Cholesterol ester transfer protein (CETP) plays a key role in remodeling triglyceride-rich particles and high-density lipoproteins (HDL). We investigated CETP sequence variants in response to long-term overfeeding (100 days) in 12 pairs of male monozygotic twins (mean age+/-S.D.: 21+/-2 years). Body fat mass (FM), abdominal subcutaneous (ASF) and visceral fat (AVF), and plasma lipoproteins were determined. The CETP variants C>T/In9 (rs289714) and G>A/Ex14 (rs5882, or I405V) were investigated by RFLP-PCR methodologies. Before overfeeding, the CETP CC/In9 (n=18) genotype was associated with lower FM compared to the C>T/In9 heterozygotes. Overfeeding induced more FM and ASF accretion in C>T/In9 carriers (P</=0.05). CETP V405V homozygotes (n=8) had lower BMI, FM, and ASF before overfeeding than those with the I405I (n=6) or I405V (n=10) genotypes. However, V405V subjects had the largest gain in AVF with overfeeding (P=0.02). Decreases from baseline were significantly different across the I405V genotypes for HDL-C, HDL-Apo AI, HDL(2), and HDL(3)(P</=0.05). Our data suggests that CETP sequence variation contributes to the undesirable changes in adiposity and HDL-C levels when exposed to excessive calorie consumption and may be potentially helpful to identify individuals with the metabolic syndrome who are at higher risk of cardiovascular disease.

OBJECTIVES: People of African descent may be at greater risk of metabolic syndrome (MS) compared with whites. We examined the associations among MS markers, body composition, and resting metabolic rate (RMR) in black Haitians and in white subjects living in Quebec, Canada. RESEARCH METHODS AND PROCEDURES: Forty randomly selected Haitians were matched with 40 white subjects for age, sex, and BMI. Glycemic status and insulin resistance were assessed based on a 3-hour glucose tolerance test. Blood lipids, blood pressure, abdominal fat (computed tomography), and waist circumference (WC) were measured. RMR was estimated by indirect calorimetry. RESULTS: Triglycerides were significantly correlated with blood pressure only in Haitians and with the area under the curve for insulin only in whites. Haitians had significantly (p < 0.05) lower triglycerides and higher high-density lipoprotein-cholesterol concentrations but higher blood pressure than whites at any given WC value. General linear models showed that Haitians had less visceral adipose tissue than whites for the same WC. RMR was lower among Haitians for any given value of BMI or WC than in whites. Also, WC was more strongly associated with glucose area under the curve and to log-homeostasis model assessment in white than in Haitian subjects. DISCUSSION: The MS may be ethnospecific in its features and etiology. The standard anthropometric indices of obesity may not be as effective in populations of African descent compared with whites, unless appropriate cut-off values are defined.

Plasma dehydroepiandrosterone sulfate (DHEA-S) and testosterone levels both decline with age in healthy men. Features of the metabolic syndrome also show age-related deteriorations. We examined the relative contribution of age and declining androgen levels to features of the metabolic syndrome in men. In a sample of 130 nonsmoking men from the Quebec Family Study, we tested the hypothesis that age-related decreases in DHEA-S and testosterone levels would explain most of the variance in alterations of the metabolic profile associated with aging. As expected, we found that plasma DHEA-S and testosterone levels were negatively associated with age. Significant negative correlations were found between androgen levels and adiposity measures, body fat distribution, and metabolic risk variables. Statistical control for age eliminated correlations with DHEA-S, whereas age-adjusted associations between testosterone and most adiposity and metabolic variables remained significant. The percentage frequency of men characterized by 3 or more features of the metabolic syndrome increased with decreasing testosterone (8.9%-44.2%, chi2 = 15.89, P <.0005 ) and DHEA-S levels (8.9%-41.5%, chi2 = 13.02, P <.005). Logistic regression analyses showed that men in the upper tertile of testosterone levels had a lower risk of being characterized by 3 or more features of the metabolic syndrome (odds ratio = 0.24, P <.04) independent of age, whereas tertiles of DHEA-S levels were not related to the metabolic syndrome independent of age. In conclusion, results suggest that age per se is an important correlate of the associations between DHEA-S and metabolic variables, whereas the association of plasma testosterone levels to features of the metabolic syndrome appears to be independent of age.

