Cardiovascular risk factors as determinants of cerebral blood flow - a cross-sectional and 6-year follow-up study.

Purpose: The parameters of cerebral blood flow are modulated by many factors. The aim of the study was to prospectively assess the relationship between the number of the established cardiovascular risk factors and hemodynamic parameters of cerebral blood flow.Material and methods: The study was cross-sectional baseline and 6-year follow-up data analysis. We analyzed data regarding cardiovascular risk factors, medications use, and ultrasonographically (transcranial Doppler) obtained mean cerebral blood flow velocity (mCBFV), pulsatility (PI), resistance (RI) indexes of middle cerebral artery.Results: After 6.0 ± 0.6 years of follow-up, there was increase in systolic (p = .047), and decrease in diastolic (p = .005) blood pressure, resulting in greater pulse pressure (p < .001). Although intima-media thickness increased during follow-up (p = .019), PI, RI and mCBFV did not differ between baseline and follow-up. In the cohort without follow-up (n = 112), we observed strong association between number of studied cardiovascular risk factors and lower mCBFV, and higher PI and RI (all p < .001), in the cohort with 6 year follow-up (n = 53), we confirmed similar association for mCBFV and PI (p = .002) at baseline, and mCBFV (p = .024) after follow-up. During follow-up, more patients were treated with vasoactive medications (p < .05). Also the median (interquartile range) of total number of taken drugs at follow-up 2 (1-3) was greater than at baseline 1 (0-2), (p < .001). The addition of vasoactive medications during follow-up was associated with increase of the mCBFV (0.012 ± 0.02 m/s, p = .013).Conclusion: The parameters of the cerebral blood flow are adversely influenced by accretion of cardiovascular risk factors, both at baseline and after 6 years of follow-up. The addition of a vasoactive medication during follow-up is associated with an increase of the mCBFV, a possibly beneficial effect.

The relation between ACE D/I and CYP11B2 C-344T polymorphisms and parameters of arterial stiffness in the context of renal sodium handling.

BACKGROUND: Sodium overload is related to the development of primary hypertension and its complications. METHODS: In 131 (65 female) treated hypertensives (average blood pressure 144/82 mmHg and duration of hypertension 11.7 years), we measured peripheral and central arterial pressures, peripheral (AIx(P)) and central (AIx(C1), AIx(C2)) augmentation indices, pulse-wave velocity (PWV) and daily urinary sodium excretion, and conducted genetic studies of ACE D/I and CYP11B2 C-344T polymorphisms. Proximal (FE(Li)) and distal (FDR(Na)) sodium reabsorption measurements were performed using endogenous lithium clearance. RESULTS: We found statistically significant interactions between FE(Li) and ACE D/I polymorphism with respect to AIx(C2) (P(INT) = 0.05) and between FE(Li) and CYP11B2 C-344T polymorphism with respect to AIx(C1) (P(INT) = 0.01), AIx(C2) (P(INT) = 0.04) and AIx(P) (P(INT) = 0.01). In the group of ACE I allele carriers compared with DD homozygotes, the AIx(C1) (154.1 vs 140.6%; p = 0.02), AIx(C2) (33.3 vs 26.9%; p = 0.02) and AIx(P) (94.6 vs 85.2%; p = 0.01) were higher in the subgroup with FE(Li) below the median value (FE(Li)1), but not in the subgroup with FE(Li) above the median value (FE(Li)2). In the group of CYP11B2 TT homozygotes compared with C allele carriers, we observed higher values of AIx(C1) (158.5 vs 146.4%; p = 0.03), AIx(C2) (36.0 vs 29.4%; p = 0.01) and AIx(P) (99.0 vs 88.7%; p = 0.005) in the FE(Li)1 but not the FE(Li)2 subgroup. Conclusions. In the population with assumed high dietary sodium intake and long-standing history of hypertension, the relation between proximal sodium reabsorption and the development of arterial stiffness depends on the genetic context of the selected genetic polymorphisms of the renin­angiotensin­aldosterone system, independent of blood pressure.

Comprehensive geriatric evaluation in former Siberian deportees with posttraumatic stress disorder.

