Daisuke Watabe

Patient characteristics and factors associated with inter-arm difference of blood pressure measurements in a general population in Ohasama, Japan.

Objectives To assess whether there is a natural difference in blood pressure (BP) measurements between the right and left arms, and to identify what factors are associated with this difference in a general population. Methods The study subjects were 1090 individuals who participated in a medical check-up in Ohasama, Japan. The BP was measured simultaneously in both arms, using an automated device. The inter-arm BP difference was expressed as the relative difference [right-arm BP (R) minus left-arm BP (L): R – L] and the absolute difference (|R – L|). The relationship between inter-arm difference and various factors was analyzed using univariate analysis. The characteristics of subjects in whom the absolute systolic BP (SBP) difference was greater than 10 mmHg were analyzed using multivariate logistic analysis. Results The relative differences in SBP and diastolic BP (DBP) were −0.6 ± 6.6 (mean ± SD) and 1.1 ± 4.7 mmHg, while the absolute differences were 4.9 ± 4.4 and 3.7 ± 3.0 mmHg. The absolute SBP difference was found to correlate significantly with age, body mass index, ankle–brachial index (ABI), and hypertension. Subjects with hypertension, hypercholesterolemia, obesity, elevated hemoglobin A1c (HbA1c) and low ABI had a significant and independent increase in the risk of an absolute SBP difference greater than 10 mmHg. Conclusions The results suggest that there is considerable difference in the measured BP in the right and left arms and that large differences in the absolute SBP are associated with risk factors for arteriosclerosis such as hypertension, hypercholesterolemia, obesity, metabolic abnormalities and low ABI.

Association of arterial stiffness with silent cerebrovascular lesions: the Ohasama study.

Background: Arterial stiffness is a risk factor for symptomatic stroke, and is associated with symptomatic cerebral infarction and cognitive impairment. Hence, we hypothesized that arterial stiffness would be a significant determinant of silent cerebrovascular lesions. Methods: The subjects were 363 individuals without symptomatic cerebrovascular lesions who had their arterial stiffness assessed by brachial-ankle pulse wave velocity (baPWV) measurement. The subjects were classified into two groups by the presence or absence of lacunar infarcts, as well as into three groups by grade of white matter hyperintensity (WMH). baPWV was compared among these groups. Results: Eighty-six subjects had lacunar infarcts. Of 138 subjects with WMHs, 102 were classified as having grade 1 and 36 as having grade 2 or 3 WMHs. baPWV was significantly higher in subjects with lacunar infarcts than in those without (17.3 ± 0.3 vs. 16.4 ± 0.2 m/s). baPWV tended to increase with higher WMH grade (16.2 ± 0.2, 16.9 ± 0.3, and 17.8 ± 0.5 m/s in grade 0, 1, and 2 or 3, respectively) after adjustments for confounding factors. The adjusted odds ratio (OR) for lacunar infarcts in subjects with middle-tertile baPWV was significantly higher (OR, 2.37; 95% confidence interval, CI, 1.10–5.11) and the OR in subjects with the highest-tertile baPWV tended to be higher (OR 2.26; 95% CI 0.99–5.45) compared with the lowest-tertile baPWV. The adjusted OR for WMH tended to increase with increased baPWV. Conclusions: Arterial stiffness appeared to be associated with the presence of a lacunar infarct and WMH, independently of the risks for other cerebrovascular diseases.

Efficacy of Combination Antihypertensive Therapy with Low-Dose Indapamide: Assessment by Blood Pressure Self-Monitoring at Home

