Fetal cells traffic to injured maternal myocardium and undergo cardiac differentiation.

RATIONALE: Fetal cells enter the maternal circulation during pregnancy and may persist in maternal tissue for decades as microchimeras. OBJECTIVE: Based on clinical observations of peripartum cardiomyopathy patients and the high rate of recovery they experience from heart failure, our objective was to determine whether fetal cells can migrate to the maternal heart and differentiate to cardiac cells. METHODS AND RESULTS: We report that fetal cells selectively home to injured maternal hearts and undergo differentiation into diverse cardiac lineages. Using enhanced green fluorescent protein (eGFP)-tagged fetuses, we demonstrate engraftment of multipotent fetal cells in injury zones of maternal hearts. In vivo, eGFP+ fetal cells form endothelial cells, smooth muscle cells, and cardiomyocytes. In vitro, fetal cells isolated from maternal hearts recapitulate these differentiation pathways, additionally forming vascular tubes and beating cardiomyocytes in a fusion-independent manner; ≈40% of fetal cells in the maternal heart express Caudal-related homeobox2 (Cdx2), previously associated with trophoblast stem cells, thought to solely form placenta. CONCLUSIONS: Fetal maternal stem cell transfer appears to be a critical mechanism in the maternal response to cardiac injury. Furthermore, we have identified Cdx2 cells as a novel cell type for potential use in cardiovascular regenerative therapy.

ABCG1: how critical for cholesterol transport?

In the current issue of Cell Metabolism, Kennedy et al. (2005) have extended our understanding of the ABCG1 transporter. Their studies demonstrate that, at least in macrophages, ABCG1 is responsible for much of the cholesterol efflux that utilizes mature HDL as an acceptor.

The common insertional polymorphism in the APOC1 promoter is associated with serum apolipoprotein C-I levels in Hispanic children.

We examined the effect of APOC1-317insCGTT allele status (HpaI RFLP, deletion [H1] and insertion [H2] alleles) on serum apolipoprotein (apo) C-I level in 362 Hispanic children in the Columbia University BioMarkers Study. The H2 allele was present in 147 subjects (40.6%). Serum apoC-I was 20% lower in the presence of the H2 allele in APOE epsilon3/epsilon3 homozygotes (P=0.003) but did not differ by H2 status in epsilon4 carriers. Insufficient numbers of epsilon2 carriers (N=45) were present for analysis. In multivariate analysis in the epsilon3/epsilon3 context, after adjusting for potential covariate effects and familial aggregation, the mean effect of H2/* versus H1/H1 on apoC-I level, was estimated to be 2.15+/-0.55mg/dl (P<0.0025). Plasma triglyceride level was weakly correlated with serum apoC-I level (Pearson's r=0.17, P<0.001) but was highly correlated with serum apoC-III (Pearson's r=0.74, P<0.0001). Nevertheless, presence of the H2 allele was not significantly associated with serum apoC-III level. Thus, the effect of APOC1 genotype on serum apoC-I level was not due to apoC-I level serving as a surrogate for triglyceride level. The APOC1-317insCGTT allele is a commonly polymorphic genetic marker that is associated with serum apoC-I level in the APOE epsilon3/epsilon3 context. These findings suggest that the mechanism of the previously described association with plasma TG is, at least in part, related to the correlation of the polymorphism with the level of expression of apoC-I.

Weight loss associated with reduced intake of carbohydrate reduces the atherogenicity of LDL in premenopausal women.