OBJECTIVES: Posttraumatic stress disorder (PTSD) develops after exposure to particularly traumatic events. Its severity depends on the nature and intensity of the stressor and the susceptibility of the exposed person. The aim of our study was to assess the relationship between PTSD resulting from deportation to Siberia in the patients' childhood and cognitive, emotional, and physical decline in advanced age. METHODS: Eighty patients with PTSD with a history of deportation to Siberia and 70 subjects without PTSD were diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; severity of the symptoms included in the criteria was also assessed. In all patients, a standardized interview (including demographic data and comprehensive geriatric assessment tools such as the Mini-Mental State Examination, Geriatric Depression Scale, activities of daily living, and instrumental activities of daily living) was performed. RESULTS: In analyses with the comparison group, patients with PTSD had a higher frequency of cognitive deficits (7.1% versus 22.5%), depression (31.4% versus 88.8%) and physical disability in activities of daily living (0% versus 21.3%), and instrumental activities of daily living (40.0% versus 88.8%). Moreover, increasing severity of PTSD was associated with significant deterioration in cognitive function, severity of depression, and the deterioration of basic and complex activities of daily living. CONCLUSIONS: Higher frequency of cognitive function deficits, depression, and physical disability was found in the group of former deportees compared with the group of individuals without history of such a traumatic experience.

Angiotensin-converting enzyme inhibitors and angiotensin-II-receptor antagonists modulate sodium handling based on endogenous lithium clearance.

BACKGROUND: Numerous studies based on assessment of lithium clearance demonstrated higher sodium reabsorption in renal proximal tubules in individuals with hypertension, overweight, obesity, metabolic syndrome, or diabetes. AIMS: We aimed to assess the influence of angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin-II-receptor antagonists (ARB) treatment on sodium handling. METHODS: In a sample of 351Caucasian subjects without diuretic treatment with prevailing sodium consumption, we studied associations between renal sodium reabsorption in proximal (FPRNa) and distal (FDRNa) tubules assessed by endogenous lithium clearance and daily sodium intake measured by 24-hour excretion of sodium (UNaV), in the context of obesity and long-term treatment with ACE-I or ARB. RESULTS: In the entire study population, we found a strong negative association between FPRNa and ACE-I/ARB treatment (b = -19.5; SE = 4.9; P <0.001). Subjects with FPRNa above the median value showed a significant adverse association between FPRNa and age (b = -0.06; SE = 0.02; P = 0.003), with no association with ACE-I/ARB treatment (P = 0.68). In contrast, in subjects with FPRNa below the median value, we found a strongly significant adverse relationship between FPRNa and ACE-I/ARB treatment (b = -30.4; SE = 8.60; P <0.001), with no association with age (P = 0.32). CONCLUSIONS: ACE-I/ARB long-term treatment modulates FPRNa in the group with lower reabsorption, but not in that with higher than median value for the entire study population.

Cardio-ankle vascular index for predicting cardiovascular morbimortality and determinants for its progression in the prospective advanced approach to arterial stiffness (TRIPLE-A-Stiffness) study.

BACKGROUND: The cardio-ankle vascular index (CAVI) measure of arterial stiffness is associated with prevalent cardiovascular risk factors, while its predictive value for cardiovascular events remains to be established. The aim was to determine associations of CAVI with cardiovascular morbimortality (primary outcome) and all-cause mortality (secondary outcome), and to establish the determinants of CAVI progression. METHODS: TRIPLE-A-Stiffness, an international multicentre prospective longitudinal study, enrolled >2000 subjects ≥40 years old at 32 centres from 18 European countries. Of these, 1250 subjects (55% women) were followed for a median of 3.82 (2.81-4.69) years. FINDINGS: Unadjusted cumulative incidence rates of outcomes according to CAVI stratification were higher in highest stratum (CAVI > 9). Cox regression with adjustment for age, sex, and cardiovascular risk factors revealed that CAVI was associated with increased cardiovascular morbimortality (HR 1.25 per 1 increase; 95% confidence interval, CI: 1.03-1.51) and all-cause mortality (HR 1.37 per 1 increase; 95% CI: 1.10-1.70) risk in subjects ≥60 years. In ROC analyses, CAVI optimal threshold was 9.25 (c-index 0.598; 0.542-0.654) and 8.30 (c-index 0.565; 0.512-0.618) in subjects ≥ or <60 years, respectively, to predict increased CV morbimortality. Finally, age, mean arterial blood pressure, anti-diabetic and lipid-lowering treatment were independent predictors of yearly CAVI progression adjusted for baseline CAVI. INTERPRETATION: The present study identified additional value for CAVI to predict outcomes after adjustment for CV risk factors, in particular for subjects ≥60 years. CAVI progression may represent a modifiable risk factor by treatments. FUNDING: International Society of Vascular Health (ISVH) and Fukuda Denshi, Japan.

