Changes In High-density Lipoprotein Cholesterol Levels Research Articles

Contemporary Trends in Dyslipidemia in the Framingham Heart Study

Recent cross-sectional population studies in the United States have shown an increase in obesity, a decrease in cholesterol values, but no changes in levels of high-density lipoprotein cholesterol (HDL-C) or triglycerides (TG). Plasma total cholesterol, HDL-C, and TG levels, measured by the same methods at the 3 most recently completed examinations of Framingham Offspring Study participants (1991-2001), were compared in 1666 participants without prevalent cardiovascular disease, lipid therapy, or hormone replacement therapy (56% were men; mean ages of participants at the first and last examinations, 53 and 60 years, respectively). Changes in age- and multivariate-adjusted mean lipid levels were related to changes in body mass index (BMI). Over the 3 examinations, comparing the findings of the earliest examination with those of the most recent examination, the mean HDL-C level was significantly increased (multivariate-adjusted means, 44.4 and 46.6 mg/dL in men; 56.9 and 60.1 mg/dL in women; P value for trend, P <.001 in both sexes), whereas levels of TG were decreased (144.5 and 134.1 mg/dL in men; 122.3 and 112.3 mg/dL in women; P value for trend, P = .004 in men and <.001 in women). Over the same time interval, BMI (calculated as weight in kilograms divided by height in meters squared) increased (27.8 and 28.5 in men; 27.0 and 27.6 in women; P value for trend, P < .001 in men and P = .001 in women). There was an inverse relationship between changes in BMI and magnitude of dyslipidemia (ie, individuals with the least increase in BMI had the most favorable changes in levels of HDL-C and TG). During a 10-year period of recent examinations in the Framingham Heart Study there was a decrease in dyslipidemia with an increase in HDL-C levels and a decrease in levels of TG despite an overall increase in BMI.

Glimepiride increases high-density lipoprotein cholesterol via increasing adiponectin levels in type 2 diabetes mellitus

The aims of the present study are to investigate the effect of glimepiride 1 mg/d on plasma adiponectin and to assess the contribution of adiponectin in changing high-density lipoprotein cholesterol (HDL-c) levels after glimepiride treatment. Forty patients with type 2 diabetes mellitus were included. Plasma adiponectin, fasting plasma glucose, insulin, hemoglobin A1c, and cholesterol were measured at study entry and after 3 months of treatment with glimepiride. Both plasma adiponectin level (7.5 ± 4.5 vs 8.3 ± 4.5 μg/mL, P = .040) and HDL-c level increased significantly (50 ± 11 vs 53 ± 10 mg/dL, P = .041) in the all-subjects group. In the low-adiponectin group (initial plasma adiponectin level <6 μg/mL), both plasma adiponectin level (4.5 ± 0.9 vs 5.9 ± 2.0 μg/mL, P = .004) and HDL-c level increased significantly (44 ± 8 vs 49 ± 9 mg/dL, P = .011). There was no significant change in the high-adiponectin group (initial plasma adiponectin level ≥6 μg/mL). Change in plasma adiponectin level was an independent factor for change in HDL-c level after adjustment for other factors (β = .574, P = .009, R2 = 0.524, P = .036). In conclusion, glimepiride improved plasma adiponectin level, especially in the subjects with type 2 diabetes mellitus with low adiponectin level before treatment, and may directly contribute to improving HDL-c level.

Cholesteryl Ester Transfer Protein Inhibition, High-Density Lipoprotein Raising, and Progression of Coronary Atherosclerosis

