The Association Between Route of Post-menopausal Estrogen Administration and Blood Pressure and Arterial Stiffness in Community-Dwelling Women.

Background: Postmenopausal hormone therapy (HT) is associated with increased cardiovascular risk. Although the route of estrogen administration may play a role in mediating risk, previous studies have not controlled for concomitant progestin use. Objective: To investigate the association between the route of estrogen therapy (oral or non-oral) HT use, without concomitant progestin, and blood pressure and arterial stiffness in postmenopausal women. Methods: Systolic blood pressure [SBP], diastolic blood pressure [DBP]), arterial stiffness (aortic pulse wave velocity [aPWV] and augmentation index at 75 beats per minute [AIx]) were measured using a validated automated brachial cuff-based oscillometric approach (Mobil-O-Graph) in a community-dwelling sample of 328 women. Results: Fifty-five participants (16.8%) were ever users (current and past use) of estrogen-only HT (oral [n = 16], transdermal [n = 20], vaginal [n = 19]), and 223 were never HT users (control). Ever use of oral estrogen was associated with increased SBP and DBP (Oral: SBP: 137 ± 4 mmHg, DBP: 79 ± 2 mmHg) compared to use of non-oral estrogen (transdermal: SBP: 118 ± 2 mmHg, DBP: 73 ± 1 mmHg; p < 0.01 & p = 0.012, respectively; vaginal: SBP: 123 ± 2 mmHg DBP: 73 ± 2 mmHg; p = 0.02 & p = 0.01, respectively.) and controls (SBP: 124 ± 1 mmHg, DBP: 74 ± 1 mmHg, p = 0.03, p = 0.02, respectively) after adjustment for covariates. aPWV was higher in oral estrogen ever users (9.9 ± 1 m/s) compared to non-oral estrogen (transdermal: 8.6 ± 0.3 m/s, p < 0.01; vaginal: 8.8 ± 0.7 m/s, p = 0.03) and controls (8.9 ± 0.5 m/s, p = 0.03) but these associations were no longer significant after adjustment for covariates. AIx was higher in oral estrogen (29 ± 2 %) compared to non-oral estrogen (transdermal: 16 ± 2 %; vaginal: 22 ± 1.7 %) but this association was no longer significant after adjustment for covariates (p = 0.92 vs. non-oral; p = 0.74 vs. control). Conclusion: Ever use of oral estrogen was associated with increased SBP and DBP compared to non-oral estrogen use and no use. Given the cardiovascular risk associated with both menopause and increased blood pressure, further studies are required exploring the potential benefits of non-oral estrogen in postmenopausal women.

Frailty-aware care: giving value to frailty assessment across different healthcare settings.

Healthcare systems need to adapt to better serve an aging population with complex presentations. Frailty assessments are a potential means to address this heterogeneity in aging to identify individuals at increased risk for adverse health outcomes. Furthermore, frailty assessments offer an opportunity to optimize patient care in various healthcare settings. While the vast number of frailty assessment tools available can be a source of confusion for clinicians, each tool has features adaptable to the constraints and goals of different healthcare settings. This review discusses and compares barriers, facilitators, and the application of frailty assessments in primary care, the emergency department/intensive care unit and surgical care to cover a breadth of settings with different frailty assessment considerations. The implementation of frailty-aware care across healthcare settings potentiates better healthcare outcomes for older adults.

Risk versus Benefit of Using Hydroxychloroquine to Treat Patients with COVID-19.

