Morning Surge-Home Blood Pressure Study Research Articles

Potential Long-Term Benefit of Home Systolic Blood Pressure Below 125 mm Hg for Cardiovascular Risk Reduction: The J-HOP Study Extended.

The long-term benefit of achieving the Japanese Society of Hypertension home systolic blood pressure (SBP) target of <125 mm Hg has not been fully evaluated. This study investigated the long-term risk of cardiovascular disease events in individuals with home SBP <125 versus 125 to <135 or ≥135 mm Hg who participated in the J-HOP study (Japan Morning Surge-Home Blood Pressure). The J-HOP study enrolled outpatients with ≥1 cardiovascular risk factor between 2005 and 2012, with follow-up until March 2015 and extended follow-up from December 2017 to May 2018. Cardiovascular disease events (stroke, coronary artery disease, congestive heart failure, and aortic dissection) were compared between home SBP subgroups. During mean 5.9 years of follow-up in 4231 participants (mean age, 65 years), cardiovascular events included stroke (n=89), coronary artery disease (n=116), congestive heart failure (n=37), and aortic dissection (n=8). The adjusted 10-year risk of total cardiovascular disease was slightly higher, and stroke risk was significantly higher when baseline home SBP was ≥135 versus <125 mm Hg (adjusted hazard ratio, 1.39 [95% CI, 0.97-2.00] for overall cardiovascular disease and 2.68 [95% CI, 1.34-5.38] for stroke; this was largely due to between-group differences in the first 5 years of follow-up, which were maintained over the subsequent 5 years). Findings were similar in the subgroup of high-risk patients (those with diabetes or stroke history). These data highlight the potential long-term benefit of strict home SBP control and validate this as an appropriate Japanese Society of Hypertension guideline target although confirmation in larger populations is needed. URL: https://www.umin.ac.jp/ctr/; University Hospital Medical Information Network Clinical Trials Registry; Unique identifier: UMIN000000894 (Japan Morning Surge-Home Blood Pressure study).

Abstract 14892: Sex Difference in the Prognostic Power of Growth Differentiation Factor 15 for Cardiovascular Event: The Japan Morning Surge-Home Blood Pressure Study

Introduction: Growth differentiation factor 15 (GDF-15), a cytokine secreted in response to cellular stress and inflammation, has been associated with cardiovascular event. Although previous studies have reported that there was a close association between sex hormones and GDF-15, data are sparse about sex difference in the prognostic power of GDF-15 for cardiovascular event. Hypothesis: We hypothesized that there is the differential prognostic power of GDF-15 for cardiovascular outcome according to gender. Methods: This prospective practitioner-based cohort study was conducted between 2005 and 2012 and included participants in the Japan Morning Surge-Home Blood Pressure Study with a history of at least one cardiovascular event who had GDF-15 measurements at baseline. Results: The study included 4066 participants (mean age 64.8 years; men, n=1897; women, n=2169). During an average 6.2 years follow-up, 249 cardiovascular events (coronary artery disease, stroke and heart failure) occurred. GDF-15 levels were significantly higher in the male vs. the female group (median [interquartile], 1014 [741.3-1432] ng/L vs. 909.9 [671.6-1257] ng/L; P&lt;0.001). In women, multivariate Cox analysis revealed that after adjusting other potential predictors, log-transformed GDF-15 was independently associated with cardiovascular events (Hazard ratio [HR], 2.09; 95% confidence interval [CI], 1.31-3.35; P=0.002), whereas this association was not found in men. In women, higher GDF-15 (≥1200 ng/L) was independently associated with cardiovascular event (HR, 2.23; 95%CI, 1.41-3.53; P=0.001), whereas this association was not found in men. The interaction between higher GDF-15 and cardiovascular event according to sex tended to be significant (P=0.087). Conclusions: There is a sex difference in the prognostic power of GDF-15 for cardiovascular event.

Abstract 16605: Differential Impact of Nighttime Home Blood Pressure on Between Patients With and Without Subclinical Heart Failure