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

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.

Stiffness of large arteries and cardiovascular risk in patients with post-traumatic stress disorder.

AIMS: Post-traumatic stress disorder (PTSD) develops after exposure to particularly traumatic events. Its severity depends on the nature and intensity of the stressor and susceptibility of the exposed person. The present study was carried out to find out whether PTSD and its severity, resulting from deportation to Siberia in the patients' childhood (from 1940 to 1946), have any association on the somatic health status and cardiovascular risk of these persons in advanced age. METHODS AND RESULTS: Eighty patients with PTSD and 70 subjects without PTSD followed up in primary care setting were enrolled in the study. Post-traumatic stress disorder was diagnosed according to the DSM-IV criteria; severity of the symptoms included in the criteria was also assessed. All patients were subject to a standardized interview including demographic data and current and past diseases, supplemented with physical examination, biochemical tests, and aortic pulse wave velocity (PWV). The group of patients with PTSD resulting from deportation to Siberia in their childhood had higher prevalence of coronary artery disease (71.3 vs. 44.3%, P < 0.001), diabetes (26.3 vs. 11.4%, P < 0.05), and hearing impairment (23.8 vs. 2.9%, P < 0.001) than controls. They also had higher incidence of blood pressure >140/90 (86.0 vs. 65.7%, P = 0.003), fasting blood glucose >5.6 mmol/L (65.0 vs. 45.7%, P = 0.018), HDL level <1.0 mmol/L (31.3 vs. 8.6%, P = 0.0006), and triglyceride level >2.3 mmol/L (62.5 vs. 321.4%, P = 0.001). Patients with PTSD had higher PWV (13.7 vs. 12.9 m/s, P= 0.042). The magnitude of PWV increased with the severity of PTSD (P = 0.001). Stepwise logistic regression has shown that PTSD was a strong factor promoting the appearance of coronary heart disease in the former deportees group (OR 3.80; 95% CI: 1.62-8.94; P = 0.002). CONCLUSION: Several-year long deportation in childhood and PTSD elevated overall cardiovascular risk in the group of former deportees compared with the group of persons without history of such a traumatic experience.

Local heat stress and skin blood flowmotion in subjects with familial predisposition or newly diagnosed hypertension.

OBJECTIVE: The aim of the study was to investigate the skin microcirculation blood flow and flowmotion response to heat stress in normotensive subjects with familial predisposition to hypertension and in hypertensive patients. METHODS: Normotensives without [NT(-)] or with [NT(+)] familial predisposition and subjects with newly diagnosed hypertension (HT) were studied. Clinic blood pressure (BP) measurements and ambulatory BP monitoring as well as laboratory assessments were performed. Resting (RF), heat (HF) and maximal heat (MHF) blood flows were measured using PeriFlux laser Doppler flowmetry (LDF) and expressed as absolute units (AU) and as index of cutaneous vascular conductance (CVC). Spectral analysis of the skin LDF signal was performed by means of the Perisoft dedicated software. Kruskall-Wallis analysis of variance, χ(2) statistic and multivariate reverse regression analysis were used for calculation. RESULTS: The studied population consisted of 70 persons (mean age 36.1 ± 10.3 years, 44.3% women): 17 NT(-), 22 NT(+) and 31 HT, age and gender matched. Higher values of body mass index (BMI), and insulin, glucose and triglyceride levels were observed in HT than in NT groups. RF, HF and MHF were similar in all study groups, but CVC of maximal heat flow differed (p=0.02); in particular, lower values were observed in the HT than in NT(-) group (p=0.01). The study groups differed with regard to total power (p=0.01) and myogenic (p=0.03) origin flowmotion with the lowest values in the NT(+) group. BMI and night BP characteristics were strong predictors of reduction of CVC, MHF and myogenic origin flowmotion. CONCLUSION: Skin microcirculation response to local heat stress is altered in hypertensive patients with decrease in maximal heat CVC values. Moreover, normotensive subjects with familial predisposition to hypertension are characterized by diminished myogenic origin of skin blood flowmotion.

Women with prehypertension in primary care - Risk profile on the basis of selected cardiovascular risk factors.

