Effect of psyllium hydrophilic mucilloid on serum cholesterol in the elderly

The effect of psyllium hydrophilic mucilloid (PHM) when used as a laxative and/or stool softener on serum cholesterol concentrations was examined in 176 ambulatory elderly participants attending a health screening program. The change in one-year serum cholesterol concentration in subjects using PHM was compared with the change in cholesterol in 741 participants who did not report the use of PHM. Serum cholesterol concentration decreased by 0.073 mmol/liter (2.82 mg/dl) in the treatment group compared with a decrease of 0.036 mmol/liter (1.39 mg/dl) in the control group. After adjusting for confounding factors, excluding psyllium dose, by using a multiple regression model there was no significant difference in the change in serum cholesterol concentration (P=0.935). PHM dosage information was available for 158 participants. After adjusting for baseline serum cholesterol and confounding factors using multiple regression analysis, it was found that the dose of PHM administered was significantly correlated with the change in serum cholesterol (P=0.0120). For every 1-g increase in daily PHM dose there was a 0.022 mmol/liter (0.84 mg/dl) decrease in serum cholesterol concentration.Supported in part by a grant from the Procter and Gamble Company and SmithKline Clinical Laboratories.     

Leptin receptor polymorphism is associated with serum lipid levels and impairment of cholesterol lowering effect by simvastatin in Japanese men

OBJECTIVE: To investigate whether leptin receptor (Ob-R) Arg223Gln polymorphism influences serum lipid levels and whether this polymorphism affects the efficiency of the cholesterol lowering HMG-CoA reductase inhibitor, simvastatin [Clin. Cardiol. 16 (1993) 317]. DESIGN: Case-control association study. SUBJECTS: We studied 201 Japanese men without medical care, and 78 Japanese who took simvastatin. METHODS: Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum lipid and leptin levels were determined. RESULTS: Subjects with the Arg/Arg homozygotes had significantly higher serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels than those with the Arg/Gln heterozygotes and Gln/Gln homozygotes (TC: Arg/Arg: 213+/-3, Arg/Gln: 196+/-6, Gln/Gln: 184+/-5, P=0.004 for comparison among three genotypes, P=0.008 for difference between Arg/Arg and Arg/Gln, and P=0.025 for difference between Arg/Arg and Gln/Gln, LDL-C: Arg/Arg: 127+/-3, Arg/Gln: 112+/-6, Gln/Gln: 114+/-8, P=0.027) for comparison among three genotypes and P=0.011 for difference between Arg/Arg and Arg/Gln. Subjects with the Arg/Arg homozygotes had significantly lower serum high density lipoprotein cholesterol (HDL-C) levels than those with the Arg/Gln heterozygotes and Gln/Gln homozygotes (Arg/Arg: 55+/-1, Arg/Gln: 62+/-3, Gln/Gln: 57+/-7, P=0.046) for comparison among three genotypes and P=0.013 for difference between Arg/Arg and Arg/Gln. In addition, in 78 patients with hypercholesterolemia who took 5 mg simvastatin, the TC lowering effect by simvastatin in subjects with the Arg/Arg homozygotes was significantly lower than in those with the Arg/Gln heterozygotes and Gln/Gln homozygotes (the reduction in serum TC levels; 62+/-4 vs. 79+/-6, P=0.044). CONCLUSIONS: We demonstrate that Ob-R Arg223Gln polymorphism in Japanese men is associated with significant elevation of serum TC and LDL-C levels. Our data also show that the Arg/Arg homozygotes tend to show lowered level of serum HDL-C. Furthermore, this polymorphism tends to show an attenuated response to an HMG-CoA reductase inhibitor in terms of the cholesterol lowering effect. These results suggest that the Ob-R gene may serve as a novel modifier gene for hypercholesterolemia in Japanese men.     

Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients: relation to basal serum cholestanol

Coronary patients with low baseline ratios of serum cholestanol and plant sterols to cholesterol (indicating low cholesterol absorption) but not those with high ratios (high absorption) experienced reduced recurrences of coronary events during simvastatin treatment in the Scandinavian Simvastatin Survival Study. Thus, in the present study, serum cholesterol, its precursor sterols (reflecting cholesterol synthesis), plant sterols (campesterol and sitosterol), and cholestanol were measured before and during a 5-year period of placebo treatment (n=433) and simvastatin treatment (n=434) in patients from a subgroup of the Scandinavian Simvastatin Survival Study to determine whether changes in cholesterol synthesis and serum levels were related to cholesterol absorption. Serum cholesterol level was unchanged, the ratios of cholesterol precursor sterols to cholesterol were decreased, and the ratios of plant sterols to cholesterol were increased in relation to increasing baseline ratios of cholestanol quartiles. The latter predicted 5-year ratios and simvastatin-induced reductions of the precursor sterols, with the lowering of the ratios (cholesterol synthesis reduction) being almost twice higher in the lowest versus the highest quartile. The ratios of plant sterols, especially campesterol, to cholesterol were markedly increased during simvastatin treatment, mostly in subjects with the highest baseline cholestanol quartiles. Simvastatin reduced serum cholesterol more (P=0.003) in the lowest versus the highest cholestanol quartile during the 5-year treatment period. The results show for the first time that baseline cholesterol metabolism, measured by serum noncholesterol sterols, predicts the effectiveness of simvastatin in reducing cholesterol synthesis and serum levels of cholesterol. The drug suppresses the synthesis of cholesterol markedly more effectively in subjects with high than with low baseline synthesis but reduces respective serum cholesterol levels less markedly than synthesis. Subjects with high cholesterol absorption and low synthesis may need a combination therapy to lower more effectively their serum cholesterol levels and prevent an increase in the levels of plant sterols.     

