苅尾 七臣

Accurate blood pressure (BP) measurement is necessary for the evaluation and treatment of hypertension to prevent the progression of subclinical vascular disease, including arterial stiffness. We investigated the associations between brachial-ankle pulse wave velocity (baPWV), a measure of arterial stiffness, and each of office brachial systolic BP (SBP) with and without an observer present (attended or unattended office brachial SBP), attended or unattended office central SBP, and home brachial SBPs (specifically, the means of morning, evening, or morning-evening home brachial SBP) in patients being treated for hypertension. Measurements were performed among 70 adults (mean age, 67.0 ± 9.4 years; women, 51.4%) with a mean attended office brachial SBP of 127.6 ± 14.5 mmHg and mean baPWV of 16.3 ± 2.8 m/s. Univariate analysis showed that higher attended office brachial SBP, morning home brachial SBP, and morning-evening home brachial SBP were each statistically significantly associated with higher baPWV (r = 0.25, P = 0.04; r = 0.37, P = 0.002; and r = 0.32, P = 0.006, respectively). Multiple linear regression analysis with adjustments for traditional cardiovascular risk factors showed that only morning home brachial SBP was statistically significantly associated with baPWV [β = 0.06, 95% confidence interval (0.01-0.11), P = 0.02). In conclusion, higher morning home brachial SBP - but none of the office-measured SBP values - was associated with arterial stiffness.

Background The aim of this study was to investigate the association between night-to-night adherence to continuous positive airway pressure (CPAP) therapy and both home blood pressure (BP) level on the following day and seasonal variation in home BP in patients with obstructive sleep apnea. Methods and Results We analyzed 105 participants who had been diagnosed with obstructive sleep apnea (average apnea-hypopnea index, 49.7±18.4 per hour) and who were already receiving CPAP therapy. Home BP (twice every morning and evening) and CPAP adherence data were automatically transmitted to a server for 1 year. A mixed-effects model for repeated measures analysis was used to examine associations of night-to-night good CPAP adherence with day-to-day home BP within the same patient after adjusting for covariates. The average number of days in which patients achieved both CPAP adherence and morning or evening home BP measurement was 206.6±122.7 days (21 487 readings) and 191.2±126.3 days (20 170 readings), respectively. Good CPAP adherence (>4 hours per night of use) was achieved on the evening or morning before home BP measurements (86.8% and 86.9%, respectively). After adjustment for confounders, good CPAP adherence was negatively associated with morning home systolic BP (β, -0.663; P=0.004) and diastolic BP (β, -0.829; P<0.001). Morning home systolic BP in winter in the individuals with good CPAP adherence was significantly lower than that in individuals without such adherence (P<0.05). These associations were not found in evening home BP. Conclusions Good adherence to CPAP therapy was negatively associated with morning home BP on the following day in patients with obstructive sleep apnea. The association was remarkable in the winter season.

In diagnosis of treatment-resistant hypertension (TRH), guidelines recommend out-of-office blood pressure (BP) measurements, ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM). Although evidence of an association between ABPM-evaluated TRH and cardiovascular disease (CVD) prognosis has accumulated, data are sparse regarding HBPM-evaluated TRH. We investigated this issue using data from the nationwide practice-based J-HOP (Japan Morning-Surge Home BP) study, which recruited 4,261 outpatients (mean age 64.9 years; 46.8% men; 91.5% hypertensives) who underwent morning and evening HBPM for 14 days. During 6.2 ± 3.8 years (26,418 person-years) follow-up, 270 total CVDs (stroke, coronary artery disease, aortic dissection, and heart failure) occurred. The adjusted hazard ratio (HR) (95% CIs) of uncontrolled TRH, i.e., uncontrolled BP using 3 classes of medications including diuretics or ≥4 classes of medications, for total CVD risk compared to controlled BP using <3 classes were 2.02 (1.38-2.94) and 1.81 (1.23-2.65) in home BP of 135/85 mmHg and 130/80 mmHg, respectively. Additionally, patients with TRH defined by guidelines, i.e., uncontrolled BP using 3 classes of medications including diuretics or controlled/uncontrolled BP using ≥4 classes of medications, also had higher total CVD risk compared to non-TRH under all home BP criteria. Moreover, in patients with uncontrolled apparent-TRH, i.e., TRH defined by office BP, uncontrolled home BP (≥135/85 mmHg) was still associated with atherosclerotic CVD (CVDs except heart failure) risk (adjusted HR [95% CI], 2.38 [1.09-5.19]). This is the first study to demonstrate an independent association between TRH evaluated by HBPM and CVD outcomes.