Introduction: Nighttime blood pressure (BP) has stronger association with cardiovascular events than office BP, 24-hr BP, and awake BP. However, it was not clear whether the impact of nighttime BP is different for patients with or without heart failure (HF). Hypothesis: Nighttime home BP has stronger association with cardiovascular events in patients with HF. Methods: We analyzed the data from the Japan Morning Surge-Home Blood Pressure study with NT-proBNP and nighttime home BP measurement. We enrolled 2494 patients who had at least one cardiovascular risk factor. Morning, evening, and nighttime home BP were measured and cardiovascular events were followed up. Results: During 7.1 years follow-up, 168 events occurred. When NT-proBNP of 125pg/ml was used as cutoff, the patients with NT-proBNP&gt;125pg/ml was higher daytime home SBP and nighttime home SBP than the patients with NT-proBNP≤125pg/ml (137±16 vs 132±13 mmHg, p&lt;0.01, 126±18 vs 120±14 mmHg, p&lt;0.01, respectively). In Cox regression analysis adjusting for significant covariates, daytime and nighttime home SBP were significant predictor for the outcome in the patients with NT-proBNP&gt;125pg/ml (HR 1.02, 95%CI:1.01-1.03, p&lt;0.01, HR 1.02, 95%CI:1.00-1.03, p=0.045, respectively). On the other hands, only nighttime home SBP was remained as a predictor for the outcome in the patients with NT-proBNP≤125pg/ml (HR 1.02, 95%CI:1.00-1.03, p=0.01). Conclusions: Nighttime home BP was associated with prognosis in patients with and without subclinical HF. Daytime home BP was associated with prognosis in patients with subclinical HF but not in the without subclinical HF.

Abstract 15801: Nighttime Hypertension is a Risk Factor for Cardiovascular Events in Stage B Heart Failure Patients

Background: Nighttime blood pressure (BP) was reported to have a stronger association with cardiovascular outcome and hypertensive organ damage than clinic BP, 24-hour BP, and daytime BP in hypertensives. However, the significance of nighttime BP was not established in stage B heart failure (HF) patients. We hypothesized that nighttime BP measured by home BP monitoring device was associated with cardiovascular outcome in stage B HF patients. Method: We used the dataset of Japan Morning Surge-Home Blood Pressure study (J-HOP study), and selected 417 of stage B HF patients. The definition of stage B HF was based on Universal definition of HF. The patients with history of HF hospitalization were excluded. BP was measured on waking, before bedtime and during the night. The cardiovascular event was followed. Result: Mean follow-up period was 6.6±3.8 years, and 59 cardiovascular events were occurred. When nighttime hypertension was defined as nighttime BP &gt;120mmHg, nighttime HT group showed higher BMI, serum creatinine, HbA1c, and higher prevalence of diabetes, atrial fibrillation, and chronic kidney disease, and lower HDL-cholesterol than nighttime normotension (NT) group. With regard to BP, nighttime HT group, clinic BP, home morning BP, home evening BP, and home nighttime BP were higher in nighttime HT group than in nighttime NT group. In Kaplan-Meier analysis, nighttime HT group had a higher incident of cardiovascular event than nighttime NT group (P&lt;0.01). In Cox multivariate analysis, nighttime HT was significant predictor for cardiovascular event adjusting by significant variables (Hazard ratio 1.84, 95% Confidence interval: 1.01-3.36, P=0.046). Conclusions: Nighttime HT was a prognostic factor in stage B HT patients. Nighttime BP was a therapeutic target to improve the outcome in stage B HT patients.

Prognosis of a malignant phenotype of obesity defined by a cardiac biomarker in hypertension: the Japan Morning Surge-Home Blood Pressure study.

Obesity with increased high-sensitive cardiac troponin T (hs-cTnT) has been reported to be more likely to progress cardiovascular disease (CVD) events, which suggests that hs-cTnT may identify a "malignant" phenotype of obesity. We classified 3513 hypertensive patients from the Japan Morning Surge-Home Blood Pressure (J-HOP) study into groups based on body mass index (BMI) (normal weight: <25 kg/m2, overweight: 25-29.9 kg/m2, obesity: ≥30 kg/m2) and elevations in biomarker levels (hs-cTnT ≥3 ng/mL: 51.3%, 54.9%, 53.3%, and N-terminal pro-brain natriuretic peptide [NT-ProBNP] ≥55 pg/mL: 51.1%, 40.7%, 36.0% in each BMI category). We evaluated the independent and combined associations of BMI and each hs-cTnT/NT-proBNP or both with CVD events (fatal and nonfatal coronary artery disease, stroke, and hospitalized heart failure). During the mean 6.4 ± 3.9-year follow-up, 232 CVD events occurred. Obesity with elevated hs-cTnT was associated with a risk of CVD events compared to normal weight without elevated hs-cTnT (hazard ratio 3.22, 95% confidence interval: 1.83-5.68). A similar pattern of results was also observed across the status of obesity and elevated NT-proBNP. There was a significant interaction between hs-cTnT and CVD events according to the obesity status (p = 0.039), while this association was marginal in NT-proBNP (p = 0.060). The magnitude of the mediation of hs-cTnT for the association between obesity and CVD risk was 41.2%, and that for NT-proBNP was 8.1%. In this Japanese hypertensive population, the elevation of hs-cTnT identified obese patients at particularly high risk for developing CVD events, suggesting that hs-cTnT may identify a 'malignant' phenotype of obesity.

