Japan Morning Surge-Home Blood Pressure Research Articles

Association of Cardiovascular Outcomes With Masked Hypertension Defined by Home Blood Pressure Monitoring in a Japanese General Practice Population

The clinical outcomes associated with masked hypertension defined by home blood pressure monitoring (HBPM) in clinical settings remain uncertain. To assess the association between masked hypertension and cardiovascular disease events in clinical settings. This observational cohort study used data from 4261 outpatients treated at 71 primary practices or university hospitals throughout Japan who were enrolled in the Japan Morning Surge-Home Blood Pressure study between January 1, 2005, and December 31, 2012. Participants had a history of or risk factors for cardiovascular disease and were followed up through March 31, 2015. Participants underwent clinic blood pressure (BP) measurements on 2 occasions as well as HBPM measurements in the morning and evening for a 14-day period. Urine albumin to creatinine ratio and circulating brain (or B-type) natriuretic peptide levels were quantified at baseline as a marker of cardiovascular end-organ damage. Data were analyzed from July 1, 2017, to October 31, 2017. Participants were categorized into 4 BP groups: (1) masked hypertension-hypertensive home BP levels (systolic, ≥135 mm Hg; diastolic, ≥85 mm Hg) and nonhypertensive clinic BP levels (systolic, <140 mm Hg; diastolic, <90 mm Hg); (2) white-coat hypertension-nonhypertensive home BP levels (systolic, <135 mm Hg; diastolic, <85 mm Hg) and hypertensive clinic BP levels (systolic, ≥140 mm Hg; diastolic, ≥90 mm Hg); (3) sustained hypertension-hypertensive home and clinic BP levels; and (4) controlled BP-nonhypertensive home and clinic BP levels. Incident stroke and coronary heart disease. Of the 4261 participants, 2266 (53.2%) were women, 3374 (79.2%) were taking antihypertensive medication, and the mean (SD) age was 64.9 (10.9) years. During a median (interquartile range) follow-up of 3.9 (2.4-4.6) years, 74 stroke (4.4 per 1000 person-years) and 77 coronary heart disease (4.6 per 1000 person-years) events occurred. The masked hypertension group had a greater risk for stroke compared with the controlled BP group (hazard ratio, 2.77; 95% CI, 1.20-6.37), independent of traditional cardiovascular risk factors, urine albumin to creatinine ratio, and circulating B-type natriuretic peptide levels. Conversely, masked hypertension yielded no association with coronary heart disease risk. In the Japanese general practice population, masked hypertension defined by HBPM may be associated with an increased risk for stroke events. Use of HBPM may improve the assessment of BP-related risks and identify new therapeutic interventions aimed at preventing cardiovascular disease events.

Integrated flow-mediated vasodilation response predicts cardiovascular events in elderly patients with cardiovascular risk factors: the Japan Morning Surge–Home Blood Pressure study

The integrated flow-mediated vasodilation (FMD) response has been associated with cardiovascular (CV) risk factors, but the association between the integrated FMD response and subsequent CV events has been unclear. We enrolled 555 patients who had at least one CV risk factor (hypertension, dyslipidemia, diabetes, or smoking). We measured the peak percentage change in diameter (ΔFMD), and integrated FMD response calculated as the area under the dilation curve over a 120-second dilation period (FMD-AUC120). Elderly patients (age ≥ 65 years, N = 270) in the lowest tertile of FMD-AUC120 (FMD-AUC120 < 5.6) had a higher rate of CV events compared with those in the two higher tertiles (FMD-AUC120 ≥ 5.6) (log rank 4.15, P = .041). The association remained significant after adjusting for covariates (hazard ratio 3.84, P = .007). In the 285 middle-aged patients (age < 65 years), the CV event rates were similar between patients in the lowest tertile and those in the two higher tertiles of FMD-AUC120 (log rank 0.39, P = .53). The CV event rates were similar between patients in the lowest tertile and those in the two higher tertiles of ΔFMD in elderly and middle-aged patient groups. In conclusion, integrated flow-mediated vasodilation response, but not ΔFMD, predicted CV events in elderly patients with CV risk factors.

Carotid atherosclerosis and the association between nocturnal blood pressure dipping and cardiovascular events

The impact of a nondipping blood pressure (BP) pattern, defined as (awake systolic BP - sleep systolic BP)/awake systolic BP<0.1, on cardiovascular events in populations with different degrees of carotid atherosclerosis is uncertain. The authors hypothesized that a nondipping BP pattern would show differential predictive power for cardiovascular events, including total cardiovascular death, sudden death, nonfatal cardiovascular events, and nonfatal stroke, between populations with and without carotid atherosclerosis. To test this hypothesis, the authors analyzed 493 patients (mean age 67.9years, 47.5% men) from the J-HOP (Japan Morning Surge-Home Blood Pressure) study for whom ambulatory BP monitoring and carotid intima-media thickness data were available. Twenty-nine cardiovascular events occurred during follow-up (1867 person-years). A nondipping BP pattern was independently associated with cardiovascular events in the population without carotid atherosclerosis, defined as carotid intima-media thickness <1.1mm after adjustment for other cardiovascular risk factors including age, sex, diabetes mellitus, chronic kidney disease, and 24-hour systolic BP (hazard ratio, 8.15; 95% confidence interval, 1.76-37.78 [P<.01]). This association was not found in the population with carotid intima-media thickness ≥1.1mm. Therefore, in the hypertensive population without carotid atherosclerosis, physicians should consider ambulatory BP monitoring to determine the nocturnal BP pattern as an alternative approach to assessing cardiovascular events.

