[The case of an octogenarian who died of acute myocardial infarction complicated with acute pulmonary embolism from a right ventricular thrombus].

An 86-year-old female on dialysis experienced a decrease in blood pressure and worsening of her respiratory condition during dialysis, for which she visited our emergency unit. She was admitted to our Department of Cardiology with a diagnosis of acute myocardial infarction complicated with heart failure because of anterior wall of left ventricular dysfunction, positive troponin T levels and negative T wave on a precordial lead electrocardiogram. On the same day, she underwent coronary angiography and stenting at left anterior descending artery #7 with 99% stenosis. She also showed an elevated D-dimer level on admission, and contrast-enhanced computed tomography (CT) was performed the day after admission, considering the likelihood of respiratory failure due to pulmonary thromboembolism. However, the findings were negative. On the 4th day of hospitalization, she showed marked hypoxemia. Her D-dimer level was further elevated, and when she underwent enhanced CT again, there was no evidence of deep vein thrombosis, but thrombus in the pulmonary artery and apex of right ventricle was noted. She was therefore diagnosed with acute pulmonary embolism due to thrombosis from the right ventricle rather than from a deep vein. She rapidly received anticoagulant therapy and non-invasive positive pressure ventilation therapy for respiratory failure, but she entered cardiopulmonary arrest and quickly died. She was suspected to have been complicated with a right ventricular infarction and an acute anterior wall myocardial infarction, resulting in a large thrombus along the apex of the right ventricle. This case of both myocardial infarction and pulmonary embolism is very rare, and we report it here with consideration.

Effects of canagliflozin on NT-proBNP stratified by left ventricular diastolic function in patients with type 2 diabetes and chronic heart failure: a sub analysis of the CANDLE trial.

BACKGROUND: Identification of the effective subtypes of treatment for heart failure (HF) is an essential topic for optimizing treatment of the disorder. We hypothesized that the beneficial effect of SGLT2 inhibitors (SGLT2i) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) might depend on baseline diastolic function. To elucidate the effects of SGLT2i in type 2 diabetes mellitus (T2DM) and chronic HF we investigated, as a post-hoc sub-study of the CANDLE trial, the effects of canagliflozin on NT-proBNP levels from baseline to 24 weeks, with the data stratified by left ventricular (LV) diastolic function at baseline. METHODS: Patients (n = 233) in the CANDLE trial were assigned randomly to either an add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The primary endpoint was a comparison between the two groups of the changes from baseline to 24 weeks in NT-pro BNP levels, stratified according to baseline ventricular diastolic function. RESULTS: The change in the geometric mean of NT-proBNP level from baseline to 24 weeks was 0.98 (95% CI 0.89-1.08) in the canagliflozin group and 1.07 (95% CI 0.97-1.18) in the glimepiride group. The ratio of change with canagliflozin/glimepiride was 0.93 (95% CI 0.82-1.05). Responder analyses were used to investigate the response of an improvement in NT-proBNP levels. Although the subgroup analyses for septal annular velocity (SEP-e') showed no marked heterogeneity in treatment effect, the subgroup with an SEP-e' < 4.7 cm/s indicated there was an association with lower NT-proBNP levels in the canagliflozin group compared with that in the glimepiride group (ratio of change with canagliflozin/glimepiride (0.83, 95% CI 0.66-1.04). CONCLUSIONS: In the subgroup with a lower LV diastolic function, canagliflozin showed a trend of reduced NT-pro BNP levels compared to that observed with glimepiride. This study suggests that the beneficial effects of canagliflozin treatment may be different in subgroups classified by the severity of LV diastolic dysfunction.

