Implications of Five Different Risk Models In Primary Prevention Guidelines.

BACKGROUND: A lack of consensus exists across guidelines as to which risk model should be used for the primary prevention of cardiovascular disease (CVD). Our objective was to determine potential improvements in the number needed to treat (NNT) and number of events prevented (NEP) using different risk models in patients eligible for risk stratification. METHODS: A retrospective observational cohort was assembled from primary care patients in Ontario, Canada between January 1st, 2010, to December 31st, 2014 and followed for up to 5 years. Risk estimation was undertaken in patients 40-75 years of age, without CVD, diabetes, or chronic kidney disease using the Framingham Risk Score (FRS), Pooled Cohort Equations (PCEs), a recalibrated FRS (R-FRS), Systematic Coronary Risk Evaluation 2 (SCORE2), and the low-risk region recalibrated SCORE2 (LR-SCORE2). RESULTS: The cohort consisted of 47,399 patients (59% women, mean age 54). The NNT with statins was lowest for SCORE2 at 40, followed by LR-SCORE2 at 41, R-FRS at 43, PCEs at 55, and FRS at 65. Models that selected for individuals with a lower NNT recommended statins to fewer, but higher risk patients. For instance, SCORE2 recommended statins to 7.9% of patients (5-year CVD incidence 5.92%). The FRS, however, recommended statins to 34.6% of patients (5-year CVD incidence 4.01%). Accordingly, the NEP was highest for the FRS at 406 and lowest for SCORE2 at 156. CONCLUSIONS: Newer models such as SCORE2 may improve statin allocation to higher risk groups with a lower NNT but prevent fewer events at the population level.

Validation of the European SCORE2 models in a Canadian primary care cohort.

AIMS: Systematic Coronary Risk Evaluation Model 2 (SCORE2) was recently developed to predict atherosclerotic cardiovascular disease (ASCVD) in Europe. Whether these models could be used outside of Europe is not known. The objective of this study was to test the validity of SCORE2 in a large Canadian cohort. METHODS AND RESULTS: A primary care cohort of persons with routinely collected electronic medical record data from 1 January 2010 to 31 December 2014, in Ontario, Canada, was used for validation. The SCORE2 models for younger persons (YP) were applied to 57 409 individuals aged 40-69 while the models for older persons (OPs) were applied to 9885 individuals 70-89 years of age. Five-year ASCVD predictions from both the uncalibrated and low-risk region recalibrated SCORE2 models were evaluated. The C-statistic for SCORE2-YP was 0.74 in women and 0.69 in men. The uncalibrated SCORE2-YP overestimated risk by 17% in women and underestimated by 2% in men. In contrast, the low-risk region recalibrated model demonstrated worse calibration, overestimating risk by 100% in women and 36% in men. The C-statistic for SCORE2-OP was 0.64 and 0.62 in older women and men, respectively. The uncalibrated SCORE2-OP overestimated risk by more than 100% in both sexes. The low-risk region recalibrated model demonstrated improved calibration but still overestimated risk by 60% in women and 13% in men. CONCLUSION: The performance of SCORE2 to predict ASCVD risk in Canada varied by age group and depended on whether regional calibration was applied. This underscores the necessity for validation assessment of SCORE2 prior to implementation in new jurisdictions.

In this study, new tools [Systematic Coronary Risk Evaluation Model 2 (SCORE2)] that were developed across Europe to predict heart attack and stroke risk in healthy individuals were tested independently for the first time in a Canadian setting. Key findings are as follows:The accuracy of predictions from SCORE2 in Canadians depends on the age group considered and whether uncalibrated or recalibrated equations are being used.Independent assessment of tools such as SCORE2 remains useful prior to widespread implementation in new jurisdictions.

Development and Validation of the CANHEART Population-Based Laboratory Prediction Models for Atherosclerotic Cardiovascular Disease.

