Age-related increase of pulse pressure and gene polymorphisms in essential hypertension: a preliminary study

Abstract

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. IntroductionIncreased brachial pulse pressure (PP) is an independent predictor of CV risk, mainly for myocardial infarction.1 The value of PP is simultaneously influenced by an increase in systolic blood pressure (SBP) and a decrease of diastolic BP (DBP). In large populations over 50 years of age, cross-sectional and longitudinal studies have shown that cardiovascular (CV) mortality is not only positively correlated to the level of SBP, 2-4 but also that, at any given SBP value, CV mortality is higher when DBP is lower.4 PP is known to be influenced by three main haemodynamic mechanisms: the degree of ventricular ejection, the level of arterial stiffness and the pattern of wave reflections. 5 The two latter, but not ventricular ejection, have been shown to be significant and independent markers of CV risk.

Vascular Stiffness and Genetic Variation at the Endothelial Nitric Oxide Synthase Locus

“…13 Another study in hypertensive individuals found a possible relation between the increase in pulse pressure with advancing age and the G298T polymorphism in women only. 6 A recent study evaluated potential relations between the Glu298Asp polymorphism and carotid artery stiffness in a small sample of black and white young adults and found an association between presence of the T-allele (GT or TT) of the G894T polymorphism and lower carotid artery stiffness in blacks. 14 This latter study parallels our finding that the T allele seems to offer a protective effect on measures of vascular function.…”

Nitric Oxide and the Regulation of Large Artery Stiffness

“…In the largest study, Lacolley et al 29 were unable to demonstrate an effect of either of the 2 eNOS polymorphisms on PWV in normotensive or hypertensive subjects. Conversely, in a smaller study, Mourad et al 30 demonstrated that the presence of the G 298 T polymorphism was associated with a steeper relationship between age and PWV, but only in women.…”

Angiotensin II type 1 receptor polymorphisms and susceptibility to hypertension: A HuGE review

“…109,119 -121,124 Neither salt sensitivity 125,126 nor renal sodium handling, 127 seems to vary according to rs5186 genotype. Studies of arterial stiffness as indicated by pulse wave velocity 110,128 or pulse pressure 129 have been conflicting.…”