ELEVATED GROWTH AND DIFFERENTIATION FACTOR 15 (GDF-15) LEVELS AMPLIFIES THE ASSOCIATION BETWEEN HOME BLOOD PRESSURE VARIABILITY AND CARDIOVASCULAR OUTCOME

Objective: Growth and differentiation factor 15 (GDF-15) is a marker of cell senescence. Although age is strongly determinant of GDF-15 level, several studies suggest that GDF-15 reflects biological age rather than chronological age. Since age is also associated with increased blood pressure variability, we hypothesized that the association between day-by-day home blood pressure variability (HBPV) and cardiovascular outcome may be steeper in patients with elevated GDF-15. Design and method: We analyzed 4030 patients from a practitioner-based population (mean±SD age 64.9±10.9 years: 79.0% taking antihypertensive medication) with at least one cardiovascular risk factor who underwent home blood pressure monitoring in the Japan Morning Surge-Home Blood Pressure Study. The standard deviation was assessed as indexes of day-by-day home systolic blood pressure variability. We divided patients into elevated (1200 ng/L or more) and non-elevated GDF-15 (less than 1200 ng/L) groups. Results: During a mean follow-up of 6.2 years, 247 cardiovascular events occurred. Participants with the highest HBPV tertile without elevated GDF-15 (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.03-2.23) or those with elevated GDF-15 without the highest BPV tertile (HR, 1.52; 95%CI, 1.03-2.16) had approximately 1.5-fold higher risk of cardiovascular events compared with those with low HBPV without elevated GDF-15. Adjusted risk of cardiovascular events was approximately 2.3-fold higher among participants with elevated GDF-15 and the highest HBPV tertile, compared with those with low HBPV without elevated GDF-15 (HR, 2.34; 95%CI, 1.58-3.45). Conclusions: We conclude that elevated GDF-15 contributes to the association between home BP variability and cardiovascular events.

Evening home blood pressure and pulse rate: age-specific associations with nocturia severity.

Previous studies have reported a significant relationship between hypertension and nocturia. However, the underlying pathophysiology associated with pulse rate (PR) remains unclear. In the Japan Morning Surge-Home Blood Pressure Study, a self-administered nocturia questionnaire and evening home blood pressure (BP) and PR measurements (taken on a mean of 11.2 days) were performed on 4310 patients with one or more cardiovascular risk factors (mean: 64.9 years old; 47% male). According to the number of nighttime voids, the study population was divided into three groups (no voids: n = 2382; 1 void: n = 847; ≥2 voids per night: n = 1082). In the multinomial logistic regression analysis adjusted for confounders, diuretic use (OR, 1.23; 95%CI, 1.01-1.50; p < 0.05) was significantly associated with one nocturnal void, whereas evening home systolic BP (SBP) (OR per 1 SD, 1.14; 95%CI, 1.05-1.24; p < 0.01) and evening home PR (OR per 1 SD, 1.12; 95%CI: 1.02-1.24; p < 0.05) were significantly associated with multiple nocturnal voids. In the younger group (<65 years), only evening home PR was significantly related to multiple nighttime voids (p < 0.01), whereas in the older group (≥65 years), only evening home SBP was significantly related to multiple nighttime voids (p = 0.02). In this study, both higher evening home PR and higher evening home SBP were associated with multiple nighttime voids, with the former playing a greater role in the younger participants, and the latter more often associating the older group. An age-stratified approach to reduce the burden of BP or PR might be important to improve sleep quality.

