Mako Nagayoshi

Obstructive sleep apnea and incident type 2 diabetes.

OBJECTIVES To determine whether severity of obstructive sleep apnea is associated with incident diabetes in middle-aged and older adults. METHODS A prospective analysis of 1453 non-diabetic participants of both the Atherosclerosis Risk in Communities Study and the Sleep Heart Health Study (mean age 63 years, 46% male) had in-home polysomnography (1996-1998) and was followed up for incident diabetes. Using the apnea-hypopnea index derived from home polysomnography, study participants were categorized as follows: <5.0 (normal), 5.0-14.9 (mild), 15.0-29.9 (moderate), and ≥30.0 events/h (severe). Incident diabetes was ascertained during annual follow-up telephone calls through 2013. RESULTS During a median follow-up of 13 years, there were 285 incident diabetes cases among the 1453 participants. Participants with severe obstructive sleep apnea were at greater risk of incident diabetes compared to persons classified as normal after adjustment for confounders including body mass index and waist circumference (1.71 [1.08, 2.71]). The association between severe obstructive sleep apnea and incident diabetes was similar when analyses were restricted to obese individuals. CONCLUSIONS Severe obstructive sleep apnea was associated with greater risk of incident diabetes, independent of adiposity in a community-based sample. Healthcare professionals should be cognizant of the high prevalence of OSA in the general population and the potential link to incident diabetes.

Objectively measured sleep characteristics and prevalence of coronary artery calcification: the Multi-Ethnic Study of Atherosclerosis Sleep study

Background We tested whether objectively measured indices of obstructive sleep apnoea (OSA) and sleep quality are associated with coronary artery calcification (CAC) prevalence independent of obesity, a classic confounder. Methods 1465 Multi-Ethnic Study of Atherosclerosis participants (mean age 68 years), who were free of clinical cardiovascular disease, had both coronary CT and in-home polysomnography and actigraphy performed. OSA categories were defined by the Apnea-Hypopnea Index (AHI). Prevalence ratios (PRs) for CAC >0 and >400 (high burden) were calculated. Results Participants with severe OSA (AHI ≥30; 14.6%) were more likely to have prevalent CAC, relative to those with no evidence of OSA, after adjustment for demographics and smoking status (PR 1.16; 95% CI 1.06 to 1.26), body mass index (1.11; 1.02 to 1.21) and traditional cardiovascular risk factors (1.10; 1.01 to 1.19). Other markers of hypoxaemia tended to be associated with a higher prevalence of CAC >0. For CAC >400, a higher prevalence was observed with both a higher arousal index and less slow-wave sleep. Overall, associations were somewhat stronger among younger participants, but did not vary by sex or race/ethnicity. Conclusions In this population-based multi-ethnic sample, severe OSA was associated with subclinical coronary artery disease (CAC >0), independent of obesity and traditional cardiovascular risk factors. Furthermore, the associations of the arousal index and slow-wave sleep with high CAC burden suggest that higher nightly sympathetic nervous system activation is also a risk factor. These findings highlight the potential importance of measuring disturbances in OSA as well as sleep fragmentation as possible risk factors for coronary artery disease.

Social Network, Social Support, and Risk of Incident Stroke Atherosclerosis Risk in Communities Study

Background and Purpose— Having a small social network and lack of social support have been associated with incident coronary heart disease; however, epidemiological evidence for incident stroke is limited. We assessed the longitudinal association of a small social network and lack of social support with risk of incident stroke and evaluated whether the association was partly mediated by vital exhaustion and inflammation. Methods— The Atherosclerosis Risk in Communities study measured social network and social support in 13 686 men and women (mean, 57 years; 56% women; 24% black; 76% white) without a history of stroke. Social network was assessed by the 10-item Lubben Social Network Scale and social support by a 16-item Interpersonal Support Evaluation List-Short Form. Results— During a median follow-up of 18.6 years, 905 incident strokes occurred. Relative to participants with a large social network, those with a small social network had a higher risk of stroke (hazard ratio [95% confidence interval], 1.44 [1.02–2.04]) after adjustment for demographics, socioeconomic variables, marital status, behavioral risk factors, and major stroke risk factors. Vital exhaustion, but not inflammation, partly mediated the association between a small social network and incident stroke. Social support was unrelated to incident stroke. Conclusions— In this sample of US community-dwelling men and women, having a small social network was associated with excess risk of incident stroke. As with other cardiovascular conditions, having a small social network may be associated with a modestly increased risk of incident stroke.

Self-reported snoring frequency and incidence of cardiovascular disease: the Circulatory Risk in Communities Study (CIRCS).