Clinical benefits and cost-effectiveness of lowering serum cholesterol levels: the case of simvastatin and cholestyramine in The Netherlands

To assess the cost-effectiveness of cholesterol-reducing therapy with cholestyramine and simvastatin in the primary prevention of coronary artery disease in The Netherlands, a model of coronary artery disease incidence was used based on multivariate logistic risk functions from the Framingham study. For men with initial cholesterol levels of 8 mmol/liter, the cost per year of life saved of cholestyramine, expressed in Dutch guilders (NLG; 1 NLG = $0.50), ranges from approximately NLG 208,000 to NLG 483,000, depending on the patient's age at initiation of therapy. For simvastatin, cost-effectiveness ranges from NLG 46,000 to NLG 98,000 per year of life saved among this group of men. Similar differences between simvastatin and cholestyramine therapy prevail among women, although the costs per year of life saved for both agents are considerably higher. These results suggest that (1) simvastatin is substantially more cost effective than is cholestyramine; (2) simvastatin therapy compares favorably with other generally accepted medical practices, especially if treatment is initiated at an early age; and (3) as its long-term safety record becomes more established, simvastatin may become accepted as a drug of first choice in the treatment of persons with elevated serum cholesterol levels.     

Effect of splitting simvastatin tablets for control of low-density lipoprotein cholesterol

The efficacy, safety, and economics of a voluntary conversion from whole simvastatin tablets to split tablets in 6 Veterans Affairs medical centers were retrospectively evaluated in 3,787 patients who received a consistent daily dose (5 to 40 mg) of simvastatin in 1999. Baseline and final low-density lipoprotein cholesterol levels and average change from baseline were not significantly different between groups (p >0.05), nor were the incidence of transaminase increases (p >0.05) or measurements of patient compliance (p = 0.07). Widespread implementation of this initiative resulted in a cost avoidance of >$1.2 million in the 6 medical centers and $10.3 million across the Veterans Affairs medical system in 1999, with >$46 million avoided in 2003.     

老年患者的他汀类药物降胆固醇治疗

过去10余年中,国内外先后完成了从4S研究到活化降脂进一步减少临床终点试验等一系列里程碑意义的他汀类降脂试验。这些研究结果有力论证了他汀类药物降TC在冠心病及相关心血管疾病一、二级预防中的重要意义。无论是冠心病及其等危症（如糖尿病、动脉粥样硬化性外周血管疾病）,还是具有多重危险因素的高危患者,积极有效的降脂治疗均可显著降低心血管疾病的发病率与病死率。[第一段]     

The Importance of lowering cholesterol in patients with coronary heart disease

Patients with prior manifestations of cardiovascular disease account for about 50% of all myocardial infarctions and 70% of deaths due to coronary disease. The benefits of lowering elevated cholesterol levels in patients with coronary disease are well documented. Recent clinical trials indicate that these benefits, in terms of reduced risk of cardiovascular morbidity and mortality, extend even to patients with “average” cholesterol levels and support the importance of reaching a target low-density lipoprotein cholesterol level of ≤ 100 mg/dl. These findings argue in favor of attaining and maintaining optimal lipid targets for secondary (and primary) prevention of atherosclerotic vascular disease in patients at risk.     

Effect of cholesterol lowering treatment on positive exercise tests in patients with hypercholesterolaemia and normal coronary angiograms

AIM—To assess the impact of cholesterol lowering on positive exercise stress tests in hypercholesterolaemic patients with normal coronary angiograms.
METHODS—43 non-diabetic patients aged 43-61 years, with total serum cholesterol concentrations of more than 7.75 mmol/l, positive exercise tests, and normal coronary angiograms, were started on the American Heart Association step 1 diet. After 12 weeks these patients were randomly assigned to treatment for another 16 weeks with the diet alone (diet group, n = 20) or with the diet plus lovastatin or simvastatin (statin group, n = 23). After this 28 week run in period, statins were withdrawn and lipid profile tests and exercise tests were done and repeated 20 weeks later.
RESULTS—At week 28, the statin group but not the diet group had significant reductions from baseline (week 12) in plasma total cholesterol (p < 0.0001), low density lipoprotein (p < 0.0001), and triglyceride (p < 0.0001). The number of patients with positive exercise tests decreased from 23 to three in the statin group and from 20 to 15 in the diet group (p = 0.01). After the final 20 weeks without statins, lipid profiles returned to baseline levels in all 17 patients remaining in the statin group, and exercise tests were again positive in 15 of these patients.
CONCLUSIONS—In hypercholesterolaemic patients with normal coronary arteries, cholesterol lowering treatment reduces myocardial ischaemia, as shown by the beneficial effects on exercise testing.


Keywords: hypercholesterolaemia; exercise stress testing; myocardial ischaemia; endothelium