Eveningness is associated with sedentary behavior and increased 10-year risk of cardiovascular disease: the SCAPIS pilot cohort.

Chronotype reflects individual preferences for timing activities throughout the day, determined by the circadian system, environment and behavior. The relationship between chronotype, physical activity, and cardiovascular health has not been established. We studied the association between chronotype, physical activity patterns, and an estimated 10-year risk of first-onset cardiovascular disease (CVD) in the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort. A cross-sectional analysis was performed in a middle-aged population (n = 812, 48% male). Self-assessed chronotype was classified as extreme morning, moderate morning, intermediate, moderate evening, or extreme evening. Time spent sedentary (SED) and in moderate to vigorous physical activity (MVPA) were derived from hip accelerometer. The newly introduced Systematic COronary Risk Evaluation 2 (SCORE2) model was used to estimate CVD risk based on gender, age, smoking status, systolic blood pressure, and non-HDL cholesterol. Extreme evening chronotypes exhibited the most sedentary lifestyle and least MVPA (55.3 ± 10.2 and 5.3 ± 2.9% of wear-time, respectively), with a dose-dependent relationship between chronotype and SED/MVPA (p < 0.001 and p = 0.001, respectively). In a multivariate generalized linear regression model, extreme evening chronotype was associated with increased SCORE2 risk compared to extreme morning type independent of confounders (ß = 0.45, SE = 0.21, p = 0.031). Mediation analysis indicated SED was a significant mediator of the relationship between chronotype and SCORE2. Evening chronotype is associated with unhealthier physical activity patterns and poorer cardiovascular health compared to morning chronotype. Chronotype should be considered in lifestyle counseling and primary prevention programs as a potential modifiable risk factor.

Insomnia and cardiorespiratory fitness in a middle-aged population: the SCAPIS pilot study.

BACKGROUND: The relationship between insomnia and cardiorespiratory fitness (CRF), a well-established risk factor for cardiovascular disease, has not been extensively studied. We aimed to assess the independent association between insomnia and CRF in a population-based cohort of subjects aged 50 to 64 years. METHODS: Subjects participating in the Swedish CArdioPulmonary bioImaging Study (SCAPIS) pilot cohort (n = 603, men 47.9%) underwent a submaximal cycle ergometer test for estimation of maximal oxygen consumption (VO2max). Data on physical activity and sedentary time were collected via waist-worn accelerometers. An insomnia severity index score ≥ 10 was used to define insomnia. RESULTS: Insomnia was identified in 31.8% of the population. The VO2max was significantly lower in insomnia subjects compared with the non-insomnia group (31.2 ± 6.3 vs. 32.4 ± 6.5 ml* kg-1 *min-1, p = 0.028). There was no difference in objectively assessed physical activity or time spent sedentary between the groups. In a multivariate generalized linear model adjusting for confounders, an independent association between insomnia status and lower VO2max was found in men, but not in women (ß = - 1.15 [95% CI - 2.23-- 0.06] and - 0.09 [- 1.09-0.92], p = 0.038 and 0.866, respectively). CONCLUSIONS: We found a modest, but significant, association between insomnia and lower CRF in middle-aged men, but not in women. Our results suggest that insomnia may link to cardiovascular disease via reduced CRF. Insomnia may require a specific focus in the context of health campaigns addressing CRF.

Perceived sleep deficit is a strong predictor of RLS in multisite pain - A population based study in middle aged females.