Background— Despite favorable effects on high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol, the cholesteryl ester transfer protein inhibitor torcetrapib failed to slow atherosclerosis progression and increased mortality. We investigated the relationship between lipid changes and progression of coronary atherosclerosis. Methods and Results— Intravascular ultrasound was performed at baseline and follow-up in 910 participants randomized to torcetrapib/atorvastatin or atorvastatin monotherapy. The relationship between changes in lipoprotein levels and the primary intravascular ultrasound end point, change in percent atheroma volume, was investigated. Compared with atorvastatin monotherapy, torcetrapib raised HDL-C by 61%, lowered low-density lipoprotein cholesterol by 20%, raised serum sodium (0.44±0.14 mmol/L, P =0.02), and lowered serum potassium (0.11±0.02 mmol/L, P &lt;0.0001). Despite substantial increases in HDL-C, no effect was found of torcetrapib on percent atheroma volume. In torcetrapib-treated patients, an inverse relationship was observed between changes in HDL-C and percentage atheroma volume ( r =−0.17, P &lt;0.001). Participants with regression had greater increases in HDL-C (mean±SE, 62.9±37.4% versus 54.0±39.1%, P =0.002). Compared with the lowest quartile, torcetrapib-treated patients in the highest quartile of HDL-C change showed the least progression (−0.31±0.27 versus 0.88±0.27%, P =0.001). The highest on-treatment HDL-C quartile showed significant regression of percent atheroma volume (−0.69±0.27%, P =0.01). In multivariable analysis, changes in HDL-C levels independently predicted the effect on atherosclerosis progression ( P =0.001). Conclusions— The majority of torcetrapib-treated patients demonstrated no regression of coronary atherosclerosis. Regression was only observed at the highest HDL-C levels. Torcetrapib raised serum sodium and lowered potassium, consistent with an aldosterone-like effect, which may explain the lack of favorable effects in the full study cohort. Accordingly, other cholesteryl ester transfer protein inhibitors, if they lack this off-target toxicity, may successfully slow atherosclerosis progression.

Abstract 908: Efficacy of Statin Treatment in Normocholesterolemic Patients with Coronary Artery Disease: Evaluation by Integrated Backscatter Intravascular Ultrasound: 6-month Prospective Study

Few data exist regarding the effect of statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, on tissue characterization on coronary plaques in normocholesterolemic patients with coronary artery disease (CAD). The aim of this study was to clarify statin-induced the change in tissue characteristics on coronary atherogenesis in normocholesterolemic patients using an integrated backscatter intravascular ultrasound (IB-IVUS). We compared plaque characteristics on IB-IVUS and serum lipid markers in normocholesterolemic patients with CAD (n = 26) at baseline and after 6-month statin treatment. Totally, 1,288 (each of 644 lesions at baseline and after 6-month) non-target coronary lesions with mild to moderate stenosis were measured. After 6-month treatment, significant decrease in percentage lipid pool area (from 49 ± 10 to 46 ± 10%, p &lt; 0.05) and increase in percentage dense fibrous plaque area (from 50 ± 9% to 53 ± 9%, p &lt; 0.05) were found. Compared to the baseline values, there were significant reduction in serum low-density lipoprotein (LDL) cholesterol (111 ± 34 vs. 97 ± 28 mg/dL, p &lt; 0.005) and significant increase in serum high-density lipoprotein (HDL) cholesterol (46 ± 13 vs. 49 ± 12 mg/dL, p &lt; 0.05). Percent changes in HDL-cholesterol levels were inversely correlated with changes in %lipid pool (r = 0.40, p &lt; 0.05) and positively correlated with changes in %fibrous plaque (r = 0.44, p &lt; 0.05). We demonstrated that six months statin treatment changed in tissue characteristics towards coronary plaque stabilization, accompanying the changes in HDL-cholesterol levels. These results provide further support for the beneficial effect of statin on tissue characteristics on coronary artery in CAD patients with not only hypercholesterolemia but also normocholesterolemia.

A 52-Week, Randomized, Open-Label, Parallel-Group Comparison of the Tolerability and Effects of Pitavastatin and Atorvastatin on High-Density Lipoprotein Cholesterol Levels and Glucose Metabolism in Japanese Patients with Elevated Levels of Low-Density Lipoprotein Cholesterol and Glucose Intolerance

