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Introduction: Although recently a matter of epidemiologic controversy, sodium overload and its interaction with genetic factors predispose to hypertension and related target organ complications., Methods: In 131 (66 male) treated hypertensives, we measured peripheral and central arterial pressures and pulse wave augmentation indexes (AIx(P), AIx(C1), AIx(C2)), pulse wave velocity (PWV), daily urinary sodium excretion and did genetic studies of AGTR1 A1166C and AGTR2 G1675A polymorphisms. Proximal (FE(Li)) and distal (FDR(Na)) sodium reabsorption measurements were performed using endogenous lithium clearance., Results: In men, we found interaction between FDR(Na) and AGTR2 G1675A polymorphism with respect to AIx(C1) (p(INT)=0.01), AIx(C2) (p(INT)=0.05) and AIx(P) (p(INT)=0.006). Arterial stiffness increased with higher sodium reabsorption in the distal tubule, in the presence of AGTR2 G allele with the opposite tendency in A allele carriers. In the subgroup with FDR(Na) below median, as compared to those with FDR(Na) above median, the AIx(C1) (139.6±3.8 vs 159.1±5.7%; p=0.009), AIx(C2) (26.3±1.8 vs 33.3±1.7%; p=0.016) and AIx(P) (83.4±2.5 vs 96.5±2.6%; p<0.0001) were lower, in the G allele carrying men and GG homozygous women., Conclusions: The relation between sodium reabsorption in the distal tubule and the development of arterial stiffness depends on the AGTR2 G1675A polymorphism in blood pressure independent fashion., (© The Author(s) 2016.)

Background: We investigated the heritability and familial aggregation of various indexes of arterial stiffness and wave reflection and we partitioned the phenotypic correlation between these traits into shared genetic and environmental components., Methods: Using a family-based population sample, we recruited 204 parents (mean age, 51.7 years) and 290 offspring (29.4 years) from the population in Cracow, Poland (62 families), Hechtel-Eksel, Belgium (36), and Pilsen, the Czech Republic (50). We measured peripheral pulse pressure (PPp) sphygmomanometrically at the brachial artery; central pulse pressure (PPc), the peripheral augmentation indexes (PAIxs) and central augmentation indexes (CAIxs) by applanation tonometry at the radial artery; and aortic pulse wave velocity (PWV) by tonometry or ultrasound. In multivariate-adjusted analyses, we used the ASSOC and PROC GENMOD procedures as implemented in SAGE and SAS, respectively., Results: We found significant heritability for PAIx, CAIx, PPc and mean arterial pressure ranging from 0.37 to 0.41; P < or = 0.0001. The method of intrafamilial concordance confirmed these results; intrafamilial correlation coefficients were significant for all arterial indexes (r > or = 0.12; P < or = 0.02) with the exception of PPc (r = -0.007; P = 0.90) in parent-offspring pairs. The sib-sib correlations were also significant for CAIx (r = 0.22; P = 0.001). The genetic correlation between PWV and the other arterial indexes were significant (rhoG > or = 0.29; P < 0.0001). The corresponding environmental correlations were only significantly positive for PPp (rhoE = 0.10, P = 0.03)., Conclusion: The observation of significant intrafamilial concordance and heritability of various indexes of arterial stiffness as well as the genetic correlations among arterial phenotypes strongly support the search for shared genetic determinants underlying these traits.