The effect of a 3-tier intervention including dietary modifications (ie, moderate energy restriction, decreased carbohydrate, increased protein), increased physical activity, and the use of carnitine as a dietary supplement was evaluated on plasma lipids and the atherogenicity of low-density lipoprotein (LDL) particles in a population of overweight and obese premenopausal (aged 20-45 years) women. Carnitine or a placebo (cellulose) was randomly assigned to the participants using a double-blind design. Carnitine supplementation was postulated to enhance fat oxidation resulting in lower concentrations of plasma triglycerides. Seventy women completed the 10-week protocol, which followed a reduction in their energy intake by 15% and a macronutrient energy distribution of 30% protein, 30% fat, and 40% carbohydrate. In addition, subjects increased the number of steps taken per day by 4500. As no differences were observed between the carnitine and placebo groups in all the measured parameters, all subjects were pooled together for statistical analysis. Participants decreased (P<.01) their caloric intake (between 4132.8 and 7770 kJ) and followed prescribed dietary modifications as assessed by dietary records. The average number of steps increased from 8950+/-3432 to 12764+/-4642 (P<.001). Body weight, plasma total cholesterol, LDL cholesterol, and triglyceride were decreased by 4.5%, 8.0%, 12.3%, and 19.2% (P<.0001), respectively, after the intervention. Likewise, apolipoproteins B and E decreased by 4.5% and 15% (P<.05) after 10 weeks. The LDL mean particle size was increased from 26.74 to 26.86 nm (P<.01), and the percent of the smaller LDL subfraction (P<.05) was decreased by 26.5% (P<.05) after 10 weeks. In addition, LDL lag time increased by 9.3% (P<.01), and LDL conjugated diene formation decreased by 23% (P<.01), indicating that the susceptibility of LDL to oxidation was decreased after the intervention. This study suggests that moderate weight loss (<5% of body weight) associated with reduced caloric intake, lower dietary carbohydrate, and increased physical activity impacts the atherogenicity of LDL.

Sex and hormonal status influence the effects of psyllium on lipoprotein remodeling and composition.

We evaluated the influence of sex and hormonal status on the effect of psyllium (PSY) supplementation on parameters of plasma lipoprotein metabolism. Twenty-four men, 23 premenopausal women, and 21 postmenopausal women (PMW) were randomly assigned to a fiber supplement (15 g PSY/d) or a control, provided via cookies, in a crossover design. Plasma lipids, insulin, apoprotein (apo) B, apo CI, apo CIII, and apo E concentrations and the composition and size of low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) particles were measured at the end of each 30-day treatment period. Compared with control, PSY intake decreased plasma LDL cholesterol by an average of 8% (P <.0001) in men and pre- and PMW. There was a fiber-sex/hormonal status interaction on plasma triglycerides (TG) in the response to the intervention. Men had a 17% decrease in TG, while PMW had a 16% increase with PSY (P <.01). Plasma levels of apo C III, apo E, and insulin followed the same pattern as plasma TG with PSY consumption and decreased by an average of 12% in men (P <.05), but increased by 10% in PMW (P <.05). These reductions in apoproteins suggest an increased peripheral removal of TG in men, perhaps due to decreased insulin resistance, while in PMW, the increases in apoproteins may be related to an enhanced VLDL production. The lack of effect of PSY on VLDL metabolism in premenopausal women could be associated with the protective effect of estrogen. No prominent changes in VLDL and LDL composition were observed with PSY intake other than an increase in LDL phospholipid (P <.05). In addition, compared with men and PMW, the amount of TG per VLDL particle was less, and VLDL diameter was smaller in premenopausal women (P <.05). These results indicate an important role of sex and hormonal status in determining the effects of PSY on lipoprotein metabolism.

Integrated role of two apoliprotein E polymorphisms on apolipoprotein B levels and coronary artery disease in a biethnic population.

BACKGROUND: Apolipoprotein E (ApoE) plays a major role in lipoprotein metabolism and genetic variability of ApoE confers susceptibility to coronary artery disease (CAD). Beyond variability in the coding region, promoter polymorphisms in the ApoE gene impact on ApoE transcription. METHODS: We determined the ApoE - 491 A/T promoter polymorphism, ApoE isoforms, lipid and lipoprotein levels, and CAD risk factors in 313 Caucasians and 215 African Americans. RESULTS: Caucasians had a lower ApoE T allele frequency compared to African Americans (18.1% vs. 32.3%, P < 0.05). Among T/* carriers, ApoB levels were significantly lower in Caucasians, but significantly higher among African Americans, in both cases compared to A/A homozygotes (P = 0.017, and P = 0.012). For a given -491A/T genotype, levels of atherogenic lipoproteins differed across ApoE2/E3/E4 isoforms among African Americans, but not Caucasians, as T/* carriers with ApoE4 had significantly higher ApoB levels compared to T/* carriers with ApoE2 (P = 0.010). Among patients with CAD, Caucasian A/A homozygotes and African American T/* carriers had higher ApoB levels compared to the same genotype without CAD (P = 0.007, P = 0.049, respectively). CONCLUSIONS: We observed an ethnicity-specific variability in ApoB levels across the ApoE - 491 A/T polymorphism and a modulatory impact on this pattern by ApoE2/E3/E4 isoforms.

