Isao Muraki

Arterial oxygen desaturation during sleep and atrial fibrillation

Atrial fibrillation is a common arrhythmia with associated complications of stroke and other adverse outcomes. We conducted a population-based study of 1763 Japanese men aged 40–74 years to examine the association between the frequency of nocturnal oxygen desaturation, estimated by a pulse oximeter, and the prevalence of atrial fibrillation. We found a significant association between the severity of sleep-disordered breathing (SDB) and the prevalence of atrial fibrillation; the odds ratios (ORs) were 2.47 for those with 5–15 events/h of 3% oxygen desaturation index (ODI) level and 5.66 for those with ⩾15 events/h of 3% ODI level (p for trend = 0.02). Although the association of SDB with atrial fibrillation has been reported in recent clinical studies,1–4 no population-based epidemiological study has examined this relationship. We investigated the association between the frequency of nocturnal oxygen desaturation and the prevalence of atrial fibrillation among community-based subjects. The subjects were 1763 Japanese men aged 40–74 years who lived in three Japanese communities. They participated in the 2000–2004 annual cardiovascular risk surveys and were recruited for the present sleep study, at a …

Caregiver Burden for Impaired Elderly Japanese with Prevalent Stroke and Dementia under Long-Term Care Insurance System

Background: Limited data are available on caregiver burden for stroke and dementia patients. We examined the associations of prevalent stroke and dementia with family caregiver burden in Japanese general populations. Methods: A total of 916 Japanese home caregivers, whose family members were covered by long-term care insurance, responded to the caregiver burden questionnaire. The questionnaire included the caregiver’s age, sex and employment status, the patient-caregiver relationship, the patient‘s history of stroke, symptoms of dementia, care levels under long-term care insurance and the Zarit Caregiver Burden Interview. Results: The mean total score from the Zarit Caregiver Burden Interview was 12% higher in patients with stroke than in those without (p = 0.02) and 40% higher in those with dementia than in those without (p < 0.001). Compared with nonstroke patients without dementia, the mean total score was 21% higher in stroke patients without dementia (p = 0.01), 49% higher in nonstroke patients with dementia (p < 0.001) and 55% higher in stroke patients with dementia (p < 0.001). After adjustment for the caregiver’s age, sex and employment status, the patient-caregiver relationship, and the patient’s care level and community, the higher scores remained statistically significant for nonstroke patients with dementia and for stroke patients with dementia but not for stroke patients without dementia. Conclusions: Prevalent stroke and, more strongly, dementia were associated with increased family caregiver burden. Among patients with dementia, the presence of stroke did not enhance caregiver burden further.

Nocturnal intermittent hypoxia and C reactive protein among middle-aged community residents: a cross-sectional survey

Background There are conflicting results for the association between obstructive sleep apnoea and raised C reactive protein (CRP) levels. A study was undertaken to investigate whether nocturnal intermittent hypoxia, a surrogate marker for obstructive sleep apnoea, was associated with CRP levels among a community-dwelling Japanese population. Methods Among participants in the Circulatory Risk in Communities Study (CIRCS), 1422 male and 2466 female community residents aged 40–69 years were tested during sleep. No nocturnal intermittent hypoxia, mild nocturnal intermittent hypoxia and moderate to severe nocturnal intermittent hypoxia were defined using 3% oxygen desaturation index cut-off points at 5 and 15 events/h, respectively. High-sensitivity CRP levels were measured using a latex particle-enhanced immunonephelometric assay. Multivariate analysis was adjusted for age, sex, body mass index, smoking status, current alcohol intake, hypertension, hypercholesterolaemia, diabetes mellitus and menopausal status for women. Results Multivariable-adjusted mean CRP levels among men were 0.70 mg/l (95% CI 0.65 to 0.75) for no nocturnal intermittent hypoxia, 0.82 mg/l (95% CI 0.74 to 0.89) for mild nocturnal intermittent hypoxia and 0.84 mg/l (95% CI 0.70 to 1.00) for moderate to severe nocturnal intermittent hypoxia (p for trend=0.03). The values for women were 0.59 mg/l (95% CI 0.57 to 0.62), 0.66 mg/l (95% CI 0.59 to 0.73) and 0.82 mg/l (95% CI 0.62 to 1.03), respectively (p for trend=0.008). Compared with no nocturnal intermittent hypoxia, the prevalence of a high CRP level (≥1.0 mg/l) was 1.4–1.7-fold higher for mild to severe nocturnal intermittent hypoxia in both sexes. Conclusions Nocturnal intermittent hypoxia is associated with raised serum CRP levels among middle-aged Japanese subjects.