BACKGROUND: Chronic pain conditions as well as Restless Legs Syndrome (RLS) are known to be associated with subjectively and objectively disturbed sleep. RLS has been recently described as highly prevalent in multisite pain and the role of sleep as a modifying factor in this RLS phenotype is unknown. This study aimed to investigate if perceived sleep deficit and other sleep related parameters predict RLS in subjects with multisite pain. CURRENT KNOWLEDGE/STUDY RATIONALE: We have recently demonstrated a strong association between Restless Legs Syndrome (RLS) and number of pain locations. In the current analysis we hypothesized that impaired sleep predicts RLS in subjects with multisite pain. METHOD: Questionnaire-based data from 2727 randomly selected women aged 18-64 years were used to analyze RLS symptoms, self-reported sleep quality, and the degree of daytime sleepiness (Epworth Sleepiness Scale (ESS)) in relation to type, degree and localization of body pain. Potential confounders including anthropometrics, pain localization, co-morbidities, and medication were adjusted for in the Generalized Linear Models (GLM). RESULTS: Perceived sleep deficit ≥90min (OR 2.4 (1.5-3.8), p<0.001) and frequent nocturnal awakenings (OR 2.3 (1.4-3.6), p<0.001) were the strongest sleep related predictors for RLS in subjects with multisite pain. Additional factors include prolonged sleep latency (≥30min, OR 1.8 (1.1-2.8), p=0.01) and daytime symptoms like elevated daytime sleepiness (ESS score ≥9, OR 1.8 (1.2-2.7), p=0.005). Accordingly, RLS diagnosis was associated with impaired sleep quality (TST (Total Sleep Time) -8.2min, sleep latency +8.0min, and number of awakenings from sleep +0.4, p<0.01). ESS score increased with RLS diagnosis (+0.74, p<0.01) and number of pain locations (0.5, 1.7, and 1.8 for 1, 3, and 5 pain areas, p<0.001). In addition, confounders like pain severity, the history of psychiatric disease, and current smoking were associated with impaired sleep quality in this group of females. CONCLUSIONS: Perceived sleep deficit and sleep fragmentation are the strongest sleep related predictors of RLS in multisite pain. Potential implication of our results are that clinical management programmes of RLS in subjects with multisite pain need to consider both sleep quality and sleep quantity for individually tailored treatment regimes. STUDY IMPACT: RLS, pain, and sleep disorders are highly interrelated. Our study strongly suggests that clinical management of RLS in patients with multisite pain needs to consider sleep quality as an independent risk factor.

Independent associations between arterial bicarbonate, apnea severity and hypertension in obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea is characterized by intermittent hypoxia and hypercapnia. CO2 production, transport and elimination are influenced by the carbonic anhydrase enzyme. We hypothesized that elevated standard bicarbonate, a proxy for increased carbonic anhydrase activity, is associated with apnea severity and higher blood pressure in patients with obstructive sleep apnea. METHODS: A retrospective analysis of a sleep apnea cohort (n = 830) studied by ambulatory polygraphy. Office systolic/diastolic blood pressure, lung function, and arterial blood gases were assessed during daytime. RESULTS: Arterial standard bicarbonate was increased with apnea severity (mild/moderate/severe 24.1 ± 1.8, 24.4 ± 1.7 and 24.9 ± 2.9 mmol/l, respectively, Kruskal-Wallis test p < 0.001). Standard bicarbonate was independently associated with apnea hypopnea index after adjustment for sex, age, body mass index, smoking, alcohol, hypertension, pO2 and pCO2 (standard bicarbonate quartile 1 vs. quartile 4, ß = 10.6, p < 0.001). Log-transformed standard bicarbonate was associated with a diagnosis of hypertension or diastolic blood pressure but not systolic blood pressure adjusting for cofounders (p = 0.007, 0.048 and 0.45, respectively). CONCLUSIONS: There was an independent association between sleep apnea severity and arterial standard bicarbonate. The link between high standard bicarbonate and daytime hypertension suggests that carbonic anhydrase activity may constitute a novel mechanism for blood pressure regulation in sleep apnea.

Vascular stiffness determined from a nocturnal digital pulse wave signal: association with sleep, sleep-disordered breathing, and hypertension.