BACKGROUND: The causal relationship between hyperuricemia and cardiovascular diseases is still unknown. We hypothesized that hyperuricemic patients after percutaneous coronary intervention (PCI) had a higher risk of major adverse cardiovascular events (MACE). METHODS: This was a large-scale multicenter cohort study. We enrolled patients with chronic coronary syndrome (CCS) after PCI between April 2013 and March 2019 using the database from the Clinical Deep Data Accumulation System (CLIDAS), and compared the incidence of MACE, defined as a composite of cardiovascular death, myocardial infarction, and hospitalization for heart failure, between hyperuricemia and non-hyperuricemia groups. RESULTS: In total, 9,936 patients underwent PCI during the study period. Of these, 5,138 patients with CCS after PCI were divided into two group (1,724 and 3,414 in the hyperuricemia and non-hyperuricemia groups, respectively). The hyperuricemia group had a higher prevalence of hypertension, atrial fibrillation, history of previous hospitalization for heart failure, and baseline creatinine, and a lower prevalence of diabetes than the non-hyperuricemia group, but the proportion of men and age were similar between the two groups. The incidence of MACE in the hyperuricemia group was significantly higher than that in the non-hyperuricemia group (13.1 vs. 6.4%, log-rank P < 0.001). Multivariable Cox regression analyses revealed that hyperuricemia was significantly associated with increased MACE [hazard ratio (HR), 1.52; 95% confidential interval (CI), 1.23-1.86] after multiple adjustments for age, sex, body mass index, estimated glomerular filtration rate, left main disease or three-vessel disease, hypertension, diabetes mellitus, dyslipidemia, history of myocardial infarction, and history of hospitalization for heart failure. Moreover, hyperuricemia was independently associated with increased hospitalization for heart failure (HR, 2.19; 95% CI, 1.69-2.83), but not cardiovascular death or myocardial infarction after multiple adjustments. Sensitive analyses by sex and diuretic use, B-type natriuretic peptide level, and left ventricular ejection fraction showed similar results. CONCLUSION: CLIDAS revealed that hyperuricemia was associated with increased MACE in patients with CCS after PCI. Further clinical trials are needed whether treating hyperuricemia could reduce cardiovascular events or not.

Little is known about the relationship of the difference between morning and evening systolic blood pressure (BP) (MEdif) in home BP with cardiovascular disease (CVD) incidence. To assess this relationship, we used data from the nationwide practice-based J-HOP (Japan Morning Surge-Home BP) study, which recruited 4258 cardiovascular risk participants (mean age 64.9 years; 46.8% men; 79.2% using antihypertensive medications) who underwent morning and evening home BP monitoring using a validated, automated device for 14 consecutive days. During a mean ± SD follow-up of 6.2 ± 3.8 years (26,295 person-years), 269 CVD events occurred. Adjusted Cox models suggested that higher MEdif (≥20 mmHg) was associated with higher CVD risks than was medium MEdif (0-20 mmHg) independent of the average morning and evening (MEave) home systolic BP (SBP) (adjusted hazard ratio [HR]: 1.40; 95% confidence interval [CI] 1.02-1.91). We also divided participants into four BP phenotype groups as follows: "both non-elevated" (MEdif < 20 mmHg and MEave SBP < 135 mmHg), "elevated-MEdif" (MEdif ≥ 20 mmHg and MEave SBP < 135 mmHg), "elevated-MEave" (MEdif < 20 mmHg and MEave SBP ≥ 135 mmHg), and "both elevated" (MEdif ≥ 20 mmHg and MEave SBP ≥ 135 mmHg). The cumulative incidence of CVD events was higher in patients with the "elevated-MEdif," "elevated-MEave," and "both elevated" phenotypes than in those with the "both non-elevated" phenotype. After adjusting for covariates, the "both elevated" phenotype was associated with higher CVD risk than the "both non-elevated" phenotype (adjusted HR: 1.64; 95% CI: 1.09-2.46). This is the first study demonstrating a direct correlation between CVD outcomes and the difference between morning and evening home SBP.

[Figure: see text].