Day-by-Day Variability of Home Blood Pressure and Incident Cardiovascular Disease in Clinical Practice: The J-HOP Study (Japan Morning Surge-Home Blood Pressure).

We assessed the relationship between day-by-day home blood pressure (BP) variability and incident cardiovascular disease (CVD) in clinical practice. J-HOP study (Japan Morning Surge-Home Blood Pressure) participants underwent home BP monitoring in the morning and evening for a 14-day period, and their BP levels and BP variability independent of the mean (VIM) were assessed. Incident CVD events included coronary heart disease and stroke. Cox models were fitted to assess the home BP variability-CVD risk association. Among 4231 participants (mean±SD age, 64.9±10.9 years; 53.3% women; 79.1% taking antihypertensive medication), mean (SD) home systolic BP (SBP) levels over time and VIMSBP were 134.2 (14.3) and 6.8 (2.5) mm Hg, respectively. During a 4-year follow-up period (16 750.3 person-years), 148 CVD events occurred. VIMSBP was associated with CVD risk (hazard ratio per 1-SD increase, 1.32; 95% confidence interval [CI], 1.15-1.52), independently of mean home SBP levels over time and circulating B-type natriuretic peptide levels or urine albumin-to-creatinine ratio. Adding VIMSBP to the CVD prediction model improved the discrimination (C statistic, 0.785 versus 0.770; C statistic difference, 0.015; 95% CI, 0.003-0.028). Changes in continuous net reclassification improvement (0.259; 95% CI, 0.052-0.537), absolute integrated discrimination improvement (0.010; 95% CI, 0.003-0.016), and relative integrated discrimination improvement (0.104; 95% CI, 0.037-0.166) were also observed with the addition of VIMSBP to the CVD prediction models. In addition to the assessments of mean home SBP levels and cardiovascular end-organ damage, home BP variability measurements may provide a clinically useful distinction between high- and low-risk groups among Japanese outpatients.

Correlation between B-Type Natriuretic Peptide and N-Terminal pro-B-Type Natriuretic Peptide in a Large Japanese Population at Risk of Stage A Heart Failure

Background: The measurements of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are useful for ruling out heart failure and as prognostic markers in not only heart failure populations but also general populations. It is not clear whether these two biomarkers are elevated in parallel or associated with demographic characteristics in large populations at risk of stage A heart failure. Here we investigated the relationship between BNP and NT-proBNP and extended the evaluation of this association to known demographic disparities in stage A heart failure. Methods: Of 4,310 ambulatory patients, we analyzed the cases of the 3,643 (mean age 65 ± 11 years, 46% male, and 79% on antihypertensive medication) patients whose serum BNP and NT-proBNP levels were both measured and who had a history of and/or risk factors for cardiovascular disease from the Japan Morning Surge-Home Blood Pressure (J-HOP) Study dataset. Results: The median (25th–75th percentiles) BNP and NT-proBNP values were 18.7 (9.3–38.5) pg/mL and 50.3 (25.5–97.4) pg/mL. There was a significant association between log-transformed BNP and log-transformed NT-proBNP (r = 818, p < 0.001). A multiple linear regression analysis showed that log-transformed NT-proBNP was significantly associated with log-transformed BNP (beta coefficient = 0.774, p < 0.001). When stratified by demographic characteristics, these associations remained (all p < 0.001). Conclusion: In a large Japanese population at risk of stage A heart failure, there was a significant association between BNP and NT-proBNP after adjustment and stratification by demographics.

OP.1B.09] NT-PROBNP IS AN INDEPENDENT PREDICTOR OF STROKE IN JAPANESE WITH CARDIOVASCULAR RISK FACTORS

Objective: NT-proBNP is a strong prognostic marker in advanced stages of cardiac diseases like heart failure or coronary artery disease (CAD) in Western population. However, little is known whether Asian subjects differ from Western subjects in the prognostic power of NT-proBNP for cardiovascular outcome. We hypothesized that NT-proBNP would be an independent predictor for stroke and CAD events in Asian population considering the reported differences in the rates of cardiovascular events compared with Western population. Design and method: The J-HOP (Japan Morning Surge-Home Blood Pressure) study included 4310 Japanese with a history of and/or risk factors for cardiovascular disease. We analyzed 3619 patients (mean age 65.0 ± 10.6 years, male 46.1%) who had been measured NT-proBNP at baseline of 4310 patients. Results: During a mean follow-up of 4.0 ± 2.1 years, 60 stroke and 69 CAD events occurred. When we divided NT-proBNP into quartiles, the incidence of stroke were significantly higher in the highest quartile (NT-proBNP > 97.38 pg/ml; hazard ratio [HR] 6.87; 95% confidence interval [CI] 1.57 to 30.07; P = 0.01) and in the second highest quartile (NT-proBNP 50.48–97.37 pg/ml; HR 4.76; 95%CI 1.07 to 21.24; P = 0.04) compared with the lowest quartile (NT-proBNP <25.48 pg/ml) after adjusted for conventional cardiovascular risk factors. However, these associations were not found in the incidence of CAD. Conclusions: NT-proBNP is an independent predictor of future stroke events in Japanese with cardiovascular risk factors. For detecting heart failure, NT-proBNP level > 125 pg/ml has been accepted. The slight elevation of NT-proBNP in the current normal range might predict the incidence of stroke in Asian population.