Effect of canagliflozin on N-terminal pro-brain natriuretic peptide in patients with type 2 diabetes and chronic heart failure according to baseline use of glucose-lowering agents.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of a deterioration in heart failure (HF) and mortality in patients with a broad range of cardiovascular risks. Recent guidelines recommend considering the use of SGLT2 inhibitors in patients with type 2 diabetes (T2D) and HF, irrespective of their glycemic control status and background use of other glucose-lowering agents including metformin. However, only a small number of studies have investigated whether the effects of SGLT2 inhibitor in these patients differ by the concomitant use of other glucose-lowering agents. METHODS: This was a post-hoc analysis of the CANDLE trial (UMIN000017669), an investigator-initiated, multicenter, open-label, randomized, controlled trial. The primary aim of the analysis was to assess the effect of 24 weeks of treatment with canagliflozin, relative to glimepiride, on N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in patients with T2D and clinically stable chronic HF. In the present analysis, the effect of canagliflozin on NT-proBNP concentration was assessed in the patients according to their baseline use of other glucose-lowering agents. RESULTS: Almost all patients in the CANDLE trial presented as clinically stable (New York Heart Association class I to II), with about 70% of participants having HF with a preserved ejection fraction phenotype (defined as a left ventricular ejection fraction ≥ 50%) at baseline. Of the 233 patients randomized to either canagliflozin (100 mg daily) or glimepiride (starting dose 0.5 mg daily), 85 (36.5%) had not been taking any glucose-lowering agents at baseline (naïve). Of the 148 patients who had been taking at least one glucose-lowering agent at baseline (non-naïve), 44 (29.7%) and 127 (85.8%) had received metformin or a dipeptidyl dipeptidase-4 (DPP-4) inhibitor, respectively. The group ratio (canagliflozin vs. glimepiride) of proportional changes in the geometric means of NT-proBNP concentration was 0.95 (95% confidence interval [CI] 0.76 to 1.18, p = 0.618) for the naïve subgroup, 0.92 (95% CI 0.79 to1.07, p = 0.288) for the non-naïve subgroup, 0.90 (95% CI 0.68 to 1.20, p = 0.473) for the metformin-user subgroup, and 0.91 (95% CI 0.77 to 1.08, p = 0.271) for the DPP-4 inhibitor-user subgroup. No heterogeneity in the effect of canagliflozin, relative to glimepiride, on NT-proBNP concentration was observed in the non-naïve subgroups compared to that in the naïve subgroup. CONCLUSION: The impact of canagliflozin treatment on NT-proBNP concentration appears to be independent of the background use of diabetes therapy in the patient population examined. Trial registration University Medical Information Network Clinical Trial Registry, number 000017669. Registered on May 25, 2015.

Cardiovascular Outcomes in the Acute Phase of COVID-19.

The cumulative number of cases in the current global coronavirus disease 19 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has exceeded 100 million, with the number of deaths caused by the infection having exceeded 2.5 million. Recent reports from most frontline researchers have revealed that SARS-CoV-2 can also cause fatal non-respiratory conditions, such as fatal cardiovascular events. One of the important mechanisms underlying the multiple organ damage that is now known to occur during the acute phase of SARS-CoV-2 infection is impairment of vascular function associated with inhibition of angiotensin-converting enzyme 2. To manage the risk of vascular dysfunction-related complications in patients with COVID-19, it would be pivotal to clearly elucidate the precise mechanisms by which SARS-CoV-2 infects endothelial cells to cause vascular dysfunction. In this review, we summarize the current state of knowledge about the mechanisms involved in the development of vascular dysfunction in the acute phase of COVID-19.

Obstructive Sleep Apnea as Possible Causal Factor for Visit-to-Visit Blood Pressure Variability.

BACKGROUND: Recent studies have shown that visit-to-visit blood pressure variability (BPV) is an independent risk factor for cardiovascular disease. However, it has not been clarified whether obstructive sleep apnea (OSA) is associated with visit-to-visit BPV. METHODS AND RESULTS: The 56 subjects with OSA and 26 control subjects without OSA were examined. Office BP was measured on 5 separate consecutive occasions prior to a polysomnography examination. The visit-to-visit BPV was expressed as the standard deviation and the coefficient of variation of the 5 systolic BP measurements. In subjects with an apnea-hypopnea index (AHI) of more than 20 episodes per hour, the visit-to-visit BPV was also measured after the start of continuous positive airway pressure (CPAP) therapy. Overall, the AHI positively correlated with the standard deviation and the coefficient of variation of systolic BP. In a multivariate analysis, the plasma noradrenaline level and the AHI were independently and positively correlated with the standard deviation and the coefficient of variation of the systolic BP. Among the patients who underwent CPAP therapy, good adherence with CPAP therapy significantly reduced the visit-to-visit BPV. CONCLUSIONS: OSA is associated with abnormal visit-to-visit BPV and sympathetic activation seems to be related in some way. (Circ J 2016; 80: 1787-1794).