PS-BPC03-2: NIGHTTIME HOME BLOOD PRESSURE WAS ASSOCIATED WITH ADVERSE OUTCOMES IN SUBCLINICAL HEART FAILURE PATIENTS

Objective: Nighttime blood pressure (BP) has stronger association with target organ damage and cardiovascular outcome than office BP, 24-hr BP, and awake BP in hypertensives. However, clinical significance of nocturnal BP, especially home nocturnal BP, was not established in heart failure (HF) patients. We hypothesized that nighttime home BP was associated with adverse outcome and investigated the association between nighttime home BP and the outcome in subclinical HF patients. Design and method: We analyzed 394 patients with NT-proBNP &gt; 125pg/ml from a practitioner-based population with at least one cardiovascular risk factor who underwent home BP monitoring in the Japan Morning Surge-Home Blood Pressure study. Morning, evening and nighttime home BP were measured by validated, automatic, and oscillometric home BP devices, and cardiovascular events were followed up. Results: During a mean follow-up of 4.2 years, 43 cardiovascular events occurred. Morning home SBP, evening home SBP and nighttime home SBP were higher in event group than in non-event group (150 ± 23 vs 140 ± 17 mmHg, p = 0.01, 142 ± 22 vs 131 ± 16 mmHg, p &lt; 0.01, 133 ± 22 vs 125 ± 17 mmHg, p &lt; 0.01, respectively). In multivariate Cox regression analysis adjusting for significant variables, average of evening home SBP, and nighttime home SBP were significant predictors of the outcome (HR 1.02, 95%CI: 1.01–1.04, p = 0.01, HR 1.02, 95%CI: 1.01–1.04, p = 0.03, respectively). When nighttime home SBP of 120mmHg was used as cutoff, nighttime home SBP &gt; 120mmHg was significantly associated with the outcome (HR 2.46, 95%CI 1.06–5.68, p = 0.04). Conclusions: Elevated nighttime home BP was significant predictor of cardiovascular outcomes in subclinical HF patients.

Abstract 10373: Associations of Triglyceride-Glucose Index and Morning Home Blood Pressure With Microalbuminuria and Chronic Kidney Disease in the Japanese at High-Risk of Cardiovascular Disease

Introduction: Triglyceride-glucose index (TyGi) was shown to serve as a simple surrogate marker of insulin resistance, which had a significant association with impaired renal function. However, the underlying pathophysiology has not been established between insulin resistance and impaired renal function in relation to home blood pressure (BP) measurement. Hypothesis: We hypothesized that morning home BP level and TyGi were associated with impaired renal function in the Japanese at high-risk of cardiovascular disease. In addition, an interaction of morning home systolic BP (MSBP) with TyGi was assessed for impaired renal function. Methods: In the Japan Morning Surge-Home Blood Pressure Study, measurements of home BP (mean 11.2 days) were performed in the 4310 patients with one or more cardiovascular risks (64.9 years old, male 47%). TyGi was calculated as ln[fasting triglycerides (mg/dL) х fasting glucose (mg/dL)/2]. While microalbuminuria was defined as urinary albumin/creatinine ratio ≥30 mg/gCr, chronic kidney disease (CKD) was defined as estimated glomerular filtration rate &lt;60 ml/min/1.73 m 2 . Results: The mean levels of MSBP and TyGi were 138±16mmHg and 8.65±0.59, respectively. While the prevalence of microalbuminuria was 25.4%, the prevalence of CKD was 22.7%. In the logistic regression analysis adjusted for confounders including age, gender, body mass index, smoking, total cholesterol, HbA1c, use of antihypertensives, use of antidiabetics, statin use, and office SBP, MSBP (OR per 1SD, 1.39, 95%CI, 1.28-1.50, p&lt;0.001) and TyGi (OR per 1Unit, 1.31, 95%CI, 1.14-1.51, p&lt;0.001) were significantly associated with microalbuminuria. MSBP (OR per 1SD, 1.13, 95%CI, 1.04-1.23, p&lt;0.01) and TyGi (OR per 1Unit, 1.38, 95%CI, 1.19-1.61, p&lt;0.001) were also significantly associated with CKD. A significant interaction of MSBP with TyGi was not observed for microalbuminuria (p=0.17) or CKD (p=0.91). Conclusions: MSBP as well as TyGi were significant indicators of microalbuminuria and CKD. Morning BP load and insulin resistance were additively associated with impaired renal function in the high-risk Japanese population. In addition to home BP measurements, TyGi might provide additional clinically relevant information for target renal damage.

Abstract 10138: Evening Blood Pressure and Heart Rate: An Age-Specific Association of Nocturia in the Japanese at High-Risk of Cardiovascular Disease