Hydroxychloroquine (HCQ), also known by its trade name Plaquenil®, has been used for over 50 years as a treatment for malaria, systemic lupus erythematosus, and rheumatoid arthritis. As the COVID-19 pandemic emerged in the United States and globally in early 2020, HCQ began to garner attention as a potential treatment and as prophylaxis against COVID-19. Preliminary data indicated that HCQ as well as chloroquine (CQ) possessed in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early clinical data from China and France reported that HCQ and CQ were associated with viral load reduction and clinical improvement in patients with COVID-19 compared to control groups; however, an overwhelming number of randomized controlled trials, meta-analyses, and systematic reviews have since concluded that HCQ used alone, or in combination with azithromycin (AZ), provides no mortality or time-to-recovery benefit in hospitalized patients with COVID-19. Additionally, these same trials reported adverse events including cardiac, neuropsychiatric, hematologic, and hepatobiliary manifestations in patients with COVID-19 whom had been treated with HCQ. This review article summarizes the available data pertaining to the adverse events associated with HCQ use, alone or in combination with azithromycin, in patients with COVID-19 in order to fully assess the risk versus benefit of treating COVID-19 patients with these agents. The results of this review lead us to conclude that the risks of adverse events associated with HCQ use (with or without AZ) outweigh the potential clinical benefits and thus recommend against its use in the treatment or prevention of COVID-19.

Protocol for the WARM Hearts study: examining cardiovascular disease risk in middle-aged and older women - a prospective, observational cohort study.

INTRODUCTION: Cardiovascular disease (CVD) is a leading cause of death in women. Novel approaches to detect early signs of elevated CVD risk in women are needed. Enhancement of traditional CVD risk assessment approaches through the addition of procedures to assess physical function or frailty as well as novel biomarkers of cardiovascular, gut and muscle health could improve early identification. The Women's Advanced Risk-assessment in Manitoba (WARM) Hearts study will examine the use of novel non-invasive assessments and biomarkers to identify women who are at elevated risk for adverse cardiovascular events. METHODS AND ANALYSIS: One thousand women 55 years of age or older will be recruited and screened by the WARM Hearts observational, cohort study. The two screening appointments will include assessments of medical history, gender variables, body composition, cognition, frailty status, functional fitness, physical activity levels, nutritional status, quality of life questionnaires, sleep behaviour, resting blood pressure (BP), BP response to moderate-intensity exercise, a non-invasive measure of arterial stiffness and heart rate variability. Blood sample analysis will be used to assess lipid and novel biomarker profiles and stool samples will support the characterisation of gut microbiota. The incidence of the adverse cardiovascular outcomes will be assessed 5 years after screening to compare WARM Hearts approaches to the Framingham Risk Score, the current clinical standard of assessing CVD risk in Canada. ETHICS AND DISSEMINATION: The University of Manitoba Health Research Ethics Board (7 October 2019) and the St Boniface Hospital Research Review Committee (7 October 2019) approved the trial (Ethics Number HS22576 (H2019:063)). Recruitment started 10 October 2020. Data gathered from the WARM Hearts study will be published in peer-reviewed journals and presented at national and international conferences. Knowledge translation strategies will be created to share our findings with stakeholders who are positioned to implement evidence-informed CVD risk assessment programming. TRIAL REGISTRATION NUMBER: NCT03938155.

Self-compassion and responses to health information in middle-aged and older women: An observational cohort study.

The aim of this study was to determine whether self-compassion-orientation to care for oneself during challenges-helps people at risk of cardiovascular disease deal with emotional reactions and assist with self-regulating health behaviors. This observational study recruited women (N = 102) who attended three research visits over 3 weeks to gather information on emotions, intentions, and engagement in health behaviors after women received news they were at risk of cardiovascular disease. Self-compassion negatively associated with emotional responses and associated with intentions and engagement in health behaviors after receiving news of their cardiovascular disease risk. Self-compassion was associated with adaptive lifestyle behaviors.

Frailty status and cardiovascular disease risk profile in middle-aged and older females.

