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.

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.

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.

Metabolic syndrome is associated with decreased heart rate variability in a sex-dependent manner: a comparison between 252 men and 249 women.

Impaired heart rate variability (HRV) is associated with increased risk of cardiovascular disease, but evidence regarding alterations of HRV in metabolic syndrome (MetS) remains elusive. In order to examine HRV in MetS, we subjected 501 volunteers without atherosclerosis, diabetes or antihypertensive medication, mean age 48 years, to passive head-up tilt. The subjects were divided to control men (n = 131), men with MetS (n = 121), control women (n = 191) and women with MetS (n = 58) according to the criteria by Alberti et al. (Circulation, 2009, 120, 1640). In unadjusted analyses (i) men and women with MetS had lower total power and high-frequency (HF) power of HRV than controls whether supine or upright (P<0·05 for all). (ii) Supine low-frequency (LF) power of HRV was lower in men (P = 0·012) but not in women (P = 0·064) with MetS than in controls, while men and women with MetS had lower upright LF power of HRV than controls (P <0·01 for both). (iii) The LF:HF ratio did not differ between subjects with and without MetS. After adjustment for age, smoking habits, alcohol intake, height, heart rate and breathing frequency, only the differences in upright total power and HF power of HRV between women with MetS and control women remained significant (P<0·05). In conclusion, reduced total and HF power of HRV in the upright position may partially explain why the relative increase in cardiovascular risk associated with MetS is greater in women than in men. Additionally, the present results emphasize that the confounding factors must be carefully taken into consideration when evaluating HRV.

Effect of present versus previous smoking on non-invasive haemodynamics.

We examined cardiovascular function in 637 volunteers (19-72 years) without antihypertensive medication in never smokers (n = 365), present smokers (n = 81) and previous smokers (n = 191, median abstinence 10 years). Haemodynamics during passive head-up tilt were recorded using whole-body impedance cardiography and radial pulse wave analysis. Results were adjusted for age, sex, body mass index, LDL cholesterol and alcohol use. Systolic and diastolic blood pressure, heart rate, and pulse wave velocity were not different between the groups. Supine aortic reflection times did not differ, while upright values were shorter in present versus previous smokers (p = 0.04). Heart rate adjusted augmentation index was increased in the supine position in present smokers versus controls (p = 0.045), and in present (p < 0.001) and previous (p = 0.031) smokers versus controls in the upright position. Supine and upright cardiac output was higher (p ≤ 0.016) and systemic vascular resistance lower (p ≤ 0.001) in present versus previous smokers. In spite of the long abstinence, in the upright position previous smokers had lower cardiac output (p = 0.032) and higher systemic vascular resistance (p = 0.014) than never smokers. In the absence of differences in blood pressure and arterial stiffness, present smokers presented with hyperdynamic circulation and enhanced wave reflection compared with previous smokers.

Late onset spinal motor neuronopathy is caused by mutation in CHCHD10.

OBJECTIVE: A study was undertaken to identify the responsible gene defect underlying late onset spinal motor neuronopathy (LOSMoN/SMAJ; Online Mendelian Inheritance in Man #615048), an autosomal dominant disease mapped to chromosome 22q11.2. METHODS: The previous genetic linkage approach by microsatellite haplotyping was continued in new families. A whole genome sequencing was performed to find all possibly pathogenic mutations in the linked area. The detected variations were verified by Sanger sequencing. RESULTS: Six new SMAJ families were identified based on the unique founder haplotype. A critical recombination in 1 family restricted the linked area to 727kb between markers SHGC-106816 and D22S345. In whole genome sequencing a previously unknown mutation c.197G>T p.G66V in CHCHD10 was identified. The mutation was shown to segregate with the disease in 55 patients from 17 families. INTERPRETATION: Mutation c.197G>T p.G66V in CHCHD10 is the cause of the lower motor neuron syndrome LOSMoN/SMAJ. During the preparation of this article other mutations were reported to cause frontotemporal dementia-amyotrophic lateral sclerosis syndrome, indicating that the CHCHD10 gene is largely important for the motor and cognitive neuronal systems.