Variable effects of weight loss on serum lipids and lipoproteins in obese patients

After a 500 calorie diet and 6 months of low fat, maintenance diet, weight, serum lipid, and lipoprotein levels were compared to baseline in 46 obese patients. Mean weight decreased by 25.9 percent (29.2 kg). Mean total (TC) and low density lipoprotein cholesterol (LDL-C), and triglycerides (TG) decreased by 5.5 percent (12.1 mg/dl), 11 percent (15.5 mg/dl) and 23.6 percent (34.5 mg/dl); mean high density lipoprotein cholesterol (HDL-C) increased by 20.6 percent (10.3 mg/dl) and TC/HDL-C decreased by 25 percent (1.2), P less than 0.01. Females and males had equal increases in HDL-C. The decrease in TG and TC in patients who continued to lose 4.2 kg during the 6 month maintenance period was significantly greater than in those who regained 7.8 kg (P less than 0.015). Greater changes in HDL-C and TC/HDL-C occurred in younger individuals (r = -0.35 and r = -0.37); in those with more abnormal initial values (r = -0.60, r = 0.64); and for HDL-C, a larger increase occurred in those with greater weight loss (r = 0.32; P less than 0.04).     

The effects of antihypertensive agents on serum lipids and lipoproteins

Hypertension is a major risk factor for arteriosclerotic vascular disease. Despite intensive antihypertensive intervention, the risk of cardiovascular disease has not declined appreciably. Many of the antihypertensive agents have been shown to elevate total serum cholesterol and triglyceride levels or lower the high-density lipoprotein-cholesterol level. Thus, the antihypertensive agents chosen may negate the beneficial effects of a lower blood pressure. Our purpose is to review all available antihypertensive medications and their influence on lipoprotein metabolism. Choosing the antihypertensive therapy least likely to worsen or precipitate other known cardiovascular risk factors is important. Cost and side effect profiles must also be considered in choosing the best antihypertensive regimen for your patients.     