Abstract 14025: Mild QTc Prolongation was Associated With Cardiovascular Events in Japanese Male Patients With Cardiovascular Risk Japan Morning Surge Home Blood Pressure (J-HOP) Study

Introduction: The relationships between QTc intervals and the risk of cardiovascular (CV) events could differ among ethnicities or between subjects with/without left ventricular hypertrophy (LVH). Hypothesis: We hypothesized that mild QTc prolongation was associated with CV events in Japanese patients with CV risk factors. Methods: Subjects were 3,592 patients enrolled in the Japan Morning Surge Home Blood Pressure Study who had one or more CV risk factors. Corrected QT intervals (QTc) were calculated using the Bazett formula. Prolonged QTc interval was defined as ≥440 ms in men and ≥460 ms in women on electrocardiogram (ECG). We divided patients into 3 subgroups according to the percentile of QTc (shortest 10%, middle 80%, and longest 10%). The primary endpoints were fatal/nonfatal CV events (myocardial infarction, stroke, hospitalization for heart failure, aortic dissection). The Sokolow-Lyon criteria (RV5(6)+SV1) ≥35 mm were used to diagnose LVH. Results: During the mean follow-up period of 48±39 months, there were 138 CV events. In male patients, those with prolonged QTc (N=57) were more likely to suffer CV events than those without prolonged QTc (N=1523) (log rank 6.22, p=0.013). A Cox proportional hazards model including age, hypertension, dyslipidemia and diabetes revealed that prolonged QTc was a significant independent predictor of CV events in male patients (hazard ratio 2.21, 95%CI 1.01-4.82, p=0.047). In female patients, CV events were similar in prolonged QTc (N=33) and non- prolonged QTc patients (N=1766, p=0.73). In male patients, the longest 10% of QTc patients (QTc≥406ms, N=157) were more likely to suffer CV events than those in the middle 80% of QTc patients (QTc 332-405ms, N=1265) and shortest 10% of QTc patients (QTc&lt;332ms, N=157) (log rank 16.57, p&lt;0.001). In the absence of LVH (N=1308), male patients in longest 10% of QTc suffered more CV events than those in the other groups (log rank 6.61, p=0.037), and in the presence of LVH (N=272), males in the longest 10% of QTc also suffered more CV events than those in the other groups (log rank 13.73, p=0.001).In female patients, CV events were similar in three subgroups. Conclusions: Mild QTc prolongation was associated with CV events in Japanese male patients with a CV risk with or without ECG-LVH.

