Response to Letter by Tsuda
We would like to thank Dr Tsuda for his interest in our recent publication which showed a difference in the effect of preadmission statins on ischemic stroke outcomes between blacks and whites.1 Dr Tsuda provides a good summary for the role that statins may play in affecting NO-mediated endothelial and vascular function. Dr Tsuda goes on to speculate that racial differences in NO production might explain, in part, the differential effect of statins observed in our study and enquires about the endothelial function in our study subjects. Unfortunately, we did not obtain measures of endothelial function within our hospital-based stroke registry and so are unable to determine whether endothelial function varied by race.
There is increasing understanding of the molecular and genetic basis for ethnic differences in drug metabolism and therapeutic effects.2 Clearly, further research on the underlying biological mechanisms for racial differences in statin effects—both the direct-lipid related and pleiotropic effects—is a fertile area of study. For example, Krauss et al3 recently identified a race-by-genotype interaction involving 2 polymorphisms in the gene encoding 3-hydroxyl-3-methylglutaryl-3 coenzyme A reductase (HMGCR). Blacks who carried the H2 and H7 alleles had a poorer LDL-C–lowering response to simvastatin than noncarriers. Such studies make an important contribution to determining the true clinical significance of the differences we observed in stroke outcomes.
Reeves MJ, Gargano JW, Luo Z, Mullard AJ, Jacobs BS, Majid A. Effect of pretreatment with statins on ischemic stroke outcomes. Stroke. 2008; 39: 1779–1785.
Krauss RM, Mangravite LM, Smith JD, Medina MW, Wang D, Guo X, Rieder MJ, Simon JA, Hulley SB, Waters D, Saad M, Williams PT, Taylor KD, Yang H, Nickerson DA, Rotter JI. Variation in the 3-hydroxyl-3-methylglutaryl coenzyme a reductase gene is associated with racial differences in low-density lipoprotein cholesterol response to simvastatin treatment. Circulation. 2008; 117: 1537–1544.