OBJECTIVE: Because leptin production by adipose tissue is under hormonal control, we examined the impact of epinephrine administration on plasma leptin concentrations. RESEARCH METHODS AND PROCEDURES: We measured plasma leptin, insulin, and free fatty acid (FFA) responses after a 60-minute epinephrine infusion (0.010 microg/kg fat free mass/min) followed by a 30-minute recovery period (no infusion) in a group of 11 lean (mean body mass index +/- SD: 22.6 +/- 1.1 kg/m(2)) and 15 obese (30.0 +/- 1.3 kg/m(2)) premenopausal women. Leptin, insulin, and FFA levels were measured in plasma before (-15 and 0 minutes) and at every 30 minutes over the 90-minute period. RESULTS: In both lean and obese individuals, plasma leptin was significantly reduced by epinephrine (p < 0.0001). Body fat mass was associated with fasting leptin levels (r = 0.64, p < 0.0005) as well as with the decrease in leptinemia (r =-0.51, p < 0.01) produced by epinephrine administration. Furthermore, we noted a large range of leptin response to epinephrine among our subjects, especially in obese women (from -12 to -570 ng/mL per 60 minutes). However, there was no association between postepinephrine leptin and FFA levels (r =-0.14, p = 0.55). DISCUSSION: Results of this study indicate that leptin levels decrease after epinephrine administration in both lean and obese premenopausal women. However, the heterogeneity in the response of leptin to catecholamines suggests potential alterations of the leptin axis that may contribute to generate a positive energy balance and, thus, may favor weight gain in some obese individuals.

Abdominal obesity and insulin resistance are characterized by low-level chronic inflammation most likely implicated in the increased cardiovascular disease risk associated with these conditions. However, not much is known of the acute regulation of circulating inflammatory markers in response to food intake. The aim of this study is to examine changes in inflammatory marker concentrations after the consumption of a high-fat meal in men and women. We measured tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and C-reactive protein concentrations in plasma samples collected at 0, 4, and 8 hours after consumption of the meal in 39 men and 41 women. Associations between these variations and physical as well as metabolic variables were then examined. We noted significant increases in plasma IL-6 concentrations at 4 and 8 hours after the meal in men (+34% and +107%, respectively; P <.005 vs 0 hour) and women (+78% and +153%, respectively; P <.0001 vs 0 hour). Postprandial plasma TNF-alpha concentrations significantly dropped at 4 hours after the high-fat meal in men (-9.5%, P <.0005 vs 0 hour) and women (-5.5%, P <.05 vs 0 hour). Plasma CRP concentrations were not affected by food intake in either men or women. We also found that postprandial plasma concentrations of IL-6 were lower in subjects with a normal glucose tolerance (n = 69) compared with individuals with an impaired glucose tolerance (n = 11). Results of the present study show that consumption of a high-fat meal is associated with a transient reduction in circulating concentrations of TNF-alpha in both men and women as well as an elevation of plasma IL-6 concentrations that was found to be greater in women than in men.

