This study examines the role of obesity and body fat distribution (ie, waist-to-hip ratio [WHR]) on cardiovascular disease (CVD) risk factors in 50 nondiabetic, obese (body mass index [BMI], 31±2 kg/m 2 , mean±SD), 45±10-year-old women. The data obtained at baseline and after weight loss were analyzed after dividing subjects by WHR into upper-body (WHR >0.80) and lower-body (WHR £0.80) groups and by median-split BMI into more obese (BMI s31) and less obese (BMI <31) groups. At baseline, the upper-body obese women, when compared with lower-body obese women, had higher plasma triglycerides (TGs) (175±85 versus 111±47 mg/dL, respectively; P<.00l) and lower high-density lipoprotein cholesterol (HDL-C) (44±10 versus 54±11, respectively, P<.01) but similar total and low-density lipoprotein cholesterol levels and blood pressure. There were no significant differences in these CVD risk factors at baseline by BMI split Although weight loss (-9±5 kg) lowered blood pressure and TGs irrespective of WHR or BMI, only upper-body obese women raised HDL-C. Moreover, the magnitude of the changes was greatest in women with an upper-body fat distribution. In women with WHR >0.80, HDL-C increased by 11%, to 49 mg/dL (P<.001), and TGs decreased by 24%, to 134 mg/dL (P<.001). The increase in HDL-C with weight loss was predicted in a linear model by the initial WHR, whereas the reductions in TGs and blood pressure were predicted by the change in body weight Thus, an upper-body fat distribution in women worsens the lipid risk factors for CVD posed by obesity, and weight loss is an effective intervention to improve lipid profiles in these women. Although weight loss improved CVD risk factors regardless of BMI or WHR, the magnitude of the increase in plasma HDL-C and decrease in TGs in women with an upper-body fat distribution suggests that weight loss in these women has the greatest potentiality of reducing their risk factors for CVD. {ArterioscUr Thromb. 1993;13:1487-1494 KEY WORDS • obesity • body fat distribution • weight loss • cardiovascular disease risk factors • women E arly descriptions, which characterized men as having an abdominal body fat distribution and women as having a predominantly gluteofemoral body fat distribution, 1 -2 confirmed gender differences in the relation of obesity to cardiovascular disease (CVD). Intermediary mechanisms by which hyperlipidemia, hypertension, diabetes, and hyperinsulinemia increase risk for CVD seem linked to an abdominal distribution of body fat rather than obesity. 35 These investigations underscore the importance of the distribution of body fat as a critical risk factor, irrespective of gender.In women as well as men an upper-body distribution of fat, indexed as waist-to-hip ratio (WHR), is an independent risk factor for ischemic heart disease, diabetes, stroke, and premature mortality.6 -8 Nevertheless, the strong relations between WHR and degree of obesity make it difficult to ascertain whether obesity per se or the distribution of body fat is the major determinant affecting risk factor...