ME 01-2 ASSESSMENT AND TREATMENT OF MORNING HYPERTENSION

Abstract The essential benefit of the management of is derived from the blood pressure (BP) lowering per se, indicating the importance of throughout 24 hours. Recent guidelines stressed the importance of home for the diagnosis and management of hypertension. It is well-known that cardiovascular events occur more frequently in the levels have been shown to increase during the period from night to early morning. Clinical research using ambulatory monitoring (ABPM) or home monitoring has clarified that and are more closely related to the cardiovascular risk than office (Kario et al. Circulation 2003;107:1401-1406).The importance of on-treatment HBPM for the cardiovascular prognosis of hypertensive individuals was recently revealed in the largest real-world prospective study, the Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure (HONEST) study which enrolled more than 21 000 hypertensive patient. In prospective results of the HONEST study, in hypertensive patients treated with antihypertensive medication, even patients whose office is well-controlled, on-treatment uncontrolled prior to taking medication frequently remains high risk for both stroke and coronary disease (Kario, et al. Hypertension 2014;64:989-996; J Am Coll Cardiol 2016;67:1519-1527). In our nationwide Japanese cohort, the Japan Morning Surge Home Blood Pressure (J-HOP) Study, home was the best predictor of stroke event (Hoshide, Kario, et al. Hypertension 2016;68:54-61). Since Asians show greater surges (Hoshide, Kario, Parati et al. Hypertension 2016;68:54-61), it is particularly important for Asians to control as the first step to achieve 'perfect 24-hr control,' i.e., the 24-hr level, nocturnal dipping, and variability including (Kario. Ann Glob Health 2016;82:254-273).The first definition of morning hypertension was defined as the average of BPs >135 mmHg for systolic BP, or >85mmHg for diastolic BP, regardless of office BPs with the definition of >135/85 mmHg regardless office in Clinician's Manual on Early Morning Risk Management in Hypertension in 2004 (Science Press, London, UK, 2004). Masked hypertension may be used for with office <140/90 mmHg. Morning could be measured by both ABPM (2 hour-average of ambulatory BPs after arsing) and home monitoring (the average of 2 measurements in the during 3 or more days). Morning could be diagnosed not only by home monitoring, but also by ABPM (ambulatory hypertension). When information on the time of arising is not available, the highest 1 hour moving average of consecutive systolic BPs between 6am and 10am could be calculate as the Moving peak systolic BP (Kario. Essential manual of 24 hour blood pressure management. Wiley, UK, pp.1-158.2015). The risk of may be underestimated by monitoring device with intermittent measurements. The innovation of wearable surge monitoring which could measure continuously will clarify the risk of (Kario. Prog Cardiovasc Dis 2016, in press).We are now proposing a three-step strategy for the BP-guided management of using home monitoring as follows. Step 1: Morning systolic <145 mmHg should be achieved by treatment; Step 2: The guideline level of 135 mmHg systolic should then be reached, and Step 3: Approx. 125 mmHg or less, which presents the lowest risk of cardiovascular events, should be achieved and maintained (Kario. Essential manual of 24 hour blood pressure management. Wiley, UK, pp.1-158.,2015). Non-specific medication for controlling includes long-acting drugs. Once-daily dosing antihypertensive agents, now widely used as conventional antihypertensive medication, has decreased the patient burden and contributed to increased patient compliance. However, conventional antihypertensive medication using once-daily use of antihypertensive drugs was insufficient for controlling hypertension. Specific treatment includes the time of dosing of antihypertensive drugs and selecting the specific class of antihypertensive drugs, such as inhibitors of sympathetic activity or the renin-angiotensin system (RAS). Practically, bedtime dosing of antihypertensive drug, especially calcium channel blocker, alpha-blocker, RAS inhibitors suppress exaggerated without excessive nocturnal hypotension during sleep. These treatments also effective for nocturnal hypertension. On the other hand, specific drug for reducing nocturnal is diuretics including thiazide-type diuretics, indapamide, and aldosterone blockers. These drugs are effective for with non-dipper/riser pattern of nocturnal BP. The renal denervation is effective for reducing and the moving peak in the combination analysis of the HTN-3 and the HTN-Japan as well as nocturnal (Kario, Bakris, et al. Hypertension 2015;66:1130-1137).The BP-guided approach using home monitoring is the most promising first step leading to the anticipation medicine for the most effective antihypertensive treatment for cardiovascular disease (Kario. Prog Cardiovasc Dis 2016, in press).

Morning and Evening Home Blood Pressure and Risks of Incident Stroke and Coronary Artery Disease in the Japanese General Practice Population: The Japan Morning Surge-Home Blood Pressure Study.

Our aim is to determine the optimal time schedule for home blood pressure (BP) monitoring that best predicts stroke and coronary artery disease in general practice. The Japan Morning Surge-Home Blood Pressure (J-HOP) study is a nationwide practice-based study that included 4310 Japanese with a history of or risk factors for cardiovascular disease, or both (mean age, 65 years; 79% used antihypertensive medication). Home BP measures were taken twice daily (morning and evening) over 14 days at baseline. During a mean follow-up of 4 years (16 929 person-years), 74 stroke and 77 coronary artery disease events occurred. Morning systolic BP (SBP) improved the discrimination of incident stroke (C statistics, 0.802; 95% confidence interval, 0.692-0.911) beyond traditional risk factors including office SBP (0.756; 0.646-0.866), whereas the changes were smaller with evening SBP (0.764; 0.653-0.874). The addition of evening SBP to the model (including traditional risk factors plus morning SBP) significantly reduced the discrimination of incident stroke (C statistics difference, -0.008; 95% confidence interval: -0.015 to -0.008; P=0.03). The category-free net reclassification improvement (0.3606; 95% confidence interval, 0.1317-0.5896), absolute integrated discrimination improvement (0.015; SE, 0.005), and relative integrated discrimination improvement (58.3%; all P<0.01) with the addition of morning SBP to the model (including traditional risk factors) were greater than those with evening SBP and with combined morning and evening SBP. Neither morning nor evening SBP improved coronary artery disease risk prediction. Morning home SBP itself should be evaluated to ensure best stroke prediction in clinical practice, at least in Japan. This should be confirmed in the different ethnic groups. URL: http://www.umin.ac.jp/ctr/. Unique identifier: UMIN000000894.

Long sleep duration: a nonconventional indicator of arterial stiffness in Japanese at high risk of cardiovascular disease: the J-HOP study

