Delirium definition influences prediction of functional survival in patients one-year postcardiac surgery.

BACKGROUND: Delirium after cardiac surgery is associated with prolonged intensive care unit (ICU) and hospital length of stay and elevated rates of mortality. The Society of Thoracic Surgery National Database (STS-ND) includes delirium in routine data collection but restricts its definition to hyperactive symptoms. The objective is to determine whether the Confusion Assessment Method for ICU (CAM-ICU), which includes hypo- and hyperactive symptoms, is associated with improved prediction of poor 1-year functional survival following cardiac surgery. METHODS: Clinical and administrative databases were used to determine the influence of postoperative delirium on 1-year poor functional survival, defined as being institutionalized or deceased at 1 year. Patients experiencing postoperative delirium using the STS-ND definition (2007-2009) were compared with patients with delirium identified by the CAM-ICU (2010-2012). A propensity score match was undertaken, and multivariable Cox proportional hazards regression models were generated to determine risk of poor 1-year functional survival. RESULTS: There were 2756 and 2236 patients in the STS-ND and CAM-ICU cohorts, respectively. Propensity matching resulted in a cohort of 1835 patients (82.1% matched). The overall rate of delirium in the matched study population was 7.6% in the STS-ND cohort and 13.0% in the CAM-ICU cohort (P < .001). Delirium in the CAM-ICU cohort was independently associated with poor 1-year functional survival (hazard ratio, 2.58; 95% confidence interval, 1.20-5.54; P = .02); delirium in the STS-ND cohort was not associated with poor 1-year functional survival (hazard ratio, 0.92; 95% confidence interval, 0.49-1.71; P = .79). CONCLUSIONS: A systematic screening tool identifies postoperative delirium with improved prediction of poor 1-year functional survival following cardiac surgery.

Acute Effect of High-Intensity Interval Versus Moderate-Intensity Continuous Exercise on Blood Pressure and Arterial Compliance in Middle-Aged and Older Hypertensive Women With Increased Arterial Stiffness.

Costa, EC, Kent, DE, Boreskie, KF, Hay, JL, Kehler, DS, Edye-Mazowita, A, Nugent, K, Papadopoulos, J, Stammers, AN, Oldfield, C, Arora, RC, Browne, RAV, and Duhamel, TA. Acute effect of high-intensity interval versus moderate-intensity continuous exercise on blood pressure and arterial compliance in middle-aged and older hypertensive women with increased arterial stiffness. J Strength Cond Res 34(5): 1307-1316, 2020-Hypertension and arterial stiffness are common in middle-aged and older women. This study compared the acute effect of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) on blood pressure (BP) and arterial compliance in middle-aged and older hypertensive women with increased arterial stiffness. Nineteen women (67.6 ± 4.7 years) participated in this randomized controlled crossover trial. Subjects completed a control, MICE (30 minutes at 50-55% of heart rate reserve [HRR]), and HIIE (10 × 1 minute at 80-85% of HRR, 2 minutes at 40-45% of HRR) session in random order. Blood pressure and large and small arterial compliance (radial artery pulse wave analysis) were measured at baseline and 30, 60, 90, and 120 minutes after sessions. A p < 0.05 was considered statistically significant. Systolic BP was reduced in ∼10 mm Hg after MICE at 30 minutes and after HIIE at all time points (30, 60, 90, and 120 minutes) after exercise compared with the control session (p < 0.05). Only HIIE showed lower systolic BP levels at 60, 90, and 120 minutes after exercise compared with the control session (∼10 mm Hg; p < 0.05). No changes were observed in diastolic BP, or in large and small arterial compliance (p > 0.05). High-intensity interval exercise elicited a longer systolic postexercise hypotension than MICE compared with the control condition, despite the absence of acute modifications in large and small arterial compliance.

Sex-differences in relation to the association between patterns of physical activity and sedentary behavior with frailty.