BACKGROUND: Prediction of atherosclerotic cardiovascular disease (ASCVD) in primary prevention assessments exclusively with laboratory results may facilitate automated risk reporting and improve uptake of preventive therapies. OBJECTIVE: To develop and validate sex-specific prediction models for ASCVD using age and routine laboratory tests and compare their performance with that of the pooled cohort equations (PCEs). DESIGN: Derivation and validation of the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) Lab Models. SETTING: Population-based cohort study in Ontario, Canada. PARTICIPANTS: A derivation and internal validation cohort of adults aged 40 to 75 years without cardiovascular disease from April 2009 to December 2015; an external validation cohort of primary care patients from January 2010 to December 2014. MEASUREMENTS: Age and laboratory predictors measured in the outpatient setting included serum total cholesterol, high-density lipoprotein cholesterol, triglycerides, hemoglobin, mean corpuscular volume, platelets, leukocytes, estimated glomerular filtration rate, and glucose. The ASCVD outcomes were defined as myocardial infarction, stroke, and death from ischemic heart or cerebrovascular disease within 5 years. RESULTS: Sex-specific models were developed and internally validated in 2 160 497 women and 1 833 147 men. They were well calibrated, with relative differences less than 1% between mean predicted and observed risk for both sexes. The c-statistic was 0.77 in women and 0.71 in men. External validation in 31 697 primary care patients showed a relative difference less than 14% and an absolute difference less than 0.3 percentage points in mean predicted and observed risks for both sexes. The c-statistics for the laboratory models were 0.72 for both sexes and were not statistically significantly different from those for the PCEs in women (change in c-statistic, -0.01 [95% CI, -0.03 to 0.01]) or men (change in c-statistic, -0.01 [CI, -0.04 to 0.02]). LIMITATION: Medication use was not available at the population level. CONCLUSION: The CANHEART Lab Models predict ASCVD with similar accuracy to more complex models, such as the PCEs. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Association of Neighborhood-Level Marginalization With Health Care Use and Clinical Outcomes Following Hospital Discharge in Patients Who Underwent Coronary Catheterization for Acute Myocardial Infarction in a Single-Payer Health Care System.

BACKGROUND: Canadian data suggest that patients of lower socioeconomic status with acute myocardial infarction receive less beneficial therapy and have worse clinical outcomes, raising questions regarding care disparities even in universal health care systems. We assessed the contemporary association of marginalization with clinical outcomes and health services use. METHODS: Using clinical and administrative databases in Ontario, Canada, we conducted a population-based study of patients aged ≥65 years hospitalized for their first acute myocardial infarction between April 1, 2010 and March 1, 2019. Patients receiving cardiac catheterization and surviving 7 days postdischarge were included. Our primary exposure was neighborhood-level marginalization, a multidimensional socioeconomic status metric. Neighborhoods were categorized by quintile from Q1 (least marginalized) to Q5 (most marginalized). Our primary outcome was all-cause mortality. A proportional hazards regression model with a robust variance estimator was used to quantify the association of marginalization with outcomes, adjusting for risk factors, comorbidities, disease severity, and regional cardiologist supply. RESULTS: Among 53 841 patients (median age, 75 years; 39.1% female) from 20 640 neighborhoods, crude 1- and 3-year mortality rates were 7.7% and 17.2%, respectively. Patients in Q5 had no significant difference in 1-year mortality (hazard ratio [HR], 1.08 [95% CI, 0.95-1.22]), but greater mortality over 3 years (HR, 1.13 [95% CI, 1.03-1.22]) compared with Q1. Over 1 year, we observed differences between Q1 and Q5 in visits to primary care physicians (Q1, 96.7%; Q5, 93.7%) and cardiologists (Q1, 82.6%; Q5, 72.6%), as well as diagnostic testing. There were no differences in secondary prevention medications dispensed or medication adherence at 1 year. CONCLUSIONS: In older patients with acute myocardial infarction who survived to hospital discharge, those residing in the most marginalized neighborhoods had a greater long-term risk of mortality, less specialist care, and fewer diagnostic tests. Yet, there were no differences across socioeconomic status in prescription medication use and adherence.

Sex-Based Differences in Severe Outcomes, Including Cardiovascular Hospitalization, in Adults With COVID-19 in Ontario, Canada.