BACKGROUND: Demographic, social and economic trends will serve to increase the importance of women as healthcare consumers. Design. The aim of the study was to assess cardiovascular (CV) risk in the normotensive female patients during single visit to primary care (PC) offices. METHODS: Demographic data, history of coronary heart disease (CHD), diabetes (DM), smoking habit and family history of CV diseases were obtained from women who visited general practitioners. Moreover, blood pressure (BP), pulse rate, weight and height used to calculation body mass index (BMI) and waist circumference (WC) were performed. Prehypertension was defined as a systolic BP (SBP) of 120-139 mmHg, and/or a diastolic BP (DBP) of 80-89mmHg. RESULTS: Prehypertension was observed in 21.5% of the whole group of female PC patients. SBP, DBP, BMI and WC revealed significant trends towards increase with age among both prehypertensives (p<0.001) and normotensives (SBP, BMI, WC: p<0.001; DBP: p<0.05) and in the whole group (p<0.001). Nevertheless, heart rate (HR) significantly increased with age only among prehypertensive women (p<0.05). The CV risk of the studied adult women increased progressively with presence of overweight, obesity and visceral obesity. The CV risk of the youngest groups was associated mainly with high prevalence of smoking, and with high prevalence of CHD and DM among the oldest female patients. CONCLUSIONS: The prevalence of majority of CV risk factors increase with age among both prehypertensive and normotensive women, which should stimulate PC practitioners to identify and modify them.

Insulin Resistance and Renal Sodium Handling Influence Arterial Stiffness in Hypertensive Patients with Prevailing Sodium Intake.

BACKGROUND: Insulin resistance and renal tubular sodium handling influence arterial structure and function and play an essential role in salt-sensitive forms of hypertension. METHODS: In a population with prevailing sodium consumption, we assessed the relationship between cardiovascular phenotypes (peripheral and central blood pressures, elastic properties of large arteries, the left ventricular structure) and sodium handling parameters (daily urinary sodium excretion, fractional urinary lithium excretion in proximal-FELi and distal tubules), as a function of insulin sensitivity-measured by homeostasis model assessment-insulin resistance (HOMA-IR), leptin-to-adiponectin (L/A) ratio, and homeostasis model assessment-adiponectin (HOMA-AD). RESULTS: In patients with FELi below the median value (corresponding to the group with increased proximal sodium reabsorption) and higher insulin resistance as measured by HOMA-IR, pulse wave augmentation indexes were significantly higher-AIxP (99.4% vs. 86.2%; P = 0.007), AIxC1 (159.4% vs. 144.2%; P = 0.04), and AIxC2 (36.1% vs. 28.3%; P = 0.02), than in patients with lower insulin resistance. The same trend was observed in relation to L/A ratio-AIxP (98.7% vs. 87.1%; P = 0.005), AIxC1 (158.6% vs. 144.5%; P = 0.02), and AIxC2 (35.6% vs. 28.5%; P = 0.01) and HOMA-AD-AIxP (99.7% vs. 83.8%; P = 0.001), AIxC1 (160.5% vs. 140.3%; P = 0.007), and AIxC2 (36.6% vs. 26.3%; P = 0.003). Such relationships were not observed in patients with FELi above the median value. CONCLUSIONS: In the hypertensive population with prevailing sodium intake, insulin resistance and increased sodium reabsorption in proximal tubules may affect arterial wall function.

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 < 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.

Effects of metabolic syndrome on arterial function in different age groups: the Advanced Approach to Arterial Stiffness study.

OBJECTIVE: The aim of the Advanced Approach to Arterial Stiffness study was to compare arterial stiffness measured simultaneously with two different methods in different age groups of middle-aged and older adults with or without metabolic syndrome (MetS). The specific effects of the different MetS components on arterial stiffness were also studied. METHODS: This prospective, multicentre, international study included 2224 patients aged 40 years and older, 1664 with and 560 without MetS. Patients were enrolled in 32 centres from 18 European countries affiliated to the International Society of Vascular Health & Aging. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI) and the carotid-femoral pulse wave velocity (CF-PWV) in four prespecified age groups: 40-49, 50-59, 60-74, 75-90 years. In this report, we present the baseline data of this study. RESULTS: Both CF-PWV and CAVI increased with age, with a higher correlation coefficient for CAVI (comparison of coefficients P < 0.001). Age-adjusted and sex-adjusted values of CF-PWV and CAVI were weakly intercorrelated (r = 0.06, P < 0.001). Age-adjusted and sex-adjusted values for CF-PWV but not CAVI were higher in presence of MetS (CF-PWV: 9.57 ±â€Š0.06 vs. 8.65 ±â€Š0.10, P < 0.001; CAVI: 8.34 ±â€Š0.03 vs. 8.29 ±â€Š0.04, P = 0.40; mean ±â€ŠSEM; MetS vs. no MetS). The absence of an overall effect of MetS on CAVI was related to the heterogeneous effects of the components of MetS on this parameter: CAVI was positively associated with the high glycaemia and high blood pressure components, whereas lacked significant associations with the HDL and triglycerides components while exhibiting a negative association with the overweight component. In contrast, all five MetS components showed positive associations with CF-PWV. CONCLUSION: This large European multicentre study reveals a differential impact of MetS and age on CAVI and CF-PWV and suggests that age may have a more pronounced effect on CAVI, whereas MetS increases CF-PWV but not CAVI. This important finding may be due to heterogeneous effects of MetS components on CAVI. The clinical significance of these original results will be assessed during the longitudinal phase of the study.