Background: Excess winter mortality caused by cardiovascular disease is particularly profound in cold houses. Consistent with this, accumulating evidence indicates that low indoor temperatures at home increase blood pressure. However, it remains unclear whether low indoor temperatures affect other cardiovascular biomarkers. In its latest list of priority medical devices for management of cardiovascular diseases, the World Health Organization (WHO) included electrocardiography systems as capital medical devices. We therefore examined the association between indoor temperature and electrocardiogram findings. Methods: We collected electrocardiogram data from 1480 participants during health checkups. We also measured the indoor temperature in the living room and bedroom for 2 weeks in winter, and divided participants into those living in warm houses (average exposure temperature ≥ 18 °C), slightly cold houses (12–18 °C), and cold houses (< 12 °C) in accordance with guidelines issued by the WHO and United Kingdom. The association between indoor temperature (warm vs. slightly cold vs. cold houses) and electrocardiogram findings was analyzed using multivariate logistic regression models, with adjustment for confounders such as demographics (e.g., age, sex, body mass index, household income), lifestyle (e.g., eating habit, exercise, smoking, alcohol drinking), and region. Results: The average temperature at home was 14.7 °C, and 238, 924, and 318 participants lived in warm, slightly cold, and cold houses, respectively. Electrocardiogram abnormalities were observed in 17.6%, 25.4%, and 30.2% of participants living in warm, slightly cold, and cold houses, respectively (p = 0.003, chi-squared test). Compared to participants living in warm houses, the odds ratio of having electrocardiogram abnormalities was 1.79 (95% confidence interval: 1.14–2.81, p = 0.011) for those living in slightly cold houses and 2.18 (95% confidence interval: 1.27–3.75, p = 0.005) for those living in cold houses. Conclusions: In addition to blood pressure, living in cold houses may have adverse effects on electrocardiogram. Conversely, keeping the indoor thermal environment within an appropriate range through a combination of living in highly thermal insulated houses and appropriate use of heating devices may contribute to good cardiovascular health. Trial registration: The trial was retrospectively registered on 27 Dec 2017 to the University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR, https://www.umin.ac.jp/ctr/, registration identifier number UMIN000030601).

Blood pressure (BP) exhibits seasonal variation, with an elevation of daytime BP in winter and an elevation of nighttime BP in summer. The wintertime elevation of daytime BP is largely attributable to cold temperatures. The summertime elevation of nighttime BP is not due mainly to temperature; rather, it is considered to be related to physical discomfort and poor sleep quality due to the summer weather. The winter elevation of daytime BP is likely to be associated with the increased incidence of cardiovascular disease (CVD) events in winter compared to other seasons. The suppression of excess seasonal BP changes, especially the wintertime elevation of daytime BP and the summertime elevation of nighttime BP, would contribute to the prevention of CVD events. Herein, we review the literature on seasonal variations in BP, and we recommend the following measures for suppressing excess seasonal BP changes as part of a regimen to manage hypertension: (1) out-of-office BP monitoring, especially home BP measurements, throughout the year to evaluate seasonal variations in BP; (2) the early titration and tapering of antihypertensive medications before winter and summer; (3) the optimization of environmental factors such as room temperature and housing conditions; and (4) the use of information and communication technology-based medicine to evaluate seasonal variations in BP and provide early therapeutic intervention. Seasonal BP variations are an important treatment target for the prevention of CVD through the management of hypertension, and further research is necessary to clarify these variations.

BACKGROUND: The incidence of cardiovascular disease (CVD) increases during winter. The risk that elevated home blood pressure (BP) poses for CVD events that occur in each of 4 seasons is unclear. We conducted a post hoc analysis using the dataset from a nationwide cohort, the Japan Morning Surge-Home Blood Pressure (J-HOP) study, to assess the association between home BP and winter-onset CVD events. METHODS: J-HOP participants who had cardiovascular risks conducted morning and evening home BP measurements for a 14-day period and were followed-up for the occurrence of CVD events. RESULTS: We analyzed 4,258 participants (mean age 64.9 years; 47% male; 92% hypertensives) who were followed-up for an average of 6.2 ± 3.8 years (26,295 person-years). We divided the total of 269 CVD events (10.2/1,000 person-years) by the season of onset as follows: 82 in the winter and 187 in the other seasons (spring, summer, and autumn). In the Cox models adjusted for covariates and the season when home BPs were measured at baseline, morning home systolic BP (SBP) was associated with both winter-onset and other season-onset CVD events: hazard ratio (HR) for winter 1.22, 95% confidence interval (CI) 1.06-1.42 per 10 mm Hg; HR for other seasons 1.11, 95% CI 1.00-1.23. Evening home SBP was associated with the other season-onset CVD events (HR 1.20, 95% CI 1.08-1.33 per 10 mm Hg), but not with the winter-onset CVD events. CONCLUSIONS: Our findings indicate that compared with evening home BP, morning home BP might be a superior predictor of winter-onset CVD events.

