Seiichi Shibasaki

Maximum Value of Home Blood Pressure: A Novel Indicator of Target Organ Damage in Hypertension

The maximum office systolic blood pressure (SBP) has been shown to be a strong predictor of cardiovascular events, independently of the mean SBP level. However, the clinical implications of maximum home SBP have never been reported. We investigated the association between the maximum home SBP and target organ damage (TOD). We assessed the left ventricular mass index (LVMI) and carotid intima-media thickness (IMT) using ultrasonography and the urinary albumin/creatinine ratio (UACR) as measures of TOD in 356 never-treated hypertensive subjects. Home BP was taken in triplicate in the morning and evening, respectively, for 14 consecutive days with a memory-equipped device. The maximum home SBP was defined as the maximum mean triplicate BP reading in the 14-day period for each individual and was significantly correlated with LVMI (r=0.51, P<0.001), carotid IMT (r=0.40, P<0.001), and UACR (r=0.29, P<0.001). The correlation coefficients with LVMI and carotid IMT were significantly larger for the maximum home SBP than the mean home SBP. In multivariate regression analyses, the maximum home SBP was independently associated with LVMI and carotid IMT, regardless of the mean home BP level. In the prediction of left ventricular hypertrophy and carotid atherosclerosis, the goodness-of-fit of the model was significantly improved when the maximum home SBP was added to the sum of the mean office and home BPs (P=0.002 and P<0.001, respectively). These findings indicate that assessment of the maximum home SBP, in addition to the mean home SBP, might increase the predictive value of hypertensive TOD in the heart and artery.

An alpha-adrenergic blocker titrated by self-measured blood pressure recordings lowered blood pressure and microalbuminuria in patients with morning hypertension: the Japan Morning Surge-1 Study.

Background The impact on microalbuminuria of strict treatment aimed at lowering of self-measured morning blood pressure using an adrenergic blockade is unclear. Methods We conducted an open-label multicenter trial, the Japan Morning Surge-1 Study, that enrolled 611 hypertensive patients, whose self-measured morning systolic blood pressure levels were more than 135 mmHg while taking antihypertensive drugs. These were randomly allocated to an experimental group, whose members received bedtime administration of 1–4 mg doxazosin (doxazosin group) or a control group whose members continued without any add-on medication (control group). The urinary albumin/creatinine ratio was investigated at the baseline and 6 months after the randomization. Results Both the morning and evening blood pressures and urinary albumin/creatinine ratio (−3.4 vs. 0.0 mg/gCr for urinary albumin/creatinine ratio; P < 0.001) were more markedly reduced in the doxazosin group than in the control group. This difference in the urinary albumin/creatinine ratio between the two groups was more marked in the patients with microalbuminuria (n = 238, −27.9 vs. −8.1 mg/gCr, P < 0.001). The reduction of urinary albumin/creatinine ratio was significantly associated with the use of doxazosin, and the change in all self-measured blood pressures (morning, evening, the average morning–evening), and these associations were independent of each other (P < 0.001). Conclusion Adding a bedtime dose of an α-adrenergic blocker titrated by self-measured morning blood pressure in treated hypertensive patients with uncontrolled morning hypertension significantly reduced blood pressure and urinary albumin excretion rate, particularly in those with microalbuminuria.

Collagen Metabolism in Extracellular Matrix May Be Involved in Arterial Stiffness in Older Hypertensive Patients with Left Ventricular Hypertrophy

Collagen metabolism in the extracellular matrix (ECM) is related to the pathogenesis of cardiovascular stiffness and remodeling in hypertension. We evaluated the association between collagen metabolism markers and the newly developed parameter, brachial-ankle pulse wave velocity (baPWV), in older hypertensive patients with left ventricular hypertrophy (LVH). We performed echocardiography and baPWV measurement using a new device, form PWV/ABI (Colin Medical Technology, Komaki, Japan), and measured plasma levels of markers of collagen metabolism such as procollagen type I C-terminal propeptide (PICP: a marker of collagen synthesis), collagen type I pyridinoline cross-linked C-terminal telopeptide (ICTP: a marker of collagen type I degradation), matrix metalloproteinase-1 (MMP-1: a marker of collagen degradation) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in 46 hypertensive patients with LVH. BaPWV was correlated with the plasma level of PICP (r=0.33, p=0.03) and ICTP (r=0.29, p=0.05) and the total TIMP-1/MMP-1 ratio (an index of collagen turnover; r=0.30, p=0.04). BaPWV was negatively correlated with the E/A ratio of left ventricular inflow (r=−0.36, p<0.05), while baPWV was not correlated with left ventricular mass index (LVMI; r=−0.175, p=0.25) or deceleration time of the mitral E wave (DCT; r=0.15, p=0.31). The measures of hypertensive heart disease, such as the E/A ratio, DCT or LVMI were not correlated with any collagen markers in this study. In multiple regression analysis adjusted for confounding factors such as age, sex, pulse pressure, mean blood pressure, pulse rate, LVMI, E/A ratio and DCT, the positive correlation between baPWV and total TIMP-1/MMP-1 ratio remained significant (p<0.05). In conclusion, arterial stiffness in high-risk older hypertensive patients may involve ECM collagen metabolism.