As visceral adipose tissue (AT) accumulation and inflammatory markers are known to increase with age, we examined whether this age-related change in regional AT distribution could contribute to the increase in the concentration of some inflammatory markers found with age. Two hundred eight healthy men aged 18.6 to 72.2 years and covering a wide range of adiposity values (body mass index, 18.5-39.3 kg/m(2)) were studied. Plasma C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels were measured by enzyme-linked immunosorbent assay. Anthropometric characteristics such as height, weight, and waist girth were measured; and body mass index was calculated. Cross-sectional areas of abdominal AT were obtained at L4-L5 by computed tomography. Fasting blood samples were collected to determine a complete lipoprotein lipid profile, and a 75-g oral glucose tolerance test was performed. Overall, visceral AT accumulation was positively correlated with age (r = 0.51, P <.0001) as well as with plasma CRP (r = 0.39, P <.0001), IL-6 (r = 0.32, P <.0001), and TNF-alpha (r = 0.14, P <.05) levels. A significant positive relationship was also observed between age and CRP (r = 0.36, P <.0001), IL-6 (r = 0.39, P <.0001), or TNF-alpha (r = 0.15, P <.05) concentrations. As middle-aged men were characterized by higher CRP (1.32 [25th percentile, 0.71; 75th percentile, 2.71] vs 0.66 [0.36, 1.62] mg/L, P <.0001) and IL-6 (1.60 [1.09, 2.28] vs 1.12 [0.77, 1.60] pg/mL, P <.0001) levels as well as by a greater amount of visceral AT (P <.0001) than young men, we have individually matched 43 young men (age, 28.6 +/- 5.82 years) with 43 middle-aged men (age, 57.6 +/- 5.15 years) on the basis of their visceral AT. Matching for visceral AT eliminated the difference between middle-aged men and younger adult men in inflammatory markers. These results suggest that the age-related variation in CRP and IL-6 is largely explained by differences in visceral AT.

The objective of the present study was to determine the respective contributions of visceral adipose tissue (AT) accumulation and cardiorespiratory fitness to variation of inflammatory markers in men and women. Circulating levels of C-reactive protein, tumor necrosis factor-alpha, interleukin-6, and adiponectin were obtained with visceral AT (computed tomography) and fitness (physical working capacity test) levels in a sample of healthy men (n = 120) and women (n = 152) covering a wide range of adiposity. An inflammation score was developed based on gender-specific percentile values of each inflammatory marker (0 or 1), which yielded a score ranging from 0 (low) to 4 (high). Visceral AT was positively associated with C-reactive protein and interleukin-6 levels (r > or =0.35, p <0.0001), but negatively associated with adiponectin (r =-0.29, p < or =0.0003) after adjustment for fitness. After adjusting for visceral AT, fitness was not associated with variation in inflammatory markers in women and only with adiponectin in men (r =-0.20, p = 0.03). In participants with low visceral AT (<130 cm(2) for men and <100 cm(2) for women), prevalences of participants with an increased inflammation score were 23.9% and 28.0%, respectively, for participants with high and low fitness, whereas in subjects with increased visceral AT, prevalences of a high inflammation score were 60.0% and 61.7%, respectively, for participants with high and low fitness. In conclusion, these results suggest that the previously reported association between poor fitness and low-grade inflammation may be largely attributable to increased visceral AT accumulation and its associated state of insulin resistance, conditions frequently observed in subjects with poor cardiorespiratory fitness.

Individuals with poor cardiorespiratory fitness have higher blood pressure than fit individuals. Individuals with low fitness levels also tend to be characterized by higher visceral adiposity compared with physically fit individuals. We tested the hypothesis that the relationship between low fitness and elevated blood pressure could be related, at least in part, to the higher level of visceral adipose tissue often found among unfit individuals. This study included 407 asymptomatic, nondiabetic participants. Visceral adipose tissue was assessed by computed tomography, and fitness was measured by a progressive submaximal physical working capacity test. Participants in the highest visceral adipose tissue tertile showed the highest systolic and diastolic blood pressures, whereas participants in the highest fitness tertile had the lowest blood pressure values (P<0.001). When participants were classified into fitness tertiles and then subdivided on the basis of visceral adipose tissue (high versus low), participants with a high visceral adipose tissue had higher systolic and diastolic blood pressure values (P=0.01), independent of their fitness category. Linear regression analyses showed that age and visceral adipose tissue, but not fitness, predicted systolic blood pressure (r(2)=0.11 [P<0.001], 0.12 [P<0.001], and 0.01 [P value nonsignificant], for age, visceral adipose tissue, and fitness, respectively) and diastolic blood pressure (r(2)=0.17 [P<0.001], 0.14 [P<0.001], and 0.01 [P value nonsignificant], for age, visceral adipose tissue, and fitness, respectively). Individuals with high visceral adipose tissue levels have higher blood pressure, independent of their fitness. Visceral adipose tissue may represent an important clinical target in the management of elevated blood pressure.