OBJECTIVE: Frailty and pre-frailty are known to increase the risk of developing cardiovascular disease (CVD). However, the risk profiles of females are not well characterized. The aim of this study is to characterize the CVD risk profiles of robust, pre-frail and frail females. METHODS: Cross-sectional analysis of 985 females ≥55 years with no self-reported history of CVD were recruited. Frailty was assessed using the Fried Criteria with the cut-points standardized to the cohort. Framingham risk scores (FRS), the 4-test Rasmussen Disease Score (RDS), and the CANHEART health index were used to characterize composite CVD risk. Individual measures of CVD risk included blood lipids, artery elasticity assessments, exercise blood pressure response, 6-min walk test (6MWT), sedentary time and PHQ-9 score. RESULTS: The cohort comprised of 458 (46.4%) robust, 464 (47.1%) pre-frail and 63 (6.4%) frail females with a mean age of 66 ± 6 (SD) years. Pre-frail females were at increased odds of taking diabetes medications (OR 3.04; 95% CI 1.27-7.27), hypertension medications (OR 2.02; 95% CI 1.44-2.82), having an exaggerated blood pressure response to exercise (OR 1.878; 95% CI 1.39-2.50), mild depression symptoms (OR 2.38; 95% CI 1.68-338), and lower fitness as assessed by 6MWT (OR 5.74; 95% CI 3.18-10.37), even after controlling for age and relevant medications. Pre-frail females were also at increased odds for having CVD risk scores indicating higher risk with the FRS (OR 1.52; 95% CI 1.12-2.05), the RDS (OR 1.60; 95% CI 1.21-2.10) and the CANHEART risk score (OR 3.07; 95% CI 2.04-4.62). These odds were higher when frail females were compared to their robust peers. CONCLUSION: Frailty and pre-frailty were associated with higher odds of presenting with CVD risk factors as compared to robust females, even after controlling for age.

Immediate post-exercise blood pressure and arterial compliance in middle-aged and older normotensive females: A cross-sectional study.

This study examined whether immediate post-exercise systolic blood pressure (SBP) is associated with arterial compliance in middle-aged and older normotensive females. A total of 548 normotensive, non-frail females aged 55 years and older with no previous history of cardiovascular disease (CVD) participated in this cross-sectional study. Large and small arterial compliance were assessed by pulse wave analysis. Reduced arterial compliance was defined based on age and sex cutoffs. SBP was measured at rest and immediately following a 3-min moderate step-test. CVD risk factors were also assessed (e.g. resting systolic and diastolic BP, fasting glucose, triglycerides, cholesterol, body mass index). A total of 15.1% and 44.0% of the participants showed reduced large and small artery compliance, respectively. Immediate post-exercise SBP was associated with reduced large (OR 1.02 per 1 mmHg increase in post-exercise SBP, 95%CI 1.01-1.04; p = 0.010) and small (OR 1.02 per 1 mmHg increase in post-exercise SBP, 95%CI 1.00-1.03; p = 0.008) arterial compliance. Participants with highest immediate post-exercise SBP (quartile 4; i.e. ≥ 165 mmHg) showed increased odds ratios for reduced large (2.67, 95%CI 1.03-6.94; p = 0.043) and small (2.27, 95%CI 1.22-4.21; p = 0.010) arterial compliance compared to those with the lowest immediate post-exercise SBP (quartile 1; i.e. ≤ 140 mmHg), independent of other established CVD risk factors. Immediate post-exercise SBP following a brief moderate step-test seems to be able to discriminate reduced arterial compliance in middle-aged and older normotensive females.

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.

Myokines as biomarkers of frailty and cardiovascular disease risk in females.

