Aldosterone synthase gene polymorphism, stroke volume and age-related changes in aortic pulse wave velocity in subjects with hypertension.
OBJECTIVE
In rats, chronic aldosterone administration with high diet intake increases aortic stiffness independent of mechanical stress. In hypertensive humans, enhanced plasma aldosterone and arterial stiffness are positively associated. Whether the aldosterone synthase gene polymorphism (ASGP) CYP11B2 influences the age-related changes in blood pressure (BP) and arterial stiffness in hypertensive subjects has never been investigated.


METHODS
In 425 untreated hypertensive men and women, ASGP was evaluated together with aortic pulse wave velocity (PWV). In 191 of these subjects, cardiac haemodynamics were measured using echo-Doppler techniques.


RESULTS
In the overall population, independently of sex, the TC and CC genotypes of ASPG had significantly higher heart rate (HR) (P < 0.05) and lower stroke index (P < 0.01) than the TT genotype, but did not affect BP. In men, the adjusted slopes of the curves relating age to PWV and HR were significantly steeper (P = 0.04; P = 0.002) for the TC and CC than for the TT genotype. Such gene-related differences were not observed for the age-systolic BP relationship.


CONCLUSIONS
In hypertensive subjects, the TC and CC genotypes of ASGP involve, by comparison with the TT genotype, significantly higher HR and reduced stroke index. In men with the C allele, the reduced stroke index (cardiac effect) compensates for the steep increase of PWV with age (arterial effect), thus modulating the cardiovascular phenotype and explaining the lack of increased incidence of systolic hypertension. The results are consistent with a local role of endogenous aldosterone on both heart and vessels.
Safar
Michel E
ME
Diagnosis Centre, Hôtel-Dieu Hospital, Paris, France. michel.safar@htd.ap-hop-paris.fr
Cattan
Valérie
V
Lacolley
Patrick
P
Nzietchueng
Robert
R
Labat
Carlos
C
Lajemi
Malika
M
de Luca
Nicolas
N
Bénétos
Athanase
A
D000328:Adult; D000367:Age Factors; D000368:Aged; D001011:Aorta / Q000502:physiology; D001783:Blood Flow Velocity; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006339:Heart Rate; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011673:Pulsatile Flow; D013318:Stroke Volume
D019405:Cytochrome P-450 CYP11B2