Effects of apoA-V on HDL and VLDL metabolism in APOC3 transgenic mice.

Apolipoprotein A-V (apoA-V) and apoC-III are exchangeable constituents of VLDL and HDL. ApoA-V counteracts the effect of apoC-III on triglyceride (TG) metabolism with poorly defined mechanisms. To better understand the effects of apoA-V on TG and cholesterol metabolism, we delivered apoA-V cDNA into livers of hypertriglyceridemic APOC3 transgenic mice by adenovirus-mediated gene transfer. In response to hepatic apoA-V production, plasma TG levels were reduced significantly as a result of enhanced VLDL catabolism without alternations in VLDL production. This effect was associated with reduced apoC-III content in VLDL. Increased apoA-V production also resulted in decreased apoC-III and increased apoA-I content in HDL. Furthermore, apoA-V-enriched HDL was associated with enhanced LCAT activity and increased cholesterol efflux. This effect, along with apoE enrichment in HDL, contributed to HDL core expansion and alpha-HDL formation, accounting for significant increases in both the number and size of HDL particles. As a result, apoA-V-treated APOC3 transgenic mice exhibited decreased VLDL-cholesterol and increased HDL-cholesterol levels. ApoA-V-mediated reduction of apoC-III content in VLDL represents an important mechanism by which apoA-V acts to ameliorate hypertriglyceridemia in adult APOC3 transgenic mice. In addition, increased apoA-V levels accounted for cholesterol redistribution from VLDL to larger HDL particles. These data suggest that in addition to its TG-lowering effect, apoA-V plays a significant role in modulating HDL maturation and cholesterol metabolism.

Carbohydrate restriction alters lipoprotein metabolism by modifying VLDL, LDL, and HDL subfraction distribution and size in overweight men.

To determine the effects of carbohydrate restriction (CR) with and without soluble fiber on lipoprotein metabolism, 29 men participated in a 12-wk weight loss intervention. Subjects were matched by age and BMI and randomly assigned to consume 3 g/d of either a soluble fiber supplement (n=14) or placebo (n=15) with a macronutrient energy distribution of approximately 10% carbohydrate, approximately 65% fat, and approximately 25% protein. Because the groups did not differ in any of the variables measured, all data were pooled and comparisons were made between baseline and 12 wk. After 12 wk, subjects had a mean weight loss of 7.5 kg (P<0.001), and abdominal fat was reduced by 20% (P<0.001). Plasma LDL cholesterol and triglycerides (TG) were significantly reduced by 8.9 and 38.6%, respectively. Similarly, apolipoproteins C-I (-13.8%), C-III (-21.2%) and E (-12.5%) were significantly lower after the intervention. In contrast plasma HDL-cholesterol concentrations were increased by 12% (P<0.05). Changes in plasma TG were positively correlated with reductions in large (r=0.615, P<0.01) and medium VLDL particles (r=0.432, P<0.05) and negatively correlated with LDL diameter (r=-0.489, P<0.01). Changes in trunk fat were positively correlated with medium VLDL (r=0.474, P<0.0) and small LDL (r=0.405, P<0.05) and negatively correlated with large HDL (r=-0.556, P<0.01). We conclude that weight loss induced by CR favorably alters the secretion and processing of plasma lipoproteins, rendering VLDL, LDL, and HDL particles associated with decreased risk for atherosclerosis and coronary heart disease.

High intake of saturated fat and early occurrence of specific biomarkers may explain the prevalence of chronic disease in northern Mexico.