Background: In this study we compared the arterial characteristics and blood pressure (BP) of normotensive offspring of two normotensive parents (OFF/NT) and normotensive offspring who had at least one hypertensive parent (OFF/HT)., Methods: A total of 174 OFF/HT (17 to 40 years of age) and 59 OFF/NT (16 to 34 years) were recruited in Cracow, Poland (n = 138) and Pilsen, Czech Republic (n = 95). Peripheral pulse pressure (PPp) was determined from conventional and 24-h ambulatory BP. A SphygmoCor device was used to measure the central (CAIx) and peripheral (PAIx) systolic augmentation indexes, central pulse pressure (PPc), and the aortic pulse wave velocity (PWV). In multivariate analyses family clusters and significant covariates were accounted for., Results: The OFF/HT had higher (.14 < P < .0007) conventional BP and PPp on conventional BP measurement (121/75 v 114/71 mm Hg and 46 v 42 mm Hg) as well as on 24-h ambulatory monitoring (118/70 v 114/67 mm Hg and 48 v 47 mm Hg). OFF/HT, compared with OFF/NT, also had higher (.05 < P < .0008) PPc (28 v 26 mm Hg), PAIx (54.7% v 44.9%), CAIx (108.8% v 99.8%), and PWV (7.4 v 6.6 m/sec). However, complex adjustment including mean arterial pressure and age removed the differences between the offspring in the PAIx, CAIx, and PWV., Conclusions: Large-artery properties are altered in OFF/HT compared with OFF/NT. The findings from this cross-sectional study suggest that the alterations in arterial function in subjects with a family history of hypertension are determined mainly by an increased BP and age-related hemodynamic changes.

Vascular stiffening, a process responsible for the development of isolated systolic hypertension, depends on dysregulation of collagen-elastine production and arrangement, yet it is not known whether the effect is uniform throughout wide blood pressure (BP) range. To check whether arterial stiffness is similarly related to increased fibrotic remodelling, in patients with systolic blood pressure (SBP) above and below 160 mmHg. Consecutive peri- and postmenopausal female outpatients treated for hypertension and free from other disorders interfering with fibrotic processes, had their BP, pulse wave velocity (PWV), and collagen (N-terminal procollagen type III propeptide (PIIINP); C-terminal procollagen type I propeptide-(PICP)) measured. The average age of 100 women was 71.8+/-10.5 years, BP was 145/83+/-25/15 mmHg, pulse pressure 63+/-17 mmHg, and mean blood pressure (MBP) 104+/-17 mmHg. PWV was 12.9+/-3.6 m/s and was significantly higher among 30 patients with SBP of > or =160 mmHg. PIIINP averaged 4.6+/-1.6 ng/ml and PICP 142.2+/-47.0 ng/ml. In the low SBP (<160 mmHg) group there was no relationship between PWV and collagen concentrations. However, in the > or =160 mmHg group there was significant correlation between PWV and PIIINP concentration. The relationship held significant after adjustment for age, and BP components. Our result can help explaining the results of recent intervention trials where older patients tended to benefit more from potentially antifibrotic drugs (ACE-I), whereas those with compliant arteries tend to benefit from diuretics.

Background: Adducin is a membrane skeleton protein consisting of alpha- and beta- or alpha- and gamma-subunits. Mutations in alpha- and beta-adducin are associated with hypertension. In the European Project on Genes in Hypertension, we investigated whether polymorphisms in the genes encoding alpha-adducin (Gly460Trp), beta-adducin (C1797T) and gamma-adducin (A386G), alone or in combination, affected pulse pressure (PP), an index of vascular stiffness., Methods: We measured peripheral and central PP by conventional sphygmomanometry and applanation tonometry, respectively. We randomly recruited 642 subjects (162 nuclear families and 70 unrelated individuals) from three European populations. In multivariate analyses, we used generalized estimating equations and the quantitative transmission disequilibrium test., Results: Peripheral and central PP averaged 46.1 and 32.6 mmHg, respectively. Among carriers of the alpha-adducin Trp allele, peripheral and central PP were 5.8 and 4.7 mmHg higher in gamma-adducin GG homozygotes than in their AA counterparts, due to an increase in systolic pressure. gamma-Adducin GG homozygosity was associated with lower urinary Na/K ratio among alpha-adducin Trp allele carriers and with higher urinary aldosterone excretion among alpha-adducin GlyGly homozygotes. Sensitivity analyses in founders and offspring separately, and tests based on the transmission of the gamma-adducin G allele across families, confirmed the interaction between the alpha- and gamma-adducin genes., Conclusions: In alpha-adducin Trp allele carriers, peripheral and central PP increased with the gamma-adducin G allele. This epistatic interaction is physiologically consistent with the heterodimeric structure of the protein and its influence on transmembranous sodium transport.