We examined the effects of the addition of low-dose indapamide to antihypertensive drugs of other classes, as well as its duration of action, using blood pressure (BP) self-monitoring at home. Seventy-six patients undergoing monotherapy with a calcium channel blocker (CCB), angiotensin converting-enzyme inhibitor (ACEI), or angiotensin AT1-receptor blocker (ARB), but had an average morning home systolic BP (SBP) ≥ 135 mmHg or diastolic BP (DBP) ≥ 85 mmHg, were studied. Indapamide (1 mg) was added to their existing treatment once daily for 4 weeks. The additional hypotensive effects of indapamide were evaluated by casual and home BPs, and the results were compared among the three groups of subjects classified according to their initial drug treatment classes. The morning/evening (M/E) ratio of BP reduction was calculated to assess the duration of the effect. Overall, indapamide significantly (P < 0.001) lowered morning home BP (147 ± 12/87 ± 9 mmHg to 135 ± 12/81 ± 9 mmHg), evening home BP (138 ± 15/79 ± 10 mmHg to 126 ± 12/73 ± 9 mmHg), and casual BP (145 ± 21/86 ± 14 mmHg to 136 ± 17/81 ± 13 mmHg). All groupsshowed significant indapamide-induced home SBP/DBP decreases, whereas only the ACEI and ARB groups, but not the CCB group, showed a home pulse pressure (PP) reduction. Evening SBP and PP decreases were significantly greater in the ARB group than in the CCB group. The mean M/E ratio with indapamide was 0.95 for SBP and 0.85 for DBP. Low-dose indapamide used in combination can provide additional anti-hypertensive efficacy lasting for 24 h. The added effect of indapamide may be more prominent on ARBs than on CCBs.

Does Antihypertensive Drug Class Affect Day-to-Day Variability of Self-Measured Home Blood Pressure? The HOMED-BP Study.

Background Recent literature suggests that blood pressure variability (BPV) predicts outcome beyond blood pressure level (BPL) and that antihypertensive drug classes differentially influence BPV. We compared calcium channel blockers, angiotensin‐converting enzyme inhibitors, and angiotensin receptor blockade for effects on changes in self‐measured home BPL and BPV and for their prognostic significance in newly treated hypertensive patients. Methods and Results We enrolled 2484 patients randomly allocated to first‐line treatment with a calcium channel blocker (n=833), an angiotensin‐converting enzyme inhibitor (n=821), or angiotensin receptor blockade (n=830). Home blood pressures in the morning and evening were measured for 5 days off treatment before randomization and for 5 days after 2 to 4 weeks of randomized drug treatment. We assessed BPL and BPV changes as estimated by variability independent of the mean and compared cardiovascular outcomes. Home BPL response in each group was significant (P≤0.0001) but small in the angiotensin‐converting enzyme inhibitor group (systolic/diastolic: 4.6/2.8 mm Hg) compared with the groups treated with a calcium channel blocker (systolic/diastolic: 8.3/3.9 mm Hg) and angiotensin receptor blockade (systolic/diastolic: 8.2/4.5 mm Hg). In multivariable adjusted analyses, changes in home variability independent of the mean did not differ among the 3 drug classes (P≥0.054). Evening variability independent of the mean before treatment significantly predicted hard cardiovascular events independent of the corresponding home BPL (P≤0.022), whereas BPV did not predict any cardiovascular outcome based on the morning measurement (P≥0.056). Home BPV captured after monotherapy had no predictive power for cardiovascular outcome (P≥0.22). Conclusions Self‐measured home evening BPV estimated by variability independent of the mean had prognostic significance, whereas antihypertensive drug classes had no significant impact on BPV changes. Home BPL should remain the primary focus for risk stratification and treatment. Clinical Trial Registration URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: C000000137.

Seasonal variation in self-measured home blood pressure among patients on antihypertensive medications: HOMED-BP study

Seasonal variation of blood pressure (BP) has been reported in small populations or by BP levels captured at only a few points in a year, for example, summer and winter. We aimed to investigate the multiyear seasonal variation in self-measured home BP among hypertensive patients receiving antihypertensive medications. We selected 1649 eligible patients receiving antihypertensive drug treatment, and weekly averaged home BPs were analyzed throughout the follow-up period. Systolic and diastolic home BPs were fitted with the cosine function: ‘Variation+Other Effects+Intercept’, in which the ‘Variation’ was expressed by a cosine curve with three parameters representing: (1) maximum–minimum difference of home BP in one cycle of the cosine curve; (2) time required for one cycle of the cosine curve for home BP variation; and (3) time at which home BP reached the maximum point. Maximum–minimum differences in home BP were 6.7/2.9 mm Hg, and the highest home BPs were observed in mid-to-late January. In the multivariable-adjusted model, a large maximum–minimum difference in home BP was associated with lower body mass index and older age, and larger differences were observed in men compared with women. Summer–winter difference in home BP was essentially similar every year, though it was marginally reduced by 0.14/0.04 mm Hg per year, under long-term antihypertensive treatment. Records of daily home BP measurements enable us to capture long-term factors such as seasonal variation. Home BP should therefore be carefully monitored, particularly in patients with increased BP in winter, to mitigate cardiovascular risk.

