REVISED ABSTRACT METHODS CONCLUSIONS Dependence of mobil-o-graph Pulse Wave Velocity on AGE and 24-hour ambulatory SYSTOLIC Blood Pressure Tanveer Hussain, Safi U. Khan, Peter J. Osmond, and Joseph L. Izzo, Jr. Department of Medicine, University at Buffalo and Erie County Medical Center, Buffalo, NY. RESULTS RESULTS   The Mobil-O-Graph (IEM, Stolberg, Germany) reports pulse wave velocities (PWV) and other hemodynamic variables as part of 24-hour ambulatory BP monitoring (ABPM). PWV is determined by a proprietary formula that includes “demographic information and pulse wave analysis”. The aim of this study was to identify the principal components of the IEM PWV algorithm. We studied 38 subjects (16 males, 22 females) with normal and elevated BP, some on treatment. Each individual wore the APBM device on the non-dominant arm for a 24 hours with measurements every 20 minutes. Within and between-individual means and 2-variable correlations for PWV with other variables were calculated. Stepwise multiple regression was used to establish various models for inter-individual variation in PWV. Mean (range) of demographic variables were: age 56 (25-80) years, weight 89 (44-136) kg, height 1.65 (1.5-1.9) m. Office systolic BP was 146 (98-179) mm Hg, diastolic BP 81 (59-105) mmHg. Mean 24-Hr brachial SBP was 141 (101-173) and DBP 85 (59-116) mmHg. Within subjects, PWV values varied quite widely over 24-hrs and within-individual PWVs correlated very closely with corresponding brachial systolic BP values (mean r2 > 0.9). Between individuals, mean 24-hour PWV correlated very strongly with age (r2 =0.86) and mean 24-hour systolic BP (r2 = 0.50). Using stepwise multiple linear regression, age explained 86% of the variation in PWV, 24-hour brachial systolic BP explained another 10% of the variation, and the combination of heart rate and P1 (the first component of systolic BP, which approximates aortic impedance)added another 2%; thus, in the 4-element model, we could explain 98% of the PWV variation in the cohort. We conclude that the main determinants of MobilOGraph PWV are age and 24-hour brachial systolic BP; minor contributions from heart rate and central P1 are negligible. Office BP values could not be substituted for 24-hour BP values in any model. The protocol was reviewed and approved by University at Buffalo Health Sciences Institutional Review Board and written informed consent was signed by each participant prior to study participation. Subjects in this convenience sample were recruited from the hospital community including our research staff. The ethnic background included African-Americans, Caucasians, and Asian Indians. Most all the study subjects were hypertensives on treatment but a special attention was paid to include a few normotensive and younger subjects. Each individual wore the APBM device on the non-dominant arm for a 24 hour with readings every 20 minutes, The Mobil-O-Graph (24 hr pulse wave analysis-ambulatory BP monitoring device with ARCSolver algorithm; IEM, Stolberg, Germany) was used to obtain conventional brachial BP and an ensemble pulse contour (after 10 sec at constant diastolic BP) which was subjected to a generalized transfer function to yield an approximated central pulse contour. To estimate aPWV, the system employs ARCSolver (pulse wave analysis and wave separation analysis) in its proprietary mathematical model that is stated to include “central pressure, and aortic impedance, but not wave timing characteristics”. Correlations between PWV and other hemodynamic variables within an individual were analyzed using Pearson Correlation analysis and then individual correlations means were added to get a collective means and standard deviations among all the subjects. Stepwise multiple linear regression (SPSS software) for PWV included demographics and peripheral and central BP data. Within-individual variation in SBP and PWV Stepwise Regression Coefficients for PWV Model Unstandardized Coefficients Standardized Coefficients t Sig. B SE Beta 1 (Constant) .427 .647   .660 .514 Age .146 .011 .924 13.277 .000 2 -3.237 .566 -5.721 .128 .006 .807 19.718 Brachial SBP .033 .004 .341 8.344 3 -4.672 .754 -6.197 .132 .834 21.521 .034 .349 9.322 HR .016 .097 2.612 .014 4 -5.075 .657 -7.722 .122 .773 20.415 .053 .007 .553 8.011 .027 .160 4.330 P1 -.022 -.220 -3.336 .002 Excluded variables were: race, gender, weight, BMI, height, all office BP parameters (systolic, diastolic, mean, pulse pressure), 24-hour brachial DBP, mean and pulse pressures, and all 24-hour central BP values except P1 (see Table 1) INTERPRETATION PWV varies widely over 24 hours in proportion to the corresponding changes in brachial systolic BP. For each 10 mmHg increase in systolic BP in this individual, PWV increases by 0.3 m/sec. RESULTS Inter-individual variation in PWV Multiple Regression Model for PWV Model R R Square Adj. R Square SE of the Estimate 1 .924a 0.855 0.85 0.629 2 .978b 0.957 0.954 0.347 3 .983c 0.966 0.962 0.317 4 .988d 0.976 0.972 0.271 a Predictors: (Constant), Age   b Predictors: (Constant), Age, brachial SBP c Predictors: (Constant), Age, brachial SBP, HR d Predictors: (Constant), Age, brachial SBP, HR, P1 Thirty-eight individuals completed the evaluation. Thirty-four among them were taking antihypertensive drugs (31 on nebivolol, valsartan or both; 1 on hydrochlorothiazide/lisinopril, 2 on amiloride). Table 1. Variable Mean (SD) Range R2 vs PWV Demographics Age (yrs) 56 (12) 25-80 ***0.862 Height (m) 1.65 (0.10) 1.5-1.9 0.025 Weight (kg) 89 (22) 44-136 0.017 Office measurements Systolic BP 147 (20) 98-179 0.030 Pulse Pressure 65 (13) 39-91 0.039 MAP 103 (14) 72-129 0.002 DBP 82 (12) 59-105 0.003 24-hour IEM data Brachial SBP 141 (18) 101-173 ***0.499 111 (15) 80-139 ***0.317 PP 56 ( 11.6) 38-88 ***0.566 85 (13) 59-116 0.102 Central 129 (18) 92-163 ***0.410 P1 113.5 (16) 82-152 **0.131 98 (22) 73-130 ***0.210 43 (9.7) 28-66 ***0.554 PWV 8.6 (1.8) 5-13 -- Systolic (S) and Diastolic (D) blood pressure) (BP),MAP (Mean arterial pressure),PP (Pulse pressure) and P1 (first component of central systolic BP) values in mmHg. PWV (Pulse wave velocity) values in m/sec. * p<0.05, ** p< 0.0025, *** p<0.0001 BACKGROUND INTERPRETATION Stepwise multiple regression revealed that age and brachial systolic BP explained 96% of the inter-individual variation in PWV Addition of heart rate and central P1 (an estimate of aortic impedance) explained another 1.5% of the observed variation. Arterial stiffness is most commonly assessed by pulse wave velocity (PWV). High PWV is correlated with adverse cardiovascular outcomes and there have been suggestions that PWV is an independent risk indicator that should be measured in all people with hypertension. PWV is extremely age-dependent; the age-related increase in PWV is caused in large measure by an increase in arterial collagen: elastin ratio Arterial stiffness is not constant, varying within and between individuals in relation to arterial size, wall composition, blood flow velocity, and distending pressure, the last of which is not universally appreciated. INTERPRETATION Mean PWV varies in proportion to the age of the individual. For each 10 years of age, PWV increases by 1.4 m/sec. The main determinants of MobilOGraph PWV in this cohort were age and 24-hour brachial systolic BP: Age alone accounted for 86% of the PWV variation. Addition of 24-hour brachial systolic BP explained another 10% of the PWV variation Addition of 24-hour heart rate and central P1 explained another 2% of the PWV variation Office systolic BP could not be substituted for 24-hr ambulatory brachial systolic BP. OBJECTIVE LIMITATIONS The objective of this survey study was to identify which demographic or BP-related variables are the most important determinants of the IEM oscillometric PWV algorithm. Major limitations of this study are the small sample size and the limitations of correlation-regression methodology to estimate relative contributions of “predictor” variables. Correlations depend on an adequate range of values (achieved here) and are strongly affected by inter-individual variation (here desirable), intra-individual physiologic variation (here undesirable) and measurement and model error (always undesirable). INTERPRETATION Age and 24-hour BP variables (brachial and central systolic, mean, pulse pressure) are closely related to PWV but office BP variables are not in this small cohort. INTERPRETATION Mean PWV varies in proportion to mean 24 hour systolic BP. For each 10 mmHg increase in brachial systolic BP, PWV increases by 0.7 m/sec.