Background: While men have experienced higher risks of SARS-CoV-2 infection compared to women, an analysis of sex differences by age in severe outcomes during the acute phase of infection is lacking. Objectives: The purpose of this study was to assess heterogeneity in severe outcome risks by age and sex by conducting a retrospective cohort study of community-dwelling adults in Ontario who tested positive for SARS-CoV-2 infection during the first 3 waves. Methods: Adjusted odds ratios were estimated using multilevel multivariable logistic regression models including an interaction term for age and sex. The primary outcome was a composite of severe outcomes (hospitalization for a cardiovascular (CV) event, intensive care unit admission, mechanical ventilation, or death) within 30 days. Results: Among 30,736, 199,132, and 186,131 adults who tested positive during the first 3 waves, 1,908 (6.2%), 5,437 (2.7%), and 5,653 (3.0%) experienced a severe outcome within 30 days. For all outcomes, the sex-specific risk depended on age (all P for interaction <0.05). Men with SARS-CoV-2 infection experienced a higher risk of outcomes than infected women of the same age, except for the risk of all-cause hospitalization being higher for young women than men (ages 18-45 years) during waves 2 and 3. The sex disparity in CV hospitalization across all ages either persisted or increased with each subsequent wave. Conclusions: To mitigate risks in subsequent waves, it is helpful to further understand the factors that contribute to the generally higher risks faced by men across all ages, and the persistent or increasing sex disparity in the risk of CV hospitalization.

Comorbidity-stratified estimates of 30-day mortality risk by age for unvaccinated men and women with COVID-19: a population-based cohort study.

BACKGROUND: The mortality risk following COVID-19 diagnosis in men and women with common comorbidities at different ages has been difficult to communicate to the general public. The purpose of this study was to determine the age at which unvaccinated men and women with common comorbidities have a mortality risk which exceeds that of 75- and 65-year-old individuals in the general population (Phases 1b/1c thresholds of the Centre for Disease Control Vaccine Rollout Recommendations) following COVID-19 infection during the first wave. METHODS: We conducted a population-based retrospective cohort study using linked administrative datasets in Ontario, Canada. We identified all community-dwelling adults diagnosed with COVID-19 between January 1 and October 31st, 2020. Exposures of interest were age (modelled using restricted cubic splines) and the following conditions: major cardiovascular disease (recent myocardial infarction or lifetime history of heart failure); 2) diabetes; 3) hypertension; 4) recent cancer; 5) chronic obstructive pulmonary disease; 6) Stages 4/5 chronic kidney disease (CKD); 7) frailty. Logistic regression in the full cohort was used to estimate the risk of 30-day mortality for 75- and 65-year-old individuals. Analyses were repeated after stratifying by sex and medical condition to determine the age at which 30-day morality risk in strata exceed that of the general population at ages 65 and 75 years. RESULTS: We studied 52,429 individuals (median age 42 years; 52.5% women) of whom 417 (0.8%) died within 30 days. The 30-day mortality risk increased with age, male sex, and comorbidities. The 65- and 75-year-old mortality risks in the general population were exceeded at the youngest age by people with CKD, cancer, and frailty. Conversely, women aged < 65 years who had diabetes or hypertension did not have higher mortality than 65-year-olds in the general population. Most people with medical conditions (except for Stage 4-5 CKD) aged < 45 years had lower predicted mortality than the general population at age 65 years. CONCLUSION: The mortality risk in COVID-19 increases with age and comorbidity but the prognostic implications varied by sex and condition. These observations can support communication efforts and inform vaccine rollout in jurisdictions with limited vaccine supplies.

Post-acute health care burden after SARS-CoV-2 infection: a retrospective cohort study.

