Differences in heart rate responses to upright posture are associated with variations in the high-frequency power of heart rate variability.

High resting heart rate is a cardiovascular risk factor, but limited data exist on the underlying hemodynamics and reproducibility of supine-to-upright increase in heart rate. We recorded noninvasive hemodynamics in 574 volunteers [age, 44.9 yr; body mass index (BMI), 26.4 kg/m2; 49% male] during passive head-up tilt (HUT) using whole body impedance cardiography and radial artery tonometry. Heart rate regulation was evaluated using heart rate variability (HRV) analyses. Comparisons were made between quartiles of supine-to-upright heart rate changes, in which heart rate at rest ranged 62.6-64.8 beats/min (P = 0.285). The average upright increases in heart rate in the quartiles 1-4 were 4.7, 9.9, 13.5, and 21.0 beats/min, respectively (P < 0.0001). No differences were observed in the low-frequency power of HRV, whether in the supine or upright position, or in the high-frequency power of HRV in the supine position. Upright high-frequency power of HRV was highest in quartile 1 with lowest upright heart rate and lowest in quartile 4 with highest upright heart rate. Mean systolic blood pressure before and during HUT (126 vs. 108 mmHg) and the increase in systemic vascular resistance during HUT (650 vs. 173 dyn·s/cm5/m2) were highest in quartile 1 and lowest in quartile 4. The increases in heart rate during HUT on three separate occasions several weeks apart were highly reproducible (r = 0.682) among 215 participants. To conclude, supine-to-upright increase in heart rate is a reproducible phenotype with underlying differences in the modulation of cardiac parasympathetic tone and systemic vascular resistance. As heart rate at rest influences prognosis, future research should elucidate the prognostic significance of these phenotypic differences.NEW & NOTEWORTHY Subjects with similar supine heart rates are characterized by variable increases in heart rate during upright posture. Individual heart rate increases in response to upright posture are highly reproducible as hemodynamic phenotypes and present underlying differences in the modulation of cardiac parasympathetic tone and systemic vascular resistance. These results indicate that resting heart rate obtained in the supine position alone is not an optimal means of classifying people into groups with differences in cardiovascular function.

The characteristics of elevated blood pressure in abdominal obesity correspond to primary hypertension: a cross-sectional study.

BACKGROUND: Obesity-related hypertension and the associated metabolic abnormalities are considered as a distinct hypertensive phenotype. Here we examined how abdominal fat content, as judged by waist:height ratio, influenced blood pressure and hemodynamic profile in normotensive subjects and never-treated hypertensive patients. METHODS: The 541 participants (20-72 years) underwent physical examination and laboratory analyses and were divided into age and sex-adjusted quartiles of waist:height ratio. Supine hemodynamics were recorded using whole-body impedance cardiography, combined with analyses of radial tonometric pulse wave form and heart rate variability. RESULTS: Mean waist:height ratios in the quartiles were 0.46, 0.51, 0.55 and 0.62. Radial and aortic blood pressure, systemic vascular resistance, pulse wave velocity, markers of glucose and lipid metabolism, leptin levels and C-reactive protein were higher in quartile 4 when compared with quartiles 1 and 2 (p < 0.05 for all). Cardiac index was lower in quartile 4 versus quartile 1, while no differences were seen in heart rate variability, augmentation index, plasma renin activity, and aldosterone concentration between the quartiles. Linear regression analyses showed independent associations of abdominal obesity with higher aortic systolic and diastolic blood pressure, systemic vascular resistance, and pulse wave velocity (p < 0.05 for waist:height ratio in all regression models). CONCLUSION: Higher waist:height ratio was associated with elevated blood pressure, systemic vascular resistance, and arterial stiffness, but not with alterations in cardiac sympathovagal modulation or activation of the circulating renin-angiotensin-aldosterone system. Although obesity-related elevation of blood pressure has distinct phenotypic features, these results suggest that its main characteristics correspond those of primary hypertension. TRIAL REGISTRATION: ClinicalTrails.gov NCT01742702 (date of registration 5th December 2012).

Urine sodium excretion is related to extracellular water volume but not to blood pressure in 510 normotensive and never-treated hypertensive subjects.