The aim of this study was to determine the independent contribution of previously reported risk factors for adult overweight and obesity. A cross-sectional (n = 537) and a longitudinal (n = 283; 6-year follow-up period) analysis was performed for nine risk factors for overweight and obesity assessed in adult participants (aged 18-64 years) of the Quebec Family Study (QFS). The main outcome measure was overweight/obesity, defined as a BMI >/=25 kg/m(2). Using logistic regression analysis adjusted for age, sex, and socioeconomic status, short sleep duration, high disinhibition eating behavior, low dietary calcium intake, high susceptibility to hunger behavior, nonparticipation in high-intensity physical exercise, high dietary restraint behavior, nonconsumption of multivitamin and dietary supplements, high dietary lipid intake, and high alcohol intake were all significantly associated with overweight and obesity in the cross-sectional sample. The analysis of covariance adjusted for age, socioeconomic status, and all other risk factors revealed that only individuals characterized by short sleep duration, high disinhibition eating behavior, and low dietary calcium intake had significantly higher BMI compared to the reference category in both sexes. Over the 6-year follow-up period, short-duration sleepers, low calcium consumers, and those with a high disinhibition and restraint eating behavior score were significantly more likely to gain weight and develop obesity. These results show that excess body weight or weight gain results from a number of obesogenic behaviors that have received considerable attention over the past decade. They also indicate that the four factors, which have the best predictive potential of variations in BMI, be it in a cross-sectional or a longitudinal analytical design, do not have a "caloric value" per se.Obesity (2009) doi:10.1038/oby.2009.116.

OBJECTIVE: To examine the long-term relationship between sleep duration and type 2 diabetes or impaired glucose tolerance (IGT). METHODS: Body composition measurements and self-reported sleep duration were determined in a longitudinal sample of 276 individuals aged 21 to 64 years followed for a mean of 6 years. Risk factors of type 2 diabetes/IGT over the follow-up were determined and relative risks (RRs) calculated for the development of type 2 diabetes/IGT by sleep duration group. RESULTS: Independent risk factors of type 2 diabetes/IGT over the follow-up included age, obesity, sleep duration, and glucose/insulin homeostasis indicators. Using adults with 7-8h of sleep as a reference, the adjusted RR for the development of type 2 diabetes/IGT was 2.78 (1.61-4.12) for those with 6h of sleep and 2.54 (1.42-3.53) for those with 9h of sleep. These elevated RRs remained significant after adjustment for body mass index, waist circumference or percent body fat. CONCLUSION: Short and long sleeping times are associated with a higher risk of developing type 2 diabetes/IGT, independent of several covariates. These results suggest that sleep duration may represent a novel risk factor for type 2 diabetes/IGT.

Body-mass index (BMI), total cholesterol (TC), lowdensity lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels are known to be highly heritable. We evaluated the genetic and environmental relationships of these measures over time in an analysis of twin pairs. Monozygotic (235 pairs) and dizygotic (260 pairs) male twins were participants in the National Heart Lung and Blood Institute Veteran Twin Study, and were followed with three clinical exams from mean age 48 years to mean age 63 years. Structural equation modeling (SEM) with adjustment for APOE genotype (a significant contributor to TC and LDL-C) was used to assess longitudinal patterns of heritability. Results indicated a contribution of genetic factors to BMI, TC, LDL-C, HLD-C, and TG. Modest increases over time were observed in the heritability of BMI (from 0.48 to 0.61), TC (from 0.46 to 0.57), LDL-C (from 0.49 to 0.64), and HDL-C (from 0.50 to 0.62), but this trend was not present for TG. There was a corresponding decrease in shared environmental influences over time for these traits, although shared environment was a significant contributor only for HDL-C. Moreover, we observed that genetic influences for all measures were significantly correlated over time, and we found no evidence of age-specific genetic effects. In summary, longitudinal analyses of twin data indicate that genetic factors do not account for a significant proportion of the variation in age-related changes of BMI or lipid and lipoprotein levels.