Continuous positive airway pressure treatment improves cardiovascular outcomes in elderly patients with cardiovascular disease and obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with the progression of cardiovascular disease (CVD), particularly in the middle-aged population. However, the clinical importance of OSA as a risk for CVD in the elderly population remains controversial. Moreover, evidence for the effectiveness of continuous positive airway pressure (CPAP) treatment for the secondary prevention of CVD in elderly patients is lacking. We assessed whether CPAP treatment improves cardiovascular outcomes in elderly patients with OSA and CVD. In this retrospective cohort study, we enrolled 130 elderly patients aged 65-86 years with moderate to severe OSA (apnea-hypopnea index ≥15/h) and a history of hospitalization due to CVD, who underwent polysomnography between November 2004 and July 2011. Patients were divided into the CPAP group (n = 64) or untreated OSA group (n = 66). The main outcome measures were cardiovascular death and hospitalization due to CVD. During the mean follow-up period of 32.9 ± 23.8 (standard deviation) months, 28 (21.5 %) patients either died or were hospitalized. The Kaplan-Meier curves indicated that event-free survival was significantly lower in the untreated OSA group than in the CPAP group (P < 0.005). A multivariate analysis showed that the risk was significantly increased in the untreated OSA group (hazard ratio 5.13; 95 % confidence interval 1.01-42.0; P < 0.05). Moderate to severe OSA not treated with CPAP was an independent risk factor for relapse of a CVD event, and adequate CPAP treatment improved cardiovascular outcomes in elderly patients.

Pathophysiological contribution of vascular function to baroreflex regulation in hypertension.

BACKGROUND: We examined which pathophysiological abnormalities of vascular function might be closely associated with abnormal baroreflex regulation in subjects with hypertension. METHODS AND RESULTS: In the cross-sectional assessment, 280 subjects with hypertension were enrolled for measurement of brachial-ankle pulse wave velocity (baPWV), radial augmentation index (rAI), flow-mediated vasodilatation (FMD) of the brachial artery and baroreceptor sensitivity (BRS). These parameters were measured again as prospective assessment in some of these subjects. In the cross-sectional assessment, after adjustment for confounding variables including anti-hypertensive medication, the baPWV, but not the rAI or FMD, was found to have a significant independent relationship with BRS (standardization coefficient, -0.149, P<0.043). In the subjects who were newly started on anti-hypertensive medication (n=40), regression of baPWV before and 1 year after the start of medication was significantly associated with change in BRS during the same period. In subjects already on anti-hypertensive medication (n=92) also, the evolutional change of baPWV over a follow-up period >1.5 years was significantly associated with change in BRS during the same period. CONCLUSIONS: Increased stiffness of the large- to middle-sized arteries, rather than abnormal central hemodynamics or endothelial dysfunction, appears to contribute to abnormal baroreflex regulation in patients with hypertension.

Central Systolic Blood Pressure as a Risk Factor for Accelerated Progression of Arterial Stiffness.

AIMS: In the arterial tree, a pressure gradient of the systolic blood pressure (SBP) is observed from the center to the periphery, with the pressure being higher in the periphery because of pressure wave reflection. However, this gradient is attenuated, with elevation of the central SBP (cSBP), in cases with abnormal pressure wave reflection in the arterial tree. It remains unclear if increase of the cSBP might be an independent risk factor for accelerated progression of arterial stiffness. We conducted this prospective observational study using latent growth curve model (LGCM) analyses to examine if elevated cSBP might be an independent risk factor for accelerated progression of the arterial stiffness in middle-aged Japanese men. METHODS: In this 9-year prospective observational study, we analyzed the data of 3862 middle-aged Japanese men (43±10years old) without cerebrocardiovascular disease at the study baseline who had undergone repeated annual measurements of the brachial-ankle pulse wave velocity (baPWV) and cSBP, as represented by the second peak of the radial pressure waveform (SBP2) in radial pressure waveform analysis. RESULTS: During the follow-up period (6.3±2.5years), significant increases of both the baPWV and SBP2 were observed in all the subjects. Analysis using the LGCM confirmed that the SBP2, a marker of the cSBP (B=0.260, P＜0.001), was a significant determinant of the slope of the annual changes of the baPWV during the study period. CONCLUSIONS: Our finding may appear to confirm elevated cSBP as an independent risk factor for accelerated progression of the arterial stiffness in middle-aged Japanese men.

