ARS | Publication request: Small dense low density lipoprotein cholesterol and coronary heart disease: results from the Framingham Offspring Study

Submitted to: Clinical Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 25, 2010
Publication Date: April 29, 2010
Citation: Ai, M., Otokozawa, S., Asztalos, B.F., Ito, Y., Nakajima, K., White, C.C., Cupples, A.L., Wilson, P.W., Schaefer, E. 2010. Small dense low density lipoprotein cholesterol and coronary heart disease: results from the Framingham Offspring Study. Clinical Chemistry. 56(6):1-10.

Interpretive Summary: Much of the cholesterol in blood is carried on low density lipoproteins or LDL. High levels of LDL cholesterol (LDL-C above 160 mg/dl) have been shown to result in significant risk for coronary heart disease (CHD), a leading cause of death and disability in our society, especially in the elderly. It is known that LDL can be divided into large buoyant LDL and small dense LDL. We tested a newly developed assay for small dense LDL cholesterol or sdLDL-C in plasma samples obtained from participants of the Framingham Offspring Study, and found that men with CHD had similar sdLDL C values to controls despite four times the higher use of cholesterol lowering medications, and significantly lower total LDL C. In women with CHD, the use of cholesterol lowering medication was about four times higher than in controls, but LDL-C values were similar to controls, and sdLDL- C were significantly higher than controls suggesting that current treatment is inadequate to lower risk of further CHD events in those who already have the disease. This information is useful to doctors, patients, and scientists working in the field of heart disease prevention.

Technical Abstract: We sought to establish reference values for a new direct assay for small dense LDL cholesterol (sdLDL-C) and to measure sdLDL-C concentrations in patients with established coronary heart disease (CHD) vs controls. Direct LDL-C and sdLDL-C were measured in samples from 3188 male and female participants of the Framingham Offspring Study, including 173 men and 74 women with CHD. Postmenopausal status and male sex were associated with higher sdLDL-C concentrations (P_0.0001). Cholesterol-lowering medication use was more frequent (P_0.0001) in CHD patients than in controls (46.8% vs 11.4% in men; 35.1% vs 8.8% in women). In men, mean LDL-C was lower in CHD than in controls (3.22 vs 3.51 mmol/L, P_0.0001), whereas mean sdLDL-C concentrations were similar (0.83 vs 0.84 mmol/L, P_0.609). In women, mean LDL-C was similar in CHD and controls (3.53 vs 3.46 mmol/L, P_0.543), but mean sdLDL-C was higher (0.83 vs 0.68 mmol/L, P_0.0015). The mean percentage of LDL-C as sdLDL-C was higher in both men and women with CHD than controls (P_0.01). Increased LDL-C and sdLDL-C were found in 10.4% and 22.0% of men and in 24.3% and 27.8% of women with CHD, respectively. Despite 4-fold the greater cholesterol-lowering therapy use, CHD patients had mean LDL-C concentrations above the LDL-C goal of 2.6 mmol/L (100 mg/dL). Although women with CHD had higher sdLDL-C concentrations than controls, this difference was not seen in men. These findings may explain some of the high residual risk of future CHD events in CHD patients.