Context: Adaptive thermogenesis is defined as the increase in energy expenditure in response to overfeeding or cold. Large inter-individual differences in adaptive thermogenesis have been described. Objective: Since there are indications for a common underlying mechanism, we studied in humans whether the increase in thermogenesis during short term overfeeding (3 days) is related to mild cold induced thermogenesis. Interventions: Therefore, 13 lean male subjects have been exposed to three experimental conditions in respiration chambers: baseline (36 hours in energy balance at thermoneutrality, 22 degrees C); overfeeding (84 hours 160% of energy balance, 22 degrees C); mild cold (84 hours in energy balance, 16 degrees C). Main outcome measures: During the interventions, total daily energy expenditure (TDEE), physical activity, skin temperatures, and core temperature were measured. After each condition, fasting plasma norepinephrine concentration was measured. Results: Overfeeding caused significant increases in TDEE (0.77 MJ/day, p<0.001). During cold exposure TDEE increased significantly (0.59 MJ/day, p<0.005), while physical activity decreased. The changes in TDEE during both overfeeding and mild cold exposure showed considerable inter-individual variation (respectively -0.11 to 1.61 MJ/day and -0.19 to 1.58 MJ/day). The individual changes in energy expenditure during mild cold exposure and overfeeding were highly correlated (p<0.005). Fasting norepinephrine plasma concentrations correlated significantly to energy expenditure in both situations (p<0.05). Conclusions: These results suggest that both overfeeding induced and mild cold induced adaptive thermogenesis share common regulating mechanisms. This indicates that cold exposure could be used as a biomarker for the individual thermogenic response to excess energy intake.

Plasm levels of lipid, lipoprotein, and apolipoprotein (APO) A-I, A-II, C-II, C-III, and E were analyzed in 180 young survivors of myocardial infarction (MI) ages 28 to 45 years and in 200 sex-and age-matched normal healthy subjects to assess the importance of apolipoprotein concentrations in comparison with lipoproteins in MI patients. In comparison with control subjects, MI patients showed marked increases in the following parameters: total cholesterol (TC), low density lipoproteins (LDL) cholesterol, triglycerides (TG), very low density (VLDL) triglycerides, and cholesterol, and LDL-TG, apo B, apo C-III and apo E. There were no significant changes in levels of HDL3; cholesterol, apo A-II and apo C-II in these patients compared with their controls. Levels of high density lipoprotein (HDL), HDL2 cholesterol, and plasma apo A-I were markedly decreased in the young MI survivors' group demonstrated that the better discriminating lipoproteins and apolipoproteins in MI patients in descending order were HDL2 cholesterol, apo C-III, apo B, apo A-I, VLDL triglycerides and HDL cholesterol discriminated between patients and controls. Results indicate that measurement of apo C-III, B and A-I beside HDL2 cholesterol were shown to be of potential use in differentiating normal controls from patients with MI.

Cholesterol ester transfer protein (CETP) plays a key role in remodeling triglyceride-rich particles and high-density lipoproteins (HDL). We investigated CETP sequence variants in response to long-term overfeeding (100 days) in 12 pairs of male monozygotic twins (mean age+/-S.D.: 21+/-2 years). Body fat mass (FM), abdominal subcutaneous (ASF) and visceral fat (AVF), and plasma lipoproteins were determined. The CETP variants C>T/In9 (rs289714) and G>A/Ex14 (rs5882, or I405V) were investigated by RFLP-PCR methodologies. Before overfeeding, the CETP CC/In9 (n=18) genotype was associated with lower FM compared to the C>T/In9 heterozygotes. Overfeeding induced more FM and ASF accretion in C>T/In9 carriers (P</=0.05). CETP V405V homozygotes (n=8) had lower BMI, FM, and ASF before overfeeding than those with the I405I (n=6) or I405V (n=10) genotypes. However, V405V subjects had the largest gain in AVF with overfeeding (P=0.02). Decreases from baseline were significantly different across the I405V genotypes for HDL-C, HDL-Apo AI, HDL(2), and HDL(3)(P</=0.05). Our data suggests that CETP sequence variation contributes to the undesirable changes in adiposity and HDL-C levels when exposed to excessive calorie consumption and may be potentially helpful to identify individuals with the metabolic syndrome who are at higher risk of cardiovascular disease.

