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—We previously reported that high density lipoprotein cholesterol (HDL-C) decreases more in hypercholesterolemic (HC) women than in HC men ingesting an National Cholesterol Education Program (NCEP) Step II diet for 6 months. We examined these subjects to determine whether the differential HDL-C reduction persists after 12 months and whether it is associated with decreased HDL2 -C and apoprotein A-I. Subjects were screened from an industrial workforce and were defined as HC if 2 low density lipoprotein cholesterol measurements were ≥75th percentile or defined as combined hyperlipidemic (CHL) if triglycerides were also ≥75th percentile. The subjects were then taught the NCEP Step II diet in 8 weekly classes and counseled quarterly. Seventy-three HC and 92 CHL women (mean ages 43 and 44 years, respectively) and 112 HC and 106 CHL men (ages 45 and 41 years, respectively) were studied. All groups reported similar total fat (24% to 26% kcal) and saturated fat (7.1% to 7.9% kcal) intakes at 1 year. HDL-C decreased 7.6% in HC women (P &lt;0.01), exceeding the nonsignificant 1.3% decrease in HC men (P =0.000). HDL2 -C decreased 16.7% in HC women (P &lt;0.01) compared with the nonsignificant 0.5% increase in HC men (P =0.000). In CHL women and men, HDL-C decreased 3.5% and 3.9% (bothP &lt;0.01); HDL2 -C decreased more in women (7.1%,P &lt;0.01) than in men (4.3%, a nonsignificant difference). Apoprotein A-I decreased significantly (5.3%,P &lt;0.01) in HC women only. Plasma triglycerides were unchanged. Low density lipoprotein cholesterol and weight changes were not different among the 4 groups. HDL-C, HDL2 -C, and apoprotein A-I levels decreased more in HC women than in HC men after following the NCEP Step II diet for 1 year, continuing a trend observed with HDL-C at 6 months. The total HDL-C and HDL2 -C reductions narrow the baseline differences between men and women by 50%. Whether this reduction impacts women’s protection from cardiovascular disease deserves future study. Nonetheless, the results point to sex-based differences in intrahepatic glucose and fatty acid metabolism linked to alterations in HDL formation and removal.

arteriosclerosis, thrombosis, and vascular biology

Differential Effect of National Cholesterol Education Program (NCEP) Step II Diet on HDL Cholesterol, Its Subfractions, and Apoprotein A-I Levels in Hypercholesterolemic Women and Men After 1 Year