Life-style and serum lipids and lipoproteins

In reviewing the trends and influences of life-style in this country on health and disease in the latter half of 20th century, we focused our attention on 4 major habits of smoking, drinking, exercise and diets, and collected data on the Japanese to conduct a meta-analysis of their relationship with serum lipids and lipoproteins, which are the metabolic risk factors most closely related to atherosclerosis. 1) The percentage of smokers was 54.0% in adult males and 14.5% in adult females in 1999. In the data of 7,256 subjects (mean age 47 years) in 16 papers, smoking increased triglycerides by 13 mg/dl (0.15 mmol/L) or in 559 non-drinkers with a mean age of 49 years in 3 papers by 18 mg/dl (0.20 mmol/L), and decreased HDL-cholesterol by 3.5 mg/dl (0.09 mmol/L) with every 20 cigarettes smoked according to the regression equation. 2) As for drinking, the annual ethanol consumption per adult was 8.5L in 1996. The effects of alcohol on serum lipids were analyzed in 27,035 males (mean age 47 years) in 24 studies. Drinking elevated triglycerides by a mean of 10 mg/dl (0.11 mmol/L), and also HDL-cholesterol by 2.5 mg/dl (0.06 mmol/L) per 23 g of alcohol intake (corresponding to 1 go of sake or 1 large bottle of beer). 3) Concerning exercise habit, 25% of males and 21% of females (mean age 47 years) regularly performed exercise such as jogging, swimming, aerobics, and tennis. However, walking was regarded as an easy exercise to be practiced by subjects of all ages. The effects of walking on serum lipids were studied in a total of 46,074 subjects (mean age 47 years) in 8 populations. Triglycerides were significantly lower by 10 mg/dl (0.11 mol/L), and HDL-cholesterol higher by 3 mg/dl (0.08 mmol/L) in those who walked 6,000 or more steps/day than in those who walked less than 2,000 steps/day. The effects of harder exercise like jogging or swimming were analyzed in 2,242 subjects in 14 papers (mean age 44 years). Triglycerides decreased by 10 mg/dl (0.11 mmol/L), and HDL-cholesterol elevated by 5 mg/dl (0.13 mmol/L) with an increase in the exercise intensity by one level of about 300 kcal. In exercise therapy, triglycerides were decreased by a mean of 20 mg/dl (0.23 mmol/L), and HDL cholesterol increased by a mean of 10 mg/dl (0.26 mmol/L) by exercise at a mean heart rate of about 135 bpm, which is equivalent to 50% VO2max for 30 minutes x 3 times/week. 4) In nutritional trends, the mean energy intake in 52 postwar years averaged 2,116+/-84 kcal with no marked changes according to nutritional surveys. However, the percentage of fat in total energy intake was lowest at 7% in 1946, increased thereafter until it exceeded 20% in 1973, and surpassed 25% in 1988. The mean total cholesterol level of the Japanese increased by 28 mg/dl (0.72 mmol/L) in the past 30 years and reached 204 mg/dl (5.28 mmol/L) in a survey in 1990. 5) Concerning dietary habits, total cholesterol was lower by a mean of 13 mg/dl (0.34 mmol/L), triglycerides lower by 40 mg/dl (0.45 mmol/L), and HDL-cholesterol higher by 5 mg/dl (0.13 mmol/L) in the group who ate 7 or more Japanese-style meals in the 9 meals during 3 days than in the group who ate 3 or less Japanese-style meals in the 9 meals. When serum lipids were compared among individuals living in cities (8 groups; 3,613 subjects; mean age 51 years), agricultural villages (13 groups; 5,364 subjects; mean age 51 years), and fishing villages (9 groups; 1,071 subjects; mean age 52 years). Total cholesterol was lower by a mean of 10 mg/dl (0.26 mmol/L) in fishing villages than in cities, and triglycerides lower by a mean of 15 mg/dl (0.17 mmol/L) in fishing villages than in cities and agricultural villages. HDL-cholesterol was 5 mg/dl (0.13 mmol/L) higher in agricultural villages and 3 mg/dl (0.08 mmol/L) higher in fishing villages than in cities. 6) The effects of dietary therapy or guidance were evaluated in 585 subjects (mean age, 53 years) in 12 papers. Total cholesterol was reduced by 20 mg/dl (0.52 mmol/L), triglycerides by a mean of 40 mg/dl (0.45 mmol/L), and HDL-cholesterol was increased by 5 mg/dl (0.13 mmol/L) by restriction of fat intake or restriction of the intake of saturated fat and dietary cholesterol. The results of these meta-analyses are considered to indicate the extent to which abnormalities of serum lipids are caused by a distorted life-style and the extent to which they are improved by correction of the life-style and exercise or dietary therapy. Correction of the life-style as a non-drug therapy may clearly improve hyperlipidemias or hypo-HDL-cholesterolemia so that this approach should be aggressively employed as part of the prevention and treatment for hyperlipidemias.     

Effect of prolonged exercise on serum lipids and lipoproteins

It has been shown that physical exercise lowers serum triglyceride levels and may increase high density lipoprotein-cholesterol levels. Understanding of the mechanisms responsible for these beneficial adaptations is still incomplete. Twenty-six men, who played soccer continuously for 64 hours to establish a world's record, were monitored for acute changes in lipid metabolism. Food intake was determined before and during the exercise period. Blood specimens were taken before and repeatedly during the match for the measurement of triglycerides (TG), total cholesterol (CH), glycerol, apolipoprotein A-I (apoA-I), and cholesterol in various lipoprotein fractions (quantitative lipoprotein electrophoresis). During exercise TG levels decreased from 116 +/- 26 to 66 +/- 13 mg/dL and CH from 180 +/- 22 to 135 +/- 25 mg/dL. Both TG and glycerol showed an initial increase followed by a continuous decrease. Alpha-CH increased by 19% whereas beta-CH and pre-beta-CH decreased markedly (39% and 78%, respectively). In contrast to alpha-CH, apo A-1 fell only slightly by 10%. These results indicate that the effect of chronic exercise on lipids and lipoproteins can be mimicked by acute prolonged exercise. Similar mechanisms may be involved in these adaptations. Moreover, the extreme length of physical exertion substantially lowered CH.     

