Reference values in white Europeans for the arterial pulse wave recorded by means of the SphygmoCor device.

Measurement of blood pressure together with applanation tonometry at the radial artery allows the reproducible assessment of various indexes of arterial stiffness, including the peripheral (PPp) and central pulse pressures (PPc) and the peripheral (Alp) and central augmentation indexes (Alc). We defined preliminary diagnostic thresholds, using the distributional characteristics of these hemodynamic measurements in a reference population. We randomly recruited 870 subjects from 3 European populations. PPp was the average difference between systolic and diastolic blood pressure measured five times at one home visit. For measurement of PPc, Alp and Alc, we used the SphygmoCor device. We selected subjects without hypertension, diabetes, dyslipidemia in need of medical treatment or previous or concomitant cardiovascular disease. The study population included 228 men and 306 women (mean age 34.9 years). All hemodynamic measurements were curvilinearly related to age, and Alp and Alc were lower in men than in women. In men at age 40, the upper 95% prediction bands of the relations of the hemodynamic measurements with age approximated 60 mmHg for PPp, 40 mmHg for PPc, 90% for Alp, and 30% for Alc. For PPc, Alp and Alc, these thresholds must be adjusted for age, leading to lower and higher thresholds at younger and older age, respectively. In addition, in women of any age, the Alp and Alc thresholds must be increased by 10% and 7%, respectively. Pending validation in prospective outcome studies, distributional characteristics of arterial stiffness indexes in a reference population can be used to generate operational thresholds for use in clinical practice.

Epistatic interaction between alpha- and gamma-adducin influences peripheral and central pulse pressures in white Europeans.

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.

Large artery stiffness and pulse wave reflection: results of a population-based study.

OBJECTIVE: To assess the determination of large artery stiffness and pulse wave reflection in a population sample. METHODS: A 1% random population sample aged 25-65 years was selected in nine districts of the Czech Republic for a survey off cardiovascular risk factors (Czech post-MONICA). Of 891 individual screened in the Pilsen centre in the year 2000, arterial properties were studied in 291 (143 males and 148 females) using the Sphygmocor device. Pulse wave velocity (PWV) in the aorta and in the lowe limbs was measured to assess large artery stiffness. Wave reflection was assessed from radial pulse wave analysis; the main estimated parameter was peripheral augmentation index (PAI) defined as P2/P1 = ratio of pulse pressures measures at the peaks of secondary and primary waves. RESULTS: Aortic PWV increased with age (p < 0.001) and was similar in both sexes. Lower extremity PWV increased with age in women, but not in mean, and its mean value was higher in men (p < 0.001). PAI was higher in females in all age groups (p < 0.001) and increased steeply with age in both sexes (p < 0.001). PAI was increased in current smokers (p < 0.001 in both sexes) and in male smokers, the reflected wave returned earlier than in male non-smokers (p < 0.05). Correlation coefficient of PAI with aortic PWV was 0.22 (p < 0.01), and with central augmentation index (CAI), derived from PAI by mathematical transformation, was 0.94 (p < 0.001). Multiple regression analyses, where age, sex, systolic blood pressure (SBP), total cholesterol level, smoking, glucose level and body mass index were included as independent variables, were performed. PAI was better predicted than aortic or lower extremity PWV is these models (41%, 14% and 10% of variance explained, respectively). Age, female sex, smoking, SBP and total cholesterol predicted PAI level whereas age, SBP and glucose level were the main determinants pf aortic PWV. CONCLUSION: Of the studied arterial parameters, PAI showed the closest association with cardiovascular risk factors. The correlation between PAI and aortic PWV was loose, and both parameters had practically different determinants. PAI, which is obtained by direct measurement above radial artery, was practically identical with the mathematically derived CAI in the studied population sample, and therefore, it is a suitable parameter for studying the phenomenon of wave reflection.

Association of peripheral and central arterial wave reflections with the CYP11B2 -344C allele and sodium excretion.

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.