Blood pressure, frailty status, and all-cause mortality in elderly hypertensives; The Nambu Cohort Study.

Antihypertensive therapy is pivotal for reducing cardiovascular events. The 2019 Guidelines for the Management of Hypertension set a target blood pressure (BP) of <140/90 mmHg for persons older than 75 years of age. Optimal BP levels for older persons with frailty, however, are controversial because evidence for the relationship between BP level and prognosis by frailty status is limited. Here, we evaluated the relationship between systolic BP and frailty status with all-cause mortality in ambulatory older hypertensive patients using data from the Nambu Cohort study. A total of 535 patients (age 78 [70-84] years, 51% men, 37% with frailty) were prospectively followed for a mean duration of 41 (34-43) months. During the follow-up period, 49 patients died. Mortality rates stratified by systolic BP and frailty status were lowest in patients with systolic BP < 140 mmHg and non-frailty, followed by those with systolic BP ≥ 140 mmHg and non-frailty. Patients with frailty had the highest mortality regardless of the BP level. The adjusted hazard ratios (95% confidence intervals) of each category for all-cause mortality were as follows: ≥140 mmHg/Non-frailty 3.19 (1.12-11.40), <140 mmHg/Frailty 4.72 (1.67-16.90), and ≥140 mmHg/Frailty 3.56 (1.16-13.40) compared with <140 mmHg/Non-frailty as a reference. These results indicated that frail patients have a poor prognosis regardless of their BP levels. Non-frail patients, however, with systolic BP levels <140 mmHg had a better prognosis. Frailty may be a marker to differentiate patients who are likely to gain benefit from antihypertensive medication among older hypertensives.

Management of Arteriovenous Graft Infection.

Objective: Arteriovenous graft (AVG) infection influences the survival and quality of life of patients, causing life-threatening sepsis reducing dialysis access. This study aimed to evaluate an appropriate treatment strategy for AVG infection. Methods: We analyzed 61 cases involving AVG infections identified at a single center. The cases were divided into two groups based on the type of AVG and surgical methods, namely, currently used AVG (cAVG) (n=29) or abandoned AVG (aAVG) (n=32) and total graft excision (TGE) (n=10) or partial graft excision (PGE) (n=46). Results: There was a significant difference in lower procedure frequency (p<0.001) and longer procedure time (p=0.014) in the cAVG group. A significant difference in lower reinfection rate (p=0.009) was found in the TGE group. Multivariable analysis confirmed that aAVG significantly independently affected the reinfection rate (hazard ratio, 2.208; 95% confidence interval, 1.069-4.561; p=0.032). Staphylococcus aureus was the most frequent cause of AVG infection (61.5%); 77.5% of Staphylococcus aureus were methicillin-resistant Staphylococcus aureus. Conclusion: We found a higher risk of reinfection after PGE than TGE, and aAVG infection was associated with approximately two times higher likelihood of reinfection. These findings suggest that TGE should be considered for patients with AVG infections, particularly aAVG infections.

WBC count predicts heart failure in diabetes and coronary artery disease patients: a retrospective cohort study.