Background: Earlier epidemiologic studies have reported a significant relationship between hypertension and nocturia. However, the underlying pathophysiology has not been established in relation to heart rate (HR). Hypothesis: We hypothesized that blood pressure (BP), HR, and the class of antihypertensive agent might be associated with severity of nocturia in the Japanese at high-risk of cardiovascular disease. In addition, these associations were hypothesized to be moderated by age. Methods: In the Japan Morning Surge-Home Blood Pressure Study, measurements of home BP as well as HR at evening (mean 11.2 days) were performed in the 4310 patients with one or more cardiovascular risks (64.9 years old, male 47%). A self-administered questionnaire included items on nocturia was used. Results: The mean levels of evening systolic BP (SBP) and HR were 130±15mmHg and 70±9.6bpm, respectively. According to the number of nocturia, we divided into the three groups (no void: n= 2382; one void: n=847; &gt; 2 voids per night: n=1082). In the multinomial logistic regression analysis adjustment for confounders including age, gender, smoking, total cholesterol, fasting blood glucose, HbA1c, log B-type natriuretic peptide, beta-adrenergic blockade use, clinic SBP and clinic HR, the use of diuretics (OR, 1.23, 95%CI, 1.01-1.50, p&lt;0.05) was significantly associated with one nocturnal void, while evening SBP (OR per 1SD, 1.14, 95%CI, 1.05-1.24, p&lt;0.01) and evening HR (OR per 1SD, 1.12, 95%CI: 1.02-1.24, p&lt;0.05) were significantly associated with multiple nocturnal voids. In the lower aged group (&lt;66yrs), only evening HR remained significant (p=0.003), while only evening SBP remained significant for multiple nocturnal voids in the higher aged group (66yrs &lt; ) (p=0.007). A significant interaction was found between age and evening HR for multiple nocturnal voids (p&lt;0.05). Conclusions: In this study, evening SBP and evening HR were significant indicators of multiple nocturnal voids in the high-risk Japanese population. Increased evening HR was specifically associated with severe nocturia in the lower aged group. Age-stratified approach to reduce BP and HR burdens might be important to improve sleep disturbance caused by nocturia.

Sex-specific associations of evening blood pressure burden and cardiac load with nocturia severity in the Japanese at high-risk of cardiovascular disease

Abstract Background Earlier epidemiologic studies have reported a significant relationship between hypertension and nocturia. However, the underlying pathophysiology has not been established. We hypothesized that blood pressure (BP) burden, the classes of antihypertensive agents and cardiac load were associated with severity of nocturia, and that these associations might be moderated by gender. Purpose To investigate the relationships of home BP (HBP) level, the class of antihypertensive agent, brain natriuretic peptide (BNP) with nocturia severity, and to investigate these associations stratified by gender in the Japanese at high-risk of cardiovascular disease. Methods In the Japan Morning Surge-Home Blood Pressure Study, measurements of HBP at evening (mean 11.2 days) as well as BNP were performed in the 4310 patients with one or more cardiovascular risks (64.9 years old, male 47%). A self-administered questionnaire included items on nocturia was used. Results According to the number of nocturia (no void: n=2382; one void: n=847; &amp;gt;2 voids per night: n=1082), significant associations of systolic BP (SBP) at evening (130 vs 130 vs 132 mmHg, p&amp;lt;0.0001) and logBNP (1.20 vs 1.30 vs 1.42, p&amp;lt;0.0001) were observed with nocturia severity. In the multinomial logistic regression analysis adjustment for confounders including age, smoking, total cholesterol, fasting blood glucose, HbA1c and clinic SBP, the use of diuretics (OR: 1.26, 95% CI: 1.06–1.52, p&amp;lt;0.05) was significantly associated with one nocturnal void, while evening SBP (OR: 1.009, 95% CI: 1.003–1.014, p&amp;lt;0.01) and logBNP (1.43, 95% CI: 1.19–1.73, p&amp;lt;0.001) were significantly associated with multiple nocturnal voids. While no significant interaction was found between evening SBP and logBNP for multiple nocturnal voids in the total population, a significant interaction was found between evening SBP and logBNP for multiple nocturnal voids in females (p&amp;lt;0.05). Conclusions In this study, the use of diuretics was a significant indicator of single nocturnal void, while evening SBP and BNP were those of multiple nocturnal voids in the high-risk Japanese population. Specifically, in the females, treatment to reduce BP burden as well as cardiac overload might be important to improve sleep disturbance caused by nocturia. Funding Acknowledgement Type of funding sources: None.

Impact of home blood pressure variability on cardiovascular outcome in patients with arterial stiffness: Results of the J-HOP study.