The effects of chlorpropamide and insulin on serum lipids,lipoproteins and fractional triglyceride removal

Summary The effects of chlorpropamide on serum lipids, lipoproteins and fractional triglyceride removal have been studied over 12 months on 10 maturity onset diabetics not controlled on diet alone. Similar studies were carried out in 6 maturity onset diabetics who had failed to respond to sulphonylureas and 6 new insulin requiring diabetics. In the chlorpropamide treated patients there was an initial fall in serum and VLDL triglyceride but this effect was lost at 12 months. There was no change in fractional triglyceride removal. At 12 months there was a fall in LDL and a rise in HDL cholesterol. An initial improvement in glucose tolerance and insulin secretion was maintained at 12 months.In the insulin treated group the initial fall in serum and VLDL triglyceride was maintained at 12 months and was accompanied by an increase in fractional triglyceride removal. There was also a fall in LDL and a rise in HDL cholesterol at 12 months.The failure of chlorpropamide to maintain the reduction in serum and VLDL triglyceride could be of importance in the genesis of coronary heart disease in maturity onset diabetics. The fall in LDL and rise in HDL cholesterol found both with chlorpropamide and insulin might be beneficial.     

高血压患者血脂和脂蛋白水平与冠状动脉狭窄的关系

目的探讨高血压患者血脂和脂蛋白水平与冠状动脉狭窄的关系。方法本研究回顾性分析1140例因胸痛住院接受冠状动脉造影且规则接受药物治疗的高血压病患者的血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDL C)水平与冠状动脉狭窄的相关性。结果①除高密度脂蛋白胆固醇(HDL C)外,高血压病患者严重冠状动脉狭窄的发生与年龄、病程、收缩压(SBP)、舒张压(DBP)、血糖、体重指数(BMI)、吸烟和TC、LDL-C相关(P<0.001)。②随着TC、LDL-C水平增高,冠状动脉狭窄级数、狭窄≥75%血管支数和狭窄≥75%的例数均明显增加(P<0.01)。③Logistic回归分析显示,TC、LDL-C与高血压病患者严重冠状动脉狭窄(≥75%)发生存在明显的相关性,TC、LDL-C每增加0.51mmol/L(分别以5.17mmol/L和3.10mmol/L为基线),严重冠状动脉狭窄发生率增加32%及33%(95%CI:1.25～1.39及1.23～1.43,P均<0.0001);在对年龄、性别、SBP、DBP、高血压病程、吸烟、糖尿病进行校对后,TC、LDL-C每增加0.51mmol/L仍显示增加严重冠状动脉狭窄发生率19%及21%(95%CI:1.12～1.23及1.15～1.27,P均<0.0001)。结论高血压合并高血脂患者血清TC、LDL-C水平与冠状动脉狭窄呈正相关关系,在高血压合并高血脂防治中,应重视血压的降低及TC、LDL C水平的改善。     

Serum lipids and lipoproteins in patients with primary gout

Summary Serum lipid and lipoprotein values of 32 male patients suffering from gout were quantitated and compared with corresponding values of a random control group which did not differ significantly with regard to age, body weight index and socio-economic status. All patients were on therapy with allopurinol which lasted on average for 6 years. The most striking differences between patients and controls were the increased triglyceride and apo B values and the decreased HDL-cholesterol (HDL-C) and HDL-phospholipid (HDL-PL) values in the patient group. The values of total cholesterol, LDL-cholesterol, apo A-I and Lp (a) were not significantly different between patients and controls. The great differences in the ratios of apo B/LDL-C, apo A-I/HDL-C and apo A-I/HDL-PL values suggest that gout is connected with changes in the chemical composition of the major lipoprotein classes. In three normolipemic individuals who were treated for 3 weeks with allopurinol no changes in lipoproteins and apolipoproteins were apparent. The results are discussed in view of the atherosclerosis risk of patients suffering from gout.     