BACKGROUND: Little is known about seasonal variation in nighttime blood pressure (BP) measured by a home device. In this cross-sectional study, we sought to assess seasonal variation in nighttime home BP using data from the nationwide, practice-based Japan Morning Surge-Home BP (J-HOP) Nocturnal BP study. METHODS: In this study, 2,544 outpatients (mean age 63 years; hypertensives 92%) with cardiovascular risks underwent morning, evening, and nighttime home BP measurements (measured at 2:00, 3:00, and 4:00 am) using validated, automatic, and oscillometric home BP devices. RESULTS: Our analysis showed that nighttime home systolic BP (SBP) was higher in summer than in other seasons (summer, 123.3 ± 14.6 mmHg vs. spring, 120.7 ± 14.8 mmHg; autumn, 121.1 ± 14.8 mmHg; winter, 119.3 ± 14.0 mmHg; all P<0.05). Moreover, we assessed seasonal variation in the prevalence of elevated nighttime home SBP (≥120 mmHg) in patients with non-elevated daytime home SBP (average of morning and evening home SBP <135 mmHg; n = 1,565), i.e., masked nocturnal hypertension, which was highest in summer (summer, 45.6% vs. spring, 27.2%; autumn, 28.8%; winter, 24.9%; all P<0.05). Even in intensively controlled morning home SBP (<125 mmHg), the prevalence of masked nocturnal hypertension was higher in summer (summer, 27.4% vs. spring, 14.2%; autumn, 8.9%; winter, 9.0%; all P<0.05). The urine albumin-creatinine ratio in patients with masked nocturnal hypertension tended to be higher than that in patients with non-elevated both daytime and nighttime SBP throughout each season. CONCLUSIONS: The prevalence of masked nocturnal hypertension was higher in summer than other seasons and the difference proved to be clinically meaningful.

BACKGROUND: Although seasonal variation of home blood pressure (BP) has been reported to be higher in winter, seasonal difference in home BP (HBP) and its association with target organ damage (TOD) remains unclear. METHODS: This is a cross-sectional study using the dataset from the Japan Morning Surge-Home Blood Pressure (J-HOP) study to assess seasonal differences in HBP, prevalence of masked hypertension, and association of HBP with TOD. The J-HOP study is a nationwide, multicenter prospective study whose participants with cardiovascular risks underwent morning and evening HBP measurements for a 14-day period in 71 institutions throughout Japan. Urine albumin-creatinine ratio (UACR) and serum-B-type natriuretic peptide (BNP) were obtained at enrollment. RESULTS: Among 4,267 participants (mean age, 64.9 ± 10.9 years; 46.9% male; 91.4% hypertensives), 1,060, 979, 1,224, and 1,004 participants were enrolled in spring, summer, autumn, and winter, respectively. Morning and evening home systolic/diastolic BP levels, and prevalence of masked hypertension (office BP <140/90 mm Hg and HBP ≥135/85 mm Hg) were significantly lower in summer than other seasons after adjustment for covariates. When we assessed the interaction between BP parameters and each season for an association with TOD, we found the association between morning home diastolic BP and each of UACR and BNP was stronger in winter than other seasons (both P for interaction <0.05). CONCLUSIONS: In this study, we revealed that the prevalence of masked hypertension was higher in other seasons than in summer and found a notable association between morning home diastolic BP and TOD in winter.