AIMS: White blood cell (WBC) count in healthy people is associated with the risk of coronary artery disease (CAD) and mortality. This study aimed to determine whether WBC count predicts heart failure (HF) requiring hospitalization as well as all-cause death, acute myocardial infarction (AMI) and stroke in patients with Type 2 diabetes mellitus and established CAD. METHODS: We conducted this retrospective registry study that enrolled consecutive patients with Type 2 diabetes mellitus and CAD based on coronary arteriography records and medical charts at 70 teaching hospitals in Japan from 2005 to 2015. A total of 7608 participants (28.2% women, mean age 68 ± 10 years) were eligible. In the cohort, the median (interquartile range) and mean follow-up durations were 39 (16.5-66.1 months) and 44.3 ± 32.7 months, respectively. The primary outcome was HF requiring hospitalization. The secondary outcomes were AMI, stroke, all-cause death, 3-point major adverse cardiovascular events (MACE) (AMI/stroke/death) and 4-point MACE (AMI/stroke/death/HF requiring hospitalization). Outcomes were reported as cumulative incidences (proportion of patients experiencing an event) and incidence rates (events/100 person-years). The primary and secondary outcomes were assessed using the Kaplan-Meier method and were compared using the log-rank test stratified by the baseline WBC count. The association between the WBC count at baseline and each MACE was assessed using the Cox proportional hazard model and expressed as the hazard ratio (HR) and 95% confidence interval (CI) after adjusting for other well-known risk factors for MACE. RESULTS: During the follow-up, 880 patients were hospitalized owing to HF. The WBC Quartile 4 (≥7700 cells/µL) had significantly lower HF event-free survival rate (log-rank test, P < 0.001). The HRs for HF events requiring hospitalization with each WBC quartile compared with the lowest in the first WBC quartile were 1 for Quartile 1 (WBC < 5300 cells/µL), 1.20 (95% CI, 0.96-1.5; P = 0.1) for Quartile 2 (5300 ≤ WBC < 6400), 1.34 (95% CI, 1.08-1.67; P = 0.009) for Quartile 3 (6400 ≤ WBC < 7700) and 1.62 (95% CI, 1.31-2.00; P < 0.001) for Quartile 4 after adjusting for covariates. Similar findings were observed for the risk of AMI and death; however, no significant difference was found for stroke. WBC Quartile 4 patients had a significantly lower 3- or 4-point MACE-free survival rate (log-rank test, P < 0.0001). CONCLUSIONS: A higher WBC count is a predictor of hospitalization for HF, all-cause death and AMI but not for stroke in patients with concurrent Type 2 diabetes mellitus and established CAD.

The association between frailty and chronic kidney disease; cross-sectional analysis of the Nambu Cohort Study.

BACKGROUND: Both frailty and chronic kidney disease (CKD) increase with age and share many similarities. Many studies have demonstrated an association between frailty and chronic kidney disease (CKD), but an association with dipstick proteinuria is limited. METHODS: This is the cross-sectional analysis of the Nambu Cohort Study at the beginning of observation. Frailty was diagnosed using Kihon Checklist. Logistic analysis was used to evaluate the association between frailty and CKD or dipstick proteinuria. RESULTS: Among a total of 630 outpatients [age, 78 (70-84) years, men, 50%], the prevalence of patients with pre-frailty and frailty was 32% and 40%, respectively. The proportion of patients with pre-frailty and frailty increased with decreasing estimated glomerular filtration rate (eGFR) and increasing dipstick proteinuria levels. The odds ratios (95% confidence intervals) for CKD stage of 60 < eGFR ≤ 45 ml/min/1.73 m2, and 45 ml/min/1.73 m2 < eGFR for frailty was 0.87 (0.56-1.35) and 2.54 (1.46-4.53), respectively, compared with non-CKD as a reference. Furthermore, the odds ratios for the frailty of dipstick proteinuria with ± and + or over were 1.36 (0.88-2.09) and 1.78 (1.00-3.17), respectively, when dipstick proteinuria-was used as a reference. Moreover, the combination of eGFR and dipstick proteinuria levels increased the odds ratio for pre-frailty and frailty. CONCLUSION: Elderly patients with CKD had a higher prevalence of pre-frailty and frailty. By adding urinary protein information to eGFR, the link between CKD and frailty becomes even more robust.

"Leafletization" of Atrialized Ventricular Septum Endocardium in Ebstein Anomaly.

This case presentation of a 73-year-old man introduces a unique tricuspid valve repair with "endocardium leafletization" for Ebstein anomaly. In this procedure, an atrialized portion of the right ventricular endocardium was delaminated, starting from the level of the true tricuspid annulus, to create a neoleaflet in continuity with the displaced true leaflet. The obtained neoleaflet was then anchored to the true tricuspid annulus. Preoperative severe tricuspid regurgitation was effectively controlled with preserving sufficient leaflet mobility. This procedure can be one of the useful options for a certain lesion of Ebstein anomaly that aims to avoid excessive leaflet rotation and restore functional valve apparatus.

Cardiovascular risk profile and frailty in Japanese outpatients: the Nambu Cohort Study.