PURPOSE: High sodium intake is an accepted risk factor for hypertension, while low Na+ intake has also been associated with increased risk of cardiovascular events. In this cross-sectional study, we examined the association of 24-h urinary Na+ excretion with haemodynamics and volume status. MATERIALS AND METHODS: Haemodynamics were recorded in 510 normotensive and never-treated hypertensive subjects using whole-body impedance cardiography and tonometric radial artery pulse wave analysis. The results were examined in sex-specific tertiles of 24-h Na+ excretion, and comparisons between normotensive and hypertensive participants were also performed. Regression analysis was used to investigate factors associated with volume status. The findings were additionally compared to 28 patients with primary aldosteronism. RESULTS: The mean values of 24-h urinary Na+ excretion in tertiles of the 510 participants were 94, 148 and 218 mmol, respectively. Average tertile age (43.4-44.7 years), office blood pressure and pulse wave velocity were corresponding in the tertiles. Plasma electrolytes, lipids, vitamin D metabolites, parathyroid hormone, renin activity, aldosterone, creatinine and insulin sensitivity did not differ in the tertiles. In supine laboratory recordings, there were no differences in aortic systolic and diastolic blood pressure, heart rate, cardiac output and systemic vascular resistance. Extracellular water volume was higher in the highest versus lowest tertile of Na+ excretion. In regression analysis, body surface area and 24-h Na+ excretion were independent explanatory variables for extracellular water volume. No differences in urine Na+ excretion and extracellular water volume were found between normotensive and hypertensive participants. When compared with the 510 participants, patients with primary aldosteronism had 6.0% excess in extracellular water (p = .003), and 24-h Na+ excretion was not related with extracellular water volume. CONCLUSION: In the absence of mineralocorticoid excess, Na+ intake, as evaluated from 24-h Na+ excretion, predominantly influences extracellular water volume without a clear effect on blood pressure.

We evaluated sodium intake in 510 subjects by measuring their 24-h sodium excretion to the urine and examined whether sodium intake was related with alterations in cardiovascular function and fluid balance. All participants were without blood pressure lowering medications.Blood pressure was recorded by a device that senses the radial artery pulsations form the wrist. The amount of blood pumped by the heart, the transfer of pressure waves following cardiac contractions and body fluid status were evaluated using bioimpedance, a method recording changes in body electrical resistance.For the analyses, the participants were divided into tertiles according to their 24-h sodium excretions. We also compared results between normotensive and hypertensive subjects.The 24-h sodium excretion in the tertiles corresponded to about 6 g, 9 g and 13 g of salt intake per day, respectively. There were no differences between the tertiles in age, routine laboratory analyses, blood pressure, large arterial stiffness, amount blood pumped by the heart and resistance to blood flow in the arteries. However, there was more extracellular fluid in the highest versus the lowest tertile of sodium excretion. Further statistics indicated that extracellular fluid volume in the body was mainly determined by body size, but it was also moderately influenced by sodium intake.No differences in 24-h sodium excretion and extracellular water volume were found between normotensive and hypertensive participants.In subjects not using blood pressure lowering medications, sodium intake predominantly influences the amount of extracellular fluid without a clear effect on blood pressure.

Resting heart rate predicts cardiac autonomic modulation during passive head-up tilt in subjects without cardiovascular diseases.

Background Resting heart rate (HR) and its variability (HRV) reflects the cardiac sympathovagal balance that is stimulated by head-up tilting. HRV is influenced by the level of HR, but how much HRV offers additional information about cardiac autonomic tone than HR alone remains unresolved. We examined the relation of resting HR with HRV during head-up tilt. Methods. Hemodynamics of 569 subjects without known cardiovascular diseases and medications with direct cardiovascular effects were recorded using whole-body impedance cardiography, radial pulse wave analysis, and electrocardiography-based HRV analysis during passive head-up tilt. Results. Higher low frequency to the high-frequency ratio (LF/HF) of HRV (reflecting sympathovagal balance) was associated with higher HR in supine (p < .05, both linear regression analysis and variance analysis comparing HR tertiles) and upright postures (p < .001, linear regression analysis). The association of HR with HRV during tilt-testing remained significant when the HR dependence of HRV was mathematically weakened by dividing the HRV power spectra with the fourth power of the average RR-interval. Conclusion. Higher resting HR is related to higher LF/HF both supine and upright, reflecting elevated sympathetic influence on cardiac autonomic modulation. Lower resting HR is associated with lower resting LF/HF, while the differences in LF/HF between the HR tertiles were minor during head-up tilt, suggesting a greater change in cardiac sympathovagal balance in response to upright posture in those with lowest resting HR. Altogether, resting HR well predicts HRV levels during head-up tilt.Trial registration: Clinicaltrialsregister.eu 2006-002065-39, first registered 5 May 2006. ClinicalTrials.gov NCT01742702, first registered 5 December 2012.

Plasma uric acid is related to large arterial stiffness but not to other hemodynamic variables: a study in 606 normotensive and never-medicated hypertensive subjects.