The value of the cardio-ankle vascular index (CAVI) increases with age. All large-scale studies of the CAVI have investigated patients <80 years old. Thus, the clinical characteristics of high CAVI in patients aged 80 or more remain unclear. Therefore, we investigated (1) the CAVI in very elderly patients and (2) the determinants of a high CAVI in high-risk patients, including very elderly patients. The Cardiovascular Prognostic Coupling Study in Japan (Coupling Registry) is a prospective observational study of Japanese outpatients with any cardiovascular risk factors. We enrolled 5109 patients from 30 institutions (average age 68.7 ± 11.4 years, 52.4% males). We investigated the determinants of the CAVI by separating the patients into three groups: 970 middle-aged (<60 years), 3252 elderly (60-79 years), and 887 very elderly (≥80 years) patients. The CAVI values of the males were significantly higher those of the females in all age groups (<60 years: 7.81 ± 1.11 vs. 7.38 ± 0.99, P < .001; 60-79 years: 9.20 ± 1.29 vs. 8.66 ± 1.07, P < .001; ≥80 years: 10.26 ± 1.39 vs. 9.51 ± 1.12, P < .001). In all age groups, the CAVI of the patients with diabetes/glucose tolerance disorder was higher than that of the patients without diabetes/glucose tolerance disorder (<60 years: 7.82 ± 1.22 vs 7.58 ± 1.03, P = .002; 60-79 years: 9.23 ± 1.20 vs 8.78 ± 1.19, P < .001; ≥80 years: 10.04 ± 1.24 vs 9.75 ± 1.32, P = .002). The determinants of the CAVI in these very elderly patients were age, male sex, low BMI, and mean blood pressure. Diabetes/glucose tolerance disorder and glucose were independently associated with the CAVI in the patients aged <60 years and 60-79 years, but not in those aged ≥80 years after adjusting for other covariates.

Vascular biomarkers, including the cardio-ankle vascular index (CAVI), are increasingly being recognized as important indicators of cardiovascular risk. CAVI has been shown to have good discriminative ability for detecting new-onset hypertension, but results of studies investigating cardiovascular risk prediction are inconsistent. Furthermore, there is a lack of data on the prognostic value of changes in CAVI over time. The Cardiovascular Prognostic Coupling study was designed to determine the impact of baseline CAVI and changes in CAVI on cardiovascular events in a Japanese cohort. The design of the ongoing, multicenter, prospective, observational registry and baseline characteristics of the enrolled population are reported. Eligible consecutive patients were aged ≥30 years, had ≥1 cardiovascular risk factor, and were being treated according to relevant Japanese guidelines. The primary outcome is time to onset of a major cardiovascular event (a composite of cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, stroke of unknown etiology, myocardial infarction, cardiovascular intervention for angina pectoris, and sudden death). Screening and enrollment occurred over a period of 3 years, followed by ≥7 years of follow-up, with CAVI determined annually. A total of 5279 patients were registered, of whom 5109 had baseline data available and will be included in future analyses. Mean CAVI at baseline was 8.8 ± 1.4. The proportion of patients with CAVI of <8, 8-10 or >10 was 25.3%, 57.0%, and 17.7%, respectively. Data from this registry should provide information on the significance of baseline CAVI and change in CAVI as indicators of cardiovascular prognosis in a representative patient population.

A 68-year-old Japanese man was admitted to our hospital with right eye pain, a sudden worsening of his eyesight, and a fever. He was diagnosed with endogenous bacterial endophthalmitis due to infectious endocarditis (IE) of Group B Streptococcus (GBS) on the day of admission. He recovered systemically, but his right eye became phthisical only with the administration of antibiotics. We conducted a review of the reported cases of IE caused by GBS complicated with endogenous bacterial endophthalmitis. IE should be considered when an undetermined etiology of endogenous endophthalmitis is encountered. The prompt diagnosis and treatment of IE will improve patients' outcomes.

Constipation is associated with cardiovascular events. Changes to the intestinal microbiota by constipation can induce atherosclerosis, blood pressure rise, and cardiovascular events. Constipation increases with age and often coexists with cardiovascular risk factors. In addition, strain at stool causes blood pressure rise, which can trigger cardiovascular events such as congestive heart failure, arrhythmia, acute coronary disease, and aortic dissection. However, because cardiovascular medical research often focuses on more dramatic interventions, the risk from constipation can be overlooked. Physicians caring for patients with cardiovascular disease should acknowledge constipation and straining with it as important cardiovascular risk, and prematurely intervene to prevent it. The authors review and discuss the relationship between constipation and cardiovascular disease.

