Marcin Cwynar

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 (AIp) and central augmentation indexes (AIc). 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, AIp and AIc, 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 AIp and AIc 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 AIp, and 30% for AIc. For PPc, AIp and AIc, 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 AIp and AIc 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 α- and β- or α- and γ-subunits. Mutations in α- and β-adducin are associated with hypertension. In the European Project on Genes in Hypertension, we investigated whether polymorphisms in the genes encoding α-adducin (Gly460Trp), β-adducin (C1797T) and γ-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 α-adducin Trp allele, peripheral and central PP were 5.8 and 4.7 mmHg higher in γ-adducin GG homozygotes than in their AA counterparts, due to an increase in systolic pressure. γ-Adducin GG homozygosity was associated with lower urinary Na+/K+ ratio among α-adducin Trp allele carriers and with higher urinary aldosterone excretion among α-adducin GlyGly homozygotes. Sensitivity analyses in founders and offspring separately, and tests based on the transmission of the γ-adducin G allele across families, confirmed the interaction between the α- and γ-adducin genes. Conclusions In α-adducin Trp allele carriers, peripheral and central PP increased with the γ-adducin G allele. This epistatic interaction is physiologically consistent with the heterodimeric structure of the protein and its influence on transmembranous sodium transport.

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.

Heritability and intrafamilial aggregation of arterial characteristics.

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 ≤ 0.0001. The method of intrafamilial concordance confirmed these results; intrafamilial correlation coefficients were significant for all arterial indexes (r ≥ 0.12; P ≤ 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 (ρG ≥ 0.29; P < 0.0001). The corresponding environmental correlations were only significantly positive for PPp (ρE = 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.

Aortic Pulse Wave Velocity and Carotid-Femoral Pulse Wave Velocity : Similarities and Discrepancies

The objectives of this study were to determine the relationship between carotid-femoral (cfPWV) and aortic pulse wave velocity (aPWV) and to compare their modulators and association with coronary artery disease (CAD). We studied 107 consecutive patients (68 men) with a mean age of 60.49±8.31 years who had stable angina and had been referred for coronary angiography. cfPWV and aPWV were measured simultaneously during cardiac catheterization using the Complior® device and aortic pressure waveform recordings, respectively. Based on the presence or absence of significant coronary artery stenosis (CAS) patients were subdivided into a CAS+ or CAS− group. The mean values of cfPWV and aPWV were 10.65±2.29 m/s and 8.78±2.24 m/s, respectively. They were significantly higher in the CAS+ (n=71) compared with the CAS− (n=36) group and predicted significant CAS independently of cardiovascular risk factors and mean or systolic aortic blood pressure. aPWV and cfPWV were significantly correlated (r=0.70; p<0.001) but the degree of correlation differed significantly (p<0.03) between the CAS+ (r=0.74, p<0.001) and CAS− group (r=0.46, p=0.003). Age and mean aortic blood pressure were independent predictors for aPWV as well as cfPWV. In the receiver operating characteristic (ROC) analysis, aPWV and cfPWV had similar accuracy in identification of significant CAS (AUC [area under the ROC curve]=0.76 and 0.69, respectively; p=0.13). However, neither cfPWV nor aPWV was effective at differentiating the extent of CAD. In conclusion, aPWV and cfPWV are highly correlated parameters with similar determinants and comparable accuracy in predicting significant CAS. The strength of correlation between these two indices differed significantly between subjects with and those without CAS.

Association of red blood cell distribution width, inflammation markers and morphological as well as rheological erythrocyte parameters with target organ damage in hypertension

OBJECTIVES To assess the relationships of red blood cell distribution width (RDW), mean corpuscular hemoglobin concentration (MCHC) and erythrocyte deformability with pathological changes of selected target organs, and with inflammation markers interleukin-6 (IL-6) and fibrinogen, in a group of newly diagnosed, never-treated and otherwise healthy hypertensive patients. METHODS The study group consisted of 101 adults divided into three sub-groups: 37 diagnosed arterial hypertension, 29 with hypercholesterolemia, and 35 healthy. The individuals with hypertension or hypercholesterolemia were otherwise healthy and were not on any therapy prior to entering the study. For each individual, data were obtained on: systolic and diastolic blood pressure (SBP, DBP), pulse wave velocity (PWV), carotid intima media thickness (IMT), left ventricle geometry, blood morphology, lipids profile, fibrinogen, CRP, IL-6 and red blood cell deformability index (DI). RESULTS In the group of hypertensives, the multivariate regression analysis showed significant relationship of RDW with PWV, IL6 and fibrinogen. Also, RDW was found to be correlated with MCHC and DI, and MCHC was significantly related to IMT and IL-6. CONCLUSIONS A hypothesis has been formulated that the development of target organ damage in hypertension is accompanied by the increasing impairment of erythropoiesis. This process may be mediated by inflammation.