Associations between alcohol consumption and sleep-disordered breathing among Japanese women

BACKGROUND The associations between alcohol consumption and sleep-disordered breathing in women are uncertain. METHODS We conducted a cross-sectional study of 3113 women aged 30-69 years. The 3% oxygen desaturation index (3% ODI), based on overnight pulse oximetry findings, was selected as an indicator of sleep-disordered breathing. RESULTS 3% ODI frequencies of ≥5 were higher for drinking women with ethanol intakes of ≥23.0 g/d than for never drinkers: the respective multivariable odds ratios and 95% confidence intervals was 1.8(1.0-3.4). The corresponding odds ratio was 3.0(1.6-5.8) for habitual snoring. The associations of ethanol intakes of ≥23.0 g/d with 3% ODI ≥ 5 was more evident among women with BMI <23.0 kg/m(2) (median) than those with higher BMI but did not vary by habitual snoring. The multivariable odds ratios of 3%ODI ≥ 5 for women with ethanol intakes of ≥23.0 g/d versus never drinkers were 2.7(1.0-6.7) for lower BMI and 1.5(0.6-3.3) for higher BMI and the corresponding odds ratio were 2.8(1.6-7.2) and 3.2(1.3-7.9) for habitual snoring, respectively. CONCLUSION Alcohol consumption was associated with higher prevalence of sleep-disordered breathing among Japanese women.

Serum Albumin and High-Sensitivity C-reactive Protein are Independent Risk Factors of Chronic Kidney Disease in Middle-Aged Japanese Individuals: the Circulatory Risk in Communities Study.

Aim: It is important to explore predictive markers other than conventional cardiovascular risk factors for early detection and treatment of chronic kidney disease (CKD), a major risk factor for end-stage renal failure. We hypothesized that serum albumin and high-sensitivity C-reactive protein (hs-CRP) to be independent markers, and examined their associations with the risk of CKD. Methods: We examined the associations of serum albumin and hs-CRP levels with the risk of incident CKD, in 2535 Japanese adults aged 40–69 years without CKD at baseline during a median 9.0-year follow-up after adjustment for known cardiovascular risk factors. Results: During the follow-up period, 367 cases of CKD developed. In multivariable analyses adjusted for known risk factors, the CKD hazard ratios (95% confidence intervals) for the highest versus lowest quartiles of serum albumin levels were 0.69 (0.40–1.17) for men and 0.42 (0.28–0.64) for women. Corresponding values for hs-CRP were 0.95 (0.54–1.67) for men and 1.85 (1.25 -2.75) for women. The association of combined serum albumin and hs-CRP with the risk of CKD was examined for women. The hazard ratio was 1.72 (1.17–2.54) for low versus higher albumin levels at lower hs-CRP levels, but such an association was not observed at high hs-CRP level. The hazard ratio was 1.96 (1.44–2.66) for high versus lower hs-CRP levels at higher serum albumin levels, but such association was not observed at low serum albumin level. Conclusion: Both low serum albumin and high hs-CRP levels were predictive of CKD for women.

