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

Anna M Tahvanainen, Antti J Tikkakoski, Jenni K Koskela, Klaus Nordhausen, Jani M Viitala, Miia H Leskinen, Mika A P Kähönen, Tiit Kööbi, Marko T Uitto, Jari Viik, Jukka T Mustonen, Ilkka H Pörsti, Anna M Tahvanainen, Antti J Tikkakoski, Jenni K Koskela, Klaus Nordhausen, Jani M Viitala, Miia H Leskinen, Mika A P Kähönen, Tiit Kööbi, Marko T Uitto, Jari Viik, Jukka T Mustonen, Ilkka H Pörsti

Abstract

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.

Keywords: Arterial stiffness; Cardiac output; Head-up tilt; Heart rate; Systemic vascular resistance.

Figures

Fig. 1
Fig. 1
Clustering to phenotypes. Cluster dendrogram according to hierarchical clustering using Ward’s criterion for the squared Euclidean distances. Dashed line indicates the cut-off point for the three phenotypic clusters (I, II and III). The classification was based on the changes in systemic vascular resistance index and cardiac index in response to passive head-up tilt (n = 470)
Fig. 2
Fig. 2
Average haemodynamics during the head-up tilt protocol. Average radial systolic (a) and diastolic (b) blood pressure, systemic vascular resistance index (c), and cardiac index (d) during the 15-min measurement protocol (5 min supine – 5 min upright – 5 min supine) in all subjects (n = 470). Mean ± 95 % confidence interval
Fig. 3
Fig. 3
Haemodynamics in the 3 phenotypes in response to upright posture. Systemic vascular resistance index and cardiac index during the measurement protocol, respectively, in the constrictor (a, d), intermediate (b, e), and sustainer phenotypes (c, f). Mean (bold line) and individual curves (grey lines)
Fig. 4
Fig. 4
Arterial stiffness in the 3 phenotypes. Boxplots depicting supine pulse wave velocity in the constrictor, intermediate and sustainer phenotypes. Median (line inside box), 25th to 75th percentile (box), range (+), and outliers (open circles); *p < 0.05, **p < 0.01, ***p < 0.001
Fig. 5
Fig. 5
Heart rate variability in the 3 phenotypes. Boxplots depicting low frequency (LF) power (a), high frequency (HF) power (b), and LF/HF ratio (c) of heart rate variability in supine and upright positions. Median (line inside box), 25th to 75th percentile (box), and range (whiskers); *p < 0.05, **p < 0.01, ***p < 0.001

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