Background Although associations between snoring and cardiovascular disease have been reported in several prospective studies, there is limited evidence from Asian populations. The objective of this study was to determine if there is an association between self-reported snoring frequency and the incidence of cardiovascular disease in Japanese. Methods The subjects were 2350 men and 4163 women aged 40 to 69 years who lived in 3 communities in Japan. All subjects were participants in the Circulatory Risk in Communities Study (CIRCS) and were followed for 6 years. Incidence of cardiovascular disease during the follow-up period comprised events of myocardial infarction, angina pectoris, sudden cardiac death and stroke. Results During the 6-year follow-up period, 97 participants (56 men and 41 women) had cardiovascular events. After adjustment for potential confounding factors, self-reported snoring frequency was associated with an increased risk of cardiovascular events among women but not men. The hazard ratios (95% CI) for cardiovascular events were 0.9 (0.4–2.0) for sometimes snoring and 2.5 (1.0–6.1) for everyday snoring in women and 0.7 (0.3–1.3) and 1.0 (0.5–2.1), respectively, in men. Further adjustment for body mass index attenuated the association in women; the respective hazard ratios for cardiovascular events were 0.9 (0.4–1.9) and 2.1 (0.9–5.4). Conclusions Self-reported habitual snoring was associated with increased risk of cardiovascular events among Japanese women. Overweight may partly mediate this association.

Obstructive Sleep Apnea and Progression of Coronary Artery Calcium: The Multi‐Ethnic Study of Atherosclerosis Study

Background Obstructive sleep apnea (OSA) is a common condition associated with cardiovascular disease. Its potential effect on progression of subclinical atherosclerosis is not well understood. We tested the hypothesis that self‐reported OSA is associated with progression of coronary artery calcium (CAC). We also evaluated whether traditional cardiovascular risk factors accounted for the association. Methods and Results In the Multi‐Ethnic Study of Atherosclerosis (MESA) prospective cohort, we studied 2603 participants who at baseline (2002–2004) completed a sleep questionnaire and underwent coronary computed tomography (CT) and, then 8 years later (2010–2011), a repeat coronary CT. Participants were categorized by symptoms of habitual snoring or reported physician diagnosis of OSA. At baseline, 102 (3.9%) reported diagnosed OSA; 666 (25.6%) reported diagnosed habitual snoring; and 1835 (70.5%) reported neither habitual snoring nor OSA (“normal”). At baseline, CAC prevalence was highest among those with OSA but similar for those with and without habitual snoring. During 8 years of follow‐up, greater progression of CAC was observed among those with OSA versus normal (mean increase of 204.2 versus 135.5 Agatston units; P=0.01), after accounting for demographics, behaviors, and body habitus. Modest attenuation was observed after adjustment for cardiovascular risk factors (188.7 versus 138.8; P=0.06). CAC progression among habitual snorers was similar to that observed in the normal group. Conclusions OSA was associated with CAC score progression after adjustment for demographics, behaviors, and body mass index. However, the association was not significant after accounting for cardiovascular risk factors, which may mediate the association between OSA and CAC.

Circulating CD34-positive cells, glomerular filtration rate and triglycerides in relation to hypertension

OBJECTIVE Serum triglycerides have been reported to be independently associated with the development of chronic kidney disease (CKD), which is known to play a role in vascular disturbance. On the other hand, circulating CD34-positve cells, including endothelial progenitor cells, are reported to contribute to vascular repair. However, no studies have reported on the correlation between triglycerides and the number of CD34-positive cells. Since hypertension is well known factor for vascular impairment, the degree of correlation between serum triglycerides and circulating CD34-positve cells should account for hypertension status. METHODS We conducted a cross-sectional study of 274 elderly Japanese men aged ≥ 60 years (range 60-79 years) undergoing general health checkups. RESULTS Multiple linear regression analysis of non-hypertensive subjects adjusting for classical cardiovascular risk factors showed that although triglyceride levels (1SD increments; 64 mg/dL) did not significantly correlate with glomerular filtration rate (GFR) (β = -2.06, p = 0.163), a significant positive correlation was seen between triglycerides and the number of circulating CD34-positive cells (β = 0.50, p = 0.004). In hypertensive subjects, a significant inverse correlation between triglycerides and GFR was observed (β = -2.66, p = 0.035), whereas no significant correlation between triglycerides and the number of circulating CD34-positive cells was noted (β = -0.004, p = 0.974). CONCLUSION Since endothelial progenitor cells (CD34-positive cells) have been reported to contribute to vascular repair, our results indicate that in non-hypertensive subjects, triglycerides may stimulate an increase in circulating CD34-positive cells (vascular repair) by inducing vascular disturbance.

Height is an indicator of vascular maintenance capacity in older men.