Association between the morning-evening difference in home blood pressure and cardiac damage in untreated hypertensive patients

Objectives The present study investigated whether the morning–evening difference in self-measured blood pressure (BP) (MEdif) can be an independent determinant of cardiac damage in untreated hypertensive patients. Methods In a cross-sectional study, the left ventricular (LV) mass, relative wall thickness, and diastolic function using echocardiography were assessed in 356 untreated hypertensive patients. Home BP measurements were taken in triplicate in the morning and evening, respectively, for 14 consecutive days with a memory-equipped device. Thereafter, the association between the MEdif in systolic BP (SBP) and the echocardiographic parameters was assessed. Results The MEdif in SBP was significantly correlated with LV mass index (r = 0.28, P < 0.001), relative wall thickness (r = 0.21, P < 0.001), ratio of E-wave to A-wave (r = −0.24, P < 0.001), and the deceleration time of the E-wave velocity (r = 0.23, P < 0.001). In a multivariable regression analysis, the MEdif in SBP was a significant determinant of these parameters, independent of age, sex, duration of hypertension, current smoking, habitual drinking, diabetes mellitus, the average of morning and evening SBP, and the heart rate at echo. When the MEdif in SBP was divided into quartiles, the highest quartile had increased likelihood of LV concentric hypertrophy (odds ratio = 2.63, 95% confidence interval = 1.20–5.87, P = 0.008) in comparison with the lowest quartile after adjusting for confounding factors. Conclusion The MEdif is a significant determinant of LV hypertrophy, LV geometry, and diastolic function, and therefore, evaluation of the MEdif combined with the average of morning and evening SBP might be useful in the early stage assessment of hypertensive patients.

Relationship between morning hypertension identified by home blood pressure monitoring and brain natriuretic peptide and estimated glomerular filtration rate: the Japan Morning Surge 1 (JMS-1) Study.

We evaluated whether morning minus evening systolic blood pressure (SBP) difference (MEdif) in home blood pressure measurements can be a marker for hypertensive target organ damage. The authors analyzed 611 hypertensive patients who had high morning SBP levels (≥135 mm Hg). The patients with morning hypertension (MEdif ≥15 mm Hg, average of morning and evening SBP [MEave] ≥135 mm Hg) were older (P<.001) and had a longer duration of hypertension and antihypertensive medication use, a higher prevalence of left ventricular hypertrophy (LVH) on electrocardiography, a lower glomerular filtration rate by the Cockcroft‐Gault equation (P=.002), and a higher brain natriuretic peptide (BNP) level (P<.001) than those with well‐controlled blood pressure (MEdif <15 mm Hg, MEave <135 mm Hg). The patients with morning hypertension had a higher BNP level than those with well‐controlled blood pressure after adjustment for the confounding factors (28.7 pg/mL vs 20.0 pg/mL; P=.033). In conclusion, morning hypertension is more likely seen among patients with older age and longer duration of hypertension and antihypertensive medication use, and it may be associated with a higher prevalence of LVH and a higher BNP level.

Effect of doxazosin on the left ventricular structure and function in morning hypertensive patients: the Japan Morning Surge 1 study.

Objectives Doxazosin is reported to increase the incidence of congestive heart failure. The benefits of doxazosin, for controlling morning blood pressure as well as its effect on the left ventricular structure and function, are herein examined. Methods In this study, 223 morning hypertensive patients were randomized into either the doxazosin group, with a once-daily bedtime dose of doxazosin, or the control group, who continued their current medication. Atenolol was added to the doxazosin group when needed. The effect of doxazosin was evaluated by measurement of echocardiographic parameters and B-type natriuretic peptide. Results The left ventricular wall thickness decreased, but the left ventricular diastolic diameter in the doxazosin group increased from the baseline. The changes in the left ventricular mass index were similar between the groups, whereas the relative wall thickness in the doxazosin group decreased more than that in the control group. The left ventricular diastolic function could deteriorate in the doxazosin group. In the doxazosin group, an increase in the left ventricular diameter was only seen in the patient who did not take diuretics throughout the study. The office and home blood pressure in the doxazosin group decreased more than that in the control group, whereas the B-type natriuretic peptide increased in the doxazosin group. Three cases of congestive heart failure were observed in the doxazosin group, but none in the control group. Conclusion Although a bedtime dose of doxazosin can significantly lower the blood pressure, it can also increase left ventricular diameter, thus increasing the risk of congestive heart failure. However, the prior use of diuretics can prevent the unfavorable effects of doxazosin on the left ventricular structure.

Morning Hypertension Assessed by Home Monitoring Is a Strong Predictor of Concentric Left Ventricular Hypertrophy in Patients With Untreated Hypertension

J Clin Hypertens (Greenwich). 2010;12:776‐783.