BACKGROUND: Elevated level of plasma uric acid (PUA) has been associated with cardiovascular disease, but whether uric acid is an independent risk factor or merely a marker remains controversial. METHODS: We investigated in a cross-sectional setting the association of PUA with hemodynamics in 606 normotensive and never-medicated hypertensive subjects (295 men, 311 women, age range 19-73 years) without cardiovascular disease or gout. In all except 15 individuals, PUA was within the normal range. Supine hemodynamics were recorded using whole-body impedance cardiography and radial tonometric pulse wave analysis. RESULTS: The mean concentrations of PUA in age, sex and body mass index adjusted quartiles were 234, 278, 314, and 373 µmol/l, respectively. The highest PUA quartile presented with higher aortic to popliteal pulse wave velocity (PWV) than the lowest quartile (8.7 vs. 8.2 m/s, p = 0.026) in analyses additionally adjusted for plasma concentrations of C-reactive protein, low density lipoprotein cholesterol, triglycerides, and mean aortic blood pressure. No differences in radial and aortic blood pressure, wave reflections, heart rate, cardiac output, and systemic vascular resistance were observed between the quartiles. In linear regression analysis, PUA was an independent explanatory factor for PWV (ß = 0.168, p < 0.001, R2 of the model 0.591), but not for systolic or diastolic blood pressure. When the regression analysis was performed separately for men and women, PUA was an independent predictor of PWV in both sexes. CONCLUSIONS: PUA concentration was independently and directly associated with large arterial stiffness in individuals without cardiovascular disease and PUA levels predominantly within the normal range. Trial registration ClinicalTrials.gov NCT01742702.

Plasma total calcium concentration is associated with blood pressure and systemic vascular resistance in normotensive and never-treated hypertensive subjects.

Purpose: The underlying causes of primary hypertension are not fully understood. Evidence on the relation of plasma calcium concentration with blood pressure (BP) is inconsistent and relies largely on studies utilizing office BP measurements in populations using cardiovascular drugs. In many studies adjustment for confounders was not optimal. In this cross-sectional study we examined the association of plasma total calcium concentration with the haemodynamic determinants of blood pressure.Subjects and methods: Supine haemodynamics were recorded using pulse wave analysis, whole-body impedance cardiography, and heart rate variability analysis in 618 normotensive or never-treated hypertensive subjects (aged 19-72 years) without diabetes, cardiovascular or renal disease, or cardiovascular medications. Linear regression analysis was used to investigate factors associated with haemodynamic variables.Results: Mean age was 45.0 years, body mass index 26.8 kg/m2, seated office BP 141/89 mmHg, and 307 subjects (49.7%) were male. Mean values of routine blood and plasma chemistry analyses were within the reference limits of the tests except for low-density lipoprotein cholesterol (3.05 mmol/l). In the laboratory, mean supine radial BP was 131/75 mmHg, and both systolic and diastolic BP correlated directly with plasma total calcium concentration (r = 0.25 and r = 0.22, respectively, p < 0.001 for both). In regression analysis plasma total calcium concentration was an independent explanatory variable for radial and aortic systolic and diastolic BP, and systemic vascular resistance, but not for cardiac output, pulse wave velocity, or any of the heart rate variability parameters.Conclusion: Plasma total calcium concentration was directly associated with systolic and diastolic BP and systemic vascular resistance in normotensive or never-treated hypertensive subjects without comorbidities and cardiovascular medications. Higher plasma calcium concentration potentially plays a role in primary hypertension via an effect on vascular resistance.

Atherogenic index of plasma is related to arterial stiffness but not to blood pressure in normotensive and never-treated hypertensive subjects.

BACKGROUND AND AIMS: Atherogenic index of plasma (AIP), defined as the logarithm of triglycerides to high-density lipoprotein cholesterol (HDL-C) ratio, is a strong predictor of future cardiovascular disease. Our aim was to examine the association of AIP with haemodynamic variables in normotensive and never-treated hypertensive subjects in a cross-sectional study. METHODS: Supine haemodynamics in 615 subjects without antihypertensive and lipid-lowering medications were examined using whole-body impedance cardiography and radial pulse wave analysis. Linear regression analysis was applied to investigate the association of AIP with haemodynamic variables and age, sex, body mass index (BMI), smoking status, alcohol consumption, plasma C-reactive protein, electrolytes, uric acid, low density lipoprotein cholesterol (LDL-C), estimated glomerular filtration rate, and quantitative insulin sensitivity check index. RESULTS: The demographics and laboratory values of the study population were (mean ± 95% confidence interval): age 44.9 ± 1.0 years, BMI 26.8 ± 0.4 kg/m2, office blood pressure 140.6 ± 1.6/89.4 ± 1.0 mmHg, total cholesterol 5.2 ± 0.08, LDL-C 3.1 ± 0.08, triglycerides 1.2 ± 0.08, HDL-C 1.6 ± 0.04 mmol/l, and AIP -0.15 ± 0.02. Age (standardized coefficient Beta 0.508, p < .001) and aortic systolic blood pressure (Beta 0.239, p < .001) presented with the strongest associations with pulse wave velocity. However, AIP was also associated with pulse wave velocity (Beta 0.145, p < .001). AIP was not related with aortic or radial blood pressure, cardiac output, systemic vascular resistance, or augmentation index. CONCLUSIONS: AIP is directly and independently associated with arterial stiffness, a variable strongly related to cardiovascular risk. This supports more widespread use of AIP in standard clinical cardiovascular disease risk evaluation.