OBJECTIVE: To investigate the sex-difference in relation to the association between moderate-vigorous physical activity (MVPA) and sedentary time (ST) patterns with frailty. METHOD: Accelerometry from ≥50 year olds from the National Health and Nutrition Examination Survey (2003-04/2005-06 cycles) were included. Bouted and sporadic MVPA were defined as MVPA in ≥10 min or <10 min durations, respectively. MVPA was analyzed based on meeting 0 %, 1-49 %, 50-99 %, and ≥100 % of the physical activity guidelines of 150 min/week. A duration of ≥30 minutes defined prolonged ST. The frequency (≥1 min interruption in ST), intensity and duration of breaks from ST were calculated. A 46-item frailty index (FI) quantified frailty. Multivariable linear regression models adjusted for demographics, total sedentary time, and accelerometer wear time. RESULTS: There were 1143 females and 1174 males available for analysis. Bouted MVPA was associated with lower frailty levels; the association peaked at meeting 50-99 % of the guidelines in females and ≥1.0 % in males (p = NS for sex-interaction). Meeting a higher proportion of the guidelines through sporadic MVPA was significantly associated with a lower FI in males only (p = NS for sex-interaction). Prolonged ST bouts were associated with worse frailty in females but not males (p < 0.05 sex-interaction). Average break intensity was associated with a lower FI in both sexes, whereas, total sedentary breaks were not (p = NS for sex-interaction). Average break duration was associated with frailty in males (p = NS for sex-interaction). CONCLUSION: Prolonged ST was more detrimentally associated with frailty in females than males, which could influence tailored movement prescriptions and guidelines.

A Quasi-Experimental Study Examining the Impact and Challenges of Implementing a Fitness-Based Health Risk Assessment and a Physical Activity Counseling Intervention in the Workplace Setting.

OBJECTIVES: Few adults participate in enough physical activity for health benefits. The workplace provides a unique environment to deliver heath interventions and can be beneficial to the employee and the employer. The purpose of the study was to explore the use of a physical activity counseling (PAC) program and a fitness-based health risk assessment (fHRA) in the hospital workplace. METHODS: A workplace-based intervention was developed utilizing a PAC program and an fHRA to improve physical activity levels of employees. Hospital employees were enrolled in a 4-month PAC program and given the option to also enroll in an fHRA program (PAC + fHRA). Physical activity was assessed by accelerometry and measured at baseline, 2 months, and 4 months. Changes in musculoskeletal fitness for those in the fHRA program were assessed at baseline and 2 months. RESULTS: For both groups (PAC n = 22; PAC + fHRA n = 16), total and moderate to vigorous physical activity in bouts of 10 minutes or more increased significantly by 18.8 (P = .004) and 10.2 (P = .048) minutes per week at each data collection point, respectively. Only participants with gym memberships demonstrated increases in light physical activity over time. Those in the fHRA group significantly increased their overall musculoskeletal fitness levels from baseline levels (18.2 vs 21.7, P < .001). There was no difference in the change in physical activity levels between the groups. CONCLUSIONS: A PAC program in the workplace may increase physical activity levels within 4 months. The addition of an fHRA does not appear to further increase physical activity levels; however, it may improve overall employee musculoskeletal fitness levels.

Exercise-induced increases in the expression and activity of cardiac sarcoplasmic reticulum calcium ATPase 2 is attenuated in AMPKα2 kinase-dead mice.

Exercise enhances cardiac sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) function through unknown mechanisms. The present study tested the hypothesis that the positive effects of exercise on SERCA2a expression and function in the left ventricle is dependent on adenosine-monophosphate-activated protein kinase (AMPK) α2 function. AMPKα2 kinase-dead (KD) transgenic mice, which overexpress inactivated AMPKα2 subunit, and wild-type C57Bl/6 (WT) mice were randomized into sedentary groups or groups with access to running wheels. After 5 months, exercised KD mice exhibited shortened deceleration time compared with sedentary KD mice. In left ventricular tissue, the ratio of phosphorylated AMPKαThr172:total AMPKα was 65% lower (P < 0.05) in KD mice compared with WT mice. The left ventricle of KD mice had 37% lower levels of SERCA2a compared with WT mice. Although exercise increased SERCA2a protein levels in WT mice by 53%, this response of exercise was abolished in exercised KD mice. Exercise training reduced total phospholamban protein content by 23% in both the WT and KD mice but remained 20% higher overall in KD mice. Collectively, these data suggest that AMPKα influences SERCA2a and phospholamban protein content in the sedentary and exercised heart, and that exercise-induced changes in SERCA2a protein are dependent on AMPKα function.

Impact of preoperative physical activity and depressive symptoms on post-cardiac surgical outcomes.

