Changes in cardiovascular risk factors by combined pharmacological and nonpharmacological strategies: the main results of the CELL Study. Randomised controlled trial of use by hypercholesterolaemic patients of a vegetable oil sterol-enriched fat spread. The beneficial effects of lipid-lowering drugs beyond lipid-lowering effects: a comparative study with pravastatin, atorvastatin, and fenofibrate in patients with type IIa and type IIb hyperlipidemia. Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS) Comparison of the effects of dietary plant sterol and stanol esters on lipid metabolism. Cardiovascular risk factors during estrogen-norethindrone and cholecalciferol treatment. The effects of statin monotherapy and low-dose statin/ezetimibe on lipoprotein-associated phospholipase A₂. Investigation of the influence of two low-dose monophasic oral contraceptives containing 20 micrograms ethinylestradiol/75 micrograms gestodene and 30 micrograms ethinylestradiol/75 micrograms gestodene, on lipid metabolism in an open randomized trial. A randomized, multicentre, open-label, parallel-group trial to compare the efficacy and safety profile of daming capsule in patients with hypercholesterolemia.
The objectives of the Cost Effectiveness of Lipid Lowering (CELL) study were twofold: (i) to evaluate the effect on overall cardiovascular risk of two types of health care advice ("usual' and "intensive') given in primary care, with or without pharmacological medication, with the target being to attain a moderate decrease in cholesterol; (ii) to evaluate the ritual of daily medication on compliance with the health care advice.
                A prospective, double-blind, randomized, controlled trial of 18 months' duration.
                The study was carried out in 32 health centres (out of a total of approximately 850) in Sweden.
                In all, 681 subjects, aged 30-59 years, were randomized. They had at least two cardiovascular risk factors in addition to moderate primary hyperlipidaemia (total cholesterol of at least 6.50 mmol L-1 on three occasions measured by Reflotron triglycerides less than 4.0 mmol L-1 and an LDL:HDL cholesterol ratio of more than 4.0). Most (87%) of the subjects were males; 626 subjects (92%) completed the 18-month follow-up.
                Half the subjects were randomized to 'intensive advice' given in group sessions led by doctors and nurses in primary care. The other half received 'usual advice'. In each of the two advice groups, one-third received an active lipid-lowering drug (pravastatin), one-third placebo, and one-third no drug at all. The tablets were titrated to achieve a 15% reduction in cholesterol.
                Changes in the overall Framingham risk score, and the development of adverse events in each group.
                The change in Framingham risk score was significantly reduced only in subjects taking lipid-lowering medication (together with intensive advice -0.13; 95% CI-0.20, -0.06, and together with usual advice -0.16; 95% CI -0.23, -0.09). The other subjects receiving intensive advice tended to fare better than those on usual advice. Lifestyle was not influenced significantly over the study period. The ritual of daily medication did not affect the outcome.