Background: Statin therapy has been found to produce substantial reductions in low-density lipoprotein cholesterol (LDL-C) levels, resulting in a reduced risk for cardiovascular events. Recently, research interest has focused on modification of high-density lipoprotein cholesterol (HDL-C) levels for the potential prevention of cardiovascular events. The effects of pitavastatin and atorvastatin on HDL-C have not been directly compared. Objectives: This study compared the effects of pitavastatin and atorvastatin on HDL-C and other lipids and glucose metabolism in Japanese patients with elevated LDL-C levels and glucose intolerance. The tolerability of the 2 treatments was also compared. Methods: This was a multicenter, open-label, parallelgroup trial. Patients with LDL-C levels ≥ 140 mg/dL and glucose intolerance (defined according to Japanese criteria for borderline diabetes and World Health Organization criteria for impaired fasting glucose and impaired glucose tolerance) were randomly assigned to receive either pitavastatin 2 mg/d or atorvastatin 10 mg/d for 52 weeks. Levels of serum lipids and lipoproteins and measures of glucose metabolism (fasting insulin, fasting glucose, glycosylated hemoglobin, and homeostasis model assessment for insulin resistance) were obtained at baseline and at 8, 26, and 52 weeks of treatment. The effect of study drug on glucose metabolism was evaluated as a tolerability outcome. Tolerability was further assessed based on adverse events, either spontaneously reported or elicited by questioning; physical examination findings; and clinical laboratory test results. Study physicians rated the relationship of adverse events to study medication as unrelated, suspected, or probable. Results: Two hundred seven patients were enrolled in the study, and efficacy was evaluated in 173 patients (88 pitavastatin, 85 atorvastatin). Thirty-four patients were excluded for reasons including failure to start medication or lack of ≥ 6 months of follow-up. Women accounted for 62% (108/173) of the evaluable population, which had a mean age of 63.3 years and a mean weight of 63.0 kg; 89% (154/173) had diabetes mellitus. The percent change in HDL-C levels was significantly greater in the pitavastatin group compared with the atorvastatin group (8.2 vs 2.9, respectively; P = 0.031), as was the percent change in apolipoprotein (Apo) A-I (5.1 vs 0.6; P = 0.019). The percent change in LDL-C levels was significantly lower with atorvastatin compared with pitavastatin (−40.1 vs −33.0, respectively; P = 0.002), as were the percent changes in non-HDL-C (−37.4 vs −31.1; P = 0.004), Apo B (−35.1 vs −28.2; P < 0.001), and Apo E (−28.1 vs −17.8; P < 0.001). The significant results for these parameters were unchanged when all 189 subjects who received ≥ 1 dose of study medication were included in the analysis, using last-value-carried-forward methodology. There were no significant differences between treatments with respect to the measures of glucose metabolism. Both statins appeared to be well tolerated. Adverse events occurred in 9% (9/96) of the pitavastatin group and 14% (13/93) of the atorvastatin group ( P = NS). Two patients in the pitavastatin group and none in the atorvastatin group had an alanine aminotransferase value >3 times the upper limit of normal ( P = NS). Conclusions: In these patients with elevated LDL-C levels and glucose intolerance, 52 weeks of treatment with pitavastatin 2 mg/d was associated with significantly greater increases in HDL-C and Apo A-I levels than atorvastatin 10 mg/d. Both treatments were well tolerated.

Common Single-Nucleotide Polymorphisms Act in Concert to Affect Plasma Levels of High-Density Lipoprotein Cholesterol

The identification of DNA sequence variants underlying human complex phenotypes remains a significant challenge for several reasons: individual variants can have small phenotypic effects or low population frequencies, and multiple allelic variants may act in concert to affect a trait. We evaluated the combined effect of allelic variants in seven genes involved in high-density lipoprotein (HDL) metabolism, using forward stepwise regression. Analysis of all known common single-nucleotide polymorphisms (SNPs) in the seven candidate genes revealed four variants that were associated with incremental changes in HDL cholesterol levels in three independent samples. Conversely, analysis of 660 polymorphisms in eight genes that do not appear to be involved in HDL metabolism did not identify any associations with plasma HDL-cholesterol levels. These data indicate that several common SNPs act in concert to influence plasma levels of HDL cholesterol.

Effect of Aerobic Exercise Training on Serum Levels of High-Density Lipoprotein Cholesterol

Aerobic exercise is believed to reduce the risk of cardiovascular disease partially through increasing serum levels of high-density lipoprotein cholesterol (HDL-C). However, this effect varies considerably among exercise intervention studies. Electronic database searches of MEDLINE (1966-2005) for randomized controlled trials that examined the effect of exercise training on HDL-C level. Twenty-five articles were included. Mean net change in HDL-C level was statistically significant but modest (2.53 mg/dL [0.065 mmol/L]; P<.001). Minimal weekly exercise volume for increasing HDL-C level was estimated to be 900 kcal of energy expenditure per week or 120 minutes of exercise per week. Univariate regression analysis indicated that every 10-minute prolongation of exercise per session was associated with an approximately 1.4-mg/dL (0.036-mmol/L) increase in HDL-C level. In contrast, there was no significant association between exercise frequency or intensity. Multiple meta-regression analyses demonstrated that subjects with a body mass index (calculated as weight in kilograms divided by height in meters squared) less than 28 and total cholesterol level of 220 mg/dL [5.7 mmol/L] or more experienced an approximately 2.1-mg/dL (0.054-mmol/L) larger increase in HDL-C level than those with a body mass index of 28 or more and total cholesterol level less than 220 mg/dL (5.7 mmol/L). Regular aerobic exercise modestly increases HDL-C level. There appears to exist a minimum exercise volume for a significant increase in HDL-C level. Exercise duration per session was the most important element of an exercise prescription. Exercise was more effective in subjects with initially high total cholesterol levels or low body mass index.

