Age-related increase of pulse pressure and gene polymorphisms in essential hypertension: a preliminary study.
Genes may modulate the changes of blood pressure (BP) with age; this possibility has never been studied for the age-related increase of pulse pressure (PP), although in older populations, PP is considered the stronger mechanical factor predicting cardiovascular mortality. In humans, the presence of the mutant allele C of the angiotensin II (Ang II) AT(1)-receptor or of the mutant allele T of the eNOS G(298) T gene polymorphisms is associated with enhanced contractile properties of conduit arteries in response to vasoconstrictive agents. In this study, we evaluated, in subjects with untreated essential hypertension, whether the presence of these mutant alleles or their combination might influence the age-related increase of PP. Three main findings emerged from the study and were particularly observed in women: 1) the presence of the C and/or of the T mutant alleles or their combination were associated with a steeper slope of the age versus PP curve, compared with subjects without the mutant allele; 2) the slope was more significantly enhanced when the two mutant alleles were associated in the same genotype; and 3) no comparable age- and gender-related changes in systolic, diastolic or mean BP were found according to this genetic classification. In subjects with essential hypertension, genes may modulate the age-mediated increase of PP. This finding gives new insights in the interactions between genes, mechanical factors and cardiovascular risk.
Mourad
Jean-Jacques
JJ
Department of Internal Medicine and INSERM U337, Broussais Hospital, Paris, France.
Ducailar
Guilhem
G
Rudnicki
Annie
A
Lajemi
Malika
M
Mimran
Albert
A
Safar
Michel E
ME
D000375:Aging / Q000235:genetics*; D000483:Alleles; D001794:Blood Pressure / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D010865:Pilot Projects; D017354:Point Mutation; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics*
D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III