Impact of Hypertension and Subclinical Organ Damage on the Incidence of Cardiovascular Disease Among Japanese Residents at the Population and Individual Levels ― The Circulatory Risk in Communities Study (CIRCS) ―

BACKGROUND In Japan, a community-based screening program for cardiovascular disease (CVD) has been effective in preventing stroke and coronary artery disease (CAD). The present study aimed to clarify which risk factors assessed at the screening examinations affect the incidence of CVD and the magnitude of the association after the late 1990 s.Methods and Results:We conducted a 12.5-year prospective study of 10,612 Japanese residents aged 40-74 years between 1995 and 2000, initially free of CVD and who underwent the screening examinations. During the follow-up, 364 cases of stroke and 137 cases of CAD were identified. The population attributable fraction of stroke was the largest for hypertension (HT; 46%), while the relative risk of stroke was the highest for atrial fibrillation (multivariable hazard ratio, 4.9; 95% confidence interval, 2.9-8.3). The population attributable fraction of CAD was relatively large for HT, current smoking, and high non-high-density lipoprotein cholesterol (20-29%). A dose-response relationship was found between the incidence of these cardiovascular events and the number of comorbid hypertensive subclinical organ damage markers: funduscopic changes, ST-T changes on ECG at rest, proteinuria and low estimated glomerular filtration rate. CONCLUSIONS HT and hypertensive subclinical organ damage are significantly associated with incident stroke and CAD at the population level, suggesting that management of HT and assessment of subclinical organ damage in hypertensive subjects at a screening program are still beneficial for community-based CVD prevention.

Long‐Term Prognosis of Brugada‐Type ECG and ECG With Atypical ST‐Segment Elevation in the Right Precordial Leads Over 20 Years: Results From the Circulatory Risk in Communities Study (CIRCS)

Background Brugada syndrome is recognized as being associated with sudden cardiac death; however, the prevalence of non–type 1 Brugada‐type ECG (BrS) or atypical ST‐segment elevation in the right precordial leads (STERP) and the long‐term prognosis for those patients remain unknown. Methods and Results We analyzed standard 12‐lead ECGs of 7178 apparently healthy participants (age range 40–64 years) who underwent health checkups from 1982 to 1986 in the Circulatory Risk in Communities Study, a prospective, large, community‐based cohort study in Japan. ECGs with J point amplitude ≥0.2 mV in the right precordial leads were divided into 3 groups: (1) type 1 BrS, (2) type 2 or 3 BrS (non‐type 1 BrS), and (3) STERP. The others served as the non–ST‐segment elevation group. We identified 8 participants (0.1%) with type1 BrS, 84 (1.2%) with non–type 1 BrS, and 228 (3.2%) with STERP. During a median follow‐up of 18.7 years (133 987.0 person‐years), sudden cardiac death was observed in no participants (0.0%) with type 1 BrS, in 1 (1.2%) with non–type 1 BrS, in 7 (3.1%) with STERP, and in 50 (0.7%) with non–ST‐segment elevation. Participants with STERP had a markedly elevated risk of sudden cardiac death (multivariable hazard ratio 3.9, 95% CI 1.7–9.0). Conclusions STERP was associated with an elevated risk of sudden cardiac death in a middle‐aged population.

Retinal Vascular Changes and Prospective Risk of Disabling Dementia: the Circulatory Risk in Communities Study (CIRCS)