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

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.

Antiobese and hypolipidemic effects of platycodin saponins in diet-induced obese rats: evidences for lipase inhibition and calorie intake restriction

To investigate how and to what extent platycodin saponin (PS) from Platycodi Radix exerts a favorable influence on obesity and hyperlipidemia. Sprague-Dawley rats were fed with a high fat (HF) diet for 4 weeks and then the animals were treated with 35 or 70 mg / kg of PS for another 4 weeks. Changes in body weight and daily calorie intake were measured regularly during the experimental period and the degree of linear correlation for the above two variables was further analyzed. The in vitro lipase inhibition of each PS compound and the in vivo fecal lipid excretion were examined in hope of revealing their relationship. The concentrations of hepatic triglyceride and cholesterol in serum. The body weight reduction (13+/-4% vs HF control, P<0.05) by PS administration was highly correlated to the food intake restriction (Pearson's linear coefficient r=0.752, P<0.005). The in vitro inhibition of lipase by each isolated compound and mixture of PS were virtually identical. Consequently, the fecal TG excretion was increased by 2.1-3.2 folds depending on the dose of PS. The serum TG and LDL-cholesterol concentrations were decreased without noticeable changes in HDL-cholesterol levels. Concomitantly, the contents of the hepatic TG, cholesterol, and the liver surface fat pads were decreased in ubiquity, but no noticeable biochemical abnormalities or histological tissue damages were observed. The administration of PS produced profound effects on the control of obesity and lipid metabolism, which resulted in LDL-cholesterol reduction. PS also caused a remarkable reduction in calorie intake, which was highly correlated to the body weight loss. These results suggest that PS has a greater role in anti-obesity, hypolipidemia, and liver protection than previously thought. Hence, PS could be a potential therapeutic alternative in the treatment of obesity and hyperlipidemia.

Increased serum high-density lipoprotein cholesterol level is associated with a reduction in peripheral monocyte count in normal individuals.

Monocytes and high-density lipoprotein cholesterol (HDL-C) both play important roles in the process of atherosclerosis. This retrospective study investigated whether an increase in serum HDL-C level would be followed by a reduction in monocyte count. A total of 781 participants in a health check program in 1996 who had received a second health check in 1997, 1998, or 1999 were included. Based on the change in HDL-C at the second health check, the subjects were divided into the following 3 groups: 1) increase in HDL-C of >or= 5% (n = 426); 2) change of HDL-C of < 5% (n = 162); and 3) decrease of HDL-C of >or= 5% (n = 193). The relations between the change in HDL-C and the change in monocyte count were analyzed. A significant inverse relation between the change in HDL-C level and the change in monocyte count was found among the 3 study groups by 1-way analysis of variance (p = 0.002). Subjects with increased HDL-C had significantly decreased monocyte count at the second check while subjects with decreased HDL-C had increased monocyte count. Multivariate regression analysis of data from all subjects revealed that the change of HDL-C was independently associated with a significant inverse change in monocyte count (p = 0.007). In view of the documented inflammatory nature of atherosclerosis, the inverse relation between the change of HDL-C level and the change of monocyte count may partly explain why a higher serum HDL-C level can protect arteries against atherosclerosis.

Can change in high-density lipoprotein cholesterol levels reduce cardiovascular risk?

