Orthostatic Hypertension As a Predisposing Factor for Masked Hypertension

SupplementaRY materials

Orthostatic hypertension as a predisposing factor for masked hypertension

The J-SHIPP study

Yasuharu Tabara, Michiya Igase, , Tetsuro Miki, Yasumasa Ohyagi, Fumihiko Matsuda,

and Katsuhiko Kohara

Correspondence to:

Yasuharu Tabara

Center for Genomic Medicine,

Kyoto University Graduate School of Medicine

Shogoinkawara-cho 53, Sakyo-ku, Kyoto 606-8507, Japan

Tel: 075-751-4157

Fax: 075-751-4167

E-mail:

Supplementary Figure 1. Distribution of orthostatic maximum SBP change.

Orthostatic systolic blood pressure (SBP) change was calculated by subtracting seated SBP from SBP measured at 1 or 3 min after active standing up. Orthostatic hypotension and hypertension was defined as the maximum postural SBP change ≤−20 mmHg and ≥10 mmHg at either standing measurement, respectively.

Supplementary Figure 2. Intra-individual reproducibility of orthostatic SBP change and office-to-awake SBP difference.

Scatter plots shows intra-individual relationship of A: orthostatic SBP change, andB: office-to-awake SBP differences at the first visit (X-axis) and the second visits (Y-axis) measurements (n=101).

Supplementary Table 1. Frequency of masked, white-coat, and sustained hypertension.

Ambulatory monitored BP
NT / HT
Office measured BP / HT / White-coat HT
134 (15.2%) / Sustained HT
248 (28.1%)
NT / NT
352 (39.8%) / Masked HT
150 (17.0%)

Values are number and frequency of subjects.

BP, blood pressure; NT, normotension; HT, hypertension.

Office HT was defined as clinic-measured systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, while awake HT was defined as average of ambulatory monitored awake systolic BP ≥135 mmHg or diastolic BP ≥85 mmHg, irrespective of antihypertensive treatment status.

Supplementary Table 2.Differences in clinical parameters between included and excluded subjects.

Included subjects / Excluded subjects / P
n / 884 / 1,013
Age (years) / 66.3±8.9 / 64.9±9.9 / 0.001
Sex (male, %) / 41.0 / 38.7 / 0.324
BMI (kg/m2) / 23.2±3.0 / 23.2±3.3 / 0.873
History of CVD (%) / 4.8 / 4.6 / 0.914
Office BP / Systolic (mmHg) / 136±20 / 133±19 / <0.001
Diastolic (mmHg) / 77±12 / 76±11 / 0.055
HR (beats/min) / 66±10 / 67±10 / 0.096
Glycemic factors / Glucose (mg/dl) / 102±16 / 104±21 / 0.019
Insulin (μU/ml) / 5.8±3.5 / 6.1±4.8 / 0.110
HOMA-IR / 1.50±1.03 / 1.66±1.88 / 0.025
Plasma lipids / Triglyceride (mg/dl) / 107±59 / 108±61 / 0.476
Total cholesterol (mg/dl) / 214±36 / 219±37 / 0.002
HDL cholesterol (mg/dl) / 66±17 / 66±18 / 0.347

Values are mean ± standard deviation.

BMI, body mass index; BP, blood pressure; HR, heart rate; HOMA-IR, homeostasis model assessment of insulin resistance.

Cardiovascular disease (CVD) includes symptomatic stroke, myocardial infarction, and angina pectoris. HOMA-IR was calculated by the following equation: (glucose × insulin) / 405.

Supplementary Table 3. Correlations between clinical parameters and the SBP phenomena.

Orthostatic
SBP change
(mmHg) / Office-to-awake
SBP differences
(mmHg)
r / P / r / P
Age (years) / 0.053 / 0.119 / 0.025 / <0.001
BMI (kg/m2) / 0.136 / <0.001 / 0.003 / 0.091
Office BP / Systolic (mmHg) / 0.363 / <0.001 / 0.520 / <0.001
Diastolic (mmHg) / 0.140 / <0.001 / 0.190 / <0.001
HR (beats/min) / 0.016 / 0.633 / 0.005 / 0.044
Awake BP / Systolic (mmHg) / 0.017 / 0.608 / 0.056 / <0.001
Diastolic (mmHg) / 0.075 / 0.025 / 0.056 / <0.001
HR (beats/min) / 0.088 / 0.010 / 0.027 / <0.001
Glucose (mg/dl) / 0.058 / 0.086 / 0.001 / 0.264
HOMA-IR / 0.112 / 0.001 / 0.000 / 0.850
Triglyceride (mg/dl) / 0.028 / 0.414 / 0.004 / 0.050
Total cholesterol (mg/dl) / 0.060 / 0.074 / 0.006 / 0.027
HDL cholesterol (mg/dl) / 0.087 / 0.010 / 0.004 / 0.055