Long and short sleep durations were reported as independently associated with hypertension, aortic stiffness, and cardiovascular disease. High-sensitivity C-reactive protein (hs-CRP) was shown to be associated with increased aortic stiffness. Here, we investigated the relationship between self-reported sleep duration and pulse wave velocity (PWV) in the elderly at high risk of cardiovascular disease. We also investigated whether hs-CRP moderates this relationship. Among 4310 patients with ≥1 cardiovascular risks recruited for the Japan Morning Surge-Home Blood Pressure Study, a questionnaire including items on daily sleep duration was completed. We measured the brachial-ankle PWV (baPWV) and hs-CRP levels in 2304 of these patients (mean age 64.7 years, 49.6% males). In accord with the patients' sleep duration (<6 hours, ≥6 to <8 hours, and ≥8 hours per night), significant associations between sleep duration and the PWV were observed (1594 vs. 1644 vs. 1763 cm/s, P < .0001). In the multiple regression analysis adjusted for age, body mass index, total cholesterol, HbA1c and clinic systolic blood pressure, long sleep duration (≥8 hours per night) (P < .05), and log hs-CRP (P < .05) were significantly positively associated with PWV when the patients with 6- to 8-hour sleep duration were defined as a reference group. Significant interactions of long sleep duration by age and that by antihypertensive medication for baPWV were observed. The effect of long sleep on PWV was greatest in the oldest age group. Long sleep duration and hs-CRP were significant indicators of increased baPWV in this elderly high-risk Japanese population. Age and antihypertensive medication use were significant modulators of the relationship between long sleep duration and arterial stiffness.

Abstract 12026: Nocturnal Blood Pressure Burden, Diuretics, and Cardiac Load: Determinants of Nocturia in the Japanese at High-Risk of Cardiovascular Disease

Introduction: The majority of epidemiologic studies reported a significant relationship between hypertension and nocturia. However, the underlying pathophysiology has not been established. Hypothesis: We hypothesized that nocturnal blood pressure (BP) burden, some classes of antihypertensive agents and cardiac load might be associated with severity of noctria. In this study, the relationships of nocturia with self-measured home BP (HBP), the class of antihypertensive agent, B-type natriuretic peptide (BNP) were investigated in the Japanese at high-risk of cardiovascular disease. Methods: Among 4310 patients with one or more cardiovascular risks recruited for the Japan Morning Surge-Home Blood Pressure Study, the measurements of HBP at morning, evening, and nighttime as well as BNP were performed in the 2785 patients (63.5 years old, male 48.9%). A self-administered questionnaire included items on nocturia was used. Results: According to the number of nocturia (no void: n= 1571; one void: n=557; 2 or more voids per night: n=657), significant associations of systolic BP (SBP) at morning (136 vs 136 vs 140 mmHg, p&lt;0.001), evening (129 vs 129 vs 131 mmHg, p&lt;0.01) and nighttime (120 vs 120 vs 125 mmHg, p&lt;0.001) as well as logBNP (1.15 vs 1.26 vs 1.39, p&lt;0.001) were observed with nocturia severity. In the multinomial logistic regression analysis adjustment for confounders including age, smoking, total cholesterol, fasting blood glucose and HbA1c, the use of diuretics (OR: 1.28, 95%CI: 1.01-1.61, p&lt;0.05) was significantly associated with one nocturnal void, while nighttime SBP (OR: 1.012, 95%CI: 1.01-1.02, p&lt;0.001) and logBNP (1.46, 95%CI: 1.16-1.84, p&lt;0.01) were significantly associated with multiple nocturnal voids. A significant interaction was found between nighttime SBP and logBNP for multiple nocturnal voids (p&lt;0.01). On the other hand, neither morning SBP nor evening SBP had a significant relationship with nocturia. Conclusions: In this study, nighttime SBP and BNP were synergetically associated with severe nocturia in the high-risk Japanese population. Antihypertensive treatment to reduce BP burden during sleep as well as cardiac overload might be important to improve sleep quality caused by nocturia.

Abstract 13043: Atrial Fibrillation is Associated With Cardiovascular Events in Obese Japanese With One or More Cardiovascular Risk Factors: Japan Morning Surge Home Blood Pressure (J-HOP) Study

Introduction: Obesity has been shown as a risk of incidence and durability of atrial fibrillation. However, the relationship between obesity and prognosis of patients with atrial fibrillation remains unclear. Hypothesis: We assessed the hypothesis that obesity was associated with cardiovascular events in atrial fibrillation patients with cardiovascular risk factors. Methods: We enrolled 3,585 patients in the Japan Morning Surge Home Blood Pressure Study who had one or more cardiovascular risk factors. We conducted 12-lead electrocardiography, and atrial fibrillation was identified based on electrocardiography. Obesity was defined as body mass index over than 25 kg/m2. The primary endpoints were fatal/nonfatal cardiovascular events (myocardial infarction, stroke, hospitalization for heart failure, aortic dissection). Results: The number of patients whose electrocardiograms revealed atrial fibrillation was eighty-four. In obese patients, atrial fibrillation patients (N=35) suffered more cardiovascular events (log rank 7.17, p=0.007) than sinus rhythm patients (N=1282), but in nonobese patients, cardiovascular events were similar (log rank 0.10, p=0.76) in atrial fibrillation (N=48) and sinus rhythm patients (N=2220). After adjusting for age, gender, hypertension, smoking, and diabetes, atrial fibrillation was an independent predictor of cardiovascular events in the obese group (hazard ratio 3.02, 95% confidence interval 1.18-7.78). Conclusions: There was a significant difference in the association between atrial fibrillation and subsequent cardiovascular events in the presence or absence of obesity. Weight reduction might improve the prognosis of atrial fibrillation patients.