Bone‐derived circulating CD34‐positive cells are reported to play an important role in vascular maintenance. Additionally, height might influence age‐related hematopoietic bone marrow decline, as it positively correlates with total bone marrow volume. As hypertension should mask the beneficial effects of circulating CD34‐positive cells, hypertension status should account for this correlation. The present study aimed to clarify the clinical importance of height on vascular maintenance in older Japanese men.

Multiple somatic symptoms and frailty: cross-sectional study in Japanese community-dwelling elderly people

BACKGROUND Physical frailty is relevant to adverse outcomes, but appropriate procedures for screening populations are lacking. We hypothesized that frailty is associated with multiple somatic symptoms because frail elderly people might have several somatic symptoms attributed to deterioration of multiple organs. OBJECTIVE To examine the association between multiple somatic symptoms and frailty. METHODS We conducted a cross-sectional study and enrolled 1818 participants aged ≥60 years from Japanese national medical check-up in 2015. Frailty status was categorized into frail, pre-frail or non-frail based on the definition of the Fried frailty phenotype model. Sixteen self-reported subjective somatic symptoms were recorded at the timing of medical check-up. Odds ratio (OR) and 95% confidence interval (CI) of frail or pre-frail were analyzed using number of somatic symptoms. RESULTS Out of total of 1818 subjects, 44 (2.4%) frail subjects, 635 (34.9%) pre-frail subjects and 1139 (62.7%) non-frail subjects were detected. More than two somatic symptoms were significantly associated with the frail phenotype (OR 6.20, 95% CI 2.95, 13.03, P < 0.001) and were associated with the pre-frail phenotype (OR 2.06, 95% CI 1.69, 2.51, P < 0.001). Associations remained significant after multi-adjustment for age, sex, past medical cardiovascular diseases and depressive mood The number of somatic symptoms ≥2 was thought to be the optimal cut-off point to predict frail with a sensitivity of 79.6%, specificity of 61.5%. CONCLUSIONS Our study shows that multiple somatic symptoms are independently associated with frailty. Using more than two multiple somatic symptoms as a prescreening tool for frailty may be appropriate.

Height indicates hematopoietic capacity in elderly Japanese men.

Previously, we reported that height is an indicator of the capacity of vascular repair in elderly men, especially hypertensive men. On the other hand, hemoglobin could act as a possible biochemical index of hypertension-induced vascular damage. However, no studies have clarified the correlation between height and hematopoietic activity. We conducted a cross-sectional study of 249 men aged 65-69 undergoing a general health check-up. Reticulocyte was used to evaluate hematopoietic activity. Because hemoglobin concentration should influence hematopoietic activity, analyses stratified by hemoglobin level were performed. Independent of known cardiovascular risk factors and other hematological parameters (white blood cell count), a significant positive correlation was seen between height and reticulocytes for total subjects and subjects with a high hemoglobin concentration (≥14.5 g/dL), but not in subjects with a low hemoglobin concentration (<14.5 g/dL). The standardized parameter estimates (β) were β=0.18, p=0.003 for total subjects, β=0.28, p=0.001 for subjects with a high hemoglobin concentration, and β=0.03, p=0.717 for subjects with low hemoglobin. Independently, height is significantly positively correlated with reticulocyte in elderly Japanese men, particularly in men with a high hemoglobin concentration. These results indicate that subjects with a short stature might have lower hematopoietic capacity than those with a high stature.

Handgrip strength and subclinical carotid atherosclerosis in relation to platelet levels among hypertensive elderly Japanese

Age-related disruption of microvascular endothelium exacerbates hypertension and sarcopenia; and atherosclerosis is a well-known biological response to vascular endothelial injury. Therefore, prevalence of atherosclerosis among hypertensive elderly subjects may partly indicate the presence of an appropriate response to endothelial injury. We conducted a cross-sectional study of 795 elderly hypertensive Japanese subjects aged 60-89 years. Since platelet level is an indicator of vascular repair activity, subjects were stratified by platelet counts. No significant association between handgrip strength and subclinical carotid atherosclerosis (carotid intima-media thickness (CIMT) ≥1.1mm) was observed for subjects with lower platelet counts, while a significant positive association was observed for subjects with higher platelets. Adjusted odds and 95% confidence intervals of subclinical carotid atherosclerosis for 1 standard deviation increments in handgrip strength were 0.86 (0.61, 1.22) for subjects with lower platelets and 1.82 (1.26, 2.64) for subjects with higher platelets. A positive association between handgrip strength and subclinical carotid atherosclerosis exists in hypertensive elderly subjects with higher, but not lower, platelet counts. These results lead us to speculate that subjects with a beneficial influence on prevention of sarcopenia (maintenance of handgrip strength) may possess the capacity of active endothelial repair that causes atherosclerosis.