Background The cardiovascular risk reduction observed in many trials of lipid-lowering agents is greater than expected on the basis of observed low-density lipoprotein cholesterol (LDL-C) level reductions. Our objective was to explore the degree to which high-density lipoprotein cholesterol (HDL-C) level changes explain cardiovascular risk reduction. Methods A systematic review identified trials of lipid-lowering agents reporting changes in HDL-C and LDL-C levels and the incidence of coronary heart disease (CHD). The observed relative risk reduction (RRR) in CHD morbidity and mortality rates was calculated. The expected RRR, given the treatment effect on total cholesterol level, was calculated for each trial with logistic regression coefficients from observational studies. The difference between observed and expected RRR was plotted against the change in HDL-C level, and a least-squares regression line was calculated. Results Fifty-one trials were identified. Nineteen statin trials addressed the association of HDL-C with CHD. Limited numbers of trials of other therapies precluded additional analyses. Among statin trials, therapy reduced total cholesterol levels as much as 32% and LDL-C levels as much as 45%. HDL-C level increases were <10%. Treatment effect on HDL-C levels was not a significant linear predictor of the difference in observed and expected CHD mortality rates, although we observed a trend in this direction ( P = .08). Similarly, HDL-C effect was not a significant linear predictor of the difference between observed and expected RRRs for CHD morbidity ( P = .20). Conclusions Although a linear trend toward greater risk reduction was observed with greater effects on HDL-C, differences were not statistically significant. The narrow range of HDL-C level increases in the statin trials likely reduced our ability to detect a beneficial HDL-C effect, if present.

Effects of antirheumatic therapy on serum lipid levels in patients with rheumatoid arthritis: a prospective study

BackgroundPatients with newly diagnosed rheumatoid arthritis have adverse serum lipid profiles. We sought to determine the effects of treating rheumatoid arthritis with antirheumatic drugs on these abnormal lipid levels. Subjects and methodsWe studied 42 patients with newly diagnosed rheumatoid arthritis who had not been treated with corticosteroids or disease-modifying antirheumatic drugs. We measured serum lipid profiles at baseline and 1 year later, and determined whether there were differences in the changes in lipid levels between patients who met the American College of Rheumatology criteria for a 20% improvement in rheumatoid arthritis and those who did not. ResultsOf the 42 patients, 27 (64%) met the criteria for a 20% improvement in rheumatoid arthritis during the 12-month study. In these patients, mean high-density lipoprotein (HDL) cholesterol levels increased by 21% (P <0.001), apolipoprotein A-I levels increased by 23% (P <0.001), and the ratio of low-density lipoprotein (LDL) cholesterol to HDL cholesterol level decreased by 13% (P = 0.10). There were significant between-group differences (responders–nonresponders) in the mean 12-month changes in HDL cholesterol levels (8.0 mg/dL; 95% confidence interval [CI]: 3 to 13 mg/dL; P = 0.002), apolipoprotein A-I levels (21 mg/dL; 95% CI: 8 to 33 mg/dL; P = 0.003), and the LDL cholesterol to HDL cholesterol ratio (–0.6; 95% CI: –0.1 to –1.0; P = 0.03), but not in LDL cholesterol, apolipoprotein B-100, or lipoprotein(a) levels. ConclusionActive rheumatoid arthritis is associated with an adverse lipid profile that improves substantially following effective treatment of rheumatoid arthritis. This improvement may reduce the risk of cardiovascular disease.

Dietary counselling effectively improves lipid levels in patients with endogenous hypertriglyceridemia: emphasis on weight reduction and alcohol limitation.

To evaluate the short-term effect of dietary counselling in patients with endogenous hypertriglyceridemia and evaluate the effects of advised nutrient changes. A prospective dietary intervention study in patients with endogenous hypertriglyceridemia from January I st 1988 to December 31 st 1996 according to the Dutch guidelines for a healthy diet. Before and after the dietary intervention period of 12 weeks, 24h food recalls were used to assess dietary intake and macronutrient composition. Effectiveness was evaluated by assessment of body weight, serum lipids, lipoproteins and insulin resistance parameters. Leiden outpatient Lipid Clinic. Forty-five newly diagnosed, untreated patients with endogenous hypertriglyceridemia. A significant reduction in energy intake and body weight as well as changes in macronutrient composition were observed. Total serum triacylglycerol and cholesterol levels decreased by 31% and 15%, respectively. No effects were observed on serum glucose and insulin levels. Weight reduction was significantly correlated with reduction of total plasma triacylglycerol levels and inversely correlated with changes in HDL cholesterol levels. Of all nutrients assessed, only reduction of alcohol intake correlated with improvement of total serum triacylglycerol. Short-term dietary counselling in patients with endogenous hypertriglyceridemia can effectively improve serum lipid and lipoprotein levels. With regard to the advised nutrient changes, weight loss and limitation of alcohol intake prove to be the best predictors of triacylglycerol reduction.