Abstract 13330: Depression is Associated With Cardiovascular Events in Male but Not Female Patients With One or More Cardiovascular Risk Factors: Japan Morning Surge Home Blood Pressure (J-HOP) Study

Introduction: Depression is associated with cardiovascular events, and the frequency of depression is higher in females than in males. However, the association between depression and cardiovascular events in patients with cardiovascular risk factors and the gender difference of the association remains unclear. Hypothesis: We assessed the hypothesis that depression was associated with a poor prognosis in patients with cardiovascular risk factors, and that the association is different in males and females. Methods: We enrolled 3,216 patients in the Japan Morning Surge Home Blood Pressure Study who had one or more cardiovascular risk factors. We conducted the Beck Depression Inventory (BDI). Depression was defined as having a BDI score ≥ 16. The primary endpoints were fatal/nonfatal cardiovascular events (myocardial infarction, stroke, hospitalization for heart failure, aortic dissection). Results: The mean follow-up period was 47±24 months, and 134 patients suffered primary endpoints. In male patients, depressive patients (N=184) were more likely to suffer cardiovascular events than non-depressive patients (N=1439) (log rank 6.79, p=0.009). In female patients, cardiovascular events were similar in depressive (N=347) and nondepressive patients (N=1246,log rank 0.06, p=0.81). A Cox proportional hazards model including age, history of hypertension, dyslipidemia and diabetes revealed that depression was a significant, independent predictor of primary endpoints in male patients (hazard ratio 2.01, 95% confidence interval 1.20-3.37, p=0.008). Conclusions: Depression is associated with cardiovascular events in male but not female patients with one or more cardiovascular risk factors.

Abstract 12837: Nondipper Pulse Rate Pattern is Associated With Cardiovascular Events, but Night Pulse Rate is Not: Japan Morning Surge Home Blood Pressure (J-HOP) Study

Introduction: Nondipper patterns of pulse rate (PR) as well as blood pressure (BP) have been associated with cardiovascular events. High night PR is also associated cardiovascular events. Hypothesis: We assessed the hypothesis that a nondipper PR pattern was independently associated with cardiovascular events in patients with cardiovascular risk factors, adjusting for night pulse rate. Methods: Ambulatory BP monitoring was conducted at baseline in 1443 patients who had one or more cardiovascular risk factors. PR nondipping status was defined as (awake PR - sleep PR)/awake PR &lt; 0.1. Results: The nondipper PR patients (N=339) were older (66.8±10.6 vs. 63.9±11.8, p&lt;0.001) and had a higher night PR (65.5±9.6 vs. 58.9±7.3/min, p&lt;0.001) than the dipper PR patients (N=1104). The mean follow-up period was 60±30 months; in that time 50 patients (4.5%) in the dipper PR group and 34 patients (10.0%) in the nondipper PR group suffered primary endpoints (log rank 22.2, p&lt;0.001). On the Cox proportional hazards model including age, gender and night systolic blood pressure, nondipper PR was an independent predictor of cardiovascular event (hazard ratio 2.38, 95% confidence interval 1.51-3.74, p&lt;0.001), but night PR was not (p=0.50). We analyzed four groups according to BP and PR dipping status, the combination of nondipper BP and nondipper PR constituted a higher risk of cardiovascular events and stroke than the sum of the other three combination risks (Log rank= 39.2, p&lt;0.001, figure). When we added the nondipper BP pattern in the model, nondipper PR remained an independent predictor of cardiovascular events (hazard ratio 2.29, 95% confidence interval 1.50-3.51, p&lt;0.001). After excluding patients who took beta blockers (N=1003), nondipper PR was an independent predictor of cardiovascular events (hazard ratio 2.16, 95% confidence interval 1.22-3.82, p=0.008). Conclusions: The nondipper PR pattern was associated with cardiovascular events, but night pulse rate was not.

LB03.01

Objective: Blood pressure (BP) self-measured at home is a more accurate prognosticator than conventionally measured BP. Home blood pressure (BP), which is mainly measured in morning and evening, is prognositically superior to office BP. Although morning BP, per se, is an important prognostic factor, much less information about this association is available in ambulatory patients. Design and method: In the Japan Morning Surge Home Blood Pressure (J-HOP) study, 4310 Japanese patients (mean age, 64.8 [SD, 10.9] years; 47% men) who had one or more than risk factor were recruited and followed up by their physicians, and measured home BP in the morning and evening on 14 consecutive days at baseline. Cardiovascular events were the combination of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, aortic dissection, and hospitalization for heart failure or angina performed with coronary angioplasty or coronary artery bypass graft surgery. Results: At the end of follow-up, clinical status was known for 99.4% of patients. During 3.9 years of follow-up (median), at least 1 cardiovascular events had occurred in 192 (incidence, 11.7/1000 patient-years), and 75 stroke events (4.3/1000 patient-years) and 122 cardiac and other vascular events (7.2/1000 patient-years) occurred. When we divided morning systolic BP (MSBP) into four groups (<135mmHg [n = 1948], 135–145mmHg [n = 1037], 145–155mmHg [n = 684], >155mmHg [n = 586]), the risk of cardiovascular events was increased in >155mmHg of MSBP compared with < 135mmHg (1.82; 95%CI [1.19–2.80]) after adjusted by covariates, and MSBP was not risk for cardiac and other vascular events. The risk for stroke events was higher in the group with 135–145mmHg (relative risk [RR], 2.48; 95% confidence interval [CI], 1.19–5.15), 145–155mmHg (2.71; 95%CI [1.25–5.85]), >155mmHg (4.13; 95%CI [1.92–8.90]) than those with <135mmHg. This association was similar after adjusting evening systolic BP. Conclusions: Uncontrolled morning BP assessed by home BP is associated with stroke in Japanese ambulatory patients.