Aim: To investigate the association of retinal vascular changes with a risk of dementia in longitudinal population-based study. Methods: We performed a nested case-control study of 3,718 persons, aged 40–89 years, enrolled between 1983 and 2004. Retinal vascular changes were observed in 351 cases with disabling dementia (average period before the onset, 11.2 years) and in 702 controls matched for sex, age, and baseline year. Incidence of disabling dementia was defined as individuals who received cares for disabilities including dementia-related symptoms and/or behavioral disturbance. Conditional logistic regression analysis was used to calculate odds ratio (OR) and multivariable adjusted OR (Models 1 and 2) for incidence of disabling dementia according to each retinal vascular change. Regarding confounding variables, Model 1 included overweight status, hypertension, hyperglycemia, dyslipidemia, and smoking status, whereas Model 2 also included incidence of stroke prior to disabling dementia for further analysis. Results: The proportion of cases (controls) with retinal vascular changes was 23.1 (15.7)% for generalized arteriolar narrowing, 7.7 (7.5)% for focal arteriolar narrowing, 15.7 (11.8)% for arteriovenous nicking, 10.5 (9.3)% for increased arteriolar wall reflex, and 11.4 (9.8)% for any other retinopathy. Generalized arteriolar narrowing was associated with an increased risk of disabling dementia: crude OR, 1.66 (95% confidence interval, 1.19–2.31); Model 1: OR, 1.58 (1.12–2.23); Model 2: OR, 1.48 (1.04–2.10). The number of retinal abnormalities was associated in a dose–response manner with the risk. Conclusion: Generalized arteriolar narrowing and total number of retinal abnormalities may be useful markers for identifying persons at higher risks of disabling dementia.

Fifty-year Time Trends in Blood Pressures, Body Mass Index and their Relations in a Japanese Community: The Circulatory Risk in Communities Study (CIRCS).

Aim: Data for long-term trends in blood pressures, body mass index (BMI), and their relations are needed to set future intervention priorities for prevention of cardiovascular disease. The objective of this study was to investigate these trends revealed by repeated cross-sectional surveys conducted from 1963 to 2013 in a Japanese community. Methods: Men and women aged 40–79 years who participated in annual cardiovascular checkups were enrolled, and the number of participants ranged between 1,776 and 2,366 with consistently high participation rates for both sexes aged 60–69 years. Sex- and age-specific mean systolic and diastolic blood pressures were calculated using mixed effects modeling for repeated measurement, and the prevalence of hypertension with and without obesity (BMI ≥ 25 kg/m2) were also calculated. Results: Sex- and age-specific mean systolic and diastolic blood pressures declined irrespective of antihypertensive medication use in both men and women from 1963–1966 to 2009–2013, while mean BMI increased among men of all ages and women of ages 60–69 and 70–79 years. For both sexes aged 60–69 years, the prevalence of hypertension with obesity increased, but the prevalence of hypertension without obesity was still higher that with obesity. Conclusions: Despite the transition to increased BMI levels, targeting non to obese hypertension remains important in addition to targeting obese hypertension for cardiovascular disease prevention.

Changes in ischaemic ECG abnormalities and subsequent risk of cardiovascular disease

Objective The prognostic importance of changes in ischaemic ECG abnormalities over time (especially ST-T abnormalities) among Asians has not been fully investigated. We examined the associations between changes in ischaemic abnormalities upon serial ECG (improvement, persistence, deterioration) and cardiovascular disease (CVD) risk. Methods A prospective study cohort was conducted with 9374 men and women aged 40–69 years in four communities. Participants had multiple ECGs at study entry and during the next 10 years, and were followed up for a median period of 23.0 years. Total CVD (stroke and coronary heart disease) was ascertained under systematic surveillance. ECG abnormalities were defined by the Minnesota Code, ST depression (Code4), abnormal T wave (Code5) and categorised into nine groups (no–no, no–minor, no–major, minor–no, minor–minor, minor–major, major–no, major–minor, major–major) by comparison with the point of entrance and maximum change. Results We documented 1196 CVD events. Compared with no–no abnormality, no–minor, minor–major and major–major in Code4, HRs (95% CI) adjusted for cardiovascular risk factors were 1.19 (1.00–1.42), 1.57 (1.15–2.12) and 1.87 (1.42–2.47). Similar results were observed in Code5. Conclusions Changes in ischaemic ECG abnormalities from none to minor, and minor to major, as well as persistent major abnormalities, were associated with an increased risk of CVD.