LDL cholesterol is associated with systemic vascular resistance and wave reflection in subjects naive to cardiovascular drugs.

BACKGROUND AND AIM: Low density lipoprotein cholesterol (LDL-C) is a primary risk factor for atherosclerosis, but it is also associated with elevated blood pressure (BP) and future development of hypertension. We examined the relationship between LDL-C and haemodynamic variables in normotensive and never-treated hypertensive subjects. METHODS: We recruited 615 volunteers (19-72 years) without lipid-lowering and BP-lowering medication. Supine haemodynamics were recorded using continuous radial pulse wave analysis, whole-body impedance cardiography, and single channel electrocardiogram. The haemodynamic relations of LDL-C were examined using linear regression analyses with age, sex, body mass index (BMI) (or height and weight as appropriate), smoking status, alcohol use, and plasma C-reactive protein, sodium, uric acid, high density lipoprotein cholesterol (HDL-C), triglycerides, estimated glomerular filtration rate, and quantitative insulin sensitivity check index as the other included variables. RESULTS: The mean (SD) characteristics of the subjects were: age 45 (12) years, BMI 27 (4) kg/m2, office BP 141/89 (21/13) mmHg, creatinine 74 (14) µmol/l, total cholesterol 5.2 (1.0), LDL-C 3.1 (0.6), triglycerides 1.2 (0.8), and HDL-C 1.6 (0.4) mmol/l. LDL-C was an independent explanatory factor for aortic systolic and diastolic BP, augmentation index, pulse wave velocity (PWV), and systemic vascular resistance index (p < 0.05 for all). When central BP was included in the model for PWV, LDL-C was no longer an explanatory factor for PWV. CONCLUSIONS: LDL-C is independently associated with BP via systemic vascular resistance and wave reflection. These results suggest that LDL-C may play a role in the pathogenesis of primary hypertension.

Central wave reflection is associated with peripheral arterial resistance in addition to arterial stiffness in subjects without antihypertensive medication.

BACKGROUND: Augmentation index, a marker of central wave reflection, is influenced by age, sex, height, blood pressure, heart rate, and arterial stiffness. However, the detailed haemodynamic determinants of augmentation index, and their relations, remain uncertain. We examined the association of augmentation index with vascular resistance and other haemodynamic and non-haemodynamic factors. METHODS: Background information, laboratory values, and haemodynamics of 488 subjects (239 men, 249 women) without antihypertensive medication were obtained. Indices of central wave reflection, systemic vascular resistance, cardiac function, and pulse wave velocity were measured using continuous radial pulse wave analysis and whole-body impedance cardiography. RESULTS: In a regression model including only haemodynamic variables, augmentation index in males and female subjects, respectively, was associated with systemic vascular resistance (ß = 0.425, ß = 0.336), pulse wave velocity (ß = 0.409, ß = 0.400) (P < 0.001 for all), stroke volume (ß = 0.256, ß = 0.278) (P = 0.001 for both) and heart rate (ß = -0.150, ß = -0.156) (P = 0.049 and P = 0.036). When age, height, weight, smoking habits, and laboratory values were included in the regression model, the most significant explanatory variables for augmentation index in males and females, respectively, were age (ß = 0.577, ß = 0.557) and systemic vascular resistance (ß = 0.437, ß = 0.295) (P < 0.001 for all). In the final regression model, pulse wave velocity was not a significant explanatory variable for augmentation index, probably due to the high correlation of this variable with age (Spearman's correlation ≥0.617). CONCLUSION: Augmentation index is strongly associated with systemic vascular resistance in addition to arterial stiffness. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01742702 .

The type of the functional cardiovascular response to upright posture is associated with arterial stiffness: a cross-sectional study in 470 volunteers.