Longitudinal Associations between Alcohol Intake and Arterial Stiffness, Pressure Wave Reflection, and Inflammation.

AIMS: This prospective observational study, which utilized repeated annual measurements performed over a 9-year period, applied mixed model analyses to examine age-related differences in longitudinal associations between alcohol intake and arterial stiffness, pressure wave reflection, and inflammation. METHODS: In 4016 middle-aged (43±9 years) healthy Japanese male employees, alcohol intake, brachial-ankle pulse wave velocity (baPWV), radial augmentation index (rAI), and serum C-reactive protein (CRP) levels were measured annually during a 9-year study period. RESULTS: The estimated marginal mean baPWV (non-drinkers=1306 cm/s, mild-moderate drinkers=1311 cm/s, and heavy drinkers=1337 cm/s, P＜0.01) and that of rAI showed significant stepped increases in an alcohol dose-dependent manner in the entire cohort, but an increase in rAI was not observed in subjects aged ≥ 50 years. The estimated slope of the annual increase in baPWV, but not rAI, was higher for heavy drinkers than for non-drinkers (slope difference, 1.84; P＜0.05), especially for subjects aged ＜50 years (slope difference, 2.84; P＜0.05). CONCLUSION: In middle-aged male Japanese employees, alcohol intake may attenuate inflammatory activity. While alcohol intake may exacerbate the progression of arterial stiffening in a dose-dependent manner without mediating inflammation, especially in subjects under 50 years of age, it may promote pressure wave reflection abnormalities with aging at earlier ages without further exacerbation at older ages.

Association of the severity of vascular damage with discordance between the fractional flow reserve and non-hyperemic pressure ratios.

BACKGROUND: While there is a discordance between fractional flow reserve (FFR) and non-hyperemic pressure ratios (NHPRs) in some cases, the mechanisms underlying these discordances have not yet been fully clarified. We examined whether vascular damage as assessed by measurement of the brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness, or ankle brachial pressure index (ABI), a marker of atherosclerotic arterial stenosis, might be associated with their discordances. METHODS: FFR and NHPRs were measured in 283 consecutive patients (69 ±â€¯10 years old). Based on previously established cut-off values of the two markers (i.e. +/- = FFR ≤/> 0.80 or =NHPRs ≤/> 0.89), the study participants were divided into four groups (the + and - signs denoting "predictive of significant stenosis" and "not predictive of significant stenosis," respectively): the FFR+/NHPRs+ group (n = 124), FFR-/NHPRs+ group (n = 16), FFR+/NHPRs- group(n = 65), and FFR-/NHPRs- group (n = 78). The baPWV and ABI were also measured in all the participants, and values of <2000 cm/s and ≥1.00 of the baPWV and ABI, respectively, were considered as representing relatively less advanced atherosclerotic systemic vascular damage. RESULTS: The prevalence of subjects with ABI ≥1.00 was higher in the FFR+/NHPRs- group than in the FFR-/NHPRs- group (p < 0.05). When the study subjects were divided into 2 groups, namely, the FFR+/NHPRs- group and the combined group, the prevalence of ABI ≥1.00 and that of baPWV <2000 cm/s were higher in the FFR+/NHPRs- group as compared with those in the combined group (p < 0.05). The results of binary logistic regression analysis demonstrated that ABI ≥1.00 was associated with a significant odds ratio (2.34, p < 0.05) for the FFR+/NHPRs- discordance. CONCLUSION: The FFR+/NHPRs- discordance appears to be observed in patients with relatively less advanced atherosclerotic systemic vascular damage. Thus, ABI ≥1.00 may be a marker of the presence of the FFR+/NHPRs- discordance.