                As expected, lipid-lowering medication reduced serum cholesterol as well as overall cardiovascular risk in subjects with several risk factors for cardiovascular disease. There was no additive effect of intensive advice to these subjects. However, there was a meagre but significant effect of intensive advice in subjects not receiving active lipid-lowering drugs. One explanation for this difference may be that those on active lipid-lowering medication who had substantial drops in cholesterol might have felt less inclined to change their lifestyle compared with those on other treatment regimens who had less successful drops in cholesterol. There was no benefit from the ritual of taking daily medication. Plant sterols may be a useful additive therapy in the treatment of hypercholesterolaemic patients. The purpose of this study was to determine the effect of a fat spread enriched with vegetable oil sterols on plasma lipid, lipoprotein and apolipoprotein concentrations. A randomised double blind placebo-controlled crossover trial with two consecutive periods of 8 weeks was conducted. 30 patients with heterozygous familial hypercholesterolaemia treated concurrently with an HMG-CoA reductase inhibitor (statin) and 32 patients with type IIa primary hypercholesterolaemia with a total cholesterol concentration >6.5 mmol/l not taking lipid-lowering drug therapy were recruited from a hospital lipid clinic. The active treatment was a fortified fat spread (25 g/day) providing 2.5 g of plant sterols. The control spread was indistinguishable in taste and appearance. Comparison at the end of the two 8-week trial periods showed a statistically significant reduction in total and LDL-cholesterol with use of the fortified spread but the results were confounded by a carry-over effect, which was partly explained by changes in the background diet. Because a carry-over effect was present, further analyses were restricted to the parallel arms of the first treatment period and were conducted on an intention to treat basis. After 4 weeks, LDL-cholesterol had decreased by 0.04 mmol/l ([0.8%] 95% confidence interval -0.44-0.37 NS) in the placebo group and decreased by -0.76 mmol/l ([15.0%] 95% CI -1.03--0.48, P<0.0001) in the active treatment group. After 8 weeks, the corresponding results were 0.0 mmol/l ([0.0%] 95% CI -0.26-0.24 NS) and -0.51 mmol/l ([10.0%] 95% CI -0.73--0.29 P<0.0001). There were no significant changes in apolipoprotein AI or B concentrations in the placebo group, but there was a small but statistically significant increase in apolipoprotein AI and a decrease in apolipoprotein B in the active treatment group. HDL cholesterol and triglyceride concentrations were unchanged. There was no difference in response between patients with statin-treated familial hypercholesterolaemia and patients with type IIa hyperlipoproteinaemia. We conclude that a fortified fat spread enriched with vegetable oil sterols reduces LDL-cholesterol by 10-15% with no difference in response between hypercholesterolaemic patients prescribed statins and those not taking lipid-lowering drug therapy. Hyperlipidemia is an important risk factor for atherosclerosis. Hemorheological factors contribute to morbidity and mortality in patients with dyslipidemia. We evaluated the effects of 3 antihyperlipidemic drugs (pravastatin, atorvastatin, and fenofibrate), which have different mechanisms of action and different patterns of action on lipid profiles, on erythrocyte deformability and fibrinogen levels in patients with type IIa and type IIb hyperlipidemia. Twenty-one patients ( 4 men and 17 women) with type IIa and IIb hyperlipidemia were randomized to 3 drugs (pravastatin 20 mg/d, atorvastatin 10 mg/d, fenofibrate 250 mg/d) for 8 weeks. Plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) analysis were performed on a BM-Hitachi 747-200 autoanalyzer (Hitachi-Roche, Tokyo, Japan). Fibrinogen analysis was performed according to Clauss method. Erythrocyte deformability was assessed with cell transit analysis device. There was no significant difference in body mass index, lipid profile, fibrinogen level, and erythrocyte deformability index values among the groups before treatment ( P > .05). In all groups, there were statistically significant reductions in total LDL-C levels ( P < .05). The triglyceride levels were significantly reduced in the atorvastatin and fenofibrate groups ( P < .05), but not in the pravastatin group ( P > .05). There was no significant change in HDL-C levels during the treatment with statins ( P > .05), but there was a significant increase in the fenofibrate group ( P < .05). Mean erythrocyte deformability index was improved in all the groups ( P < .05). There was no significant change in fibrinogen levels during the treatment of pravastatin and atorvastatin ( P > .05), but in fenofibrate group, fibrinogen levels were significantly decreased ( P < .05). The 3 groups of antihyperlipidemic drugs have beneficial effects on the erythrocyte deformability index. Only fenofibrate has significant beneficial effects on the fibrinogen levels. To assess the effect of dietary reduction of plasma cholesterol concentrations on coronary atherosclerosis, we set up a randomised, controlled, end-point-blinded trial based on quantitative image analysis of coronary angiograms in patients with angina or past myocardial infarction. Another intervention group received diet and cholestyramine, to determine the effect of a greater reduction in circulating cholesterol concentrations. 