Relationship between physical activity and HDL-cholesterol in healthy older men and women: a cross-sectional and exercise intervention study

We used cross-sectional and exercise intervention studies to examine whether physical activity levels or increases in peak aerobic capacity (peak VO 2) explain variation in high density lipoprotein cholesterol (HDL-C) levels in older men and women. In the cross-sectional study, 307 older individuals (169 men; 138 women; 67 ± 7 years) were characterized for HDL-C, leisure time physical activity, peak VO 2, body composition, body fat distribution and dietary intake. HDL-C was 19% higher ( P < 0.001) in women (57 ± 14 mg/dl) versus men (48 ± 14 mg/dl). Thirty-two percent of the variation in HDL-C in older men was explained by the waist circumference ( r 2 = 16%), percent dietary intake of alcohol ( r 2 = 11%), and carbohydrate ( r 2 = 6%). Waist circumference was also the best predictor of HDL-C in older women, ( r 2 = 7%); with percent dietary intake of carbohydrate adding an additional 6% to the model. Neither peak VO 2 nor leisure time physical activity were independent predictors of HDL-C. Statistical control for the aforementioned variables diminished, but did not abolish gender differences in HDL-C. Thirty-seven older individuals (23 men; 14 women) participated in a 2-month exercise program in which individuals by week eight were expending approximately 900 kcal per week in exercise energy expenditure. Subjects were maintained in energy balance throughout the exercise program. Endurance training significantly increased peak VO 2 by 15% in both men and women, and by design, body composition and body fat distribution did not change. No changes in HDL-C levels were noted. In conclusion, variations in leisure time physical activity or increases in peak VO 2 are not independent predictors of HDL-C levels in healthy older men and women. Instead, central adiposity, as estimated by the waist circumference, and to a lesser extent, dietary intake of carbohydrate and alcohol, are significant predictors of variation in plasma HDL-C levels. Furthermore, short-term exercise training, generating less than 900 kcal per week in exercise energy expenditure, in the absence of weight loss, fails to influence HDL-C levels.

Changes in plasma lipoprotein concentrations and composition in response to a low-fat, high-fiber diet are associated with changes in serum estrogen concentrations in premenopausal women

We have investigated the effects of a low-fat, high-fiber diet on plasma lipid and lipoprotein levels and serum sex hormone concentrations in 22 normal premenopausal women (mean age, 25.8 ± 3.8 years). Participants consumed a baseline diet for 4 weeks (40% of calories as fat, 16% as saturated fatty acids, 8% as polyunsaturated fatty acids, 400 mg/d cholesterol, and 12 g/d dietary fiber) and then a low-fat, high-fiber diet for 8 to 10 weeks (16% to 18% of calories as fat, 4% as saturated fatty acids, 4% as polyunsaturated fatty acids, 150 mg/d cholesterol, and 40 g/d fiber). Blood samples for determination of plasma lipids and serum hormones were obtained during the follicular and luteal phases of the menstrual cycle during both diets. Compared with the baseline diet, the low-fat, high-fiber diet resulted in significant decreases in total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations during both the follicular and luteal phases (TC, −14% and −16%; LDL cholesterol, −14% and −17%; and HDL cholesterol, −15% and −18%, respectively). During the follicular phase but not the luteal phase on the low-fat, high-fiber diet, women exhibited significant increases in plasma triglyceride ([TG] 22%) and very-low-density lipoprotein (VLDL)-TG (36%) concentrations. During the follicular phase, serum estrone sulfate concentrations decreased by 25% ( P < .0001) when subjects were fed the low-fat, high-fiber diet. During this phase of the low-fat, high-fiber diet relative to the baseline diet, changes in HDL cholesterol levels were significantly and positively associated with changes in estrone levels ( r = .49, P < .02), and the ratio of TC to HDL cholesterol was inversely associated with the changes in estradiol and free estradiol levels ( r = −.47 and r = −.43, P < .05, respectively). Our data are consistent with the concept that in premenopausal women, low-fat, high-fiber diets reduce estrone sulfate levels and both LDL cholesterol and HDL cholesterol levels without affecting the TC to HDL cholesterol ratio. Moreover, changes in estrone and estradiol levels are associated with changes in HDL cholesterol and HDL-TG levels.