Nutritional Status and Sleep Quality Are Associated with Atrial Fibrillation in Patients with Obstructive Sleep Apnea: Results from Tokyo Sleep Heart Study.

The prevalence of obstructive sleep apnea (OSA) in patients with atrial fibrillation (AF) has been observed to be much higher than in control participants without AF. Limited data exist regarding the prevalence of AF in patients with OSA. The clinical characteristics, nutritional status, and sleep parameters associated with AF in patients with OSA remain unclear. In this study, we aimed to determine the prevalence and factors associated with AF in patients with OSA from a large Japanese sleep cohort (Tokyo Sleep Heart Study). This was a single-center explorative cross-sectional study. Between November 2004 and June 2018, we consecutively recruited 2569 patients with OSA who underwent an overnight full polysomnography at our hospital. They were assessed using a 12-lead ECG and echocardiography. The clinical characteristics, sleep parameters, and medical history were also determined. Of the OSA patients, 169 (6.6%) had AF. Compared with the non-AF patients, OSA patients with AF were older and male, and they had higher prevalence of a history of alcohol consumption, hypertension, chronic kidney disease, and undernutrition, as well as a reduced ejection fraction. With regard to the sleep study parameters, OSA patients with AF had reduced slow-wave sleep and sleep efficiency, as well as higher periodic limb movements. There were no significant differences in the apnea-hypopnea index or hypoxia index between the two groups. The logistic regression analysis demonstrated that age (OR = 4.020; 95% CI: 1.895-8.527; p < 0.001), a history of alcohol consumption (OR = 2.718; 95% CI: 1.461-5.057; p = 0.002), a high CONUT score (OR = 2.129; 95% CI: 1.077-4.209; p = 0.030), and reduced slow-wave sleep (OR = 5.361; 95% CI: 1.505-19.104; p = 0.010) were factors significantly related to AF. The prevalence of AF in patients with OSA was 6.6%. Age, a history of alcohol consumption, undernutrition, and reduced sleep quality were independent risk factors for the presence of AF in patients with OSA, regardless of the severity of OSA.

Lifelong Heterogeneous Contribution of Cardiovascular Risk Factors to Slow and Fast Progression of Arterial Stiffness.

BACKGROUND: Although some cardiovascular risk factors (CVRFs) are known to be associated with increased arterial stiffness, increased arterial stiffness does not mediate the cardiovascular risk associated with all CVRFs. Here, based on long-term repeated-measurement data, we examined the association of the lifelong status of each CVRF with the rate of progression of arterial stiffness. METHODS: We utilized the data from annual health checkups with the brachial-ankle pulse wave velocity measurements over a 16-year period in middle-aged Japanese occupational cohort. RESULTS: Totally, 29 090 brachial-ankle pulse wave velocity data were obtained during the follow-up of 3763 subjects ranging in age from around 30 to 70 years. Smoking, heavy alcohol intake, hypertension, diabetes, hypertriglyceridemia, and hyperuricemia were independently associated with the fast progression of arterial stiffness. Also, lower values in nondisease range in blood pressure, glycosylated hemoglobin A1c, triglyceride, and uric acid were independently associated with the slow progression of arterial stiffness. For body mass index and low-density lipoprotein cholesterol, no clear associations with the progression of arterial stiffness were observed. CONCLUSIONS: The present prospective study provided more robust epidemiological evidence for the heterogeneity of the significance of contribution of lifelong status of each CVRF to the slow and fast rate of progression of arterial stiffness. These findings suggest the important need to examine, in further studies, the effects of global early interventions to control the levels of the culprit CVRFs, even from middle age, not only to prevent a fast progression of the arterial stiffness but also to maintain a relatively slow progression of arterial stiffness.