To investigate whether the high prevalence of coronary heart disease (CHD) and type II diabetes prevalent in Northern Mexico could be related to the presence at a young age of biomarkers for chronic disease, 25 boys and 29 girls (8-12 y old) from a low socioeconomic group were recruited. Plasma lipids, LDL phenotype, apolipoproteins (apos), glucose, and insulin were evaluated. Analysis of 3-d dietary records indicated the typical intake of this region to be high in total fat (37-43% energy) and saturated fat (11-13% energy). Boys and girls had an average of 6623 +/- 2892 and 6112 +/- 2793 steps/d, respectively, as measured by a pedometer, suggesting a low level of activity. Plasma total and LDL cholesterol (LDL-C) were within the 50th percentile. In contrast, the study population was characterized by having high triglycerides (TG) (95th percentile, 1.25 +/- 0.37 mmol/L in boys and 1.19 +/- 0.38 mmol/L in girls). HDL cholesterol (HDL-C) concentrations were low (25th percentile), 1.22 +/- 0.20 mmol/L in girls and 1.29 +/- 0.20 mmol/L in boys. There was also a high prevalence of the small dense LDL phenotype B (69%), which is associated with increased risk for CHD. These results suggest that the population of children studied may have 2 different components of risk, one being the high-fat diet, which could be associated with the elevated levels of plasma LDL-C present in the adult population. A second component, related to the insulin resistance syndrome, may be principally genetic and associated with the high TG, low HDL, and LDL phenotype B observed in these Mexican children.

Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress.

To evaluate the effects of grape polyphenols on plasma lipids, inflammatory cytokines, and oxidative stress, 24 pre- and 20 postmenopausal women were randomly assigned to consume 36 g of a lyophilized grape powder (LGP) or a placebo for 4 wk. The LGP consisted of 92% carbohydrate and was rich in flavans, anthocyanins, quercetin, myricetin, kaempferol, and resveratrol. After a 3-wk washout period, subjects were assigned to the alternate treatment for an additional 4 wk. The placebo consisted of an equal ratio of fructose and dextrose and was similar in appearance and energy content (554 kJ) to LGP. Plasma triglyceride concentrations were reduced by 15 and 6% in pre- and postmenopausal women, respectively (P < 0.01) after LGP supplementation. In addition, plasma LDL cholesterol and apolipoproteins B and E were lower due to LGP treatment (P < 0.05). Further, cholesterol ester transfer protein activity was decreased by approximately 15% with intake of LGP (P < 0.05). In contrast to these beneficial effects on plasma lipids, LDL oxidation was not modified by LGP treatment. However, whole-body oxidative stress as measured by urinary F(2)-isoprostanes was significantly reduced after LGP supplementation. LGP also decreased the levels of plasma tumor necrosis factor-alpha, which plays a major role in the inflammation process. Through alterations in lipoprotein metabolism, oxidative stress, and inflammatory markers, LGP intake beneficially affected key risk factors for coronary heart disease in both pre- and postmenopausal women.

Overexpression of apoC-I in apoE-null mice: severe hypertriglyceridemia due to inhibition of hepatic lipase.

Apolipoprotein C-I (apoC-I) has been proposed to act primarily via interference with apoE-mediated lipoprotein uptake. To define actions of apoC-I that are independent of apoE, we crossed a moderately overexpressing human apoC-I transgenic, which possesses a minimal phenotype in the WT background, with the apoE-null mouse. Surprisingly, apoE-null/C-I mice showed much more severe hyperlipidemia than apoE-null littermates in both the fasting and non-fasting states, with an almost doubling of cholesterol, primarily in IDL+LDL, and a marked increase in triglycerides; 3-fold in females to 260 +/- 80 mg/dl and 14-fold in males to 1409 +/- 594 mg/dl. HDL lipids were not significantly altered but HDL were apoC-I-enriched and apoA-II-depleted. Production rates of VLDL triglyceride were unchanged as was the clearance of post-lipolysis remnant particles. Plasma post-heparin hepatic lipase and lipoprotein lipase levels were undiminished as was the in vitro hydrolysis of apoC-I transgenic VLDL. However, HDL from apoC-I transgenic mice had a marked inhibitory effect on hepatic lipase activity, as did purified apoC-I. LPL activity was minimally affected. Atherosclerosis assay revealed significantly increased atherosclerosis in apoE-null/C-I mice assessed via the en face assay. Inhibition of hepatic lipase may be an important mechanism of the decrease in lipoprotein clearance mediated by apoC-I.

Overexpression of apoC-III produces lesser hypertriglyceridemia in apoB-48-only gene-targeted mice than in apoB-100-only mice.