Orthostatic Hypertension Detected by Self-Measured Home Blood Pressure Monitoring: A New Cardiovascular Risk Factor for Elderly Hypertensives

Orthostatic blood pressure (BP) dysregulation is a risk factor for both falls and cardiovascular events. Selfmeasured BP, carried out at home, is both highly reproducible and useful for evaluating antihypertensive treatment. However, there have been a few reports on the clinical implications of orthostatic BP changes in home BP monitoring (HBPM). In the baseline examination for the Japan Morning Surge-1 Study, a multicenter randomized control trial, we evaluated 605 hypertensive outpatients who had a morning systolic BP above 135 mmHg. The plasma brain natriuretic peptide (BNP) level and urinary albumin excretion were measured. When the patients were divided into 10 groups, according to orthostatic BP change evaluated by HBPM, after adjusting for age, gender, body mass index and sitting home BP level, those in the top decile (n=60, orthostatic BP increase >7.8 mmHg) had a higher urinary albumin/creatinine ratio (UAR) than the lowest decile group (geometric mean [SEM range]: 209.1 [134.7–318.7] vs. 34.1 [20.1–56.2] mg/g creatinine [Cr], p=0.003) and the pooled second to ninth decile groups (n=485, 209.1 [134.7–318.7] vs. 39.7 [33.2–47.3] mg/g Cr, p<0.02). Additionally, patients in the top decile had a higher BNP level than the second to ninth decile groups (75.7 [55.0–103.1] vs. 23.6 [20.8–26.6] pg/mL, p=0.003). Evaluation of orthostatic hypertension at home might be a high-risk factor for cardiovascular events in hypertensive subjects with increased levels of BNP and a higher UAR, independent of the home sitting BP level.

Association between home arterial stiffness index and target organ damage in hypertension: Comparison with pulse wave velocity and augmentation index

OBJECTIVES To clarify the implications of the home arterial stiffness index (HASI), we compared HASI with other arterial stiffness measures and investigated the association between HASI and hypertensive target organ damage (TOD). METHODS We assessed brachial-ankle pulse wave velocity (baPWV) and the carotid augmentation index (cAIx) as measures of arterial stiffness and wave reflection, and the left ventricular mass index (LVMI), carotid intima-media thickness (IMT) using ultrasonography, and the urinary albumin/creatinine ratio (UACR) as measures of TOD in 356 never-treated hypertensive subjects. Home blood pressure (BP) was taken in triplicate in the morning and evening, respectively, for 14 consecutive days with a memory-equipped device. HASI was defined as 1 minus the respective regression slope of diastolic on systolic BP. RESULTS HASI was significantly correlated with age (r = 0.32, P < 0.001), home pulse pressure (r = 0.36, P < 0.001), morning-evening difference in home systolic BP (r = -0.29, P < 0.001), baPWV (r = 0.18, P < 0.001), cAIx (r = 0.16, P = 0.002), carotid IMT (r = 0.26, P < 0.001), and UACR (r = 0.24, P < 0.001), but not with LVMI (r = 0.05, P = 0.38). After adjustment for age and sex, the significant correlation between HASI and baPWV/cAIx was lost. In multivariate regression analyses, HASI and baPWV were significantly associated with carotid IMT (standardized β = 0.21, P<0.001; β = 0.14, P = 0.014) and UACR (β = 0.13, P = 0.018; β = 0.21, P < 0.001), independently of age, sex, and home mean arterial pressure. On the other hand, cAIx was independently associated only with LVMI (β = 0.24, P < 0.001). CONCLUSION These findings indicate that HASI adds nothing to the existing measures of arterial stiffness, but might be a BP component that can aid in the detection of carotid atherosclerosis and renal damage, similar to PWV.

Impact of arterial stiffness reduction on urinary albumin excretion during antihypertensive treatment: the Japan morning Surge-1 study.

Objectives There has been no report investigating the impact of the arterial stiffness reduction induced by antihypertensive medications on the improvement of target organ damage in hypertension. The aim of this study was to assess the association of the change in pulse wave velocity (PWV) with that in urinary albumin excretion as a measure of renal damage. Methods We studied 404 treated hypertensive patients (mean age, 70.5 ± 9.5 years), who were allocated to either an active treatment group (doxazosin and atenolol when needed) or a control group. Blood pressure, urinary albumin-to-creatinine ratio (UACR), and brachial–ankle PWV (baPWV) were measured at baseline and after 6 months of treatment. Results In the total population, home/office SBP, UACR, and baPWV decreased significantly from the baseline. In multivariate regression analyses, ΔbaPWV was significantly associated with ΔUACR, independent of Δhome SBP (β = 0.21, P < 0.001). When the patients were divided into a group with ΔbaPWV of at least 0 cm/s (positive ΔPWV) and a group with ΔbaPWV of less than 0 cm/s (negative ΔPWV), the reduction of UACR was greater in the latter group, even after adjustment for the covariates including the change in home SBP. These results were essentially the same when office SBP was entered in place of home SBP, and similar both in the active treatment group and the control group. Conclusion These findings suggest that the arterial stiffness reduction induced by antihypertensive medications is associated with the improvement of renal damage, independent of home/office SBP reduction.