Background: Maximum home systolic blood pressure (maximum SBP) has been reported as a parameter of blood pressure (BP) variability. We tested the hypothesis that maximum SBP is one of the risk factors of hypertensive target organ damage (TOD).Methods: We conducted a cross-sectional study of 4,310 subjects with>1 cardiovascular risk factor. The subjects measured their home BP for 14 consecutive days. Mean and maximum SBPs were used as independent variables. As dependent variables, we used left ventricular mass index (LVMI), brachial-ankle pulse wave velocity (baPWV), maximum carotid intima-media thickness (CIMT), and urine albumin creatinine ratio (UACR).Results: In a multiple regression analysis, the subjects' mean and maximum SBPs were significantly associated with the above TOD markers. Compared to mean SBP, maximum SBP demonstrated a significantly stronger association with CIMT (p<0.001).Conclusion: Based on its clinical significance herein, measurement of maximum home SBP is warranted in addition to measurement of mean home SBP.

OBJECTIVE: This study investigated the changes of ambulatory blood pressure (ABP) profiles on the same participants over a 19-year follow-up. PARTICIPANTS AND METHODS: This is a longitudinal study. We conducted 24-h ABP monitoring at baseline in November 1997 and at follow-up in November 2016 for the same participants who were outpatients in a solitary island clinic. To estimate ambulatory blood pressure variability (ABPV), SD, coefficient of variation, and average real variability of ABP were calculated. ABP levels and ABPV at baseline and follow-up were compared using paired t-test. RESULTS: A total of 35 participants were recruited at follow-up (79.3±6.7 years at follow-up). Mean systolic blood pressure levels in 24-h, daytime, and night-time did not change significantly. However, ABPV of systolic/diastolic blood pressure in 24-h and daytime increased at follow-up compared with baseline (P<0.01 in all variables: SD, coefficient of variation, and average real variability), whereas ABPV in night-time did not change significantly. CONCLUSION: Our observations suggested that 24-h and daytime ABPV increase with aging in community-dwelling elderly people.

Randomized controlled trials and meta-analyses have established the benefits of blood pressure (BP) lowering. The 2017 American Heart Association/American College of Cardiology (AHA/ACC) guidelines for the management of hypertension established 130/80 mmHg as the threshold for the diagnosis- and treatment-target BP level. Area covered: The global trends are thought to be heading toward intensive BP-lowering management. In this paper, authors summarize the evidence on lowering the BP target in hypertensive patients with a focus on the 2017 AHA/ACC guidelines. Expert commentary: According to the results of clinical research, meta-analyses and the 2017 AHA/ACC guidelines, the target systolic BP may change from less than 140/80 mmHg to 130/80 mmHg in any other international hypertension guidelines. However, this direction of intensive BP control is still controversial.

Research suggests that oxygen desaturation and sleep stage during obstructive sleep apnea (OSA) are related to the magnitude of high blood pressure (BP) in a laboratory setting. However, in a clinical setting, these associations have not been well studied. We used a noninvasive oscillometric BP measurement device to investigate the association between oxygen-triggered BP levels at the end of each OSA episode and the characteristics of the preceding OSA episode. In 42 newly diagnosed OSA patients (average age, 63.5±12.5 years; average apnea-hypopnea index, 32.6±18.2 per hour), 258 BP measurements were obtained at the end of OSA episodes. Hypoxia-peak systolic BP (SBP), defined as the maximum oxygen-triggered SBP value, was significantly higher in rapid eye movement sleep (144.9±19.9 mm Hg) than in non-rapid eye movement stage 1 sleep (129.5±15.1 mm Hg; P<0.001) and non-rapid eye movement stage 2 sleep (129.4±14.7 mm Hg; P<0.001). In a multivariate-linear mixed model, the lowest oxygen saturation percentage during each OSA episode was associated with increased hypoxia-peak SBP (-0.501 mm Hg; P<0.001), nocturnal SBP surge (-0.395 mm Hg; P<0.001), defined as the difference between the hypoxia-peak SBP and the mean nocturnal SBP, and maximum value of SBP surge (-0.468 mm Hg; P<0.001), defined as the difference between the hypoxia-peak SBP and the minimum nocturnal SBP independent of sleep stage. These values were not associated with the duration of each OSA episode. The contribution of rapid eye movement sleep and severe oxygen desaturation to OSA-related BP elevation measured with a noninvasive oscillometric method was determined in a clinical setting.