OBJECTIVE: To determine the independent and combined impact of preoperative physical activity and depressive symptoms with hospital length of stay (HLOS), and postoperative re-hospitalization and mortality in cardiac surgery patients. METHODS: A cohort study including 405 elective and in-house urgent cardiac surgery patients were analyzed preoperatively. Physical activity was assessed with the International Physical Activity Questionnaire to categorize patients as active and inactive. The Patient Health Questionnaire-9 was used to evaluate preoperative depressive symptoms and categorize patients as depressed and not depressed. Patients were separated into four groups: 1) Not depressed/active (n = 209), 2) Depressed/active (n = 48), 3) Not depressed/inactive (n = 101), and 4) Depressed/inactive (n = 47). Administrative data captured re-hospitalization and mortality data, and were combined into a composite endpoint. Models adjusted for demographics, comorbidities, and cardiac surgery type. Multiple imputation was used to impute missing values. RESULTS: Preoperative physical activity behavior and depression were not associated with HLOS examined in isolation or when analyzed by the physical activity/depressive symptom groups. Physical inactivity (HR: 1.60, 95% CI 1.05 to 2.42; p = 0.03), but not depressive symptoms, was independently associated with the composite outcome. Freedom from the composite outcome were 76.1%, 87.5%, 68.0%, and 61.7% in the Not depressed/active, Depressed/active, Not depressed/inactive, and Depressed/inactive groups, respectively (P = 0.02). The Active/Depressed group had a lower risk of the composite outcome (HR: 0.35 95% CI 0.14 to 0.89; p = 0.03) compared to the other physical activity/depression groups. CONCLUSION: Preoperative physical activity appears to be more important than depressive symptoms on short-term postoperative re-hospitalization and mortality.

Standardization of the Fried frailty phenotype improves cardiovascular disease risk discrimination.

BACKGROUND: Standardizing the Fried criteria (S-FC) using cutoffs specific to the patient population improves adverse outcome prediction. However, there is limited evidence to determine if a S-FC assessment can improve discrimination of cardiovascular disease (CVD) risk in middle-aged and older women. DESIGN: The objective of this cross-sectional analysis was to compare the ability of the Fried frailty phenotype criteria (FC) to discriminate between individuals at higher risk for CVD according to the Framingham Risk Score and Rasmussen Disease Score in comparison to the S-FC. SETTING: Asper Clinical Research Institute, St. Boniface Hospital Research Centre. PARTICIPANTS: 985 women 55 years of age or older with no previous history of CVD. MEASUREMENTS: Discrimination of individuals with high CVD risk according to the Framingham and Rasmussen Disease scores was assessed using receiver operating characteristic (ROC) curves, integrated discrimination index (IDI) and net reclassification index (NRI). RESULTS: The S-FC showed superior ability to discriminate CVD risk as assessed by area under the ROC curve (AUROC) based on the Framingham (0.728 vs 0.634, p < 0.001), but not for the Rasmussen (0.594 vs 0.552, p = 0.079) risk score. Net reclassification index identified improved discrimination for both the Framingham (67.9%, p < 0.001) and Rasmussen Disease scores (26.0%, p = 0.003). Integrated discrimination index also identified improved CVD risk discrimination with the Framingham (3.0%, p < 0.001) and Rasmussen Disease scores (1.5%, p < 0.001). CONCLUSION: In this study, the Fried frailty phenotype better discriminated cardiovascular disease risk when standardized to the study population.

Pre-Operative Frailty Status Is Associated with Cardiac Rehabilitation Completion: A Retrospective Cohort Study.

While previous investigations have demonstrated the benefit of cardiac rehabilitation (CR) on outcomes after cardiac surgery, the association between pre-operative frailty and post-operative CR completion is unclear. The purpose of this retrospective cohort study was to determine if pre-operative frailty scores impacted CR completion post-operatively and if CR completion influenced frailty scores in 114 cardiac surgery patients. Frailty was assessed with the use of the Clinical Frailty Scale (CFS), the Modified Fried Criteria (MFC), the Short Physical Performance Battery (SPPB), and the Functional Frailty Index (FFI). A Mann-Whitney test was used to compare frailty scores between CR completers and non-completers and changes in frailty scores from baseline to 1-year post-operation. CR non-completers were more frail than CR completers at pre-operative baseline based on the CFS (p = 0.01), MFC (p < 0.001), SPPB (p = 0.007), and the FFI (p < 0.001). A change in frailty scores from baseline to 1-year post-operation was not detected in either group using any of the four frailty assessments. However, greater improvements from baseline to 1-year post-operation in two MFC domains (cognitive impairment and low physical activity) and the physical domain of the FFI were found in CR completers as compared to CR non-completers. These data suggest that pre-operative frailty assessments have the potential to identify participants who are less likely to attend and complete CR. The data also suggest that frailty assessment tools need further refinement, as physical domains of frailty function appear to be more sensitive to change following CR than other domains of frailty.

