To the Editor: The authors of ALLHAT-LLT1 explored several possible reasons for the failure
of lipid-lowering therapy to translate into any change in the risk of CHD.
It is possible, however, that there may be a threshold value of the total
cholesterol/HDL-C (high-density lipoprotein cholesterol) ratio, below which
further lowering will not produce any significant reduction in CHD.2 The average baseline ratios in several studies
were greater than 5, which may be a critical value. Following treatment there
was a significant reduction in CHD, especially in those studies that reported
a ratio less than 5. Particularly noteworthy were the VA-HIT results, in which
gemfibrozil produced a 24% decrease in CHD yet had no effect on LDL-C levels.3 The baseline ratio in ALLHAT-LLT was 4.67, so it
is not surprising that further lowering of the ratio offered no CHD benefit.
In the BIP study,4 a 41% reduction in CHD
occurred in patients with a baseline HDL-C level lower than 35 mg/dL (0.91
mmol/L) and virtually all of the 24% CHD benefit in the PROSPER study occurred
in patients in the lowest HDL tertile.5 Patients
with the lowest HDL-C levels would undoubtedly have the highest ratio at baseline
and could most likely benefit from treatment.
Lipid-Lowering Therapy and Risk of Coronary Events. JAMA. 2003;289(16):2070. doi:10.1001/jama.289.16.2071-b