Epidemiologic findings indicate that unfavorable cardiovascular (CV) risk profiles, such as elevated systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and overweight, decelerate with aging. Few studies, however, have evaluated the association between the CV risk profile and frailty. We performed a cross-sectional analysis using the baseline data of a prospective cohort study. A total of 599 subjects (age, 78 [range: 70-83] years; men, 50%) were analyzed in an outpatient setting. Frailty was diagnosed in 37% of the patients according to the Kihon Checklist score. An unfavorable CV risk profile was associated with a lower risk of frailty. The adjusted odds ratios (ORs; 95% confidence interval [CI]) of each CV risk factor for frailty were as follows: SBP (each 10 mmHg increase) 0.83 (0.72-0.95), LDL-C (each 10 mg/dl increase) 0.96 (0.86-1.05), and body mass index (each 1 kg/m2 increase) 1.03 (0.97-1.10). Moreover, the total number of CV risk factors within the optimal range was significantly associated with the risk of frailty with the following ORs (95% CI): 1, 2.30 (0.75-8.69); 2, 3.22 (1.07-11.97); and 3, 4.79 (1.56-18.05) compared with patients having no risk factors within optimal levels (p for trend 0.008). Abnormal homeostasis might lead to lower levels of CV risk factors, which together result in "reverse metabolic syndrome." Our findings indicate that a favorable CV risk profile is associated with frailty.

Cause of Death and Associated Factors in Elderly Patients With Atrial Fibrillation　- Long-Term Retrospective Study.

Background: Oral anticoagulant (OAC) therapy reduces the risk of stroke in patients with atrial fibrillation (AF). This study elucidated the causes of death and related factors in elderly Japanese AF patients. Methods and Results: Over a median (interquartile range [IQR]) follow-up period of 46 (20-76) months, there were 171 all-cause deaths (28% cardiovascular, 46% non-cardiovascular, and 26% unknown causes) among 389 AF patients (median [IQR] age 80 [74-85] years; CHAD2DS2-VASc score 5 [4-6]). Cox regression analysis indicated that diabetes was associated with an increase in all-cause death (hazard ratio [HR] 1.48; 95% confidence interval [CI] 1.02-2.13), whereas hypercholesterolemia (HR 0.53; 95% CI 0.35-0.79), pre-existing heart failure (HR 0.67; 95% CI 0.48-0.95), and OAC use (HR 0.62; 95% CI 0.44-0.88) were associated with reductions in all-cause death. Pre-existing heart failure was associated with both cardiovascular (HR 3.03; 95% CI 1.33-8.20) and non-cardiovascular (HR 0.44; 95% CI 0.30-0.65) deaths, in opposite directions. OAC use was associated with a reduction in cardiovascular death (HR 0.34, 95% CI 0.17-0.69). The predominance of non-cardiovascular death and death-related factors were equivalent regardless of when observations started (before 2009 or in 2009 and later). Conclusions: The predominant cause of death in elderly Japanese AF patients was non-cardiovascular. Distinct clinical factors were associated with cardiovascular and non-cardiovascular death.

Development of Electrocardiographic Left Ventricular Hypertrophy and Resting Heart Rate Over Time: Findings From the OGHMA Study.

Both elevated resting heart rate (HR) and electrocardiographic left ventricular hypertrophy (ECG-LVH) are signs of a poor prognosis. Although elevated resting HR is a known risk factor for cardiovascular disease and target organ damage, the association between resting HR and the development of ECG-LVH is unclear. In the present study, 6860 subjects (4203 men, 2657 women, 19-89 years of age) without ECG-LVH at baseline were evaluated and followed for a mean duration of 3.7±1.4 years. During the follow-up period, 484 (7.1%) subjects developed ECG-LVH. Cox regression analysis revealed that each 10 beats/min increase in resting HR was associated with a 22% reduction in the development of ECG-LVH (95% confidence interval: 12%-30%, P < .0001) in men. While an increase in HR tended to be associated with the development of ECG-LVH in women, the relationship was not significant. In contrast to the concept that an elevated resting HR is a cardiovascular risk factor, these findings revealed that resting HR was negatively associated with the development of ECG-LVH in men.