A systematic review of the association between sedentary behaviors with frailty.

OBJECTIVE: Lifestyle factors such as physical activity are known to reduce the risk of frailty. However, less is known about the frailty-sedentary behavior relationship. A systematic review was conducted to synthesize the available evidence concerning associations between sedentary behaviors and frailty levels in adults. METHOD: MEDLINE, Embase, Web of Science, CINAHL, SPORTDiscus, Scopus, and the World Health Organization Clinical Trials Registry were searched up to August 2017 for observational studies in adults >18 years for cohort studies. Included studies identified frailty as a specified outcome using a multi-component tool. Sedentary behavior was measured by self-report or objectively. Studies with statistical models adjusting for at least one covariate were included. Meta-analysis could not be performed due to the heterogeneity in frailty and sedentary behavior measures. RESULTS: Six longitudinal and ten cross-sectional studies were identified (n = 14, 693 unique participants); sample sizes ranged from 26 to 5871. Studies were generally at a low to moderate risk of bias. Most studies (n = 9) used the Fried criteria to measure frailty. Five studies measured sedentary behavior by questionnaire, with three studies specifically measuring television viewing time. Seven studies measured sedentary time by accelerometry. Thirteen of sixteen studies observed a detrimental association between high amounts of sedentary behaviors and an increased prevalence of frailty or higher frailty levels. Six of seven studies adjusting for physical activity behaviors demonstrated an independent association between sedentary behaviors and frailty. All six longitudinal studies found a negative association between sedentary behaviors and frailty. CONCLUSIONS: Sedentary behaviors were associated with a higher prevalence of frailty or higher frailty levels. Longitudinal studies are needed that adjust for physical activity when determining the association between sedentary behaviors and frailty. The efficacy of sedentary behavior reduction outside of physical activity interventions to treat and reverse frailty should also be tested.

The association between bouts of moderate to vigorous physical activity and patterns of sedentary behavior with frailty.

OBJECTIVES: To determine if bouts of moderate-vigorous physical activity (MVPA) and patterns of sedentary behavior are associated with frailty. METHOD: Accelerometry from community-dwelling adults ≥50 years old (n = 2317) enrolled in the 2003-04 and 2005-06 National Health and Nutrition Examination Survey were used. Bouted (≥10 min) and sporadic (<10 min) durations of MVPA were analyzed based on meeting 0%, 1-49%, 50-99%, and ≥100% of physical activity guidelines (150 min/week of MVPA). Prolonged sedentary behavior were bouts lasting ≥30 min. Breaks from sedentary behavior were defined as any ≥1 min interruption in sedentary behavior. Average intensity (counts/min) and duration (minutes) during breaks were also analyzed. Frailty was measured with a 46-item frailty index. RESULTS: Multivariable linear regression models adjusting for age, sex, education, ethnicity, income, marital status, smoking, alcohol consumption, body mass index, total sedentary time and accelerometer wear time indicated that meeting any percentage of the activity guidelines with bouted and sporadic MVPA was associated with reduced frailty. This relationship peaked at meeting 50-99% of guidelines and was associated with a 1.5 and 2.0 point reduction in the frailty index for bouted and sporadic MVPA, respectively. Two additional prolonged sedentary behavior bouts/day were associated with an additional frailty index deficit while every additional 100 cpm in average break intensity and every 2 min in average break duration were associated with one less deficit. Total sedentary breaks were not associated with frailty. CONCLUSION: These population-level data give justification for determining if interventions which target short bouts of MVPA and interrupting prolonged, uninterrupted time spent in sedentary behaviors can treat or prevent frailty worsening.

Protocol for the HAPPY Hearts study: cardiovascular screening for the early detection of future adverse cardiovascular outcomes in middle-aged and older women: a prospective, observational cohort study.