Effects of an American Heart Association step I diet and weight loss on lipoprotein lipid levels in obese men with silent myocardial ischemia and reduced high-density lipoprotein cholesterol

Reduced plasma concentrations of high-density lipoprotein cholesterol (HDL-C) are a risk factor for coronary artery disease (CAD). In this study, we examined the sequential effects of an isocaloric American Heart Association (AHA) step I diet and a hypocaloric AHA step I diet (AHA step I diet + weight loss) on lipoprotein lipid levels in 14 middle-aged and older (60 ± 6 years, mean ± SD) obese (body mass index [BMI] > 27 kg/m 2) nondiabetic men with exercise-induced silent myocardial ischemia (SI) and reduced HDL-C levels (0.85 ± 0.14 mmol/L). Nine men of comparable age and obesity and with no evidence of exercise-induced ischemia that were evaluated longitudinally served as metabolic controls. In men with SI, after 3 months on the isocaloric AHA step I diet plasma triglyceride (TG) levels decreased by 26% (2.25 ± 0.66 to 1.67 ± 0.69 mmol/L, P < .005), cholesterol by 12% (5.24 ± 0.84 to 4.62 ± 0.78 mmol/L, P < .01), and low-density lipoprotein cholesterol (LDL-C) by 10% (3.40 ± 0.69 to 3.05 ± 0.70 mmol/L, P < .01). However, plasma HDL-C levels also decreased by 7% (0.85 ± 0.14 to 0.79 ± 0.13 mmol/L, P < .05). Subsequent weight loss (11 ± 4 kg) in conjunction with the AHA step I diet resulted in an additional decrease of 24% in TG ( P < .005), 10% in cholesterol ( P < .05), and 10% in LDL-C ( P < .05). Plasma HDL-C levels increased by 8% ( P < .01), thereby correcting the decline seen on the AHA step I diet alone. Postheparin hepatic lipase (HL) activity decreased with weight loss ( P < .005), with no significant change in lipoprotein lipase (LPL) activity. There were no significant changes in lipoprotein lipids or postheparin lipolytic activity in the metabolic controls. Therefore, in men with SI, the sequential interventions of an isocaloric AHA step I diet and an AHA step I diet with weight loss decreased plasma TG levels by 44% ( P < .0001), LDL-C levels by 18% ( P < .0001), and the LDL-C to HDL-C ratio by 19% ( P < .005), with no significant change in HDL-C levels. Additional treatment modalities that include supervised exercise programs and drug therapy may be warranted in older obese subjects whose HDL-C levels do not normalize with diet and weight-loss interventions alone.

Changes in Leisure Time Physical Activity and High-Density Cholesterol Levels Among White and African American Women

ABSTRACT The objective was to assess the effect of changes in leisure time physical activity on high-density lipoprotein cholesterol (HDL-C) levels among community-based participants. Data from a randomly selected cohort were obtained in 1987, with follow-up measurements in 1991. Two medium-sized South Carolina communities were study sites. The study population included women participants of the 1987 survey and assessment who were available for follow-up measurements in 1991, including 1,003 white and 348 African American women aged 18–89 years. Changes in HDL-C levels in four leisure time physical activity groups, adjusting for age, education, body composition, baseline HDL-C levels, and cigarette smoking status, were measured. Overall, over the 4-year period, mean HDL-C levels increased among women in both age groups, but this change was significant only among women age 50 and older. However, HDL-C increases for inactive women who increased their reported physical activity level at the time of the follo...

Effects of different doses of norethisterone on ovarian function, serum sex hormone binding globulin and high density lipoprotein-cholesterol

The ovarian effects of different doses of norethisterone (NET) were compared in 45 normally menstruating women in order to find the lowest effective dose of the Chinese NET “visiting pill”. Subjects were randomly divided into 3 groups. Each subject in each group was taking 0.5, 1.5 or 3.0 mg per day from days 5 to day 18 of the cycle. Blood samples were taken on days 5, 8, 11, 14, 17, 20, 23, 26 and 29 of the cycle. Serum oestradiol (E 2), progesterone (P), sex hormone binding globulin (SHBG), high density-lipoprotein cholesterol (HDL-C), and NET concentrations were measured. Ovulation, delayed ovulation, ovulation inhibition and follicular activity were classified by the analysis of the peripheral serum levels of sex hormones. Ovulation occurred in 7 women in the 0.5 mg group, in 2 women in the 1.5 mg group and in none of the 3.0 mg group. Mean serum SHBG levels were reduced progressively by 6.6% (Group 0.5), 15.5% (Group 1.5) and 23.4% (Group 3.0). There were no significant changes in HDL-C levels in any group. There was a significant correlation of mean serum NET concentrations with dose. The lack of complete inhibition of ovulation in most women in the 1.5 mg and 0.5 mg groups might suggest that the dose of NET required when used as a visiting pill could not be reduced below 3.0 mg.