Values are correlation coefficient (r).

BMI, body mass index; HOMA-IR, homeostasis model assessment of insulin resistance; BP, blood pressure; HR, heart rate.

Orthostatic BP was measured at 1 and 3 minutes after active standing up, and maximum differences with basal seated BP was considered as orthostatic BP change. Awake BP was calculated as average of ambulatory monitored awake BPs.

Supplementary Table 4. Differences in the SBP phenomena.

Orthostatic
SBP change
(mmHg) / Office-to-awake
SBP differences
(mmHg)
n / Mean ± SD / P / Mean ± SD / P
Sex / Men / 362 / −2.2 ± 12.2 / <0.001 / 2.5 ± 17.4 / 0.139
Women / 522 / −6.9 ± 12.1 / 4.3 ± 18.2
History of CVD / + / 42 / −6.5 ± 14.4 / 0.414 / 3.0 ± 17.4 / 0.851
− / 842 / −4.9 ± 12.2 / 3.6 ± 17.9

Values are mean ± standard deviation.

Cardiovascular disease (CVD) includes symptomatic stroke and myocardial infarction, and angina pectoris.

Orthostatic BP was measured at 1 and 3 minutes after active standing up, and maximum differences with basal seated BP was considered as orthostatic BP change. Awake BP was calculated as average of ambulatory monitored awake BPs.

Statistical significance was assessed by analysis of variance.

Supplementary Table 5. Regularly using antihypertensive drugs and the SBP phenomena.

Orthostatic
SBP change
(mmHg) / Office-to-awake
SBP differences
(mmHg)
n / Mean ± SD / P / Mean ± SD / P
Any class / − / 564 / -5.2±12.2 / 0.311 / 2.5±17.0 / 0.020
+ / 320 / -4.4±12.7 / 5.4±19.1
Diuretics / − / 857 / -5.1±12.3 / 0.064 / 3.5±17.8 / 0.695
+ / 27 / -0.6±14.1 / 4.9±20.8
Alpha-blockers / − / 872 / -4.9±12.4 / 0.498 / 3.4±17.8 / 0.043
+ / 12 / -7.3±10.9 / 13.9±21.8
Beta-blockers / − / 846 / -4.8±12.3 / 0.337 / 3.1±17.6 / 0.001
+ / 38 / -6.8±14.3 / 12.9±20.6
CCB / − / 671 / -5.2±12.4 / 0.293 / 3.3±17.7 / 0.504
+ / 213 / -4.2±12.2 / 4.2±18.2
ACE inhibitors / − / 869 / -4.9±12.4 / 0.301 / 3.4±17.8 / 0.044
+ / 15 / -8.2±8.9 / 12.7±17.6
ARB / − / 717 / -5.1±12.2 / 0.410 / 3.3±17.3 / 0.374
+ / 167 / -4.2±13.1 / 4.6±20.0
Nitrates / − / 881 / -4.9±12.4 / 0.844 / 3.5±17.9 / 0.944
+ / 3 / -6.3±4.5 / 2.8±13.9

Values are mean ± standard deviation.

CCB, Calcium channel blockers; ACE, angiotensin converting enzyme; ARB, Angiotensin-receptor blockers.

Orthostatic BP was measured at 1 and 3 minutes after active standing up, and maximum differences with baseline seated BP was considered as orthostatic BP change. Awake BP was calculated as average of ambulatory monitored awake BPs.

Statistical significance was assessed by analysis of variance.