Objective: Angiotensin II and aldosterone, generated by the angiotensin-converting enzyme (ACE) and aldosterone synthase (CYP11B2), respectively, not only regulate sodium and water homeostasis, but also influence vascular remodeling in response to high blood pressure. In the European Project on Genes in Hypertension (EPOGH), we therefore investigated whether the ACE I/D and CYP11B2 C-344T polymorphisms influence early arterial wave reflections, a measure of vascular stiffness., Methods: We measured the peripheral and central augmentation index of systolic blood pressure by applanation tonometry at the level of the radial artery in 622 subjects (160 families and 64 unrelated individuals) randomly recruited from three European populations, whose average urinary sodium excretion ranged from 196 to 245 mmol/day. In multivariate analyses, with sodium excretion analyzed as a continuous variable, we explored the phenotype-genotype associations by means of generalized estimating equations and the quantitative transmission disequilibrium test., Results: The peripheral and central augmentation indexes were significantly higher in CYP11B2 -344C allele carriers than in -344T homozygotes. In offspring, early wave reflections increased with the transmission of the -344C allele. This effect of the CYP11B2 polymorphism occurred in subjects with a higher than median urinary sodium excretion (210 mmol/day). The ACE I/D polymorphism did not influence augmentation of systolic blood pressure., Conclusions: The CYP11B2 C-344T polymorphism affects arterial stiffness. However, sodium intake seems to modulate this genetic effect.

Assessment of the pulse character is one of the earliest recorded medical skills, but objective recordings of pulse waveform emerged only in the nineteenth century. This technique fell into disuse with the advent of the sphygmomanometer, but interest has recently been rekindled with the introduction of computer technology and high fidelity applanation tonometry. Sphygmocardiography is a non-invasive and accurate technology which utilizes tonometric analysis of the radial or carotid artery pulse wave and measurement of peripheral arterial blood pressure to derive a central arterial pulse wave, central arterial blood pressure and related indices. In clinical studies pulse wave analysis is a highly reproducible method and easy to apply. This measure provides important information about arterial stiffness and heart-vascular interactions. This technique may provides better cardiovascular risk assessment associated with increased arterial stiffness and allow treatment to be targeted to those most in need.

In a population with high sodium consumption, we assessed relation between brachial and central blood pressures, elastic properties of large arteries, echocardiographic left ventricular diastolic function and sodium reabsorption as fractional urinary lithium excretion in proximal (FELi) and fractional sodium reabsorption in distal tubules assessed using the endogenous lithium clearance. Mean±s.d. age of 131 treated hypertensive patients (66 men and 65 women) was 61.9±7.5 years. We found significant interaction between left ventricular diastolic function and FELi with respect to the values of brachial blood pressure: systolic (SBP), diastolic (DBP) and mean blood pressure (MBP) (all PINT<0.03). In patients with FELi below the median value and impaired left ventricular diastolic function, the values of SBP (149.3 vs 132.5 mm Hg; P=0.005), DBP (85.1 vs 76.1 mm Hg; P=0.001), MBP (106.5 vs 94.9 mm Hg; P=0.001), central SBP (SBPC) (137.4 vs 122.0 mm Hg; P=0.01), central DBP (DBPC) (84.8 vs 76.0 mm Hg; P=0.003), central MBP (MBPC) (106.9 vs 95.9 mm Hg; P=0.007), aortic pulse wave augmentation (18.0 vs 13.5 mm Hg; P=0.03), pulse wave velocity (14.6 vs 12.5 m s−1; P=0.02) and central aortic pulse wave augmentation index (155.7% vs 140.9%; P=0.01) were significantly higher than in patients with normal left ventricular diastolic function. Such relationships were not observed in the entire group and patients with FELi above the median value. In the hypertensive population with high sodium intake, increased sodium reabsorption in proximal tubules may affect blood pressure parameters and arterial wall damage, thus contributing to the development of left ventricular diastolic function impairment. [ABSTRACT FROM AUTHOR]