Frailty is a risk factor for cardiovascular disease (CVD). Biomarkers have the potential to detect the early stages of frailty, such as pre-frailty. Myokines may act as biomarkers of frailty-related disease progression, as a decline in muscle health is a hallmark of the frailty phenotype. This study is a secondary analysis of 104 females 55 years of age or older with no previous history of CVD. Differences in systemic myokine concentrations based on frailty status and CVD risk profile were examined using a case-control design. Propensity matching identified two sets of 26 pairs with pre-frailty as the exposure variable in low or elevated CVD risk groups for a total 104 female participants. Frailty was assessed using the Fried Criteria (FC) and CVD risk was assessed using the Framingham Risk Score (FRS). Factorial ANOVA compared the main effects of frailty, CVD risk, and their interaction on the concentrations of 15 myokines. Differences were found when comparing elevated CVD risk status with low for the concentrations of EPO (384.76 ± 1046.07 vs. 206.63 ± 284.61 pg/mL, p = .001), FABP3 (2772.61 ± 3297.86 vs. 1693.31 ± 1019.34 pg/mL, p = .017), FGF21 (193.17 ± 521.09 vs. 70.18 ± 139.51 pg/mL, p = .010), IL-6 (1.73 ± 4.97 vs. 0.52 ± 0.89 pg/mL, p = .023), and IL-15 (2.62 ± 10.56 vs. 0.92 ± 1.25 pg/mL, p = .022). Pre-frail females had lower concentrations of fractalkine compared to robust (27.04 ± 20.60 vs. 103.62 ± 315.45 pg/mL, p = .004). Interaction effects between frailty status and CVD risk for FGF21 and OSM were identified. In elevated CVD risk, pre-frail females, concentrations of FGF21 and OSM were lower than that of elevated CVD risk, robust females (69.10 ± 62.86 vs. 317.24 ± 719.69, p = .011; 1.73 ± 2.32 vs. 24.43 ± 69.21, p = .018, respectively). These data identified specific biomarkers of CVD risk and biomarkers of frailty that are exacerbated with CVD risk.

Acute antihypertensive effect of self-selected exercise intensity in older women with hypertension: a crossover trial.

PURPOSE: Acute reduction in blood pressure (BP) following an exercise session is evidenced in controlled settings with formal supervision in hypertensive older populations. This study investigated the effect of a self-selected exercise (SSE)-intensity session on ambulatory BP in hypertensive older women in a "real-world" setting. METHODS: Twenty inactive older women with hypertension (64.9±4.5 years) were included in this randomized, controlled, crossover trial. After baseline assessments, participants performed 30 minutes of an SSE-intensity session on an outdoor track and a control session, separated by 7-10 days. Heart rate (HR), rating of perceived exertion (RPE), and affective response were assessed. Ambulatory BP was monitored for 20 hours following both sessions. Paired t-tests and generalized estimation were used for data analysis. RESULTS: Participants exercised at 5.1±1.1 km/h, spent ~90% of the exercise time at moderate-vigorous intensity (≥40% of heart rate reserve). SSE-intensity session was reported as light (RPE 11.0±1.5) and pleasant (affect 3.4±1.2). SSE-intensity session elicited reductions in systolic BP in the first 6 hours postexercise (6.0 mmHg, CI 2.7-9.3 mmHg; P<0.001). Average systolic BP in the 20-hour (-3.4 mmHg, CI -5.9 to -0.9 mmHg; P=0.010) and awake (-4.0 mmHg, CI -6.4 to -1.6 mmHg; P=0.003) periods were lower following SSE-intensity session compared to control session. No differences were observed in average systolic BP during asleep period and diastolic BP during the 20-hour awake and asleep periods between the SSE-intensity session and control session (P>0.05). CONCLUSION: An SSE-intensity session elicited a reduction in ambulatory systolic BP in inactive older women with hypertension during awake and 20-hour periods. Also, the SSE-intensity session was reported as light and pleasant.

Prehabilitation: The Right Medicine for Older Frail Adults Anticipating Transcatheter Aortic Valve Replacement, Coronary Artery Bypass Graft, and Other Cardiovascular Care.

The wait before elective cardiac intervention or surgery presents an opportunity to prevent further physiologic decline preoperatively in older patients. Implementation of prehabilitation programs decreases length of hospital stay postoperatively, decreases time spent in the intensive care unit, decreases postoperative complications, and improves self-reported quality of life postsurgery. Prehabilitation programs should adopt multimodal approaches including nutrition, exercise, and worry reduction to improve patient resilience in the preoperative period. High-quality research in larger cohorts is needed, and interventions focusing on underrepresented frailer populations and women. Creative ways to improve accessibility, adherence, and benefits received from prehabilitation should be explored.