BACKGROUND: In a cross-sectional study we examined whether the haemodynamic response to upright posture could be divided into different functional phenotypes, and whether the observed phenotypes were associated with known determinants of cardiovascular risk. METHODS: Volunteers (n = 470) without medication with cardiovascular effects were examined using radial pulse wave analysis, whole-body impedance cardiography, and heart rate variability analysis. Based on the passive head-up tilt induced changes in systemic vascular resistance and cardiac output, the principal determinants of blood pressure, a cluster analysis was performed. RESULTS: The haemodynamic response could be clustered into 3 categories: upright increase in vascular resistance and decrease in cardiac output were greatest in the first (+45 % and -27 %, respectively), smallest in the second (+2 % and -2 %, respectively), and intermediate (+22 % and -13 %, respectively) in the third group. These groups were named as 'constrictor' (n = 109), 'sustainer' (n = 222), and 'intermediate' (n = 139) phenotypes, respectively. The sustainers were characterized by male predominance, higher body mass index, blood pressure, and also by higher pulse wave velocity, an index of large arterial stiffness, than the other groups (p < 0.01 for all). Heart rate variability analysis showed higher supine and upright low frequency/high frequency (LF/HF) ratio in the sustainers than constrictors, indicating increased sympathovagal balance. Upright LF/HF ratio was also higher in the sustainer than intermediate group. In multivariate analysis, independent explanatory factors for higher pulse wave velocity were the sustainer (p < 0.022) and intermediate phenotypes (p < 0.046), age (p < 0.001), body mass index (p < 0.001), and hypertension (p < 0.001). CONCLUSIONS: The response to upright posture could be clustered to 3 functional phenotypes. The sustainer phenotype, with smallest upright decrease in cardiac output and highest sympathovagal balance, was independently associated with increased large arterial stiffness. These results indicate an association of the functional haemodynamic phenotype with an acknowledged marker of cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT01742702.

Alcohol Abuse Increases Rebleeding Risk and Mortality in Patients with Non-variceal Upper Gastrointestinal Bleeding.

BACKGROUND: No current data are available on rebleeding and mortality risk in patients who use alcohol excessively and are admitted for non-variceal upper gastrointestinal bleeding (NVUGIB). This information could help in planning interventions and follow-up protocols for these patients. AIM: This study provides contemporary data on the long-term outcome after first-time NVUGIB in alcohol abusers (AAs) compared to non-abusers (NAs). METHODS: Consecutive patients hospitalized for their first acute gastrointestinal bleeding from 2009 through 2011 were retrospectively recorded and categorized as AA or NA. Risk factors for one-year mortality and rebleeding were identified, and patients were further monitored for long-term mortality until 2015. RESULTS: Alcohol abuse was identified in 19.7% of patients with NVUGIB (n = 518). The one-year rebleeding rate was 16.7% in AAs versus 9.1% in NAs (P = 0.027). Alcohol abuse was associated with a twofold increase in rebleeding risk (P = 0.025); the risk especially increased 6 months after the initial bleeding. The study groups did not differ significantly in 30-day (6.0%) or one-year mortality rates (20.5%). However, there was a tendency for higher overall mortality in AAs than NAs after adjustment of comorbidities. CONCLUSION: AAs with NVUGIB are at high risk of rebleeding, and mortality is increased in AA patients. A close follow-up strategy and long-term proton pump inhibitor therapy are recommended for AA patients with peptic ulcer or esophagitis.

Light-fuelled transport of large dendrimers and proteins.

This work presents a facile water-based supramolecular approach for light-induced surface patterning. The method is based upon azobenzene-functionalized high-molecular weight triazine dendrimers up to generation 9, demonstrating that even very large globular supramolecular complexes can be made to move in response to light. We also demonstrate light-fuelled macroscopic movements in native biomolecules, showing that complexes of apoferritin protein and azobenzene can effectively form light-induced surface patterns. Fundamentally, the results establish that thin films comprising both flexible and rigid globular particles of large diameter can be moved with light, whereas the presented material concepts offer new possibilities for the yet marginally explored biological applications of azobenzene surface patterning.

Volume overload is a major characteristic in primary aldosteronism: a 3-year follow-up study.