Background: Previous catheter-based renal denervation studies have reported variable efficacy results. We aimed to evaluate safety and blood pressure response after renal denervation or sham control in patients with uncontrolled hypertension on antihypertensive medications with drug adherence testing. Methods: In this international, randomised, single-blind, sham-control, proof-of-concept trial, patients with uncontrolled hypertension (aged 20–80 years) were enrolled at 25 centres in the USA, Germany, Japan, UK, Australia, Austria, and Greece. Eligible patients had an office systolic blood pressure of between 150 mm Hg and 180 mm Hg and a diastolic blood pressure of 90 mm Hg or higher a 24 h ambulatory systolic blood pressure of between 140 mm Hg and 170 mm Hg at second screening and were on one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned to undergo renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were masked to randomisation assignments. The primary efficacy endpoint was blood pressure change from baseline (measured at screening visit two), based on ambulatory blood pressure measurements assessed at 6 months, as compared between treatment groups. Drug surveillance was used to assess medication adherence. The primary analysis was done in the intention-to-treat population. Safety events were assessed through 6 months as per major adverse events. This trial is registered with ClinicalTrials.gov, number NCT02439775, and follow-up is ongoing. Findings: Between July 22, 2015, and June 14, 2017, 467 patients were screened and enrolled. This analysis presents results for the first 80 patients randomly assigned to renal denervation (n=38) and sham control (n=42). Office and 24 h ambulatory blood pressure decreased significantly from baseline to 6 months in the renal denervation group (mean baseline-adjusted treatment differences in 24 h systolic blood pressure −7·0 mm Hg, 95% CI −12·0 to −2·1 p=0·0059, 24 h diastolic blood pressure −4·3 mm Hg, −7·8 to −0·8 p=0.0174, office systolic blood pressure −6·6 mm Hg, −12·4 to −0·9 p=0·0250, and office diastolic blood pressure −4·2 mm Hg, −7·7 to −0·7 p=0·0190). The change in blood pressure was significantly greater at 6 months in the renal denervation group than the sham-control group for office systolic blood pressure (difference −6·8 mm Hg, 95% CI −12·5 to −1·1 p=0·0205), 24 h systolic blood pressure (difference −7·4 mm Hg, −12·5 to −2·3 p=0·0051), office diastolic blood pressure (difference −3·5 mm Hg, −7·0 to −0·0 p=0·0478), and 24 h diastolic blood pressure (difference −4·1 mm Hg, −7·8 to −0·4 p=0·0292). Evaluation of hourly changes in 24 h systolic blood pressure and diastolic blood pressure showed blood pressure reduction throughout 24 h for the renal denervation group. 3 month blood pressure reductions were not significantly different between groups. Medication adherence was about 60% and varied for individual patients throughout the study. No major adverse events were recorded in either group. Interpretation: Renal denervation in the main renal arteries and branches significantly reduced blood pressure compared with sham control with no major safety events. Incomplete medication adherence was common. Funding: Medtronic.

Obstructive sleep apnea causes blood pressure (BP) surges during sleep, which may lead to increased sleep-onset cardiovascular events. The authors recently developed an oxygen-triggered nocturnal BP monitoring system that initiates BP measurements when oxygen desaturation (SpO2) falls below a variable threshold. The association between nocturnal BP parameters obtained by nocturnal BP monitoring and simultaneously examined polysomnography-derived sleep parameters in 116 patients with obstructive sleep apnea (mean age 57.9 years, 85.3% men) was studied. In multivariable analysis with independent factors of age, body mass index, sex, and polysomnography-derived measures (apnea-hypopnea index, apnea index, arousal index, lowest SpO2, and SpO2 &lt  90%), apnea-hypopnea index (β =.26, P =.02) and lowest SpO2 (β = −.34, P &lt .001) were independent determinants of hypoxia-peak systolic BP (SBP), defined as the maximum SBP value measured by nocturnal BP monitoring. Similarly, apnea-hypopnea index (β =.21, P =.04) and lowest SpO2 (β = −.49, P &lt .001) were independent determinants of nocturnal SBP surge, defined as the difference between the hypoxia-peak SBP and the average of the SBP values within 30 minutes before and after the hypoxia-peak SBP, measured by the fixed-interval function in the manner of conventional ambulatory BP monitoring. In conclusion, in polysomnography-derived parameters, lowest SpO2, defined as the minimum SpO2 value during sleep, is the strongest independent determinant of hypoxia-peak SBP and nocturnal SBP surge measured by nocturnal BP monitoring. Our findings suggest that the severity of the decrease in SpO2 and the frequency of such decreases would be important indicators to identify high-risk patients who are likely to develop cardiovascular events specifically during sleep.

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 &lt 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 &lt 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.