Valve-sparing aortic root re-implantation for commissural detachment with fibrous strand.

Both aortic valve commissural detachment and commissural fenestration are rare causes of aortic regurgitation. In general, aortic valve replacement is the mainstay treatment for aortic regurgitation caused by commissural detachment or commissural fenestration. We herein describe valve-sparing aortic root re-implantation and aortic valve repair for aortic regurgitation and aortic root dilatation in an extremely rare case accompanied by both commissural detachment and commissural fibrous strand of fenestrated cusp.

Associations between serum uric acid levels and the incidence of hypertension and metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan.

The purpose of this study was to examine the associations between serum uric acid (SUA) levels and the incidences of hypertension and metabolic syndrome (MetS) in a large screened cohort of Japanese men and women. We evaluated 4812 subjects (males, 2528; females, 2284; mean age, 47.5 years) who underwent health checkups between 2006 and 2010 and were free of hypertension and MetS in 2006. After 4 years, 618 (13%), 764 (16%) and 158 (3%) subjects developed hypertension, MetS and hypertension with MetS, respectively. Increased SUA levels were significantly and positively associated with the incidences of hypertension, MetS and hypertension with MetS. Compared with the first quartile of SUA levels, the odds ratios (95% confidence intervals) for the third and fourth quartiles, respectively, were as follows: 1.5 (1.1-2.1; P = 0.0128) and 1.8 (1.2-2.5; P = 0.0022) for hypertension, 1.3 (0.9-1.9; P = 0.1910) and 1.8 (1.2-2.7; P = 0.0039) for MetS and 2.7 (1.1-6.6; P = 0.0276) and 3.2 (1.3-8.0; P = 0.0115) for hypertension with MetS. In conclusion, increased SUA levels were significantly and independently associated with the incidences of hypertension and MetS in subjects without hypertension or MetS at baseline. Increased SUA levels might also be correlated with the incidence of hypertension with MetS.

Laryngeal neuroma in multiple endocrine neoplasia type 2B.

Multiple endocrine neoplasia (MEN) type 2 syndrome is an autosomal dominant inherited disease caused by mutations of the RET proto-oncogene, and is clinically divided into three phenotypes: MEN2A, MEN2B, and familial medullary thyroid carcinoma. Although multiple mucosal neuromas are commonly observed in patients with MEN2B, there are only a few reports of laryngeal neuroma. We present here a rare case of laryngeal mucosal neuromas with MEN2B.

Hyperuricemia predicts future metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan.

The aim of this study was to determine whether hyperuricemia could predict future metabolic syndrome (MetS) in a large screened cohort of Japanese male and female subjects. We evaluated 5936 subjects (3144 male subjects, 2792 female subjects; mean age 48.7 years) who underwent health checkup programs in 2006 and 2010, who were MetS free in 2006. At baseline, hyperuricemia was detected in 927 male subjects (29.5%) and 276 female subjects (9.9%). Subjects with baseline hyperuricemia had significantly higher MetS prevalence in 2010 than those without (male subjects: 34.8 vs. 20.6%, P<0.0001; female subjects: 15.6 vs. 4.8%, P<0.0001). Compared with subjects in the first quintile of uric acid levels at baseline, the age-adjusted odds ratios (ORs) for MetS cumulative incidence among subjects in the third, fourth and fifth quintiles were, 1.8 (95% confidence interval (CI): 1.4-2.4: P<0.0001), 2.1 (95% CI: 1.6-2.8: P<0.0001) and 3.2 (95% CI: 2.4-4.1: P<0.0001), respectively, for male subjects and 2.4 (95% CI: 1.3-4.7: P=0.0075), 3.0 (95% CI: 1.6-5.7: P=0.0010) and 4.8 (95% CI: 2.6-8.8: P<0.0001), respectively for female subjects. Multivariable logistic analysis revealed that hyperuricemia was significantly associated with MetS cumulative incidence in male subjects (OR 1.5: 95% CI: 1.3-1.8, P<0.0001) and female (OR 2.0, 95% CI: 1.3-3.0, P<0.0001). In conclusion, hyperuricemia is a significant and independent predictor of MetS in Japanese male and female subjects. For both genders, MetS risk increases with increased serum uric acid levels.