Effect of Breaks in Prolonged Sitting or Low-Volume High-Intensity Interval Exercise on Markers of Metabolic Syndrome in Adults With Excess Body Fat: A Crossover Trial.

BACKGROUND: This study analyzed the effect of walking breaks or low-volume high-intensity interval exercise (LV-HIIE) on markers of metabolic syndrome relative to a day of prolonged sitting. METHODS: Twenty-five adults with excess body fat participated in this crossover trial: (1) 10-hour sitting day (SIT), (2) LV-HIIE followed by a sitting day (EX+SIT), and (3) sitting day with 5-minute walking breaks for every 20 minutes (SIT+WB). Glucose and blood pressure (BP) were measured before and 1 hour after 4 meals and 2 hours after lunch. Triglycerides were measured at baseline, 2, and 3.5 hours after lunch. Generalized mixed models were used to identify differences in the area under the curve (AUC) of BP and incremental AUC (iAUC) of glucose and triglycerides among the sessions. RESULTS: iAUC-glucose was lower in SIT+WB than SIT (ß = -35.3 mg/dL·10 h; 95% confidence interval, -52.5 to -8.2). AUC-diastolic BP was lower in SIT+WB than SIT (ß = -14.1 mm Hg·10 h; 95% confidence interval, -26.5 to -1.6) and EX+SIT (ß = -14.5 mm Hg·10 h; 95% confidence interval, -26.9 to -2.1). There were no differences in triglycerides and systolic BP levels among the sessions. CONCLUSION: Adults with excess body fat present lower glucose and diastolic BP during a day with breaks in sitting time compared with a prolonged sitting day with or without an LV-HIIE session.

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.

Effects of High-Intensity Interval Training Versus Moderate-Intensity Continuous Training On Blood Pressure in Adults with Pre- to Established Hypertension: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Aerobic exercise reduces blood pressure (BP), but it is unknown whether a high-intensity training approach can elicit a greater BP reduction in populations with elevated BP. This systematic review compared the efficacy of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) for reducing BP in adults with pre- to established hypertension. METHODS: Five electronic databases (MEDLINE, EMBASE, CENTRAL, PEDro, and SPORTDiscus) were searched for randomized trials comparing the chronic effects of HIIT versus MICT on BP in individuals with resting systolic BP ≥ 130 mmHg and/or diastolic BP ≥ 85 mmHg and/or under antihypertensive medication. Random-effects modelling was used to compare changes from pre- to post-intervention in resting and ambulatory BP between HIIT and MICT. Changes from pre- to post-intervention in maximal oxygen uptake ([Formula: see text]O2max) between HIIT and MICT were also meta-analyzed. Data were reported as weighted mean difference (MD) and 95% confidence interval (CI). RESULTS: Ambulatory BP was excluded from the meta-analysis due to the limited number of studies (two studies). Comparing changes from pre- to post-intervention, no differences in resting systolic BP (MD - 0.22 mmHg [CI 95%, - 5.36 to 4.92], p = 0.93, I2 = 53%) and diastolic BP (MD - 0.38 mmHg [CI 95%, - 3.31 to 2.54], p = 0.74, I2 = 0%) were found between HIIT and MICT (seven studies; 164 participants). HIIT improved [Formula: see text]O2max to a greater magnitude than MICT (MD 2.13 ml/kg/min [CI 95%, 1.00 to 3.27], p < 0.01, I2 = 41%) with similar completion rates of the intervention and attendance at the exercise training sessions (nine studies; 245 participants). Limited data were available to compare the incidence of adverse events between HIIT and MICT. CONCLUSION: HIIT and MICT provided comparable reductions in resting BP in adults with pre- to established hypertension. HIIT was associated with greater improvements in [Formula: see text]O2max when compared to MICT. Future randomized trials should investigate the efficacy of HIIT versus MICT for reducing ambulatory BP in adults with pre- to established hypertension. REGISTRATION: PROSPERO registration (2016: CRD42016041885).

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.