Supplementary Table 6. Clinical characteristics of study subjects at second visit (n=101)

Age (years) / 70.2±8.0
Sex (male/female) / 52/49
BMI (kg/m2) / 22.9±3.0
History of CVD (%) / 4.0
Orthostatic BP
1 min / 3 min
Office BP / Systolic (mmHg) / 130±17 / 129±17 / 129±16
Diastolic (mmHg) / 72±12 / 77±12 / 76±11
HR (beats/min) / 66±11 / 71±12 / 72±12
Awake / Sleeping
Ambulatory BP / Systolic (mmHg) / 134±13 / 116±14
Diastolic (mmHg) / 79±8 / 67±8
HR (beats/min) / 72±8 / 61±8
Antihypertensive / Diuretics (%) / 5.9
medications / Alpha-blockers (%) / 2.0
Beta-blockers (%) / 2.0
Calcium channel blockers (%) / 27.7
ACE inhibitors (%) / 2.0
Angiotensin-receptor blockers (%) / 23.8
Nitrates (%) / 1.0
Any classes (%) / 40.6
Glycemic factors / Glucose (mg/dl) / 103±19
Insulin (μU/ml) / 6.5±5.1
HOMA-IR / 1.66±1.34
Plasma lipids / Triglyceride (mg/dl) / 98±43
Total cholesterol (mg/dl) / 205±33
HDL cholesterol (mg/dl) / 64±17

Values are mean ± standard deviation.

BMI, body mass index; BP, blood pressure; HR, heart rate; ACE, angiotensin-converting enzyme.

Cardiovascular disease (CVD) includes symptomatic stroke, myocardial infarction, and angina pectoris. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated by the following equation; (glucose × insulin)/405.

Supplementary Table 7. Clinical characteristics of sustained, white-coat, and masked hypertension.

Normotension / Masked HT / White-coat HT / Sustained HT / P
(352) / (150) / (134) / (248) / Crude / Adjusted
Age (years) / 64.6±9.6 / 65.8±9.8 / 68.8±6.2 / 67.8±8.1 / <0.001
Sex (male, %) / 35.2 / 52.0 / 35.1 / 45.6 / 0.001
BMI (kg/m2) / 22.7±2.9 / 23.8±3.1 / 23.0±3.0 / 23.8±3.0 / <0.001
History of CVD(%) / 3.1 / 6.7 / 3.7 / 6.5 / 0.160
Office BP / Systolic (mmHg) / 122±12 / 125±10 / 151±9 / 157±15 / <0.001 / <0.001
Diastolic (mmHg) / 71±9 / 73±9 / 81±10 / 85±11 / <0.001 / <0.001
HR (beats/min) / 65±9 / 66±10 / 68±12 / 66±10 / 0.043 / 0.037
Awake BP / Systolic (mmHg) / 121±9 / 142±7 / 127±6 / 147±10 / <0.001 / <0.001
Diastolic (mmHg) / 74±6 / 84±6 / 75±6 / 86±8 / <0.001 / <0.001
HR (beats/min) / 72±7 / 73±8 / 70±9 / 72±8 / 0.005 / 0.004
Antihypertensive medication (%) / 25.0 / 36.7 / 49.3 / 44.8 / <0.001
Glucose (mg/dl) / 99±14 / 104±18 / 103±13 / 105±17 / <0.001 / 0.033
HOMA-IR / 1.27±0.89 / 1.75±1.30 / 1.57±0.99 / 1.63±1.00 / <0.001 / 0.009
Triglyceride (mg/dl) / 96±48 / 113±68 / 111±70 / 115±60 / 0.001 / 0.034
Total cholesterol (mg/dl) / 214±35 / 210±39 / 213±32 / 216±36 / 0.526 / 0.134

Values are mean ± standard deviation.

HT, hypertension; BMI, body mass index; BP, blood pressure; HR, heart rate.

Cardiovascular disease (CVD) includes symptomatic stroke, myocardial infarction, and angina pectoris. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated by the following equation; (glucose × insulin)/405.

Office HT was defined as clinic-measured SBP ≥140 mmHg or DBP ≥90 mmHg. Awake HT was defined as awake SBP ≥135 mmHg or DBP ≥85 mmHg. Masked HT, awake HT and office NT; white-coat HT, awake NT and office HT; sustained HT, awake HT and office HT.

Adjusted factors were age, sex, BMI, history of CVD, and antihypertensive treatment.