The effects of soy-derived phytoestrogens on serum lipids and lipoproteins in moderately hypercholesterolemic postmenopausal women.

Postmenopausal women are at an increased risk of developing coronary artery disease (CAD). This increase is due primarily to elevated cholesterol concentrations accompanying the loss of endogenous estrogen secretion. Recently, the consumption of soy foods has been shown to reduce serum cholesterol concentrations. Phytoestrogens (PE) have been proposed as the responsible agents of the hypocholesterolemic effect of soy foods. However, few studies have investigated the effect of PE supplementation on serum lipoproteins. The purpose of the present study is to investigate the effects of PE supplementation (150 mg) on serum lipids and lipoproteins in moderately hypercholesterolemic, elderly, postmenopausal women. Thirty-six subjects were randomized into two groups and received either a 150-mg PE supplement/d (n = 20) or a placebo (n = 16). Serum samples obtained at baseline and 2 months were analyzed for total triacylglycerol, total cholesterol, and high density lipoprotein cholesterol using standard Lipid Research Clinic procedures. In addition, total triacylglycerol and cholesterol were measured after 6 months of treatment. The t test and ANOVA were employed to compare the two groups. The results (mean +/- SEM) indicated no significant differences in total triacylglycerol (1.3 +/- 0.2 vs. 1.2 +/- 0.2 mmol/liter), total cholesterol (6.4 +/- 0.4 vs. 6.5 +/- 0.2 mmol/liter), or high density lipoprotein cholesterol (1.0 +/- 0.1 vs. 1.0 +/- 0.1 mmol/liter) between the placebo and the PE groups, respectively, after 2 months of treatment. Moreover, total triacylglycerol and cholesterol remained unchanged after 6 months. Our findings suggest that PE supplementation with 150 mg/d over a 6-month period does not significantly alter serum lipoproteins in postmenopausal women and, therefore, may not effectively reduce the risk of CAD in this population.     

The effect of atorvastatin on serum lipids and lipoproteins in patients with homozyous familial hypercholesterolemia undergoing LDL-apheresis therapy

The efficacy of atorvastatin, a new hydroxymethylglutaryl (HMG)-CoA reductase inhibitor, in reducing serum lipid levels, modifying lipoprotein composition, and suppressing cholesterol synthesis was evaluated in patients with homozygous familial hypercholesterolemia (homozygous FH) undergoing LDL-apheresis therapy. Atorvastatin was given in escalating doses (10, 20, and 40 mg/day) to nine patients with homozygous FH. Five of nine patients responded well to atorvastatin; four of these patients were receptor-defective and the remaining one was receptor-negative. The change in LDL-cholesterol in the receptor-defective patients averaged -20.6% compared to the baseline level at the highest dose of atorvastatin. Of five receptor-negative type patients, only one showed good response to atorvastatin therapy with a LDL-cholesterol reduction of 14.9%. Although the other four receptor-negative patients did not show a change in LDL-cholesterol, all of them exhibited a considerable increase in HDL-cholesterol. All patients showed reduced urinary excretion of mevalonic acid, suggesting that atorvastatin decreases LDL-cholesterol by inhibiting cholesterol biosynthesis even where LDL-receptor activity is not present. Atorvastatin also decreased serum triglycerides in both receptor-negative and defective patients, especially in the latter. As cholesterol level rebounds quickly after each apheresis procedure, a combination therapy using atorvastatin and apheresis may increase the efficacy of the apheresis treatment, improving cost-benefit effectiveness by reducing the frequency of the apheresis treatment.     