Heart rate as a possible therapeutic guide for the prevention of cardiovascular disease.

Epidemiologic evidence indicates that an elevated heart rate (HR) is an independent predictor of all-cause and cardiovascular (CV) mortality. Ivabradine, a pure HR-lowering agent, reduces CV events in patients with coronary artery disease (CAD) and chronic heart failure, and indicate that an HR greater than 70 b.p.m. is hazardous. These findings demonstrate not only that an elevated HR is an epiphenomenon of CV risk status but also that an elevated HR itself should be a therapeutic target. In addition, recent epidemiologic evidence demonstrates that the in-treatment HR or HR change predicts subsequent all-cause and CV mortality, independent of the HR-lowering strategy. Characteristics of the in-treatment HR or HR change are also important as possible therapeutic guides for risk management. However, there have been concerns regarding deleterious effects on CV event prevention owing to ß-blocker-derived pharmacologic HR reduction. The potential role of HR and its modulation should be considered in future guidance documents.

Elevated resting heart rate is an independent predictor of all-cause death and cardiovascular events in Japanese ambulatory hemodialysis patients.

BACKGROUND: Elevated heart rate (HR) is an independent risk factor for all-cause death or cardiovascular events in non-hemodialysis subjects; however, the clinical significance of elevated HR in hemodialysis patients is not well studied. METHODS: We prospectively evaluated the relationship between HR and adverse outcome in a total of 229 ambulatory hemodialysis patients (57 % men; mean age 62.2 years) recruited from two dialysis clinics in 2009. Mean (SD) HR of this cohort was 74.1 (11.0) beats per minute (bpm). RESULTS: Receiver operating characteristic curves identified an HR cut-off level of ≥80 bpm for increased adverse outcome. After a mean follow-up of 525 days (range 7-760 days) a total of 30 primary endpoints (21 all-cause deaths, 4 acute coronary syndromes and 8 strokes) and 38 secondary endpoints (30 primary endpoints, 8 congestive heart failures, and 5 other cardiovascular events) were detected. Cox regression analysis revealed that HR >80 bpm was not an independent predictor of primary endpoints [hazard ratio 1.81, 95 % confidence interval (CI) 0.79-4.11, p = NS], but of secondary endpoints (hazard ratio 2.01, 95 % CI 1.01-4.22, p < 0.05) after adjusting for age, sex, hemodialysis duration, and cardiovascular risks. CONCLUSIONS: Elevated HR is an independent predictor of all-cause death and cardiovascular events in Japanese ambulatory hemodialysis patients.

Elevated resting heart rate is associated with white blood cell count in middle-aged and elderly individuals without apparent cardiovascular disease.

We investigated the association between resting heart rate (HR) and inflammation markers in a healthy population. White blood cell (WBC) count was used as a surrogate marker of subclinical inflammation. Smoking status, body mass index, resting HR, high-density lipoprotein cholesterol, triglycerides, uric acid, and glycated hemoglobin were significantly associated with WBC in both men and women. Blood pressure and fasting plasma glucose levels, however, were associated with WBC only in women. Logistic regression analysis indicated that for every 10 beats per minute increase in HR, the odds ratio of an increase in the WBC was approximately 1.3 in both men and women. These findings indicate the clinical significance of resting HR for identifying individuals at risk of subclinical inflammation and a future cardiovascular event.

Effect of heart rate on the risk of developing metabolic syndrome.

High heart rate and metabolic syndrome are risk factors for cardiovascular morbidity and mortality. The relationship between heart rate and risk of developing metabolic syndrome has not been studied in a large cohort. We examined the relationship between heart rate and the risk of developing metabolic syndrome in individuals who participated in a health evaluation program from 1997 to 2002. Among the 7958 individuals who participated in the program, 1677 were excluded from our study because they were being treated for heart disease or had been diagnosed with metabolic syndrome at baseline examination. A total of 6281 individuals (3789 men and 2492 women, 20-89 years of age) were evaluated. They were categorized according to their baseline heart rate and were followed up for a mean of 47+/-16 months (range: 7-71 months). Over the 5-year period, 619 individuals (9.9%) developed metabolic syndrome. Men with elevated baseline heart rates were more likely to experience metabolic syndrome than were those with normal heart rates. This was not true for female patients. The odds ratio (95% confidence interval) of developing metabolic syndrome among men in the highest quartile for heart rate was 1.725 (1.282-2.320) compared with those in the lowest quartile. Each increase in the heart rate category led to an approximately 1.2-fold increase in the risk of developing metabolic syndrome for men only, even after adjusting for age and lifestyle. Elevated heart rate is a risk factor for developing metabolic syndrome in men.