OBJECTIVES: We examined haemodynamics, focusing on volume balance and forward and backward wave amplitudes, before and after 2.8 years of targeted treatment of primary aldosteronism. Patients with essential hypertension and normotensive individuals were examined for comparison ( n  = 40 in each group). METHODS: Recordings were performed using radial artery pulse wave analysis and whole-body impedance cardiography. Unilateral aldosteronism was treated with adrenalectomy ( n  = 20), bilateral aldosteronism with spironolactone-based medication ( n  = 20), and essential hypertension with standard antihypertensive agents. RESULTS: Aortic SBP and DBP, forward and backward wave amplitudes, and systemic vascular resistance were equally elevated in primary aldosteronism and essential hypertension. All these haemodynamic variables were similarly reduced by the treatments. Primary aldosteronism presented with 1 litre (∼10%) extracellular water excess ( P  < 0.001) versus the other groups, and this excess was normalized by treatment. Initial pulse wave velocity (PWV) was similarly increased in primary aldosteronism and essential hypertension, but final values remained higher in primary aldosteronism ( P  < 0.001). In regression analyses, significant explanatory factors for treatment-induced forward wave amplitude reduction were decreased systemic vascular resistance ( ß â€Š= 0.380) and reduced extracellular water volume ( ß â€Š= 0.183). Explanatory factors for backward wave amplitude reduction were changes in forward wave amplitude ( ß â€Š= 0.599), heart rate ( ß â€Š= -0.427), and PWV ( ß â€Š= 0.252). CONCLUSION: Compared with essential hypertension, the principal haemodynamic difference in primary aldosteronism was higher volume load. Volume excess elevated forward wave amplitude, which was subsequently reduced by targeted treatment of primary aldosteronism, along with normalization of volume load. We propose that incorporating extracellular water evaluation alongside routine diagnostics could enhance the identification and diagnosis of primary aldosteronism.

Association of resting heart rate with cardiovascular function: a cross-sectional study in 522 Finnish subjects.

BACKGROUND: High resting heart rate (HR) is associated with increased cardiovascular risk in general populations, possibly due to elevated blood pressure (BP) or sympathetic over-activity. We studied the association of resting HR with cardiovascular function, and examined whether the hemodynamics remained similar during passive head-up tilt. METHODS: Hemodynamics were recorded using whole-body impedance cardiography and continuous radial pulse wave analysis in 522 subjects (age 20-72 years, 261 males) without medication influencing HR or BP, or diagnosed diabetes, coronary artery, renal, peripheral arterial, or cerebrovascular disease. Correlations were calculated, and results analysed according to resting HR tertiles. RESULTS: Higher resting HR was associated with elevated systolic and diastolic BP, lower stroke volume but higher cardiac output and work, and lower systemic vascular resistance, both supine and upright (p < 0.05 for all). Subjects with higher HR also showed lower supine and upright aortic pulse pressure and augmentation index, and increased resting pulse wave velocity (p < 0.001). Upright stroke volume decreased less in subjects with highest resting HR (p < 0.05), and cardiac output decreased less in subjects with lowest resting HR (p < 0.009), but clear hemodynamic differences between the tertiles persisted both supine and upright. CONCLUSIONS: Supine and upright hemodynamic profile associated with higher resting HR is characterized by higher cardiac output and lower systemic vascular resistance. Higher resting HR was associated with reduced central wave reflection, in spite of elevated BP and arterial stiffness. The increased cardiac workload, higher BP and arterial stiffness, may explain why higher HR is associated with less favourable prognosis in populations.

Ambulatory daytime blood pressure versus tonometric blood pressure measurements in the laboratory: effect of posture.

OBJECTIVE: To compare blood pressure (BP) in tonometric radial artery recordings during passive head-up tilt with ambulatory recordings and evaluate possible laboratory cutoff values for hypertension. METHODS: Laboratory BP and ambulatory BP were recorded in normotensive (n = 69), unmedicated hypertensive (n = 190), and medicated hypertensive (n = 151) subjects. RESULTS: Mean age was 50.2 years, BMI 27.7 kg/m 2 , ambulatory daytime BP 139/87 mmHg, and 276 were male (65%). As supine-to-upright changes in SBP ranged from -52 to +30 mmHg, and in DBP from -21 to +32 mmHg, the mean values of BP supine and upright measurements were compared with ambulatory BP. The mean(supine+upright) systolic laboratory BP was corresponding to ambulatory level (difference +1 mmHg), while mean(supine+upright) DBP was 4 mmHg lower ( P  < 0.05) than ambulatory value. Correlograms indicated that laboratory 136/82 mmHg corresponded to ambulatory 135/85 mmHg. When compared with ambulatory 135/85 mmHg, the sensitivity and specificity of laboratory 136/82 mmHg to define hypertension were 71.5% and 77.3% for SBP, and 71.7% and 72.8%, for DBP, respectively. The laboratory cutoff 136/82 mmHg classified 311/410 subjects similarly to ambulatory BP as normotensive or hypertensive, 68 were hypertensive only in ambulatory, while 31 were hypertensive only in laboratory measurements. CONCLUSION: BP responses to upright posture were variable. When compared with ambulatory BP, mean(supine+upright) laboratory cutoff 136/82 mmHg classified 76% of subjects similarly as normotensive or hypertensive. In the remaining 24% the discordant results may be attributed to white-coat or masked hypertension, or higher physical activity during out-of-office recordings.