INTRODUCTION: Efforts to identify individuals at a higher risk for adverse cardiovascular outcomes focus on traditional risk factors, such as age, sex, smoking status, blood pressure and and cholesterol; however, this approach does not directly assess cardiovascular function and may underestimate the risk of experiencing adverse cardiovascular outcomes in women. This prospective, observational cohort study will examine the ability of the Heart Attack Prevention Program for You (HAPPY) Hearts screening protocol, a series of non-invasive procedures to identify middle-aged and older women who are at an elevated risk for experiencing an adverse cardiovascular event in the 5-year period after screening. The predictive value of the HAPPY Hearts protocol will also be compared with the Framingham Risk Score to determine the sensitivity for estimating risk for an adverse cardiovascular outcome. METHODS AND ANALYSIS: One thousand women 55 years of age or older will be recruited to be screened by the HAPPY Hearts protocol. This involves the cardiovascular assessment of resting blood pressure, blood pressure response to 3 min of moderate intensity exercise and large and small arterial elasticity. The participants will be classified into risk categories based on these measures. The incidence of the following adverse cardiovascular outcomes will be assessed in the 5-year period after screening in both groups: ischaemic heart disease, acute myocardial infarction, stroke, percutaneous coronary intervention, coronary bypass surgery, congestive heart failure and new hypertension. ETHICS AND DISSEMINATION: Information gathered in this research will be published in peer-reviewed journals and presented in a programme evaluation report to inform Manitoba Health and key stakeholders about the outcomes of the study. The University of Manitoba Health Research Ethics Board has approved the study protocol V.2.0, dated 29 September 2014 (H2014:224). TRIAL REGISTRATION NUMBER: NCT02863211.

Systematic review of preoperative physical activity and its impact on postcardiac surgical outcomes.

OBJECTIVES: The objective of this systematic review was to study the impact of preoperative physical activity levels on adult cardiac surgical patients' postoperative: (1) major adverse cardiac and cerebrovascular events (MACCEs), (2) adverse events within 30 days, (3) hospital length of stay (HLOS), (4) intensive care unit length of stay (ICU LOS), (5) activities of daily living (ADLs), (6) quality of life, (7) cardiac rehabilitation attendance and (8) physical activity behaviour. METHODS: A systematic search of MEDLINE, Embase, AgeLine and Cochrane library for cohort studies was conducted. RESULTS: Eleven studies (n=5733 patients) met the inclusion criteria. Only self-reported physical activity tools were used. Few studies used multivariate analyses to compare active versus inactive patients prior to surgery. When comparing patients who were active versus inactive preoperatively, there were mixed findings for MACCE, 30 day adverse events, HLOS and ICU LOS. Of the studies that adjusted for confounding variables, five studies found a protective, independent association between physical activity and MACCE (n=1), 30-day postoperative events (n=2), HLOS (n=1) and ICU LOS (n=1), but two studies found no protective association for 30-day postoperative events (n=1) and postoperative ADLs (n=1). No studies investigated if activity status before surgery impacted quality of life or cardiac rehabilitation attendance postoperatively. Three studies found that active patients prior to surgery were more likely to be inactive postoperatively. CONCLUSION: Due to the mixed findings, the literature does not presently support that self-reported preoperative physical activity behaviour is associated with postoperative cardiac surgical outcomes. Future studies should objectively measure physical activity, clearly define outcomes and adjust for clinically relevant variables. REGISTRATION: Trial registration number NCT02219815. PROSPERO number CRD42015023606.

The impact of frailty on functional survival in patients 1 year after cardiac surgery.

OBJECTIVE: This study determined whether frailty provides incremental value to the European System for Cardiac Operative Risk Evaluation II in identifying patients at risk of poor 1-year functional survival. METHODS: This prospective study in patients undergoing cardiac surgery defined frailty using 3 common definitions: (1) the Modified Fried Criteria; (2) the Short Physical Performance Battery; and (3) the Clinical Frailty Scale. The primary outcome was functional survival, defined as being alive at 1 year postsurgery with a health-related quality of life score greater than 60 on the EuroQol-Visual Analogue Scale. RESULTS: Of the 188 participants, 49.5%, 52.6%, and 31.9% were deemed frail according to the Modified Fried Criteria, Short Physical Performance Battery, and Clinical Frailty Scale, respectively. The median age of our cohort was 71.0 years (29.3% female). The probability of functional survival at 1 year for the entire cohort was 73.9%. After adjusting for the European System for Cardiac Operative Risk Evaluation II, patients deemed frail under the Modified Fried Criteria, Short Physical Performance Battery, and Clinical Frailty Scale had an increased odds ratio for poor functional survival of 3.44, 3.47, and 2.08, respectively. When compared with the European System for Cardiac Operative Risk Evaluation II alone, the Modified Fried Criteria, Short Physical Performance Battery, and Clinical Frailty Scale showed an absolute improvement in the discrimination slope of 6.7%, 6.5%, and 2.4% with a category-free classification improvement of 59.6%, 59.2%, and 35.1%, respectively. CONCLUSIONS: Preoperative frailty was associated with a 2- to 3.5-fold higher risk of poor functional survival 1 year after cardiac surgery. The addition of frailty to the European System for Cardiac Operative Risk Evaluation II provides incremental value in identifying patients at risk of poor functional survival 1 year postsurgery, regardless of frailty definition.

