Small, dense, low-density lipoprotein cholesterol levels in patients with coronary heart disease: results from framingham offspring study

Abstract

Elevated plasma small dense low-density lipoprotein cholesterol (sdLDL-C) levels have been associated with an increased risk of coronary heart disease (CHD). Our aim was to evaluate a new automated assay for direct total LDL-C and sdLDLC in patients with CHD and compare them with controls. Study subjects were: 1508 male and 1680 female participants in cycle 6 (1995-1998) of the Framingham Offspring Study, which included 173 male and 74 female patients with CHD. Fasting plasma samples stored at -80 degrees were used. The LDL-C and sdLDL-C assay (Denka-Seiken Co.) had intra- and inter-assay coefficients of variation (CV) of < 5%. The percentage of CHD subjects on cholesterol-lowering medications was significantly (p<0.0001) higher than in controls of each gender (46.8% vs 11.4% in men, and 35.1% vs 8.8% in women). However LDL-C levels in female CHD patients were similar to those in controls (136.5(plus or minus)33.7mg/dL vs 133.9(plus or minus)35.8mg/dL, p=0.543), but were significantly (p<0.0001) lower (in male CHD patients than in controls (124.7(plus or minus)31.2mg/dL vs 135.6(plus or minus)32.6mg/dL, p<0.0001). Mean sdLDL-C levels in male CHD patients were similar to those in controls (32.2(plus or minus)15.1mg/dL vs 32.4(plus or minus)15.9mg/dL, p=0.609), while in female CHD patients they were significantly higher than in controls (32.0(plus or minus)17.1mg/dL vs 26.2(plus or minus)16.2mg/dL, p=0.0015). Mean sdLDLC per LDLC ratios were significantly (p<0.0001) higher in CHD patients than those in controls of each gender (26.1 (plus or minus)10.0% vs 23.7(plus or minus)9.5%, p=0.0019 in men and 23.6(plus or minus)12.8% vs 19.0(plus or minus)8.9%, p= 0.0003 in women). Mean high-density lipoprotein (HDL) cholesterol levels were also significantly lower in CHD patients than in controls in men (p<0.0001) but not in women (p= 0.0725). In conclusion, our data indicate that despite significantly higher use of cholesterol-lowering medications, female CHD patients did not have lower LDL-C levels, and had higher sdLDL-C levels than controls, while for male CHD patients LDL-C levels were lower, but sdLDL-C levels were not. Our findings indicate that despite greater cholesterol lowering therapy, CHD patients still have a lot of residual risk, and that these high-through-put direct assays for LDL-C and sdLDL-C hold considerable promise for CHD risk assessment.