A New Proposal for the Target Value for Home BP in Type 2 Diabetes Patients: The J-HOP Study

The target levels of home-monitored blood pressure (BP) in patients with type 2 diabetes mellitus (T2DM) have not yet been established. We sought to examine the appropriate target home BP level in T2DM. This is a subanalysis of the Japan Morning Surge-Home Blood Pressure (J-HOP) study. We enrolled 4,310 patients who had at least 1 cardiovascular risk factor, and clinic and home BP monitoring was performed. The urinary albumin-to-creatinine ratio (UACR) was measured as a marker of microvascular disease. Quadratic equations of the relationship between clinic/home systolic BP (SBP) and log-transformed UACR were used to determine the home BP value. Home BP levels corresponding to clinic SBP/diastolic BP (DBP) level using the UACR values were calculated separately by the presence/absence of diabetes. The mean age of the patients was 64.9±10.9 years; 47.0% were males. Of the 4,310 subjects enrolled, 1,057 (24.5%) had T2DM (the DM group) and 3,253 (75.5%) did not (non-DM group). The home BP levels equivalent to clinic BP 140/90 mm Hg were 135/84 and 135/83 mm Hg in the DM and non-DM groups, respectively. The home SBP levels equivalent to clinic SBP 130/80 mm Hg were 122/79 mm Hg in the non-DM group and 129/78 mm Hg in the DM group. Regardless of diabetic status, the home BP level that corresponds to the clinic SBP 140/90 mm Hg was 135/85 mm Hg. In patients with T2DM, the home SBP level equivalent to clinic SBP 130/80 mm Hg was 129/78 mm Hg with regard to the extent of microvascular disease.

Abstract 16094: Association of Diurnal Blood Pressure Variation and Nocturnal Hypoxia in Patients With Cardiovascular Risk Factors: Japan Morning Surge-Home Blood Pressure (J-HOP) SAS Study

Introduction: Abnormal diurnal blood pressure (BP) variation, such as riser or extreme-dipper, is known as risk factors of target organ damage and subsequent cardiovascular events. Nocturnal hypoxia due to sleep apnea syndrome (SAS) is likely to influence diurnal BP variation and risk increase; however, little has been evaluated in large scale cohort in Asian population. Hypothesis: We assessed the hypothesis that diurnal BP variation is associated with nocturnal hypoxia in high risk Japanese patients. Methods: The study subjects were 1087 participants of the J-HOP Study with one or more cardiovascular risk factors (n=4019). Pulse oximetry oxygen saturation (SpO2) was measured with a validated device (PULSOX Me-300; Teijin Pharma, Tokyo, Japan) simultaneously with ambulatory BP monitoring (ABPM). Results: The frequency of each diurnal BP variation are as follows; dipper (normal circadian rhythm) 42.8%, non-dippers 34.6%, extreme-dipper 13.2%, riser 9.4%. When assessed by 3% oxygen desaturation index (ODI; times/h), 14.2% of patients showed 3%ODI≥15 (suspected moderate sleep apnea), and 2.8% of patients showed 3%ODI≥30 (suspected severe sleep apnea). The likelihood of coexisting severe sleep apnea (3%ODI≥30) was significantly higher (5.9%) in patients with riser pattern compared with that in dipper pattern (1.9%) (odd ratio 3.17; 95%CI 1.10-9.11, p&lt;0.03). Three percent ODI was significantly higher in patients with riser pattern than that in dipper pattern (6.6 vs 5.1 times/h; p=0.01). Furthermore, the patients in the longest time spent with SpO2 &lt;90% category in quintiles had an increased likelihood of extreme-dipper pattern compared with those in the shorter categories (odds ratio 1.71; 95%CI 1.10-2.65; p&lt;0.03). Conclusion: Abnormal diurnal BP variation was associated with nocturnal hypoxia in patients with cardiovascular risk factors. For the patients with riser or extreme-dipper pattern, further evaluations are recommended to detect higher risk patients with nocturnal hypoxia, such as SAS, heart failure or chronic pulmonary diseases.

