Cardiac aldosterone in subjects with hypertrophic cardiomyopathy.
Left ventricular (LV) hypertrophy in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors. Here, we determined whether aldosterone modulates hypertrophy in HCM. Cardiac and/or plasma aldosterone were measured in organ donors and HCM patients. The effect of the aldosterone synthase ( CYP11B2 ) C-344T polymorphism on LV mass index (LVMI) and interventricular septum thickness (IVS) was determined in 79 genetically independent subjects with HCM. Aldosterone in HCM hearts and plasma was similar to that in normal hearts and plasma. In HCM women, no associations between CYP11B2 genotype and any of the measured parameters were observed, whereas in HCM men, LVMI increased with the presence of the T allele. Similar T allele-related increases were observed for IVS. Multiple regression analysis revealed that the T allele-related effect on IVS occurred independently of renin, the ACE I/D polymorphism, the AT1-receptor A/C(1166)polymorphism and the AT2-receptor A/C(3123) polymorphism. In conclusion, circulating and cardiac aldosterone are normal in HCM, thereby arguing against selectively increased cardiac aldosterone production in HCM. Thus, the association between the CYP11B2 C-344T polymorphism and hypertrophy in HCM most likely relates to the T allele-related increases in circulating aldosterone. This finding raises the need for studies determining the benefit of aldosterone blockade in HCM.
Chai
Wenxia
W
Department of Pharmacology, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Hoedemaekers
Yvonne
Y
van Schaik
Ron H N
RH
van Fessem
Marianne
M
Garrelds
Ingrid M
IM
Saris
Jasper J
JJ
Dooijes
Dennis
D
ten Cate
Folkert J
FJ
Kofflard
Marcel M J
MM
Danser
A H Jan
AH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000450:Aldosterone / Q000378:metabolism*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics / Q000378:metabolism*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide
D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2