OBJECTIVES: Reflection of the finger pulse wave form is a valid measure of arterial stiffness, which may be continuously assessed during sleep. We investigated the relationships between sleep, sleep-disordered breathing, hypertension, and pulse propagation time (PPT) in patients with suspected sleep apnea. METHODS: The digital photoplethysmographic signal derived from finger pulse oximetry was recorded during overnight sleep studies in 440 patients (64% men, age 55 ±â€Š12 years, BMI 30 ±â€Š6 kg/m, apnea-hypopnea index 19 ±â€Š19 n/h). PPT, defined as the time interval between the systolic and diastolic peak of the finger pulse wave, was calculated. The influence of sleep stages on PPT were assessed in patients undergoing polysomnography. Generalized linear models were used to study predictors of PPT and hypertension. RESULTS: Mean overnight PPT was independently associated with age (ß = -1.34, P < 0.001), height (ß = 0.47, P = 0.047), history of smoking (ß = -9.44, P = 0.005), and apnea-hypopnea index (ß = -0.18, P = 0.043). PPT was shorter in hypertensive patients compared with normotensive patients (160 ±â€Š33 vs. 177 ±â€Š47 ms, P < 0.001) and independently associated with a diagnosis of hypertension (P = 0.043). PPT was influenced by sleep stage (highest PPT during slow wave sleep compared with wake and all other sleep stages, all P < 0.001) and varied across sleep apnea severity groups in normotensive but not in hypertensive patients (P = 0.028 and 0.64, respectively). CONCLUSION: Overnight PPT by oximetry was strongly associated with factors known to determine daytime vascular stiffness. In addition, PTT provides information on functional and structural vascular properties during sleep. This novel technique offers new opportunities to noninvasively monitor vascular function during the sleeping period.

Parameters of Overnight Pulse Wave under Treatment in Obstructive Sleep Apnea.

BACKGROUND: Sleep-related breathing disorders may promote cardiovascular (CV) diseases. A novel and differentiated approach to overnight photoplethysmographic pulse wave analysis, which includes risk assessment and measurement of various pulse wave characteristics, has been evaluated in obstructive sleep apnea (OSA). OBJECTIVES: The purpose of this study was to assess if and which of the differentiated pulse wave characteristics might be influenced by OSA treatment with positive airway pressure (PAP). METHODS: The study included two protocols. In the case-control study (group A), pulse wave-derived CV risk indices recorded during PAP therapy were compared with those obtained in age, body mass index, and CV risk class-matched patients with untreated OSA (n = 67/67). In the prospective PAP treatment study (group B), 17 unselected patients undergoing a full-night sleep test at baseline and after 23 ± 19 weeks of treatment were analyzed. RESULTS: In untreated OSA patients (group A), the overnight hypoxic load was increased (SpO2 index 38.7 ± 17.5 vs. 24.0 ± 11.1, p < 0.001) and the pulse wave attenuation index (PWA-I) was lower (29.4 ± 9.2 vs. 33.5 ± 11.8, p = 0.022) than in treated patients. In group B, PAP therapy reduced the hypoxic load and increased the PWA-I significantly. The composite CV risk index was slightly but not significantly reduced. CONCLUSIONS: PAP therapy modified the hypoxic load and pulse wave-derived markers. The PWA-I - associated with sympathetic vascular tone - was most prominently modified by PAP. This novel approach to markers of CV function should be further evaluated in prospective studies.

[Effect of isoflurane delayed preconditioning on myocardial ischemia reperfusion injury in rabbits].