Abstract 11600: Long Sleep Duration and Low-Grade Inflammation: New Indicators of Arterial Stiffness in the Japanese at High-risk of Cardiovascular Disease

Background: Recently, several studies have reported that long sleep duration was independently associated with increased aortic stiffness. On the other hand, high-sensitive C-reactive protein (hs-CRP) was associated with increased aortic stiffness. In this study, the relationships among self-reported sleep duration, hs-CRP and pulse wave velocity (PWV) were investigated in the Japanese at high-risk of cardiovascular disease. In addition, we investigated whether antihypertensive treatment moderated these relationships or not. Methods: Among 4310 patients with one or more cardiovascular risks recruited for the Japan Morning Surge-Home Blood Pressure Study, brachial-ankle PWV and hs-CRP measurement were performed in the 2304 patients (64.7 years old, male 49.6%). A self-administered questionnaire included items on daily sleep duration was used. Results: According to the sleep duration (6h or less,6h to 8h,8h or more per night), significant associations of sleep duration were observed with PWV (1594 vs 1644 vs 1763 cm/s, p&lt;0.0001).In the multiple regression analysis adjustment for confounders including age body mass index, total cholesterol, HbA1c and clinic systolic blood pressure (SBP), long sleep duration (8h or more per night) (B: 29, 95%CI: 1.0-56, p&lt;0.05) and log hs-CRP (B: 25, 95%CI: 3.1-48, p&lt;0.05) were significantly positively associated with PWV. A significant interaction was found between long sleep duration and antihypertensive agent non-use for PWV (p&lt;0.05). Especially, in the group without calcium channel blockers (CCBs), long sleep duration was significantly associated with PWV (p&lt;0.01), while a marginal significant synergetic relationship was observed between long sleep duration and log hs-CRP for PWV (p=0.07). On the other hand, there were no significant interactions between long sleep duration and angiotensin receptor blockers non-use. Conclusions: Long sleep duration and hs-CRP were significant indicators of increased PVW in the high-risk Japanese population. In those without CCBs, long sleep duration served as a strong determinant for arterial stiffness, marginally interacted by low-grade inflammation. CCBs use might be important not to aggravate artery remodeling caused by long sleep duration.

Abstract 14799: Home Blood Pressure Range and 24-hr Ambulatory Blood Pressure Control: The Japan Morning Surge Home Blood Pressure (J-HOP) Study-ABPM Substudy

Background: Measures of home and ambulatory blood pressure monitoring (HBPM and ABPM) are crucial to evaluate BP control status in hypertensive patients. HBPM is widely used in clinical practice, but ABPM is used less frequently. Few studies have examined the threshold of home BP, suggesting well controlled BP in 24-hour BP, daytime BP, and nighttime BP . Methods: We analyzed data from the Japan Morning Surge Home Blood Pressure (J-HOP) Study, which included 1,439 patients with at least one cardiovascular risk factor (mean age 64.6 years, 47.8% men, 82.3% used antihypertensive medications). Both HBPM (three measures each in the morning and evening over 14 days, using the same semiautomatic HBP device with data memory and 24-hr ABPM were performed in all patients). Results: Of 355 patients with home systolic BP (HSBP) &lt;125mmHg, 78.9%, 76.9%, and 81.4% were classified as having well-controlled 24-hr SBP (&lt;130mmHg), daytime SBP (&lt;135mmHg), and nighttime SBP (&lt;120mmHg), respectively). In contrast, of 656 subjects with HSBP ≥135 mmHg, 67.5% were classified as having uncontrolled 24-hr SBP (≥130mm Hg). Of 428 patients with HSBP between 125mmHg and 134mmHg, only 54.9% were classified as having well-controlled 24-hr SBP. Conclusions: Among patients with high cardiovascular risk, nearly 80% of those with home systolic BP &lt;125mmHg were well-controlled for 24-hr SBP including nighttime systolic BP, whereas nearly 70% of those with &gt;135mmHg were uncontrolled for 24-hr systolic BP. The patients with HBP at 125-134mmHg require ABPM for the evaluation of their 24-hr BP control status.

Target home BP in type 2 diabetes could be the same as non-diabetes - the J-HOP study

The target levels of home BP are not determined in patients with type 2 diabetes. We sought to examine the appropriate target home BP level in type 2 diabetes. This is a subanalysis of the Japan Morning Surge Home Blood Pressure (J-HOP) study. We enrolled 4306 patients who have at least one cardiovascular risk factor, and performed clinic and home BP monitoring. Home BP was calculated as the mean of morning and evening values for 14 days. The urinary albumin creatinine ratio (UACR) was measured and defined as a marker of microvascular disease. Quadratic equations of the relationship between clinic/home SBP and logUACR were used to determine the cutoff value of home BP. Values of UACR which correspond to each clinic SBP/DBP levels were determined, and home BP levels corresponding to these UACR values were calculated separately by the presence/ absence of diabetes. The mean age was 64.9 10.9 years; 47.0% were male; and 87% had hypertension. There were 1055 (24.4%) patients with diabetes, and 3251 (75.2%) with non-diabetes. Figures show home SBP/DBP levels corresponds to clinic SBP/DBP levels in patients with diabetes and non-DM. Home BP level equivalent to clinic BP 140/90mmHg was 135/85 mmHg in both DM and non-DM. On the other hand, home SBP levels equivalent to clinic SBP 130/80mmHg was 122/79mmHg in non-DM, and 129/78mmHg in DM. In conclusion, regardless of diabetic status, home BP level which corresponds to clinic SBP 140/90mmHg was 135/85mmHg. In patients with type 2 diabetes, home SBP level equivalent to clinic SBP 130/80mmHg was 130/ 80mmHg with regard to the extent of microvascular disease.