Canagliflozin independently reduced plasma volume from conventional diuretics in patients with type 2 diabetes and chronic heart failure: a subanalysis of the CANDLE trial.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce the risk of heart failure progression and mortality rates. Moreover, osmotic diuresis induced by SGLT2 inhibition may result in an improved heart failure prognosis. Independent of conventional diuretics in patients with type 2 diabetes (T2D) and chronic heart failure, especially in patients with heart failure with preserved ejection fraction (HFpEF), it is unclear whether SGLT2i chronically reduces estimated plasma volume (ePV). As a subanalysis of the CANDLE trial, which assessed the effect of canagliflozin on N-terminal pro-brain natriuretic peptide (NT-proBNP), we examined the change (%) in ePV over 24 weeks of treatment based on the baseline level associated with diuretic usage. In the CANDLE trial, nearly all patients were clinically stable (NYHA class I-II), with approximately 70% of participants presenting a baseline phenotype of HFpEF. A total of 99 (42.5%) patients were taking diuretics (mostly furosemide) at baseline, while 134 (57.5%) were not. Relative to glimepiride, canagliflozin significantly reduced ePV without worsening renal function in patients in both groups: -4.00% vs. 1.46% (p = 0.020) for the diuretic group and -6.14% vs. 1.28% (p < 0.001) for the nondiuretic group. Furthermore, canagliflozin significantly reduced serum uric acid without causing major electrolyte abnormalities in patients in both subgroups. The long-term beneficial effect of SGLT2i on intravascular congestion could be independent of conventional diuretic therapy without worsening renal function in patients with T2D and HF (HFpEF predominantly). In addition, the beneficial effects of canagliflozin are accompanied by improved hyperuricemia without causing major electrolyte abnormalities.

Strength of relationships of the pulse wave velocity and central hemodynamic indices with the serum N-terminal fragment B-type natriuretic peptide levels in men: a worksite cohort study.

BACKGROUND: It has not been fully clarified as to which marker related to arterial stiffness or central hemodynamics might be most closely associated with the blood natriuretic peptide levels. The present cross-sectional study was conducted to examine the strength of the relationships of the arterial stiffness and central hemodynamic indices with the serum N-terminal fragment B-type natriuretic peptide (NT-pro BNP) levels. METHODS AND RESULTS: In a total of 2,657 male employees of a company (46±9 years old), the first and second peaks of the radial systolic pressure waveform (SBP1 and SBP2, respectively), the radial augmentation index (rAI), the PP2 (SBP2 minus the diastolic blood pressure), the brachial-ankle pulse wave velocity (baPWV), and the serum NT-pro BNP levels were measured. Even after adjustments for confounding variables, the SBP1, SBP2, PP2, rAI and baPWV showed a significant positive association with the serum NT-pro BNP levels. A stepwise multivariate linear regression analysis demonstrated that among these variables, only PP2 contributed significantly to the serum NT-pro BNP levels (ß=0.176, partial R-square=0.017, P<0.001). CONCLUSIONS: In middle-aged Japanese men, among the parameters related to arterial stiffness and central hemodynamics, PP2 showed the closest relationship with the serum NT-pro BNP levels. Therefore, elevation of the serum NT-pro BNP levels appears to reflect, at least in part, the pathophysiological abnormalities related to increased central pulse pressure.

Obstructive sleep apnea as a potential risk factor for aortic disease.

Obstructive sleep apnea (OSA) is not only a cause of hypertension; it also possibly affects the pathogenesis and progression of aortic disease because an inspiratory effort-induced increase in negative intrathoracic pressure generates mechanical stress on the aortic wall. The objective of the present study was to examine the incidence by location of OSA as a complication in patients with aortic aneurysm and patients with aortic dissection (AD). An overnight sleep study was conducted in the following study groups: the aortic disease group (n = 95) consisting of patients with thoracic aortic aneurysm (TAA, n = 32), patients with abdominal aortic aneurysm (AAA, n = 36), and patients with AD (n = 27); and a control group (n = 32), consisting of patients with coronary risk factors who were matched with the aortic disease group for age, gender, and body mass index (BMI). The 3% oxygen desaturation index (ODI) was significantly higher in all the TAA, AAA, and AD groups (P = 0.045, P = 0.003, and P = 0.005, respectively) than in the control group. The incidence of moderate to severe OSA [apnea hypopnea index (AHI) ≥15 events/h] was significantly higher in the first three groups (P = 0.026, P = 0.001, P = 0.003, respectively) than in the control group, while no significant difference was found between the TAA group and the AAA group with respect to these variables. Furthermore, no significant differences were found between the thoracic AD subgroup and the abdominal AD subgroup with respect to AHI and 3% ODI, as well as with respect to the incidences of moderate to severe OSA. Patients with TAA, patients with AAA, and patients with AD showed high incidences of moderate to severe OSA. Although this result suggests that OSA may be one of risks for aortic disease, unelucidated mechanism(s) other than negative intrathoracic pressure may be involved in the pathogenesis of aortic disease.