Heart rate as a risk factor for developing chronic kidney disease: longitudinal analysis of a screened cohort.

BACKGROUND: High heart rate and chronic kidney disease (CKD) are both risk factors for cardiovascular morbidity and mortality. The relationship between heart rate and the risk of developing CKD, however, has not been studied in a large screened cohort. METHODS AND RESULTS: We examined the relationship between heart rate and the risk of developing CKD in participants in a health evaluation program. CKD was diagnosed as glomerular filtration rate of less than 60 mL/min/1.73 m(2), calculated using the Modification of Diet in Renal Disease (MDRD) study equation or dipstick proteinuria. Among 7,958 subjects, 1,199 subjects diagnosed with CKD or with arrhythmia at baseline examination were excluded. A total of 6,759 subjects (4,268 men, 2,491 women, 20-84 years of age) were evaluated. The subjects were quadrisected according to baseline heart rate. The subjects were followed up for a mean of 47 +/- 16 months (range 7-71 months). Seven hundred and thirty-four subjects developed CKD over the 5-year follow-up period. Subjects with a high heart rate had greater magnitude of decreasing glomerular filtration rate (eGFR) and higher odds ratio of developing proteinuria. Cox analysis indicated that each heart rate category increment led to approximately 1.1 times increase in the risk of developing CKD, eGFR less than 60 mL/min/1.73 m(2), and 1.2 times increase of the risk of developing proteinuria in middle-aged or older subjects. CONCLUSIONS: High heart rate is a risk factor for developing CKD in middle-aged or older subjects.

[Prevension of hypertension by angiotensin receptor blockers in human--TROPHY study].

Prevention of hypertension is one of the important strategies for decreasing future cardiovascular accidents. Antihypertensive drugs have never been used for the prevention of hypertension in clinical setting, however several animal studies have shown the renin-angiotensin inhibitors can prevent development of hypertension. TROPHY trial was designed to test whether candesartan, an angiotensin receptor blocker could prevent development of hypertension in subjects with high normal blood pressure level. From the TROPHY trial, candesartan did prevent development of hypertension by 66% at the end of its 2 year-administration. Candesartan also prevented development of hypertension by 42% even 2 years after session of its administration. TROPHY trial has shown that a use of angiotensin receptor blocker for the prevention of hypertension appears to be feasible in human.

Association between heart rate and multiple risk factor syndrome: cross-sectional analysis of a screened cohort in Okinawa, Japan.

BACKGROUND: Increased heart rate (HR) and metabolic syndrome are risk factors for cardiovascular morbidity and mortality, but their relationship has not been studied in a large, screened cohort. METHODS AND RESULTS: The association between HR and multiple risk factor syndrome, resembling metabolic syndrome, was examined in participants of a health evaluation program in 1997. Of the 8,432 subjects (5,223 males, 3,209 females, 18-89 years of age), 1,502 (1,185 males, 317 females) were diagnosed with multiple risk factor syndrome and these subjects had higher HR than those without the syndrome (p<0.0001); subjects with a higher number of risk factors had higher HR than those with fewer risk factors (males, p<0.0001; females, p<0.0001). After adjusting for age, sex, and lifestyle factors, subjects within the highest HR quartile had a 2.5-fold higher risk for multiple risk factor syndrome than those in the lowest quartile (p<0.0001). An increase of 10 beats/min was associated with an approximately 30% increase in the risk for multiple risk factor syndrome. CONCLUSIONS: A higher HR is closely associated with multiple risk factor syndrome.