90 men with coronary heart disease (CHD), who had a mean (SD) plasma cholesterol of 7.23 (0.77) mmol/l were randomised to receive usual care (U, controls), dietary intervention (D), or diet plus cholestyramine (DC), with angiography at baseline and at 39 (SD 3.5) months. Mean plasma cholesterol during the trial period was 6.93 (U), 6.17 (D), and 5.56 (DC) mmol/l. The proportion of patients who showed overall progression of coronary narrowing was significantly reduced by both interventions (U 46%, D 15%, DC 12%), whereas the proportion who showed an increase in luminal diameter rose significantly (U 4%, D 38%, DC 33%). The mean absolute width of the coronary segments (MAWS) studied decreased by 0.201 mm in controls, increased by 0.003 mm in group D, and increased by 0.103 mm in group DC (p less than 0.05), with improvement also seen in the minimum width of segments, percentage diameter stenosis, and edge-irregularity index in intervention groups. The change in MAWS was independently and significantly correlated with LDL cholesterol concentration and LDL/HDL cholesterol ratio during the trial period. Both interventions significantly reduced the frequency of total cardiovascular events. Dietary change alone retarded overall progression and increased overall regression of coronary artery disease, and diet plus cholestyramine was additionally associated with a net increase in coronary lumen diameter. These findings support the use of a lipid-lowering diet, and if necessary of appropriate drug treatment, in men with CHD who have even mildly raised serum cholesterol concentrations. To compare the cholesterol-lowering efficacy and other metabolic effects of plant sterol and stanol esters, both of which are commonly used in the dietary management of hypercholesterolaemia.
                The cholesterol-lowering efficacy of equivalent intakes of sterol and stanol esters and of different intakes of stanol esters were compared at 1 and 2 months, both in normal subjects and treated patients with familial hypercholesterolaemia. Systemic effects were assessed by measuring serum levels of plant sterols and of lathosterol and 7alpha-hydroxy-cholestenone, indices of sterol absorption and of cholesterol and bile acid synthesis respectively. There were no significant differences during the study between 1.6g daily of sterol and stanol esters in reducing total cholesterol (by 3-7%) or low density lipoprotein cholesterol (by 4-8%), nor between 1.6 and 2.6 g daily of stanol. However, the cholesterol-lowering effect of plant sterol esters was attenuated between 1 and 2 months. This was accompanied by increased serum plant sterols and decreased levels of 7alpha-hydroxy-cholestenone, especially in statin-treated hypercholesterolaemic patients not taking bile acid sequestrants.
                These findings suggest that absorption of dietary plant sterols suppressed bile acid synthesis, thereby diminishing their cholesterol-lowering efficacy. In contrast, plant stanols reduced plant sterol absorption and maintained their cholesterol-lowering efficacy. The effect of cholecalciferol and estrogen-norethindrone treatment on total cholesterol level, high-density lipoprotein cholesterol level, blood pressure, and body mass index was investigated in 74 postmenopausal women in a double-blind, randomized trial. Blood pressure and body mass index did not change throughout the study. We demonstrated a decrease (11%) in serum cholesterol level after 1 year of treatment with estrogen-norethindrone. When this treatment was combined with cholecalciferol, a similar decrease (13%) was observed. The hypocholesterolemic effect was correlated to body mass index in a way that indicated the most pronounced decrease in lean women. The high-density lipoprotein cholesterol/total cholesterol fraction increased by 45% after 1 year of estrogen-norethindrone treatment, while an increase of 25% after 1 year was seen when cholecalciferol was added to the treatment. The latter increase was not different from a similar increase in the placebo group. The possible dyslipidemic effect of cholecalciferol, along with the risk of hypercalcemia, emphasizes the caution necessary in cholecalciferol treatment. Many of the pleiotropic effects of statins remain to be elucidated.