OBJECTIVES: To examine the relationship between plasma triglycerides (TG) to HDL-cholesterol (HDL-C) or HDL apo A-I. DESIGN AND METHODS: Bivariate and multiple linear regression analyses in a large cohort of 1886 subjects. RESULTS: Higher plasma TG levels were associated with lower concentrations of both HDL-C and HDL-apo A-I. However, the HDL-C/HDL-apo A-I ratio was inversely correlated with plasma TG indicating that the overall composition of the HDL changed as plasma TG changed. Plasma TG levels contributed to 15.9% of the variance of the HDL-C/HDL-apo A-I ratio, whereas gender, HDL-TG, LDL-TG, body mass index and plasma apo B levels represented between 0.15% and 2.21% of this variance. CONCLUSIONS: These results indicate that increasing levels of plasma TG result in greater reduction in HDL-C levels than in HDL-apo A-I and this might explain, at least in part, the differences that have been observed in the magnitude of the association of HDL-C versus HDL-apo A-I with the risk of cardiovascular disease.

This study deals with the pattern of body weight gain during an overfeeding period with a constant energy intake, in order to assess whether total daily energy expenditure (TEE) increased with body weight and thus could account for the progressive slow down in body weight gain over time. Twenty-four young adult males (12 pairs of identical twins) were overfed by 4.2 MJ per day, six days a week, for a total of 84 days during a 100-day overfeeding period. The total excess amount each man consumed was 353 MJ. It was assumed that, at a given time, the TEE increase (E) was dependent on body weight gain and energy cost (C) was proportional to the daily body weight gain. Results show an exponential increase in body weight, fat free mass, and fat mass (with half-times of 86, 57, and 84 days, respectively) that allows the calculation of E (246 +/- 37 kJ x kg(-1) x d(-1), mean +/- SE) and C (32.3 +/- 2.4 MJ x kg(-1)). Energy expenditure from other sources besides resting metabolic rate, such as physical activity and thermic effect of food, may represent as much as 65% of E. At the beginning of the overfeeding period, almost all the energy surplus was recovered as body substances but this proportion decreased to 60% after 100 days of overfeeding. It is concluded that 1) TEE changes were related to body weight change, 2) about 65% of E were accounted for by physical activity, thermic effect of food, or some other components, and 3) the fraction of the energy surplus stored as body substances decreased with the duration of overfeeding.

BACKGROUND: Lipoprotein and weight differences between vigorously active and sedentary monozygotic (MZ) twins were used to (1) estimate the effects of training while controlling for genotype and (2) estimate genetic concordance (ie, similarity) in the presence of divergent lifestyles. METHODS AND RESULTS: Thirty-five pairs of MZ twins (25 male, 10 female) were recruited nationally who were discordant for vigorous exercise (running distances differed by > or =40 km in male and > or =32 km in female twins). The active twins ran an average (mean+/-SD) of 63.0+/-20.4 km/wk, whereas the mostly sedentary twins averaged 7.0+/-13.5 km/wk. The active twins had significantly lower body mass index (difference+/-SE,-2.12+/-0.57 kg/m2, P=0.0007) and significantly higher HDL cholesterol (0.14+/-0.04 mmol/L, P=0.004), HDL2 (2.71+/-1.04 U, P=0.01), and apolipoprotein (apo) A-I (0.10+/-0.03 g/L, P=0.004). Despite the difference in lifestyle, when adjusted for sex, the correlations between the discordant MZ twin pairs were significant (P<0.01) for HDL cholesterol (r=0.69), apoA-I (r=0.58), and HDL2 (r=0.67). There was no significant MZ twin correlation for body mass index (r=0.17). None of the active twins having an overweight twin were themselves overweight. CONCLUSIONS: Behavior (vigorous exercise) may reduce genetic influences on body mass index. In contrast, genetics (or shared environment) substantially influences HDL cholesterol and HDL subclasses, even in the presence of extreme behavioral differences. There may be greater individual control over moderate degrees of obesity, whereas low HDL cholesterol may be largely predetermined and less effectively treated by vigorous exercise.

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.