Individual Assessment of Inherent Arterial Stiffness Using Nomogram and Pulse Wave Velocity Index: The Ohasama Study

Abstract We measured the brachial-ankle pulse wave velocity (baPWV) in 491 normotensives and determined the “PWV index” (measured baPWV–theoretical baPWV) in 491 normotensives and 83 controlled hypertensives. Linear regression analysis revealed that the theoretical baPWV (cm/sec) was 0.21 × age2 (years2)−13.73 × age (years) + 0.05 × mean arterial pressure2 (mmHg2) + 3.95 × heart rate (bpm) + 36.49 × gender (1 male; 0 female) + 733 (R2 = 0.53). The calculated PWV index was significantly higher in 13 smokers than 70 nonsmokers among controlled hypertensives. The calculated PWV index might provide more precise information about inherent arterial stiffness.

Association Between Amplitude of Seasonal Variation in Self‐Measured Home Blood Pressure and Cardiovascular Outcomes: HOMED‐BP (Hypertension Objective Treatment Based on Measurement By Electrical Devices of Blood Pressure) Study

Background The clinical significance of long‐term seasonal variations in self‐measured home blood pressure (BP) has not been elucidated for the cardiovascular disease prevention. Methods and Results Eligible 2787 patients were classified into 4 groups according to the magnitude of their seasonal variation in home BP, defined as an average of all increases in home BP from summer (July–August) to winter (January–February) combined with all decreases from winter to summer throughout the follow‐up period, namely inverse‐ (systolic/diastolic, <0/<0 mm Hg), small‐ (0–4.8/0–2.4 mm Hg), middle‐ (4.8–9.1/2.4–4.5 mm Hg), or large‐ (≥9.1/≥4.5 mm Hg) variation groups. The overall cardiovascular risks illustrated U‐shaped relationships across the groups, and hazard ratios for all cardiovascular outcomes compared with the small‐variation group were 3.07 (P=0.004) and 2.02 (P=0.041) in the inverse‐variation group and large‐variation group, respectively, based on systolic BP, and results were confirmatory for major adverse cardiovascular events. Furthermore, when the summer‐winter home BP difference was evaluated among patients who experienced titration and tapering of antihypertensive drugs depending on the season, the difference was significantly smaller in the early (September–November) than in the late (December–February) titration group (3.9/1.2 mm Hg versus 7.3/3.1 mm Hg, P<0.001) as well as in the early (March–May) than in the late (June–August) tapering group (4.4/2.1 mm Hg versus 7.1/3.4 mm Hg, P<0.001). Conclusions The small‐to‐middle seasonal variation in home BP (0–9.1/0–4.5 mm Hg), which may be partially attributed to earlier adjustment of antihypertensive medication, were associated with better cardiovascular outcomes.

Predictive power of home blood pressure indices at baseline and during follow-up in hypertensive patients: HOMED-BP study

We compared the predictive power for a major adverse cardiovascular event (MACE) of four home blood pressure (BP) indices (systolic BP, diastolic BP, mean BP, and pulse pressure (PP)) obtained at baseline before treatment and during the on-treatment follow-up period in 3147 patients with essential hypertension (women: 50.1%, mean age: 59.5 years). Associations between MACE and each index were determined using Cox proportional hazard models and the likelihood ratio (LR) test. During a median follow-up of 5.4 years, 46 patients experienced MACE, which was a composite of cardiovascular death, non-fatal stroke, and non-fatal myocardial infarction. The LR test showed that systolic, diastolic, and mean BP during follow-up was more closely associated with cardiovascular risk than the corresponding indices at baseline (LR χ2 for baseline versus follow-up: systolic BP, (6.0, P = 0.014) versus (11.3, P = 0.0008); diastolic BP, (0.4, P = 0.53) versus (12.4, P = 0.0004); mean BP, (3.2, P = 0.074) versus (15.0, P = 0.0001)), whereas neither PP at baseline nor that during follow-up was significantly associated with MACE risk. Among home BP indices during follow-up, mean BP further improved prediction models in which systolic or diastolic BP was already included (P ≤ 0.042), but neither systolic nor diastolic BP improved models with mean BP (P = 0.80). In addition to home systolic and diastolic BP, mean BP during follow-up period provides essential information in predicting future cardiovascular diseases, whereas its utilization should be further assessed by an intervention trial targeting mean BP levels.