Blood Haemoglobin Concentration Is Directly and Independently Related with Pulse Wave Velocity, a Measure of Large Artery Stiffness.

High haemoglobin level has been associated with metabolic syndrome, elevated blood pressure (BP), and increased mortality risk. In this cross-sectional study, we investigated the association of blood haemoglobin with haemodynamics in 743 subjects, using whole-body impedance cardiography and pulse wave analysis. The participants were allocated to sex-stratified haemoglobin tertiles with mean values 135, 144, and 154 g/L, respectively. The mean age was similar in all tertiles, while body mass index was higher in the highest versus the lowest haemoglobin tertile. The highest haemoglobin tertile had the highest erythrocyte and leukocyte counts, plasma C-reactive protein, uric acid, renin activity, and aldosterone. The lipid profile was less favourable and insulin sensitivity lower in the highest versus the lowest haemoglobin tertile. Aortic BP, cardiac output, and systemic vascular resistance were similar in all tertiles, while the pulse wave velocity (PWV) was higher in the highest versus the lowest haemoglobin tertile. In linear regression analysis, age (Beta 0.478), mean aortic BP (Beta 0.178), uric acid (Beta 0.150), heart rate (Beta 0.148), and aldosterone-to-renin ratio (Beta 0.123) had the strongest associations with PWV (p < 0.001 for all). Additionally, haemoglobin concentration was an explanatory factory for PWV (Beta 0.070, p = 0.028). To conclude, blood haemoglobin concentration had a small direct and independent association with a measure of large artery stiffness.

Dietary phosphate binding and loading alter kidney angiotensin-converting enzyme mRNA and protein content in 5/6 nephrectomized rats.

BACKGROUND: Vitamin D receptor activation with paricalcitol can modulate the transcription of renin-angiotensin system components in the surgical 5/6 nephrectomy rat model (5/6 NX) of chronic renal insufficiency. We tested the hypothesis whether dietary modification of phosphate influences kidney renin-angiotensin system gene expression at the mRNA level in 5/6 NX rats. METHODS: Fifteen weeks after surgery, rats were given control diet (0.3% calcium, 0.5% phosphate), phosphate-lowering diet (3% calcium as carbonate) or high-phosphate diet (1.5%) for 12 weeks. Sham-operated rats were on control diet. RESULTS: Blood pressure, plasma phosphate, parathyroid hormone, glomerulosclerosis, tubulointerstitial damage, and FGF-23 were increased in remnant kidney rats, whereas creatinine clearance was decreased. Phosphate, parathyroid hormone, glomerulosclerosis, tubulointerstitial damage, and FGF-23 were further elevated by the high-phosphate diet, but were reduced by the phosphate-lowering diet. Plasma calcium was increased with the phosphate-lowering diet and decreased with the high-phosphate diet. Remnant kidney rats on control diet showed upregulated kidney angiotensin-converting enzyme (ACE) and angiotensin (Ang) IV receptor (AT(4)) transcription, while ACE2, Ang II type 2 receptor and renin receptor transcription were downregulated in comparison with sham rats. Phosphate-lowering diet reduced whereas high-phosphate diet increased kidney ACE, and these effects were observed at both mRNA and protein levels. Dietary phosphate loading also resulted in lower AT(1a) gene transcription. CONCLUSION: Dietary phosphate loading was associated with elevated kidney ACE expression, increased tissue damage and lower AT(1a) transcription in 5/6 NX rats. Phosphate binding with 3% calcium carbonate had opposite effects on ACE and kidney damage.

Allelic variant of NOS1AP effects on cardiac alternans of repolarization during exercise testing.

INTRODUCTION: A repolarization abnormality manifested as T-wave alternans (TWA) in electrocardiogram (ECG) predicts cardiovascular mortality. A common variant in the NOS1AP gene is associated with mortality and QT interval duration, possibly in a gender-specific manner, but data is lacking on potential association with TWA. This study tested association between rs10494366 in NOS1AP and both TWA and 4-year mortality. MATERIAL AND METHODS: A total of 1963 Finnish Cardiovascular Study participants (36.6% female, 57.1 ± 13.0 years) were genotyped and their maximal TWA values were measured from continuous ECG recordings during clinical exercise test at rest, exercise and recovery. RESULTS: We observed a significant gender-specific effect of NOS1AP genotype on TWA. In all subjects, there was no statistically significant difference between the three genotypes (TT, TG, GG) in the responses of TWA over the entire exercise test (time-by-genotype interaction p = 0.057). In women, after adjustment for age, coronary heart disease and ß-blocker medication status, changes of TWA over different phases of exercise test were significantly associated with NOS1AP genotype (time-by-genotype interaction p = 0.001). In men, NOS1AP rs10494366 was not associated with TWA. During follow-up (mean 47 months), 113 patients died. NOS1AP rs10494366 was not a statistically significant predictor of mortality. CONCLUSION: The NOSIAP variant rs10494366 influences TWA and TWA response during clinical exercise test in females. Gender-specific effects have also been previously reported for the influence of the variant on QT interval. If replicated, these findings should prompt studies to further elucidate the mechanisms underlying the gender differences in NOS1AP effects on repolarization.