Pharmacologic consequences of cholesterol absorption inhibition: alteration in cholesterol metabolism and reduction in plasma cholesterol concentration induced by the synthetic saponin beta-tigogenin cellobioside (CP-88818; tiqueside).

Natural and synthetic saponins inhibit cholesterol absorption and reduce plasma cholesterol levels in experimental animals and are therefore of potential pharmacologic utility in the treatment of hypercholesterolemia. To determine the effects of this class of compounds on cholesterol absorption and metabolism, we evaluated the effects of the synthetic saponin, beta-tigogenin cellobioside (tiqueside; CP-88818), on male golden Syrian hamsters. When administered as either a single oral bolus or as a dietary supplement for up to 2 weeks, tiqueside inhibited cholesterol absorption in a dose-dependent manner in both the presence and absence of dietary cholesterol. Administration of tiqueside to chow-fed hamsters as a 0.2% dietary supplement (150 mg/kg per day) for 4 days resulted in a 68% decrease in intestinal cholesterol absorption with no change in either bile absorption or cholesterol 7 alpha-hydroxylase activity, suggesting that tiqueside inhibits cholesterol absorption without interfering with enterohepatic bile acid recirculation. Under these conditions, hepatic cholesterol levels were also reduced in a dose-dependent manner. Hepatic cholesterol reduction was highly correlated with cholesterol absorption inhibition, and induced compensatory increases in both hepatic HMG-CoA reductase activity and hepatic low density lipoprotein (LDL) receptor levels. Compensatory increases in intestinal HMG-CoA reductase activity were also noted after tiqueside administration, and are consistent with a luminal mechanism for tiqueside action. As a consequence of these changes to cholesterol metabolism, tiqueside administration induced plasma cholesterol reductions that were highly correlated with both hepatic cholesterol reduction and cholesterol absorption inhibition. Tiqueside also produced comparable plasma cholesterol lowering in a variety of other species fed either cholesterol-free diets (hamster, rat, mouse, dog) or cholesterol-containing diets (hamster, rat, rabbit, mouse, cynomolgus monkey, rhesus monkey, SEA quail) indicating the ubiquity of tiqueside action. For all species evaluated except the dog, the reduction in plasma cholesterol was due primarily to a reduction in circulating non-HDL cholesterol levels with little or no change in HDL cholesterol levels. Taken together, these results indicate that inhibition of cholesterol absorption by tiqueside produces profound effects on cholesterol metabolism without affecting bile acid metabolism, and that these changes lead to reductions primarily in plasma non-HDL cholesterol concentrations. The synthetic saponin, tiqueside, may thus represent a prototypical form of therapy for the treatment of hypercholesterolemia.

The relation between serum insulin levels and 8-year changes in lipid, lipoprotein, and blood pressure levels.

Hyperinsulinemia is associated with an adverse pattern of cardiovascular risk factors, including obesity, elevated triglyceride levels, low levels of high-density lipoprotein (HDL) cholesterol, and elevated blood pressure. Whether hyperinsulinemia precedes (and perhaps causes) this deterioration in the risk factors or merely accompanies the deterioration is controversial. We therefore examined the 8-year changes in lipids, lipoproteins, and blood pressure as a function of baseline levels of fasting insulin in 1,383 nondiabetic Mexican-American and non-Hispanic white subjects enrolled between October 1979 and November 1982 in the San Antonio Heart Study, a population-based longitudinal study of cardiovascular risk factors and diabetes in San Antonio, Texas. After age and concomitant changes in body mass index were adjusted for, fasting insulin at baseline was found to be correlated positively with 8-year changes in triglyceride levels and negatively with 8-year changes in HDL cholesterol levels (p less than 0.05). Among the non-Hispanic whites, insulin was more strongly correlated with a decline in HDL cholesterol levels in women than in men (p less than 0.001). Fasting insulin was also positively correlated with changes in both systolic and diastolic blood pressure in non-Hispanic whites, but not in Mexican Americans, although these correlations were slightly diminished and no longer achieved statistical significance after subjects receiving antihypertensive medications were excluded. These results support the hypothesis that in nondiabetic subjects, insulin has a direct regulatory effect on triglyceride and HDL cholesterol levels. These data provide evidence for a possible role for insulin in blood pressure regulation, at least in non-Hispanic whites, although further analysis of this issue is warranted.