Effect of amlodipine, efonidipine, and trichlormethiazide on home blood pressure and upper-normal microalbuminuria assessed by casual spot urine test in essential hypertensive patients

ABSTRACT The aim of this study was to assess the effects of irbesartan alone and combined with amlodipine, efonidipine, or trichlormethiazide on blood pressure (BP) and urinary albumin (UA) excretion in hypertensive patients with microalbuminuria (30≤UA/creatinine (Cr) ratio [UACR] <300 mg/g Cr) and upper-normal microalbuminuria (10≤UACR<30 mg/g Cr). This randomized controlled trial enrolled 175 newly diagnosed and untreated hypertensive patients (home systolic blood pressure [SBP]≥135 mmHg; 10≤UACR<300 mg/g Cr of casual spot urine at the first visit to clinic). All patients were treated with irbesartan (week 0). Patients who failed to achieve home SBP ≤125 mmHg on 8-week irbesartan monotherapy (nonresponders, n = 115) were randomized into three additional drug treatment groups: trichlormethiazide (n = 42), efonidipine (n = 39), or amlodipine (n = 34). Irbesartan monotherapy decreased home SBP and first morning urine samples (morning UACR) for 8 weeks (p < 0.0001). At 8 weeks after randomization, all three additional drugs decreased home SBP (p < 0.0002) and trichlormethiazide significantly decreased morning UACR (p = 0.03). Amlodipine decreased morning UACR in patients with microalbuminuria based on casual spot urine samples (p = 0.048). However, multivariate analysis showed that only higher home SBP and UACR at week 8, but not any additional treatments, were significantly associated with UACR reduction between week 8 and week 16. In conclusion, crucial points of the effects of combination therapy on UACR were basal UACR and SBP levels. The effect of trichlormethiazide or amlodipine treatment in combination with irbesartan treatment on microalbuminuria needs to be reexamined based on a larger sample size after considering basal UACR and SBP levels.

Left ventricular hypertrophy by electrocardiogram as a predictor of success in home blood pressure control: HOMED-BP study

Few studies have focused on the effect of organ damage on achievement of long-term home blood pressure (BP) control. Based on the nationwide home BP-based trial data, we aimed to investigate the factors associated with home BP control, in particular, left ventricular hypertrophy (LVH) using the electrocardiogram in patients who started antihypertensive drug treatment. According to the trial protocol, we defined BP as controlled when systolic home BP reached specified targets (125–134 mm Hg in usual control (UC), n=1261; <125 mm Hg in tight control (TC), n=1288). At baseline, before drug treatment started, the mean Sokolow–Lyon voltage was 2.57±0.87 mV, and the mean Cornell product was 1573±705 mm·ms. The numbers of patients who achieved the target BP level in the UC and TC groups were 892 (70.7%) and 576 (44.7%), respectively. In both the UC and TC groups, systolic home BP at baseline was significantly lower in patients who achieved target levels than in those who did not achieve target levels (P<0.0001). Sokolow–Lyon voltage was significantly lower in patients who achieved target levels than in those who did not (P⩽0.0055). The Cornell product levels in each group were similar (P⩾0.12), although significantly different between patients who did or did not achieve the target level when the UC and TC groups were combined for analysis (P=0.031). Sokolow–Lyon voltage was significantly associated with achievement of home BP control in the multivariable-adjusted model (odds ratio, 1.13; 95% confidence intervals, 1.02–1.26; P=0.015), but Cornell product was not (P=0.13). These results indicate the difficulty of sufficient antihypertensive treatment when untreated patients had target organ damage, that is, LVH diagnosed by Sokolow–Lyon voltage.