OBJECTIVE: To investigate the protective effect of isoflurane delayed preconditioning on myocardial ischemia reperfusion injury and the potential mechanism in rabbits. METHODS: Thirty New Zealand male white rabbits were randomly assigned to 3 groups: Control group; I/R group; and 2.0% isoflurane group. Isoflurane group was exposed to 2.0% isoflurane-100% oxygen for 2 hours. Control group and I/R group were exposed to 100% oxygen for 2 hours and served as untreated controls. Twenty-four hours later I/R group and isoflurane group underwent 40 minutes of coronary occlusion followed by 2 hours of reperfusion. Blood samples were taken from the arterial line at 20 minutes before the occlusion(T1), 20 minutes after the occlusion(T2), 40 minutes after the occlusion(T3), 1 hours after the reperfusion(T4), and 2 hours after the reperfusion(T5) to determine the plasma level of TNF-alpha. At the end of the reperfusion, infarct size and area at risk were defined by Evans and TTC staining. The heart was harvested and levels of the p38MAPK activity were determined by Western blot, and ultrastructures were observed under the electron microscope. RESULTS: The p38MAPK activity of isoflurane group was significantly lower than that of I/R group (P<0.05). Isoflurane significantly (P<0.05) reduced the infarct size(19.7%+/-2.8% in isoflurane group) of the left ventricular area at risk as compared with the controls (37.8%+/-1.7% in I/R group).The injury of I/R group was worse than that of isoflurane group under the light microscope. Isoflurane group had a lower level of TNF-alpha than I/R group. CONCLUSION: Isoflurane can inhibit p38MAPK activity during myocardial ischemia reperfusion and modulate the cytokine expression, which may be one of the molecular mechanisms of isoflurane delayed preconditioning on cardioprotection.

[Effects of ulinastatin on cerebral inflammatory response during cardiopulmonary bypass].

OBJECTIVE: To investigate the effects of ulinastatin (UTI) on cerebral inflammatory response during cardiopulmonary bypass (CPB). METHODS: Twenty-four NYHA II-III patients (13 males and 11 females) aged 23-45 years, undergoing elective cardiac valve replacement under hypothermic CPB were randomly divided into 2 groups: ulinastatin group (Group U, n=12) and control group (Group C, n=12). In group U, UTI (1.2 x 10(4) U/kg) was given intravenously after the induction of anesthesia, 0.6 x 10(4) U/kg UTI was added to the priming solution, and 0.6 x 10(4) U/kg UTI was given about 5 min before the aortic decamping. In Group C, normal saline was given instead of UTI. Internal jugular vein was cannulated and the catheter was advanced retrogradely till jugular bulb. Blood samples were taken simultaneously from artery and jugular bulb after induction of anesthesia (T1), 60 min (T2) and 6 h (T3) after discontinuation of CPB for determination of TNFalpha, IL-6, IL-8 and IL-10. The juguloarterial gradients of these cytokines (deltaTNFalpha, deltaIL-6, deltaIL-8, and deltaIL-10) were calculated. RESULTS: In Group C, arterial levels of TNFalpha, IL-6, IL-8, IL-10 at T2 and T3, deltaTNFalpha, deltaIL-8 and deltaIL-10 at T2, deltaTNFalpha, deltaIL-6 and deltaIL-10 at T3 significantly increased (P < 0.01). deltaIL-8 increased at T3 (P < 0.05). In Group U, arterial levels of IL-6, IL-8, IL-10 at T2, arterial levels of IL-6, IL-8,IL-L-10 and deltaTNFalpha, deltaIL-8 at T3 significantly increased (P < 0.01). Arterial levels of TNFalpha at T2 and T3, deltaTNFalpha, deltaIL-10 at T2, deltaIL-6 at T3 increased (P < 0.05). Arterial levels of TNFalpha, IL-6 and deltaTNFalpha, deltaIL-8 at T2, arterial levels of TNFalpha and deltaIL-6 at T3 in Group U were lower than those in Group C (P < 0.05). Arterial levels of IL-6 at T3, IL-8 at T2 and T3 in Group U were significantly lower than those in Group C (P < 0.01). Arterial levels of IL-10 and deltaIL-10 at T3 in Group U were higher than those in Group C (P < 0.05). CONCLUSION: Systemic and cerebral activation of inflammatory response during CPB can be alleviated by ulinastatin.