This study sought to investigate whether the relation between increased blood pressure (BP) variability and increased arterial stiffness confers a risk for cardiovascular disease (CVD) events. We analyzed 2648 patients from a practitioner‐based population (mean ± SD age 64.9 ± 11.4 years: 75.8% taking antihypertensive medication) with at least one cardiovascular risk factor who underwent home BP monitoring in the Japan Morning Surge‐Home Blood Pressure Study. The standard deviation (SDSBP), coefficient of variation (CVSBP), and average real variability (ARVSBP) were assessed as indexes of day‐by‐day home systolic BP (SBP) variability. The authors assessed arterial stiffness by brachial‐ankle pulse wave velocity (baPWV) and divided patients into lower (< 1800 cm/s, n = 1837) and higher (≥1800 cm/s, n = 811) baPWV groups. During a mean follow‐up of 4.4 years, 95 cardiovascular events occurred (8.1 per 1000 person‐years). In Cox proportional hazard models adjusted for traditional cardiovascular risk factors including average home SBP, the highest quartiles of SDSBP (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.23‐4.32), CVSBP (HR, 2.89; 95%CI, 1.59‐5.26) and ARVSBP (HR, 2.55; 95%CI, 1.37‐4.75) were predictive of CVD events compared to the other quartiles in the higher baPWV group. Moreover, 1SD increases in SDSBP (HR, 1.44; 95%CI, 1.13‐1.82), CVSBP (HR, 1.49; 95%CI, 1.16‐1.90) and ARVSBP (HR, 1.37; 95%CI, 1.09‐1.73) were also predictive of CVD events. These associations remained even after N‐terminal pro‐brain natriuretic peptide was added to the models. However, these associations were not observed in the lower baPWV group. We conclude that arterial stiffness contributes to the association between home BP variability and CVD incidence.

Automatically assessed P-wave predicts cardiac events independently of left atrial enlargement in patients with cardiovascular risks: The Japan Morning Surge-Home Blood Pressure Study.

A prolonged P‐wave in electrocardiography (ECG) reflects atrial remodeling and predicts the development of atrial fibrillation (AF). The authors enrolled 810 subjects in the Japan Morning Surge Home Blood Pressure (J‐HOP) study who had ≥1 cardiovascular (CV) risk factor. The duration of P‐wave was automatically analyzed by standard 12‐lead electrocardiogram. Left atrial (LA) enlargement and left ventricular hypertrophy (LVH) were measured on echocardiography. The primary end points were fatal/nonfatal cardiac events: myocardial infarction, sudden death, and hospitalization for heart failure. The maximum P‐wave duration (Pmax) from the 12 leads was selected for analysis. The authors compared four prolonged P‐wave cutoffs (Pmax = 120, 130, 140, 150 ms) and cardiac events. LA diameter and left ventricular mass index (LVMI) were significantly associated with Pmax (r = 0.08, P = .02 and r = 0.17, P < .001, respectively). When the cutoff level was Pmax 120 or 130 ms, prolonged P‐wave was not associated with cardiac events (P = .45 and P = .10), but when a prolonged P‐wave was defined as Pmax ≥ 140 ms (n = 50) or Pmax ≥ 150 ms (n = 19), the patients in those groups had significantly higher incidence of cardiac events than others (P < .001 and P = .03). A Cox proportional hazards model including age, gender, body mass index, smoking, regular drinker, hypertension, dyslipidemia, diabetes, office systolic blood pressure, heart rate, LA enlargement, and LVH revealed that prolonged P‐wave defined as Pmax ≥ 140 ms was independently associated with cardiac events (hazard ratio: 4.23; 95% confidence interval: 1.30–13.77; P = .02). In conclusion, the automatically assessed prolonged P‐wave was associated with cardiac events independently of LA enlargement and LVH in Japanese patients with CV risks.

Association of lower nighttime diastolic blood pressure and hypoxia with silent myocardial injury: The Japan Morning Surge-Home Blood Pressure study.

Whether marked nocturnal blood pressure (BP) reduction is associated with cardiovascular disease (CVD) is still controversial. In addition, no report has yet discussed the relationship between lower nocturnal BP and CVD, involving modification by nighttime hypoxia. We evaluated 840 patients who had one or more cardiovascular risk factors by measuring their high‐sensitivity cardiac troponin T (Hs‐cTnT), N‐terminal pro‐B‐type natriuretic peptide (NT‐pro BNP), and nighttime saturation levels and performing ambulatory BP monitoring. The lowest tertile in nighttime diastolic BP (DBP) (≤66 mmHg) had increased likelihood of the presence of ≥0.014 ng/ml of Hs‐cTnT compared with the second tertile (odds ratio [OR] 1.91, 95% confidence interval [CI] 1.01–3.63), and the lowest tertile of minimum blood oxygen saturation (≤81%) had increased likelihood of the presence of ≥0.014 ng/ml of Hs‐cTnT compared with the third tertile (OR 2.15, 95% CI 1.13–4.10). Additionally, the patients with both lowest tertile of nighttime DBP and minimum SpO2 showed increased likelihood of the presence of ≥0.014 ng/ml of Hs‐cTnT compared with those without this combination (OR 2.93, 95% CI 1.40–6.16). On the other hand, these associations were not found in the presence of ≥125 pg/ml of NT‐pro BNP. In the clinical population, each of lower nocturnal DBP and nighttime hypoxia was associated with asymptomatic myocardial injury, which was represented as higher Hs‐cTnT, and coexisting lower nocturnal DBP and nighttime hypoxia had an additive effect on the risk of myocardial injury.

