Search for an optimal atherogenic lipid risk profile: from the Framingham Study

Recent guidelines have targeted low-density lipoprotein (LDL) cholesterol for treatment of dyslipidemia. A lack of clear demarcation of potential coronary heart disease (CHD) cases solely on the basis of LDL cholesterol indicates the need to consider the dyslipidemic risk in the context of a lipid and risk factor profile. We prospectively examined the influence of individual lipids and their ratios on 20-year CHD development in 2,439 men and 2,812 women participating in the Framingham Offspring Study. The influence of the total/high-density (HDL) cholesterol ratio on CHD risk was examined in tertiles of LDL cholesterol and total cholesterol levels. During the 20-year period, 566 CHD events occurred in men and 327 events in women. The CHD risk increased stepwise two- to threefold in men and women from the first to third tertile of total/HDL cholesterol ratio, irrespective of the level of total or LDL cholesterol level. In men, the LDL cholesterol level reflected the lowest risk factor adjusted quintile 5 to quintile 1 relative risk (1.85), and the total/HDL cholesterol ratio predicted the greatest risk (relative risk 2.9). In women, LDL cholesterol imparted the highest risk of the individual lipids (relative risk 3.9), and this was not exceeded by the lipid ratio (relative risk 3.8). In conclusion, the levels of components of the total/HDL cholesterol ratio have little influence on its prediction of CHD. In men, elevated LDL need not be treated aggressively if the total/HDL cholesterol ratio is low. Conversely, modest elevations of LDL may warrant more aggressive treatment if the ratio is high. In women, the ratio is also a good CHD predictor, but a combination of a high ratio accompanied by high LDL cholesterol may warrant more aggressive therapy.