Disparate Information Provided by Pulse Wave Velocity versus Other Measures of Aortic Compliance in End-Stage Renal Disease.

INTRODUCTION: Unfavorable changes in cardiac and arterial function are related to poor prognosis in chronic kidney disease (CKD). We compared hemodynamic profiles between subjects with end-stage renal disease and 2 control groups with corresponding pulse wave velocities (PWVs). METHODS: Noninvasive hemodynamics were recorded during passive head-up tilt in CKD stage 5 patients (n = 35), patients with primary hypertension (n = 35, n = 30 with antihypertensive medications), and subjects without cardiovascular or renal diseases and cardiovascular medications (n = 70). The groups were selected to have corresponding age, sex, body mass index, and PWV. Hemodynamic data were captured using whole-body impedance cardiography and radial tonometric pulse wave analysis. RESULTS: Supine blood pressure did not differ between the groups, but upright diastolic blood pressure was lower in CKD patients than in the 2 control groups (p ≤ 0.001 for both, RANOVA). Despite similar PWV, supine aortic pulse pressure was higher in CKD patients versus nonmedicated subjects (p = 0.029). Two additional measures indicated reduced aortic compliance in CKD patients versus both control groups: lower ratio of stroke index to aortic pulse pressure (p ≤ 0.023) and higher aortic characteristic impedance (p ≤ 0.003). The subendocardial viability ratio was lower in the CKD group than in both control groups (p ≤ 0.039). CONCLUSION: In the absence of differences in PWV, higher aortic pulse pressure and characteristic impedance, and lower ratio of stroke index to aortic pulse pressure, suggest reduced aortic compliance and impaired left ventricular function in CKD patients. A lower subendocardial viability ratio predisposes the CKD patients to impaired cardiac oxygen supply versus hypertensive patients and nonmedicated controls.

Reduced systemic vascular resistance in healthy volunteers with presyncopal symptoms during a nitrate-stimulated tilt-table test.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Nitrates may facilitate syncope through various pathways, but the precise mechanism of nitrate-induced syncope is still under debate. The purpose of the present study was to compare the underlying haemodynamic mechanisms in subjects without and with presyncopal symptoms during a nitroglycerin-stimulated tilt-table test. WHAT THIS STUDY ADDS: A major decrease in systemic vascular resistance was documented in subjects with presyncope during 0.25 mg nitroglycerin-stimulated tilt-table test, in the absence of changes in cardiac output. These findings indicated that even a small dose of nitroglycerin significantly decreased arterial resistance and cardiac afterload. AIMS The mechanism of nitrate-induced syncope remains controversial. We examined the haemodynamic changes in healthy volunteers during nitroglycerin-stimulated tilt-table test. METHODS: Continuous radial pulse wave analysis, whole-body impedance cardiography and plethysmographic finger blood pressure were recorded in a supine position and during head-up tilt in 21 subjects with presyncopal symptoms (6 male/15 female, age 43 ± 3 years) after 0.25 mg sublingual nitroglycerin and 21 control subjects (6 male/15 female, age 43 ± 2 years). The drug was administered in the supine position and a passive head-up tilt followed 5 min later. Additionally, nitroglycerin was only administered during head-up tilt in 19 subjects and the haemodynamics were recorded. RESULTS: Supine and upright haemodynamics were similar before nitroglycerin administration in the two groups. During the nitroglycerin-stimulated tilt test, aortic and radial mean blood pressure decreased significantly more in the presyncope group when compared with the controls (P= 0.0006 and P= 0.0004, respectively). The decreases in systemic vascular resistance (P= 0.0008) and heart rate (P= 0.002), and increase in aortic reflection time (P= 0.0002) were greater in the presyncope group, while the change in cardiac index was not different between the groups (P= 0.14). If nitroglycerin was administered during the upright tilt and not in supine position, the haemodynamic changes were quite corresponding. CONCLUSIONS: Presyncopal symptoms during nitrate-stimulated tilt test were explained by decreased systemic vascular resistance and increased aortic reflection time, while cardiac output remained unchanged. These findings indicated reduced arterial resistance in nitroglycerin-induced presyncope.