Abstract 15551: Evening Blood Pressure Burden and Cardiac Load: A Sex-specific Association of Nocturia in the Japanese at High-risk of Cardiovascular Disease

Introduction: Earlier epidemiologic studies have reported a significant relationship between hypertension and nocturia. However, the underlying pathophysiology has been unclear. Hypothesis: We assessed the hypothesis that blood pressure (BP) burden and cardiac load might be associated with severity of nocturia. In addition, this association was hypothesized to be moderated by sex. Methods: In the Japan Morning Surge-Home Blood Pressure Study, measurements of home BP (HBP) at evening (mean 11.2 days) as well as brain natriuretic peptide (BNP) were performed in the 4310 patients with one or more cardiovascular risks (64.9 years old, male 47%). A self-administered questionnaire included items on nocturia was used. Results: According to the number of nocturia (no void: n= 2382; one void: n=847; ≥ 2 voids per night: n=1082), significant associations of systolic BP (SBP) at evening (130 vs 130 vs 132 mmHg, p&lt;0.0001) and logBNP (1.20 vs 1.30 vs 1.42, p&lt;0.0001) were observed with nocturia severity. In the multinomial logistic regression analysis adjustment for confounders including age, smoking, total cholesterol, fasting blood glucose, HbA1c and clinic SBP, the use of diuretics (OR: 1.26, 95%CI: 1.06-1.52, p&lt;0.05) was significantly associated with one nocturnal void, while evening SBP (OR: 1.009, 95%CI: 1.003-1.014, p&lt;0.01) and logBNP (1.43, 95%CI: 1.19-1.73, p&lt;0.001) were significantly associated with multiple nocturnal voids. While no significant interaction was found between evening SBP and logBNP for multiple nocturnal voids in the total population (p=0.1), a significant interaction was found between evening SBP and logBNP for multiple nocturnal voids only in females (p&lt;0.05). Conclusions: In conclusion, the use of diuretics was a significant indicator of single nocturnal void, while evening SBP and BNP were those of multiple nocturnal voids in the high-risk Japanese population. Specifically, in the females, treatment to reduce BP burden as well as cardiac overload might be important to improve sleep disturbance caused by nocturia.

Sex-dependent association between day-by-day morning blood pressure variability and common carotid artery intima-media thickness: the J-HOP study

Abstract Background Day-by-day home systolic blood pressure variability (BPV) was shown to be associated with increased common carotid artery (CCA) intima-media thickness (IMT) in the hypertensives. Recently, 24 hour ambulatory BPV was revealed to serve as an indicator of higher CCA-IMT only in males. However, there have been no studies that reported the sex-dependent relationship between day-by-day BPV and CCA-IMT. Purpose We assessed the hypothesis that day-by-day BPV was associated with higher CCA-IMT in the Japanese males 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, carotid ultrasound in CCA was performed in the 1365 patients (mean age 65.6 years old, male 52%). The home blood pressure (BP) readings during mean 11.2 days were used to calculate home mean levels and variability in morning systolic BP (SBP). Day-by-day BPV was measured as standard deviation [SD] and delta (maximum-minimum) in SBP. Results Average mean CCA-IMT of left and right side was 1.046±0.4mm. Mean (r=0.118, p&amp;lt;0.0001), SD (r=0.120, p&amp;lt;0.0001) and delta (r=0.149, p&amp;lt;0.0001) in morning SBP were significantly correlated with CCA-IMT. In the multiple regression analysis adjustment for confounders including age, gender, body mass index, total cholesterol, high density lipoprotein and mean morning SBP, SD (B: 0.008, 95% CI: 0.001–0.015, p&amp;lt;0.05) or delta (B: 0.004, 95% CI: 0.002–0.006, p&amp;lt;0.001) in morning SBP each had a significant association with CCA-IMT. According to the gender, SD (p&amp;lt;0.01) or delta (p&amp;lt;0.01) in morning SBP each was significantly associated with CCA-IMT only in the male group while neither SD (p=0.4) nor delta (p=0.4) in morning SBP was associated with CCA-IMT in the female group. Conclusions In addition to the conventional risk factors, day-by-day morning SBP variability was a significant indicator of increased CCA-IMT in the high-risk Japanese population. The significant relationship between day-by-day morning SBP variability and CCA-IMT was observed only in the males. Gender specific impact of day-by-day morning home systolic BPV on carotid artery atherosclerosis should be taken into account in the high-risk elderly at cardiovascular disease. Funding Acknowledgement Type of funding source: None

Sex differences and the prognosis of depressive and nondepressive patients with cardiovascular risk factors: the Japan Morning Surge-Home Blood Pressure (J-HOP) study.