Prevalence of frailty in Canadians 18-79 years old in the Canadian Health Measures Survey.

BACKGROUND: There is little certainty as to the prevalence of frailty in Canadians in younger adulthood. This study examines and compares the prevalence of frailty in Canadians 18-79 years old using the Accumulation of Deficits and Fried models of frailty. METHODS: The Canadian Health Measures Study data were used to estimate the prevalence of frailty in adults 18-79 years old. A 23-item Frailty Index using the Accumulation of Deficits Model (cycles 1-3; n = 10,995) was developed; frailty was defined as having the presence of 25% or more indices, including symptoms, chronic conditions, and laboratory variables. Fried frailty (cycles 1-2; n = 7,353) included the presence of ≥3 criteria: exhaustion, physical inactivity, poor mobility, unintentional weight loss, and poor grip strength. RESULTS: The prevalence of frailty was 8.6 and 6.6% with the Accumulation of Deficits and the Fried Model. Comparing the Fried vs. the Accumulation of Deficits Model, the prevalence of frailty was 5.3% vs. 1.8% in the 18-34 age group, 5.7% vs. 4.3% in the 35-49 age group, 6.9% vs. 11.6% in the 50-64 age group, and 7.8% vs. 20.2% in the 65+ age group. Some indices were higher in the younger age groups, including persistent cough, poor health compared to a year ago, and asthma for the accumulation of deficits model, and exhaustion, unintentional weight loss, and weak grip strength for the Fried model, compared to the older age groups. CONCLUSIONS: These data show that frailty is prevalent in younger adults, but varies depending on which frailty tool is used. Further research is needed to determine the health impact of frailty in younger adults.

Protocol for the PREHAB study-Pre-operative Rehabilitation for reduction of Hospitalization After coronary Bypass and valvular surgery: a randomised controlled trial.

INTRODUCTION: Frailty is a geriatric syndrome characterised by reductions in muscle mass, strength, endurance and activity level. The frailty syndrome, prevalent in 25-50% of patients undergoing cardiac surgery, is associated with increased rates of mortality and major morbidity as well as function decline postoperatively. This trial will compare a preoperative, interdisciplinary exercise and health promotion intervention to current standard of care (StanC) for elective coronary artery bypass and valvular surgery patients for the purpose of determining if the intervention improves 3-month and 12-month clinical outcomes among a population of frail patients waiting for elective cardiac surgery. METHODS AND ANALYSIS: This is a multicentre, randomised, open end point, controlled trial using assessor blinding and intent-to-treat analysis. Two-hundred and forty-four elective cardiac surgical patients will be recruited and randomised to receive either StanC or StanC plus an 8-week exercise and education intervention at a certified medical fitness facility. Patients will attend two weekly sessions and aerobic exercise will be prescribed at 40-60% of heart rate reserve. Data collection will occur at baseline, 1-2 weeks preoperatively, and at 3 and 12 months postoperatively. The primary outcome of the trial will be the proportion of patients requiring a hospital length of stay greater than 7 days. POTENTIAL IMPACT OF STUDY: The healthcare team is faced with an increasingly complex older adult patient population. As such, this trial aims to provide novel evidence supporting a health intervention to ensure that frail, older adult patients thrive after undergoing cardiac surgery. ETHICS AND DISSEMINATION: Trial results will be published in peer-reviewed journals, and presented at national and international scientific meetings. The University of Manitoba Health Research Ethics Board has approved the study protocol V.1.3, dated 11 August 2014 (H2014:208). TRIAL REGISTRATION NUMBER: The trial has been registered on ClinicalTrials.gov, a registry and results database of privately and publicly funded clinical studies (NCT02219815).

