HYPERTENSIVE CARDIAC-HYPERTROPHY - IS GENETIC VARIANCE THE MISSING LINK

1 Hypertensive cardiac hypertrophy is a major independent predictor of adverse cardiovascular events, In man the cardiac response to increas ed afterload is very variable, even when ambulatory blood pressure mon itoring is used. Analysis of breeding experiments using normotensive a nd hypertensive rat strains, human twin studies and other data indicat e that genetic factors play a significant role in regulating cardiac m ass; in other words, a large component of total variability is account ed for by genetic variance. 2 The observation that some patients with only mild-to-moderate hypertension exhibit gross left ventricular hype rtrophy (LVH) similar to the inherited hypertrophic cardiomyopathies s uch as familial hypertrophic cardiomyopathy (FHC) and Friedreich's ata xia (FA) has prompted us to investigate the hypothesis that genetic fa ctors associated with excessive myocardial hypertrophy, viz, mutations in FHC and FA genes alter the hypertrophic response of the heart to p ressure overload. Here we review briefly three lines of study: (i) ass ociation analysis to test whether the allele frequencies differ in hyp ertensive patients with or without left ventricular hypertrophy; (ii) characterization of the cardiac manifestations of FA to understand the mechanism by which the heart is affected in a disease associated with pathology in a subgroup of neurons, and (iii) creation of transgenic models to facilitate the investigation of the interaction between hype rtrophic stimuli and underlying genetic predisposition. 3 Information on the nature of the cardiac-mass-modifying genes involved may be usef ul not only for selecting high risk patients in strategies aimed at pr eventing the development of LVH, but also in opening new avenues of re search on the reprogramming of cardiac myocytes to encourage them to h ypertrophy in situations where cardiac muscle has been damaged or is h ypoplastic.