Study design
This cross-sectional study included a random subgroup of 75 patients measured within an inception cohort of geriatric outpatients who were consecutively referred to the outpatient clinic of a middle-sized teaching hospital (Bronovo hospital, The Hague, The Netherlands) between March 2011 and January 2012. This subgroup is part of a bigger cohort, which was described in detail earlier [20]. Patients were referred to the outpatient clinic by a general practitioner for reasons including but not limited to, mobility problems, falls, complaints of dizziness and/or memory problems. All patients underwent a comprehensive geriatric assessment (CGA) assessing somatic, psychological and social factors, obtained during a two-hour visit. Both intermittent BP measurements and CoP measurements were available in 75 patients. Due to availability of equipment (continuous BP measurements after June 2011) continuous blood pressure data was available in 62 patients. Data of four patients were excluded because of technical problems, leaving 58 patients for analysis. In 38 patients of this subgroup, complete data on intermittent BP, CoP measurements and continuous BP measurements were available. See Fig. 1 for a visual representation. The institutional review board of the Leiden University Medical Center (Committee Medical Ethics (CME), Leiden, the Netherlands) reviewed and approved the study. The need for individual informed consent was waived, as this retrospective research was based on regular clinical care.
Characteristics of geriatric outpatients
Questionnaires were used to obtain information about age, sex, living situation, current smoking, history of falls during the preceding twelve months, self-reported impaired standing balance and use of walking aid. Body mass index (BMI) was calculated using measurements of height and weight, using a bioelectrical impedance analysis or a scale if patients had a pacemaker, to the nearest decimal (0.1). The number of medication used and information on diseases was extracted from medical charts. Multimorbidity was defined as the presence of two or more diseases, including chronic obstructive pulmonary disease, diabetes mellitus, hypertension, malignancy, myocardial infarction, Parkinson’s disease and (osteo)arthritis. The Mini Mental State Examination (MMSE) was used to assess global cognitive functioning [24]. Handgrip strength was measured in standing position with arm stretched and parallel to the body using a hand dynamometer (Jamar, Sammons Preston, Inc., Bolingbrook, IL, USA). Three trials were performed alternately for each hand; maximum performance of both hands was determined [25]. Gait speed was measured with a 10 m walking test during preferred pace. The Short Physical Performance Battery (SPPB) was used to assess physical functioning. The SPPB includes the ability to maintain standing balance with eyes open in three different standing positions, a timed chair stand test and a timed four meter walking test [26].
Measurement protocol and BP measurements
Postural changes were imposed after lying supine and fully supported for at least 5 min by an automatic lift chair (Vario 570, Fitform B.V., Best, The Netherlands) assisting the patients to a full standing position with eyes open in a standardized way, i.e. controlling the speed of transition from supine to standing position. Patients subsequently resumed full standing position in an active way.
Intermittent BP measurements were performed using an automated sphygmomanometer on the left arm (Welch Allyn, Skaneateles, USA). Supine BP was measured preceding postural change and after the patient spent at least 5 min in supine position. After 1 and 3 min in standing position, BP measurements were repeated. BP change was determined by subtracting BP at 1 or 3 min from the supine BP; a positive BP change therefore indicates a decrease in BP from supine to standing position.
In the random subgroup (n = 38), BP was measured continuously and non-invasively concurrent with the intermittent BP measurement during supine and standing position using a digital photoplethysmograph with a cuff placed on the right middle finger (Finometer PRO, Finapres Medical Systems BV, Amsterdam, The Netherlands) [27]. Beat-to-beat BP data was obtained using BeatScope 1.1 software (Finapres Medical systems BV, Amsterdam, The Netherlands). Beat-to-beat BP data was averaged over 5 s time periods using MATLAB (The MathWorks, Natick, Mass., USA) [28]. Supine BP was defined as the mean BP during the last 60 s in supine position preceding postural change. During the 3 min of stance, twelve consecutive time periods of 15 s were examined. BP change was calculated by subtracting the lowest BP per interval from the supine BP for each time period, yielding 12 measurements.
OH was defined as a drop in systolic BP (SBP) of at least 20 mmHg and/or a drop in diastolic BP (DBP) of 10 mmHg or more within 3 min of standing position [15]. OH intermittent was defined using the BP change at 1 min and 3 min of standing position. Presence of OHcontinuous was determined for every consecutive time period of 15 s, during the 3 min of standing position. iOH was defined as a transient decrease in BP within 15 s after postural change with a decline in SBP of at least 40 mmHg and/or 20 mmHg in DBP [16] and could only obtained from the continuous BP measurements.
Center of pressure movement
CoP movement was measured directly after standing up, concurrently with BP measurements, during the 3 min of standing position on a triangular 6 degrees of freedom force plate (ForceLink BV, Culemborg, The Netherlands). A trigger was sent to the force plate by the experimenter at the moment the patient was standing on the force plate. As a safety measure, a support was present in case the patient needed some assistance to prevent from actual falling. Data were recorded with a sample frequency of 1 kHz and were processed in MATLAB (The MathWorks, Natick, Mass., USA). Before analysis, data were low-pass filtered with a cut-off frequency of 10 Hz. CoP movement was expressed in five different CoP parameters (i.e. mean amplitude, amplitude variability, range, mean velocity and velocity variability) and were calculated per 15 s time period for the entire duration of standing upright. For each CoP parameter the time period of its maximal value representing maximum CoP movement (maximum CoP) was determined [29]. Each CoP parameter was transformed into standardized CoP parameters, resulting in Z-score. Direction-specific CoP composite scores (i.e. anterior-posterior (AP) and medial-lateral (ML) direction) were calculated from the standardized single CoP parameters for each consecutive time period by averaging Z-scores of the CoP parameters [22]. Both CoP composite scores and single CoP parameters in AP and ML direction were used for further analysis.
Statistical analyses
Mean and standard deviation (SD) are used to present continuous variables with a Gaussian distribution. Continuous variables with a non-Gaussian distribution are presented as median and interquartile range (IQR).
Spearman’s rho correlation analysis was used to assess the association between BP change and CoP movement in three ways: (i) the correlation between intermittently measured BP change at 1 and 3 min and CoP parameters respectively in the 15 s intervals before (45-60 s) and after (60-75 s) 1 min of standing, and in the 15 s interval before (165-180 s) 3 min of standing; (ii) the correlation between the continuously measured maximum BP change and the CoP parameters in the 15 s intervals before, during and after the maximum BP change; (iii) the correlation between the maximum of each CoP parameter and the BP change in the 15 s intervals before, during and after the maximum CoP. As only SBP showed the largest change, this parameter was used for further analysis. Figure 2 shows a visual representation of the abovementioned analysis, with the SBP change and CoP amplitude in ML-direction of a representative patient during supine position and over 3 min after postural change. To minimize type I errors, a Bonferroni correction was applied and the alpha was set at 0.005.
Mann-Whitney U-test was used to assess possible differences in each single CoP parameter between the OHcontinuous group and non-OHcontinuous group. Each CoP parameter was averaged between 30 and 180 s after standing, since it was previously shown that patients needed at least 30 s to find their balance after postural change, regardless of having OH or not [30]. For the Mann-Whitney U test, the median of each single CoP parameter was determined and compared between the OH and non-OH group. P values lower than 0.05 were considered statistically significant for the Mann-Whitney U-test.
Both iOH and OHintermittent groups were too small to use in separate analyses.
Statistical Package for the Social Sciences (SPSS Inc., Chicago, USA) version 20.0 was used for statistical analyses. GraphPad Prism version 5.01 was used to perform visualization.