Age dependency of central and peripheral systolic blood pressures: Cross-sectional and longitudinal observations in European populations

Abstract Background. As arteries become stiffer with ageing, reflected waves move faster and augment late systolic pressure. We investigated the age dependency of peripheral and central systolic pressure, pressure amplification (peripheral systolic blood pressure − central systolic blood pressure), and peripheral and central systolic augmentation (maximal systolic pressure minus the first peak of the pressure wave). Methods. We randomly recruited 1420 White Europeans (mean age, 41.7 years). peripheral systolic blood pressure and central systolic blood pressure were measured by means of an oscillometric sphygmomanometer and pulse wave analysis, respectively. Results. In cross-sectional analyses (731 women, 689 men), central systolic blood pressure and central systolic augmentation increased more with age than peripheral systolic blood pressure and peripheral systolic augmentation. These age-related increases were greater in women than men. The age-related decrease in pressure amplification was similar in both sexes. In longitudinal analyses (208 women, 190 men), the annual increases in central systolic blood pressure and central systolic augmentation were steeper (p < 0.001) than those in peripheral systolic blood pressure and peripheral systolic augmentation with no sex differences (p ≥ 0.068), except for peripheral systolic augmentation, which was larger in women (p = 0.002). Longitudinally, pressure amplification decreased more with age in women than men (p = 0.012). In multivariable-adjusted analyses, age was the overriding determinant of peripheral systolic blood pressure and central systolic blood pressure. Conclusion. With ageing, peripheral systolic blood pressure approximates to central systolic blood pressure. This might explain why in older subjects peripheral systolic blood pressure becomes the main predictor of cardiovascular complications.

Arterial stiffness is increased in hypertensive centenarians

Background. The aim of our study was to assess the relationship between blood pressure and arterial stiffness in Polish centenarians. Materials and methods. We examined 59 centenarians with the mean age of 101.3 years. Peripheral blood pressure was estimated upon mean value of three measurements and arterial stiffness by pulse wave analysis (PWA). Pressure waveforms were recorded from the radial artery and the waveform data were then processed by SphygmoCor to produce the estimated aortic pressure waveform. All subjects were divided into the three subgroups: normotensives (<140/90 mmHg), systolic hypertensives (ISH, SBP⩾140 and DBP<90 mmHg) and systolo‐diastolic hypertensives (⩾140/90 or treated). Results. The mean values of peripheral BP for the entire group were: 149.5/76.8 mmHg for SBPP/DBPP and 136.1/77.8 mmHg for central SBPC/DBPC, respectively. The mean value of pulse pressures were: 72.7/58.4 mmHg for peripheral (PPP)/central (PPc). Arterial stiffness indices calculated from PWA were: 96.6%, 33.2% and 32.2% for peripheral (AIxP), central (AIxC) and central normalized for heart rate (AIxC75) augmentation indexes, respectively. The PPc was the lowest in the normotensive group (40.1 mmHg) when compared both with the ISH group (71.1 mmHg) and the systolo‐diastolic group (58.1 mmHg). The lowest arterial stiffness indices (AIxP, AIxC75) calculated from PWA were found in the normotensive group: 85.4% and 28.5%, comparing with 96.1% and 33.7% in the ISH group and 104.8% and 32.9% for the systolo‐diastolic group. Conclusions: In centenarians, similarly to younger subjects, those with hypertension present with arterial stiffness.

Pulse wave velocity in patients with coronary artery disease or type 2 diabetes mellitus.

Objective — To check whether the presence of coronary artery disease (CAD) or type 2 diabetes mellitus (DM) has a differentiating effect on arterial stiffness assessed with pulse wave velocity (PWV) - a simple, reproducible and clinically feasible measure of arterial stiffening. Methods and results — The mean age of 101 participants was 63.5±19.7years. Fifty-one % of them had CAD, 31.0% had DM and 52.5% were hypertensive subjects.The aortic PWV ranged from 3.40 to 27.50m/s, with an average of 11.73±4.69m/s. PWV was significantly higher (P<0.01) in both CAD and DM positive groups as compared with CAD and DM negatives, respectively. After adjustment for established co-variables, patients with CAD had significantly higher PWV when compared to CAD negatives (13.0 vs. 10.5m/s, P<0.01). After adjustment, DM did not seem to affect PWV. Conclusions — CAD patients had higher values of PWV when compared to those without the disease. DM, a metabolic equivalent of arterial damage, after adjustment for possible confounders, did not seem to contribute per se to arterial stiffening. The presence of high PWV values in that group of patients should be viewed as an indicator of established widespread atherosclerosis possibly affecting the coronary arteries.

There Is More to Salt Than Just a Pinch of Sodium

See related article, pp 836–843 Much of what human life is about is water (60% of body mass) and a handful of solutes. Of the latter, main cations include sodium, potassium, calcium, and magnesium, and the anions include chloride, bicarbonate, phosphate and organic anions, and proteins. The concentrations of sodium (135–145 mmol/L) and chloride (95–106 mmol/L) predominate in serum and constitute the bulk of serum’s osmolarity. In the course of evolution, complex regulatory mechanisms developed to keep the osmolarity (≈280 mosm/L) and thus amount of water at desired level. With it came the role of main solutes and their regulatory mechanisms (ie, renin–angiotensin–aldosterone system [RAAS]) in the regulation of blood pressure. Numerous studies demonstrated the role of sodium-based mechanisms in water homeostasis and blood pressure regulation. Recently, several well-designed studies showed that the level of ingested sodium correlated with the level of blood pressure or cardiovascular risk, and that the relationship is likely to assume a J-curve shape in population of patients with cardiovascular involvement or diabetes mellitus.1 However, experimental studies performed over several decades pointed to the possibility that the form of ingested or infused sodium is of importance. Both in animal models and in human studies, Kurtz and Morris2 and then Luft et al3 were among those who showed that blood pressure elevated when sodium chloride was ingested or infused, but not when the salt used was sodium bicarbonate or sodium citrate. These and other similar studies led to the consideration of chloride as a possible factor in the regulation of blood pressure. Paradoxically, different picture arose when researchers related …