Background: Although prasugrel exerts stronger antiplatelet effects compared with clopidogrel, the factors affecting platelet reactivity under prasugrel have not been fully determined. This study aimed to find the novel mechanistic differences between two thienopyridines and identify the factor that influence platelet reactivity to each drug. Methods: Forty patients with stable angina who underwent elective percutaneous coronary intervention were randomly assigned to receive either prasugrel (20 mg) or clopidogrel (300 mg) as a loading dose. Platelet function (light transmission, laser light scattering, and vasodilator-stimulated phosphoprotein phosphorylation) and plasma active metabolite levels were measured after the loading dose. Results: Prasugrel consistently inhibited adenosine diphosphate receptor P2Y12 signalling to abolish amplification of platelet aggregation. Prasugrel abolished even small platelet aggregates composed of less than 100 platelets. On the other hand, clopidogrel inhibited large aggregates but increased small and medium platelet aggregates. Diabetes was the only independent variable for determining antiplatelet effects and active metabolite concentration of prasugrel, but not clopidogrel. Sleep-disordered breathing was significantly correlated with platelet reactivity in patients who had clopidogrel. Conclusions: Prasugrel efficiently abolishes residual P2Y12 signalling that causes small platelet aggregates, but these small aggregates are not inhibited by clopidogrel. Considering the differential effect of diabetes on antiplatelet effects between these two drugs, the pharmacokinetics of prasugrel, other than cytochrome P450 metabolism, might be affected by diabetes.

The impact of a nondipping blood pressure (BP) pattern, defined as (awake systolic BP – sleep systolic BP)/awake systolic BP &lt  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 67.9 years, 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 &lt  1.1 mm 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 &lt .01]). This association was not found in the population with carotid intima-media thickness ≥ 1.1 mm. 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.

Background: Although higher blood pressure (BP) levels and BP variability have been associated with cognitive impairment, data are sparse regarding the relationship between BP variability and cognitive function in elderly patients with well BP control. Methods: We analyzed 232 ambulatory patients with one or more cardiovascular risk factors. All patients underwent ambulatory BP monitoring and the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Results: The mean age was 77.7 ± 8.3 years 33.6% were male, and 85.3% were taking antihypertensive drugs. The average 24-hour BP level was 118.7 ± 10.0/68.3 ± 6.4 mm Hg. When we divided the weighted SD of systolic BP (SBP) as a measure of BP variability into quartiles, the top quartile group (≥19.6 mm Hg) had a significantly lower total MoCA-J score (15.4 [95% confidence interval 14.2-16.7] vs. 17.9 [17.2-18.6], P = 0.001) and lower scores on several domains, visuoexecutive (2.2 [1.9-2.6] vs. 2.8 [2.6-2.9], P = 0.012), abstraction (1.0 [0.7-1.2] vs. 1.3 [1.1-1.4], P = 0.015), attention (2.8 [2.4-3.1] vs. 3.6 [3.4-3.8], P = 0.001), and naming (2.1 [1.9-2.3] vs. 2.5 [2.4-2.6], P = 0.001) than quartiles 1 through 3 combined, after adjustment for age and 24-hour SBP. These associations were not found in the quartiles of 24-hour SBP. Conclusions: In elderly patients with well ambulatory BP control, higher BP variability but not average ambulatory BP level was associated with cognitive impairment.

The appropriate target blood pressure (BP) in elderly patients with hypertension remains uncertain. We investigated the relationship between morning home systolic blood pressure (MHSBP) during follow-up and cardiovascular (CV) risk in outpatients receiving olmesartan-based treatment aged <75 years (n = 16799) and ≥75 years (n = 4792) in the HONEST study. In the follow-up period (mean 2.02 years), the risk for major CV events was significantly higher in patients with MHSBP ≥155 mmHg compared with <125 mmHg in both age groups in Cox proportional hazards model adjusted for other risk factors and there was no significant difference in trend between the two groups (interaction P = 0.9917 for MHSBP). Hazard ratios for CV events for 1-mmHg increase in MHSBP were similar in patients aged <75 years and in patients aged ≥75 years. The incidence of adverse drug reactions related to excessive BP lowering was lower in patients <75 years than in patients ≥75 years (0.73 vs 1.02%, P = 0.0461). In conclusion, the study suggests even in patients ≥75 years antihypertensive treatment targeting the same MHSBP levels in patients <75 years may be beneficial in reducing CV risk when treatment is tolerated.