Dear Dr Topol,

As you have been hinting for a long time, the concept of Genotypic Autonomic Modulation accounts for various observations in clinical cardiovascular science including prognosis(1) and drug response. Evidence is apparently accumulating at a fast rate and the current paper is yet another breakthrough. As you would remember, Zaroff et al presented strong prospective evidence of adrenoceptor modulation. They found that specific combinations of adrenoceptor single nucleotide polymorphism (SNP) genotypes can influence the degree of LV dysfunction, myocardial injury and regional WMAs in patients with subarachnoid hemorrhage associated cardiomyopathy.(3,4) Greater clinical research may be promoted targeting an invidualized constituition rather than the usual and somewhat irrational mass-medicine, for the greater good. 

References: 

1. Heckbert SR, Hindorff LA, Edwards KL, Psaty BM, Lumley T, Siscovick DS, Tang Z, Durda JP, Kronmal RA, Tracy RP. ß2-adrenergic receptor polymorphisms and risk of incident cardiovascular events in the elderly. Circulation 2003; 107: 2021–2024
 

2. Zaroff JG, Pawlikowska L, Miss JC, Yarlagadda S, Ha C, Achrol A, Kwok PY, McCulloch CE, Lawton MT, Ko N, Smith W, Young WL. Adrenoceptor polymorphisms and the risk of cardiac injury and dysfunction after subarachnoid hemorrhage. Stroke 2006;37:1680-5.

3. Naidech AM. Adrenoreceptor polymorphisms and subarachnoid hemorrhage. Stroke 2006;37:1635.

Hi Dr. Topol, This is a fascinating study that has captured the imagination of much of the cardiovascular community and provides real insights into the future of personal medicine, albeit on a larger scale than the individual patient. Many would argue that the A-HEFT trial was the first study with clinical end-points highlighting the importance of self-reported ethnicity on outcomes. It seems, however, that the first such study may have the BEST trial with bucindolol, in which a sub-analysis (not pre-planned), revealed that bucindolol was not helpful in African-American patients mwith HF. Could this effect have been due to the "genetic beta-blockade"? This is exciting because a RCT in this field with patients of AA descent vs. non-AA descent would be promising...Your thoughts?

Regards,

 Ashish Aneja MD

May also explain why blacks seem to get less benefit in BP lowering with beta blockers than whites