Coexistence of obstructive sleep apnoea and metabolic syndrome is independently associated with left ventricular hypertrophy and diastolic dysfunction.

PURPOSE: This study was conducted to investigate the impact of the severity of obstructive sleep apnoea (OSA) and metabolic syndrome (MS) on left ventricular (LV) hypertrophy and LV diastolic function. METHODS: Echocardiography for evaluation of LV hypertrophy (defined by relative wall thickness (RWT) and LV mass index (LVMI)) and for diastolic function (defined by the early rapid/atrial filling velocity (E/A ratio)) was performed on 660 OSA patients. RESULTS: In patients with both MS and severe OSA, LVMI and RWT were significantly higher and the E/A ratios were significantly lower compared to patients with neither MS nor severe OSA. Multivariate analysis after adjustment for other descriptive variables demonstrated that (1) coexistent MS and severe OSA was independently associated with increased LVMI and RWT and (2) severe OSA, MS and coexistence of both disorders were independently associated with a decreased E/A ratio. Significant interaction between MS and severe OSA was not observed with respect to LVMI and RWT, but was observed for the E/A ratio. CONCLUSIONS: Coexistent severe OSA and MS can exacerbate LV concentric hypertrophy. However, not only the coexistence of these two disorders, but also either severe OSA or MS can impair LV diastolic function.

Longitudinal Association of Arterial Stiffness and Pressure Wave Reflection with Decline of the Cardiac Systolic Performance in Healthy Men.

AIMS: This prospective observational study aimed to examine the individual longitudinal associations of the increases in the arterial stiffness and pressure wave reflection with the decline in the cardiac systolic performance during the study period in healthy middle-aged Japanese men. METHODS: In 4016 middle-aged Japanese healthy men (43±9 years), the brachial-ankle pulse wave velocity (baPWV), radial augmentation index (rAI), and pre-ejection period/ejection time (pre-ejection period (PEP)/ET) were measured annually during a 9-year study period. RESULTS: The baPWV, rAI, and PEP/ET showed steady annual increases during the study period. According to the results of multivariate linear regression analyses, both the baPWV and rAI measured at the baseline showed significant independent associations with the PEP/ET measured at the baseline (baPWV: beta=0.17, p＜0.01 and rAI: beta=0.11, p＜0.01), whereas neither showed any association with the PEP/ET measured at the end of the study period. The results of the mixed-model linear regression analysis of the repeated-measures data collected over the 9-year study period revealed that the baPWV, but not the rAI, showed a significant longitudinal association with the PEP/ET (estimate=0.69 x 10-4, p＜0.01). CONCLUSION: In apparently healthy middle-aged Japanese men, the annual increase of the arterial stiffness, rather than the annual increase of the pressure wave reflection, appears to be more closely associated with the annual decline of the cardiac systolic performance as assessed by the systolic time interval.

Moderate to severe obstructive sleep apnea is independently associated with inter-arm systolic blood pressure difference: Tokyo Sleep Heart Study.

