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.

Exercise-induced irisin release as a determinant of the metabolic response to exercise training in obese youth: the EXIT trial.

The mechanisms underlying the metabolic improvements following aerobic exercise training remain poorly understood. The primary aim of this study was to determine if an adipomyokine, irisin, responded to acute exercise was associated with the metabolic adaptations to chronic aerobic exercise in obese youth. The acute response to exercise was assessed in 11 obese youth following 45-min acute bouts of aerobic (AE) and resistance exercise (RE). The irisin area under the curve (pre-exercise, 15, 30, and 45 min) during these AE sessions were the main exposure variables. The primary outcome measure was the change in insulin sensitivity using the Matsuda index, following 6 weeks of RE training, delivered for 45 min, three times per week at 60-65% 1RM. Participants were also categorized as either responders (above) or nonresponders (below) based on the percentage change in the Matsuda index following the 6-week intervention. Irisin increased significantly during the acute bout of AE from 29.23 ± 6.96 to 39.30 ± 7.05 ng/mL; P = 0.028, but not significantly during the RE session (P = 0.182). Absolute and relative change in irisin during the acute bout of AE was associated with absolute and relative change in Matsuda index (r = 0.68; P = 0.022 and r = 0.63; P = 0.037) following the 6-week RE intervention. No such association was observed with the irisin response to acute RE (all P > 0.05). Responders to the 6-week RE intervention displayed a fourfold greater irisin response to acute AE (90.0 ± 28.0% vs. 22.8 ± 18.7%; P = 0.024) compared to nonresponders. Irisin increases significantly following an acute bout of AE, but not RE, and this response is associated with a greater improvement in insulin sensitivity in response to chronic resistance training.

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.

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.