                Different statin regimens with similar lipid-lowering efficacy may have different effects on biomarkers of atherothrombosis including lipoprotein-associated phospholipase A₂ (Lp-PLA₂ ).
                After a 4-week dietary lead-in, 82 hypercholesterolemic patients were randomized to 1 of 2 treatment groups: atorvastatin 20 mg or atorvastatin/ezetimibe 5 mg/5 mg. After 8 weeks of drug treatment, the groups were compared for percent change in lipid parameters, Lp-PLA₂ , interleukin-6 (IL-6), monocyte chemoattractant protein-1, and fibrinogen.
                Low-density lipoprotein cholesterol (LDL-C) lowering was comparable between the 2 groups (-47% ± 11% and -49% ± 7% in the atorvastatin and combination groups, respectively). Although Lp-PLA₂ was reduced in both groups, the reduction was greater in the atorvastatin group (-42% and -9% [median], respectively, P = 0.03). Although IL-6 was decreased only in the atorvastatin group, IL-6 changes were not significantly different between the 2 groups. The changes in monocyte chemoattractant protein-1 and fibrinogen were similar in each group.
                Atorvastatin monotherapy was stronger at reducing plasma Lp-PLA₂ than the low-dose atorvastatin/ezetimibe combination after equivalent LDL-C lowering. This result may provide evidence of potential statin effects beyond the lowering of LDL-C.
                © 2011 Wiley Periodicals, Inc. An open comparison at a single center was performed in volunteers (n = 58) randomly allocated to two treatment groups, one receiving tablets containing 20 micrograms ethinylestradiol (EE) + 75 micrograms gestodene, and the other 30 micrograms EE + 75 micrograms gestodene. The study consisted of three treatment-free pre-cycles, followed by thirteen 28-day treatment cycles. Analysis of results revealed that there were no statistically significant differences between the two groups with regard to the plasma levels of HDL-cholesterol and its subfractions, LDL-cholesterol and apolipoproteins. There was, however, a trend toward a more favorable effect on HDL-cholesterol in the 20 micrograms EE group, where levels increased by 3% compared with the 30 micrograms EE group, where levels decreased by 9%. There was a statistically significant difference between the adjusted mean values of total triglycerides in the two groups in favor of the 20 micrograms EE group (+21%), compared with the 30 micrograms EE group (+64%) (p = 0.029). Two serious adverse events were reported (lymphadenopathy and vertigo), but neither were considered to be causally related to either study medication. The formulation containing 75 micrograms gestodene and 20 micrograms EE was shown to be a reliable and well tolerated oral contraceptive, with a favorable lipid profile. To study the efficacy and tolerability of Daming capsule (DMC) in Chinese patients with hyperlipidemia, a randomized, multi-centre, open-label, parallel-group trial was conducted. Sixty enrolled patients with hyperlipidemia allocated to six medical centers were randomly divided into two groups of 30 individuals each. One group received DMC 2 g b.i.d. for 6 weeks, and the other received pravastatin 10 mg o.d. for 6 weeks. For efficacy assessment, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were measured before and after drug treatment. Serum TC and LDL-C levels in the DMC-treatment group were significantly decreased compared with those before treatment (p < 0.05), while TG and HDL-C levels did not change much. Tolerability was assessed by heart rate (HR), blood pressure (BP), body mass index (BMI), alanine aminotransferase (ALT) and creatinine (Cr), which were not changed in either the DMC or pravastatin groups at 3 and 6 weeks (p > 0.05). Besides, eight patients experienced diarrhea during DMC treatment and two experienced myalgia and epigastric discomfort during pravastatin treatment. Based on the above results, it was concluded that DMC may be a good candidate for the treatment of hyperlipidemia and further clinical trials are warranted.
                Copyright 2009 John Wiley & Sons, Ltd.
Some herbal medicines may have cholesterol-lowering effects. Our findings have to be interpreted with caution due to high or unclear risk of bias of the included trials.