The adaptive value of apolipoprotein B-48 (apoB-48), the truncated form of apoB produced by the intestine, in lipid metabolism remains unclear. We crossed human apoC-III transgenic mice with mice expressing either apoB-48 only (apoB48/48) or apoB-100 only (apoB100/100). Cholesterol levels were higher in apoB48/48 mice than in apoB100/100 mice but triglyceride levels were similar. Lipid levels were increased by the apoC-III transgene. However, triglyceride levels were significantly higher in apoB100/100C-III than in apoB48/48C-III mice (895 +/- 395 mg/dl vs. 690 +/- 252 mg/dl; P <0.01), whereas cholesterol levels were higher in the apoB48/48C-III mice than in apoB100/100C-III (144 +/- 35 mg/dl vs. 94 +/- 30 mg/dl; P <0.00001). Triglyceride clearance from VLDL was impaired to a greater extent in apoB100/100C-III vs. apoB100/100 mice than in apoB48/48C-III vs. apoB48/48 mice. Triglyceride secretion rates were no different in apoC-III transgenic mice than in their nontransgenic littermates. ApoB-48 triglyceride-rich lipoproteins were more resistant to the triglyceride-increasing effects of apoC-III but appeared more sensitive to the remnant clearance inhibition. Our findings support a coordinated role for apoB-48 in facilitating the delivery of dietary triglycerides to the periphery. Consistent with such a mechanism, glucose levels were significantly higher in apoB48/48 mice vs. apoB100/100 mice, perhaps on the basis of metabolic competition.

Pre-menopausal women, classified as hypo- or hyperresponders, do not alter their LDL/HDL ratio following a high dietary cholesterol challenge.

BACKGROUND: Cholesterol is the dietary component that has elicited the most public interest in conjunction with coronary heart disease. However, the impact of excess dietary cholesterol intake on plasma cholesterol levels cannot be accurately predicted; therefore, its role in disease progression is not straightforward. Individual response variation can be due to factors such as ethnicity, hormonal status, obesity and genetic predisposition. OBJECTIVE: The purpose of this study was to evaluate the differences that occur within the plasma compartment of normolipidemic pre-menopausal women, classified based on their response to a high dietary cholesterol challenge. DESIGN: We recruited 51 pre-menopausal women (29 Caucasian and 22 of Hispanic origin) aged 18 to 49 years with initial plasma cholesterol concentrations ranging from 3.62 to 5.17 mmol/L. Using a cross-over research design, women were randomly allocated to an egg (640 mg additional dietary cholesterol per day) or placebo group (0 mg additional dietary cholesterol per day) initially, and the two 30 day periods were separated by a three-week washout. RESULTS: An initial evaluation of the ethnicity effects revealed elevations in both plasma LDL-C (p < 0.0001) and HDL-C (p < 0.001) concentrations in both Hispanics and Caucasians during the high dietary cholesterol period. However, these increases were not accompanied by a change in the LDL/HDL ratio. Subjects were then classified as hypo- (< 0.05 mmol/L increase in total plasma cholesterol per each additional 100 mg of dietary cholesterol consumed per day) or hyper-responders (> or =0.06 mmol/L increase in total blood cholesterol per each additional 100 mg of dietary cholesterol consumed per day), based on their reaction to the additional dietary cholesterol provided. Hypo-responders did not experience an increase in LDL-C or HDL-C during the egg period, while both lipoproteins were elevated in hyper-responders. However, the LDL/HDL ratio, an important parameter of coronary heart disease risk, was maintained for all subjects during the egg period independent of response. Furthermore, hyper-responders had higher concentrations of apo C-III (p < 0.001), apo B (p < 0.001) and cholesterol ester transfer protein (CETP) (p < 0.05) during this period. CONCLUSION: These data revealed that excess dietary cholesterol does not increase the risk of developing an atherogenic lipoprotein profile in pre-menopausal women, regardless of their response classification. Although the addition of 640 mg of cholesterol to the diet did result in an increase in plasma cholesterol in hyperresponders, the LDL/HDL ratio was maintained. This result, accompanied by increases in CETP activity, leads to the speculation that hyper-responders may process the excess cholesterol in the plasma compartment through an enhancement of the reverse cholesterol transport pathway. With this mechanism identified, further measurement of additional parameters is needed to verify this conclusion.

Men classified as hypo- or hyperresponders to dietary cholesterol feeding exhibit differences in lipoprotein metabolism.