The regulation of sarco(endo)plasmic reticulum calcium-ATPases (SERCA).

The sarco(endo)plasmic reticulum calcium ATPase (SERCA) is responsible for transporting calcium (Ca(2+)) from the cytosol into the lumen of the sarcoplasmic reticulum (SR) following muscular contraction. The Ca(2+) sequestering activity of SERCA facilitates muscular relaxation in both cardiac and skeletal muscle. There are more than 10 distinct isoforms of SERCA expressed in different tissues. SERCA2a is the primary isoform expressed in cardiac tissue, whereas SERCA1a is the predominant isoform expressed in fast-twitch skeletal muscle. The Ca(2+) sequestering activity of SERCA is regulated at the level of protein content and is further modified by the endogenous proteins phospholamban (PLN) and sarcolipin (SLN). Additionally, several novel mechanisms, including post-translational modifications and microRNAs (miRNAs) are emerging as integral regulators of Ca(2+) transport activity. These regulatory mechanisms are clinically relevant, as dysregulated SERCA function has been implicated in the pathology of several disease states, including heart failure. Currently, several clinical trials are underway that utilize novel therapeutic approaches to restore SERCA2a activity in humans. The purpose of this review is to examine the regulatory mechanisms of the SERCA pump, with a particular emphasis on the influence of exercise in preventing the pathological conditions associated with impaired SERCA function.

Cardiovascular complications of type 2 diabetes in youth.

The prevalence of type 2 diabetes mellitus (T2DM) in youth has increased dramatically over the past decades. The literature also suggests that the progression from an impaired glucose tolerance state to established T2DM is more rapid in youth, compared to adults. The presence of significant cardiovascular complications in youth with T2DM, including cardiac, macrovascular, and microvascular remodeling, is another major issue in this younger cohort and poses a significant threat to the healthcare system. However, this issue is only now emerging as a major public health concern, with few data to support optimal treatment targets and strategies to reduce cardiovascular disease (CVD) risk in youth with T2DM. Accordingly, the purpose of this minireview is to better understand the cardiovascular complications in youth with T2DM. We briefly describe the pathophysiology from youth studies, including oxidative stress, inflammation, renin-angiotensin aldosterone system, and epigenetics, which link T2DM and CVD. We also describe the literature concerning the early signs of CVD in youth and potential treatment options to reduce cardiovascular risk.

Differential regulation of the fiber type-specific gene expression of the sarcoplasmic reticulum calcium-ATPase isoforms induced by exercise training.

The regulatory role of adenosine monophosphate-activated protein kinase (AMPK)-α2 on sarcoplasmic reticulum calcium-ATPase (SERCA) 1a and SERCA2a in different skeletal muscle fiber types has yet to be elucidated. Sedentary (Sed) or exercise-trained (Ex) wild-type (WT) and AMPKα2-kinase dead (KD) transgenic mice, which overexpress a mutated and inactivated AMPKα2 subunit, were utilized to characterize how genotype or exercise training influenced the regulation of SERCA isoforms in gastrocnemius. As expected, both Sed and Ex KD mice had >40% lower AMPK phosphorylation and 30% lower SERCA1a protein than WT mice (P < 0.05). In contrast, SERCA2a protein was not different among KD and WT mice. Exercise increased SERCA1a and SERCA2a protein content among WT and KD mice, compared with their Sed counterparts. Maximal SERCA activity was lower in KD mice, compared with WT. Total phospholamban protein was higher in KD mice than in WT and lower in Ex compared with Sed mice. Exercise training increased phospholamban Ser(16) phosphorylation in WT mice. Laser capture microdissection and quantitative PCR indicated that SERCA1a mRNA expression among type I fibers was not altered by genotype or exercise, but SERCA2a mRNA was increased 30-fold in WT+Ex, compared with WT+Sed. In contrast, the exercise-stimulated increase for SERCA2a mRNA was blunted in KD mice. Exercise upregulated SERCA1a and SERCA2a mRNA among type II fibers, but was not altered by genotype. Collectively, these data suggest that exercise differentially influences SERCA isoform expression in type I and type II fibers. Additionally, AMPKα2 influences the regulation of SERCA2a mRNA in type I skeletal muscle fibers following exercise training.