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.

Sodium excretion as a modulator of genetic associations with cardiovascular phenotypes in the European Project on Genes in Hypertension.

Hypertension is a chronic age-related disorder, affecting nearly 20% of all adult Europeans. This disease entails debilitating cardiovascular complications and is the leading cause for drug prescriptions in Europeans older than 50 years. Intensive research over the past two decades has so far failed to identify common genetic polymorphisms with a major impact on blood pressure or associated cardiovascular phenotypes, suggesting that multiple genes each with a minor impact, along with gene-gene and gene-environment interactions, play a role. The European Project on Genes in Hypertension (EPOGH) is a large-scale, family-based study in which participants from seven different populations were phenotyped and genotyped according to standardized procedures. This review article summarizes the initial 5-year findings and puts these observations into perspective against other published studies. The EPOGH demonstrated that phenotype-genotype relations strongly depend on host factors such as gender and lifestyle, in particular salt intake as reflected by the 24-h urinary excretion of sodium. The EPOGH therefore highlights the concept that phenotype-genotype relations can only be studied within a defined ecogenetic context.

Arterial characteristics in normotensive offspring of parents with or without a history of hypertension.

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.

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.

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 +/- 19.7 years. Fifty-one % of them had CAD, 31.0% had DM and 52.5% were hypertensive subjects. The aortic PWV ranged from 3.40 to 27.50 m/s, with an average of 1.73 +/- 4.69 m/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. 10.5 m/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.

Blood pressure, arterial stiffness and endogenous lithium clearance in relation to AGTR1 A1166C and AGTR2 G1675A gene polymorphisms.

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.

Osteoprotegerin and osteoprotegerin/TRAIL ratio are associated with cardiovascular dysfunction and mortality among patients with renal failure.

PURPOSE: The high prevalence of cardiovascular morbidity and mortality among patients with chronic kidney disease (CKD) is observed especially in those undergoing dialysis. Osteoprotegerin (OPG) and its ligands, receptor activator of nuclear factor kappa-B ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been associated with cardiovascular complications. Our aim was to study their role as cardiovascular risk factors in stage 5 CKD patients. PATIENTS AND METHODS: OPG, RANKL and TRAIL concentrations were measured in 69 hemodialyzed CKD patients and 35 healthy volunteers. In CKD patients, cardiovascular dysfunction was assessed with aortic pulse wave velocity (AoPWV), carotid artery intima-media thickness (CCA-IMT), coronary artery calcium score (CACS) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentrations. Cardiovascular and overall mortality data were collected during a 7-years follow-up. RESULTS: OPG plasma concentrations were higher in CKD patients comparing to controls. Total soluble RANKL was lower and OPG/RANKL ratio higher in patients. Soluble TRAIL concentrations did not differ between the groups and OPG/TRAIL ratio was higher in CKD patients. OPG and OPG/TRAIL positively predicted long-term mortality (all-cause and cardiovascular) in CKD patients. OPG positively correlated with AoPWV, CCA-IMT and NT-proBNP whereas OPG/TRAIL with AoPWV and NT-proBNP. Described relationships were independent of classical and non-classical cardiovascular risk factors, with exception of age. CONCLUSIONS: Our study confirmed the role of OPG as a biomarker of cardiovascular dysfunction and a predictor of mortality in stage 5 CKD. OPG/TRAIL ratio can be proposed as a predictor of cardiovascular dysfunction and mortality.

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.