OBJECTIVE: Obstructive sleep apnea (OSA) is recognized as an independent risk factor for cardiovascular disease. On the other hand, inter-arm systolic blood pressure difference (IAD), inter-ankle systolic blood pressure difference (IAND), and ankle-brachial index (ABI) are all known predictors of cardiovascular events. The aim of the present study was to investigate the association between OSA and four-limb blood pressure differences. METHODS: We conducted this cross-sectional study in a large sleep cohort from Tokyo Sleep Heart Study. In 2643 consecutive patients who visited our sleep clinic for polysomnography between 2005 and 2017, all the patients underwent blood pressure measurement simultaneously in all the four limbs by oscillometric methods. RESULTS: The prevalence rate of IAD ≥10 mmHg was significantly higher in the moderate OSA (15 ≤ apnea-hypopnea index [AHI] < 30) group (4.2%) and severe OSA (AHI ≥ 30) group (4.6%) than that in the no/mild (AHI < 15) OSA group (1.4%). Multivariate logistic regression analysis also identified moderate to severe OSA as being significantly associated with IAD ≥10 mmHg, even after adjustments for confounding variables (moderate OSA: odds ratio [OR], 4.869; 95% confidence interval [CI], 1.080-21.956; P = 0.039; severe OSA: OR, 5.301; 95% CI, 1.226-22.924; P = 0.026). However, there were no significant associations of the OSA severity with IAND ≥15 mmHg or ABI <0.9. CONCLUSIONS: Moderate to severe OSA was independently associated with the IAD, not but with the IAND or ABI.

Bidirectional Longitudinal Relationships Between Arterial Stiffness and Hypertension Are Independent of Those Between Arterial Stiffness and Diabetes: A Large-Scale Prospective Observational Study in Employees of a Japanese Company.

Background Hypertension and diabetes frequently coexist; however, it has not yet been clarified if the bidirectional longitudinal relationships between arterial stiffness and hypertension are independent of those between arterial stiffness and diabetes. Methods and Results In this 16-year prospective observational study, 3960 middle-aged employees of a Japanese company without hypertension/diabetes at the study baseline underwent annual repeated measurements of blood pressure, serum glycosylated hemoglobin A1c levels, and brachial-ankle pulse wave velocity. By the end of the study period, 664, 779, 154, and 406 subjects developed hypertension, prehypertension, diabetes, and prediabetes, respectively. Increased brachial-ankle pulse wave velocity at the baseline was associated with a significant odds ratio (per 1 SD increase) for new onset of prehypertension/hypertension with (2.45/3.28; P<0.001) or without (2.49/2.76; P<0.001) coexisting prediabetes/diabetes, but not for new onset of prediabetes/diabetes without coexisting hypertension. Analyses using the latent growth curve model confirmed the bidirectional relationships between brachial-ankle pulse wave velocity and hypertension, but no such relationship was observed between brachial-ankle pulse wave velocity and abnormal glucose metabolism. Conclusions In middle-aged employees of a Japanese company, while bidirectional relationships were found to exist between increased arterial stiffness and hypertension, such a relationship was not found between increased arterial stiffness and diabetes. Therefore, it appears that increased arterial stiffness may be associated with the development of hypertension but not with that of diabetes.

Differential effect of a xanthine oxidase inhibitor on arterial stiffness and carotid atherosclerosis: a subanalysis of the PRIZE study.

Atherosclerosis and arterial stiffness are phenotypes of atherosclerotic vascular damage. Atherosclerosis originates from endothelial vascular damage and forms focal morphological lesions; arterial stiffness originates from diffuse medial-layer damage in the arterial tree. Thus, the two phenomena reflect different facets of atherosclerotic vascular damage, and they both gradually progress. We conducted a subanalysis to compare the long-term effects of febuxostat on atherosclerosis and arterial stiffness in the PRIZE study (a multicenter, prospective, randomized, open-label, blinded-endpoint clinical trial to examine the effect of febuxostat on carotid atherosclerosis). Among 514 study participants, arterial stiffness parameters (brachial-ankle pulse wave velocity or cardio-ankle vascular index) were obtained at baseline, 12 months, and 24 months in 100 subjects. Among them, 48 subjects were allocated to the control group (i.e., nonpharmacological lifestyle modification for hyperuricemia), and 52 subjects were allocated to the febuxostat treatment group. While the decrease in serum uric acid was greater in the febuxostat group than in the control group, the adjusted percentage decrease in arterial stiffness parameters at month 24 was greater in the febuxostat group than in the control group, with a mean between-group difference (febuxostat - control) of -5.099% (95% confidence interval (CI) -10.009% to -0.188%, p = 0.042). Thus, long-term treatment with febuxostat may exert beneficial effects on arterial stiffness without improving carotid atherosclerosis. A long-term study to examine the effect of febuxostat on cardiovascular outcomes related to increased arterial stiffness is warranted.