The effect of ezetimibe on serum lipids and lipoproteins in patients with homozygous familial hypercholesterolemia undergoing LDL-apheresis therapy

LDL-apheresis is now commonly used as the only practical treatment for homozygous familial hypercholestreolemia (homozygous FH). However, even when applying apheresis therapy, the use of a drug or drugs is recommended to suppress the rapid rebound of cholesterol, which usually takes place after each apheresis procedure, and keep the LDL-cholesterol level within or near the optimal range for as long as possible. In this study, the usefulness of ezetimibe, a novel cholesterol-lowering drug, in enhancing the efficacy of apheresis therapy was evaluated in six Japanese patients with homozygous FH undergoing LDL-apheresis in combination with atorvastatin or simvastatin. With the exception of one patient, significant decreases in LDL-cholesterol at 2 weeks after each apheresis procedure were obtained during the period from 4 to 12 weeks of treatment, with an average reduction rate of 9.0% and a range of 4.3-12.6%. This corresponds to a suppression of rebound by approximately 36 mg/dl, from 391 to 355 mg/dl on average, in LDL-cholesterol values. Although the effect is not very strong, ezetimibe nevertheless appears to be a useful drug in combination with statins for those with homozygous FH undergoing LDL-apheresis.     

Effects of atorvastatin on serum lipids, lipoproteins, and hemostasis

Serum levels of lipids and lipoproteins were examined in individuals with hyperlipidemia treated with atorvastatin or colestimide and in healthy volunteers. Modified low-density lipoprotein (LDL) was measured by its faster electrophoretic mobility and expressed as charge modification frequency (CMF). Serum levels of total cholesterol (t-chol), triglyceride (TG), very low-density lipoprotein (VLDL)-chol, low-density lipoprotein (LDL)-chol, and CMF were significantly higher in hyperlipidemia, but there was no significant difference in serum high-density lipoprotein (HDL)-chol levels between hyperlipidemic and healthy subjects. Treatment with atorvastatin resulted in significant decreases of serum t-chol, TG, and LDL-chol levels but not serum HDL-chol and VLDL-chol. Treatment with colestimide significantly reduced serum t-chol, HDL-chol, and LDL-chol levels but not those of TG and VLDL-chol. CMF was significantly reduced by treatment with atorvastatin but not by colestimide. Atorvastatin significantly reduced plasma levels of thrombomodulin, thrombin antithrombin complex (TAT) and tissue type plasminogen activator-plasminogen activator inhibitor-I complex. Colestimide moderately prolonged activated partial thromboplastin time and reduction of TAT. Based on its actions of lowering modified LDL and improving hemostatic abnormalities, we postulate that atorvastatin might inhibit the onset of ischemic diseases.     

Varied effects of dietary sucrose and cholesterol on serum lipids, lipoproteins and apolipoproteins in rhesus monkeys.

Serum lipid, lipoproteins, apolipoproteins and plasma insulin and glucose were studied in rhesus monkeys (Macaca mulatta) fed high sucrose diets (69%, w/w), with and without added cholesterol. When compared to basal diet, a high sucrose diet with no added cholesterol fed for 6 weeks increased serum total cholesterol and triglycerides by factors of 1.2 and 2.8, respectively. Cholesterol supplementation of sucrose diets increased the serum total cholesterol levels by a factor of 2.2 and decreased the serum triglycerides by 0.47. The serum cholesterol response to experimental diets was reflected predominantly in beta-lipoprotein and to a lesser extent in alpha-lipoprotein. Sucrose diets without cholesterol enriched the beta- and pre-beta-lipoproteins with triglycerides and protein at the expense of cholesterol. On the same diet, the protein content of alpha-lipoprotein increased at the expense of cholesterol and triglycerides. In contrast, dietary cholesterol decreased the triglyceride content and increased the cholesterol content of all the lipoprotein classes. Sucrose feeding seems to increase ApoB more than non-ApoB proteins. The proportion of ApoC-II relative to ApcoC-III increased in each animal on a sucrose diet; exogenous cholesterol further increased this trend. While sucrose diet decreased ApoA-I/ApoA-II ratios, cholesterol supplementation reversed this trend. Dietary sucrose increased the plasma glucose, insulin, and insulin-glucose ratios. The addition of cholesterol also tended to decrease plasma glucose and insulin levels. These observations indicate varied responses of serum lipoproteins and apoproteins to dietary sucrose with and without cholesterol supplementation.