Depression is associated with mortality in patients with cardiovascular risk factors. The frequency and severity of depression and the association between depression and cardiovascular events have sex-specific and ethnic differences. We conducted this study to evaluate the sex-specific difference in the association between depression and cardiovascular prognosis in patients with cardiovascular risk factors. We enrolled 4025 patients (64.7 ± 10.9 years, 53% women, 47% men) with cardiovascular risk factors in the Japan Morning Surge-Home Blood Pressure study. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). The follow-up period was 47 ± 24 months. The primary end points were all-cause mortality and nonfatal cardiovascular events. The BDI scores and the prevalence of depression were significantly higher in women than in men. When a BDI score of 16 was the cutoff, the primary end points in the depression group (n = 217) were significantly higher than those in the nondepression group (n = 1677) among men (adjusted hazard ratio 1.76, 95% confidence interval: 1.17, 2.64; P = 0.007). In women, the primary end points in the depression and nondepression groups were similar when BDI scores of 16, 14, and 10 were the cutoffs. In conclusion, depression defined by a BDI score ≥16 was associated with cardiovascular events in men with cardiovascular risk factors.

Sex Differences in the Prognostic Power of Brain Natriuretic Peptide and N-Terminal Pro-Brain Natriuretic Peptide for Cardiovascular Events - The Japan Morning Surge-Home Blood Pressure Study.

Brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are prognostic biomarkers. Although these 2 peptides differ with regard to biological characteristics, there are few reports on the differences between BNP and NT-proBNP with regard to cardiovascular events or according to sex.Methods and Results:Between 2005 and 2012, this study analyzed 3,610 of 4,310 Japanese outpatients (mean age, 65 years; men, n=1,664; women, n=1,947) with a history of at least one cardiovascular event who were recruited to the Japan Morning Surge-Home Blood Pressure Study. During an average 4-year follow-up, there were 129 cardiovascular events. Both median BNP (21.1 pg/mL; IQR, 10.9-40.6 pg/mL vs. 16.2 pg/mL, IQR, 7.2-36.2 pg/mL, P<0.001) and median NT-proBNP (54.7 pg/mL; IQR, 30.2-102.6 pg/mL vs. 44.9 pg/mL, IQR, 20.7-92.6 pg/mL, P<0.001) were significantly higher in women than in men. A 1-SD increment in log-transformed BNP (hazard ratio [HR], 2.18; 95% CI: 1.53-3.10) and NT-proBNP (HR, 2.39; 95% CI: 1.73-3.31) was associated with a significant increase in cardiovascular events in women; in men, only NT-proBNP showed this association. There was an interaction between log-transformed BNP (P=0.007) or NT-proBNP (P=0.001) and cardiovascular events according to sex. Both BNP and NT-proBNP predicted cardiovascular outcomes in a large Japanese clinical population. BNP and NT-proBNP were significantly stronger predictors in women than in men.

Increased Resting Heart Rate on Electrocardiogram Relative to In-office Pulse Rate Indicates Cardiac Overload: The J-HOP Study.

Heart rate (HR) assessed by electrocardiogram (ECG-HR) and pulse rate (PR) measured in a physician's office (office-PR) are taken with subjects in different body positions-i.e., supine vs. sitting. Although analysis of HR differences according to body position could provide new practical insights, there have been few studies on the subject. We herein investigated whether the difference between office-PR and ECG-HR (delta HR) was associated with brain natriuretic peptide (BNP) levels and left ventricular mass (LVM). Among the 4,310 patients with 1 or more cardiovascular risk factors recruited for the Japan Morning Surge-Home Blood Pressure study, we excluded those with atrial fibrillation or a prescribed β-blocker. We analyzed the 2,972 patients who had ECG-HR, office-PR, and BNP data and 1,061 patients with echocardiography data. In the complete patient series, office-PR was significantly higher than ECG-HR (72.1 ± 10.3 vs. 66.6 ± 11.9 bpm, P < 0.001). When we divided patients into quintiles based on the delta HR, the BNP level and LVM index (LVMI) decreased across categories after adjustment for traditional cardiovascular risk factors (each P ≤ 0.001). In a multiple linear regression analysis, the delta HR was independently and significantly associated with both the log-transformed BNP level (β = -0.179, P < 0.001) and LVMI (β = -0.113, P = 0.001) adjusted for covariates. A decreased delta HR was positively associated with the BNP level and LVMI. Without the requirement of a special technique, this evaluation might indicate potential cardiac overload and provide a clinical sign related to heart failure.

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.