The purpose of this study was to evaluate the differences that occur within the plasma compartment of normolipidemic men, classified on the basis of their response to prolonged consumption of additional dietary cholesterol. Using a crossover design, 40 men aged 18-57 y were randomly allocated to an egg (640 mg/d additional dietary cholesterol) or placebo group (0 mg/d additional dietary cholesterol), for two 30-d periods, which were separated by a 3-wk washout period. Subjects were classified as hypo- [increase in plasma total cholesterol (TC) of <0.05 mmol/L for each additional 100 mg of dietary cholesterol consumed] or hyperresponders (increase in TC of > or =0.06 mmol/L for each additional 100 mg of dietary cholesterol consumed) on the basis of their plasma reaction to the additional dietary cholesterol provided. Male hyporesponders did not experience an increase in LDL cholesterol (LDL-C) or HDL cholesterol (HDL-C) during the egg period, whereas both lipoproteins were significantly (P < 0.0001 and P < 0.05, respectively) elevated in hyperresponders. Although the LDL/HDL ratio was increased in male hyperresponders after the high cholesterol period, the mean increase experienced by this population was still within National Cholesterol Education Program guidelines. Furthermore, male hyperresponders had higher lecithin cholesterol acyltransferase (P < 0.05) and cholesteryl ester transfer protein (P < 0.05) activities during the egg period, which suggests an increase in reverse cholesterol transport. These data suggest that additional dietary cholesterol does not increase the risk of developing an atherogenic lipoprotein profile in healthy men, regardless of their response classification.

Fatty acids increase presenilin-1 levels and [gamma]-secretase activity in PSwt-1 cells.

Presenilin-1 (PS1) is an important determinant of the gamma-secretase activity necessary for the generation of beta-amyloid (Abeta), likely the central pathogenic molecule in Alzheimer's disease. Most presenilin is rapidly degraded, and determinants of the level of the active cleaved form are unknown. We examined the influence of fatty acids on PS1 levels and gamma-secretase activity using stably transfected CHO cells that express human PS1 and the human amyloid precursor protein. Cells cultured with 0.4 mM oleic acid (OA), with 0.1 mM linoleic acid, or with a triglyceride emulsion expressed increased PS1 and Abeta. This effect was independent of any secondary increase in cellular cholesterol. Cells cultured in 0.4 mM OA also exhibited significantly increased gamma-secretase activity. PS1 mRNA levels were unchanged, and pulse-chase experiments indicated that OA slowed presenilin holoprotein degradation. Nontransfected human neuroblastoma cells also showed increased presenilin when cultured in 0.4 mM OA. Lipids may be important biological determinants of PS1 level and gamma-secretase activity.

Waist circumference is a better predictor than body mass index of coronary heart disease risk in overweight premenopausal women.

Waist circumference (WC) has been postulated to have stronger associations with biomarkers of coronary heart disease (CHD) than BMI. In this study, we measured the level of activity by determining steps walked per day and select biomarkers for CHD risk in 80 overweight or obese (BMI = 25-37 kg/m(2)) premenopausal women to evaluate whether these biomarkers are associated with WC or BMI. The plasma biomarkers measured, using samples from women who had fasted for 12 h, were lipids, apolipoproteins (apo), LDL peak diameter, LDL susceptibility to oxidation, glucose, leptin, and insulin. We identified subjects with the metabolic syndrome (11%) and insulin resistance (30%) to further distinguish subjects at increased risk for CHD. Both BMI and WC were positively correlated with insulin (r = 0.376 and 0.384, respectively, P < 0.05) and leptin (r = 0.614 and 0.512, respectively, P < 0.01) and negatively correlated with the number of steps taken per day (r = -0.245 and -0.354, respectively, P < 0.05). In addition, WC had positive correlations with diastolic blood pressure (r = 0.250, P < 0.05), plasma triglycerides (TG) (r = 0.270, P < 0.05), and apo C-III (r = 0.240, P < 0.05). Women with BMI > or = 30 kg/m(2) or WC > 88 cm had significantly higher leptin concentrations than women having a BMI < 30 kg/m(2) or a WC < or = 88 cm; women with WC > 88 cm also had higher diastolic pressure (P < 0.05), and higher plasma TG (P < 0.05) and apo C-III (P < 0.05) concentrations than those with WC < or = 88. In addition, subjects with the higher WC walked an average of 1000 fewer steps per day (P < 0.01). These results suggest that WC is a stronger predictor of CHD risk than BMI and is more closely associated with the level of exercise in premenopausal women.