levels of both LDL cholesterol (< or =130 mg/dl) and total cholesterol/HDL cholesterol ratios (4.9% vs 4.6%). In contrast, subjects with "low-risk" LDL cholesterol levels (< or =130 mg/dl) and high total cholesterol/HDL cholesterol ratios (>5) had a 2.5-fold higher incidence of CHD than those with similar LDL cholesterol levels but low total cholesterol/HDL cholesterol ratios (p <0.001). Compared with using an LDL cholesterol level of 130 mg/dl as the cut-off point, using a total cholesterol/HDL cholesterol ratio of 5 was associated with superior specificity (73% vs 59%, p <0.001) and accuracy (72% vs 58%, p <0.001), and similar sensitivity (50% vs 53%). Our data indicate that current guidelines for lipid management may misclassify subjects with high levels of HDL and LDL cholesterol as well as those with low levels of HDL and LDL cholesterol. Using the ratio of total to HDL cholesterol as the initial screening tool can obviate this discrepancy.

Efficacy of cholesterol-lowering treatment in Japanese elderly patients with coronary artery disease and normal cholesterol level using 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor
Chikamori, T., K. Sugimoto, et al. (2000), J Cardiol 35(2): 95-101.
Abstract: The clinical benefit of cholesterol-lowering treatment is unknown in the Japanese elderly in whom the prevalence of morbidity and mortality related to coronary artery disease are known to be low. To evaluate the efficacy of cholesterol-lowering treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor in Japanese elderly patients with documented coronary artery disease, 121 patients with serum cholesterol > or = 150 mg/dl prospectively received HMG-CoA reductase inhibitor, and 271 patients undergoing cholesterol-lowering treatment based on dietary therapy alone served as historical controls. The 143 elderly patients age > or = 65 years in the 2 groups had similar baseline serum total cholesterol level (201 +/- 30 vs 202 +/- 31 mg/dl), age (71 +/- 4 vs 70 +/- 4 years), proportion of men (37/53 vs 64/90), number of diseased vessels (1.7 +/- 0.9 vs 1.5 +/- 1.0), and incidences of other classical coronary risk factors, including hypertension, diabetes mellitus, smoking, obesity and family history of coronary artery disease. In all 392 patients, similar trends were observed, including serum total cholesterol level (208 +/- 33 vs 201 +/- 34 mg/dl). With HMG-CoA reductase inhibitors, serum total cholesterol level was reduced by 14% in the elderly subjects and by 13% in all patients. During the follow-up of approximately 3 years, cardiac events occurred in 5 patients (one elderly) in the treatment group and 38 patients (12 elderly) in the control group. Kaplan-Meier survival estimates revealed a higher event-free survival rate with HMG-CoA reductase inhibitors in the elderly subjects (98% vs 85%, p < 0.05) and in all patients (94% vs 86%, p < 0.05). Cox proportional hazard modeling also demonstrated a significant reduction in risk for cardiac events with drug therapy (relative risk 0.32, p < 0.05), in addition to the number of diseased vessels (relative risk 1.8, p < 0.01). In contrast, no additional risk was observed with advancing age. Cholesterol-lowering treatment with HMG-CoA reductase inhibitors is effective to improve the prognosis of Japanese elderly patients, including those with normal serum cholesterol level.


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