BACKGROUND: The post-acute burden of health care use after SARS-CoV-2 infection is unknown. We sought to quantify the post-acute burden of health care use after SARS-CoV-2 infection among community-dwelling adults in Ontario by comparing those with positive and negative polymerase chain reaction (PCR) test results for SARS-CoV-2 infection. METHODS: We conducted a retrospective cohort study involving community-dwelling adults in Ontario who had a PCR test between Jan. 1, 2020, and Mar. 31, 2021. Follow-up began 56 days after PCR testing. We matched people 1:1 on a comprehensive propensity score. We compared per-person-year rates for health care encounters at the mean and 99th percentiles, and compared counts using negative binomial models, stratified by sex. RESULTS: Among 531 702 matched people, mean age was 44 (standard deviation [SD] 17) years and 51% were female. Females who tested positive for SARS-CoV-2 had a mean of 1.98 (95% CI 1.63 to 2.29) more health care encounters overall per-person-year than those who had a negative test result, with 0.31 (95% CI 0.05 to 0.56) more home care encounters to 0.81 (95% CI 0.69 to 0.93) more long-term care days. At the 99th percentile per-person-year, females who tested positive had 6.48 more days of hospital admission and 28.37 more home care encounters. Males who tested positive for SARS-CoV-2 had 0.66 (95% CI 0.34 to 0.99) more overall health care encounters per-person-year than those who tested negative, with 0.14 (95% CI 0.06 to 0.21) more outpatient encounters and 0.48 (95% CI 0.36 to 0.60) long-term care days, and 0.43 (95% CI -0.67 to -0.21) fewer home care encounters. At the 99th percentile, they had 8.69 more days in hospital per-person-year, with fewer home care (-27.31) and outpatient (-0.87) encounters. INTERPRETATION: We found significantly higher rates of health care use after a positive SARS-CoV-2 PCR test in an analysis that matched test-positive with test-negative people. Stakeholders can use these findings to prepare for health care demand associated with post-COVID-19 condition (long COVID).

Patient clustering in primary care settings: Outcomes and quality of care.

OBJECTIVE: To determine whether neighbours who share the same family physicians have better cardiovascular and health care outcomes. DESIGN: Retrospective cohort study using administrative health databases. SETTING: Ontario. PARTICIPANTS: The study population included 2,690,482 adult patients cared for by 1710 family physicians. INTERVENTIONS: Adult residents of Ontario were linked to their family physicians and the geographic distance between patients in the same panel or list was calculated. Using distance between patients within a panel to stratify physicians into quintiles of panel proximity, physicians and patients from close-proximity practices were compared with those from more-distant-proximity practices. Age- and sex-standardized incidence rates and hazard ratios from cause-specific hazards regression models were determined. MAIN OUTCOME MEASURES: The occurrence of a major cardiovascular event during a 5-year follow-up period (2008 to 2012). RESULTS: Patients of panels in the closest-proximity quintile lived an average of 3.9 km from the 10 closest patients in their panel compared with 12.4 km for the 10 closest patients of panels in the distant-proximity quintile. After adjusting for various patient and physician characteristics, patients in the most-distant-proximity practices had a 24% higher rate of cardiovascular events (adjusted hazard ratio=1.24 [95% CI 1.20 to 1.28], P<.001) than patients in the closest-proximity practices. Age- and sex-standardized all-cause mortality and total per patient health care costs were also lowest in the closest-proximity quintile. In sensitivity analyses restricted to large urban communities and to White long-term residents, results were similar. CONCLUSION: The better cardiovascular outcomes observed in close-proximity panels may be related to a previously unrecognized mechanism of social connectedness that extends the effectiveness of primary care practitioners.

Population-Based Recalibration of the Framingham Risk Score and Pooled Cohort Equations.

BACKGROUND: The Framingham Risk Score (FRS) and Pooled Cohort Equations (PCEs) overestimate risk in many contemporary cohorts. OBJECTIVES: This study sought to determine if recalibration of these scores using contemporary population-level data improves risk stratification for statin therapy. METHODS: Five-year FRS and PCEs were recalibrated using a cohort of Ontario residents alive January 1, 2011, who were 30 to 79 years of age without cardiovascular disease. Scores were externally validated in a primary care cohort of routinely collected electronic medical record data from January 1, 2010, to December 31, 2014. The relative difference in mean predicted and observed risk, number of statins avoided, and number needed to treat with statins to reduce a cardiovascular event at 5 years were reported. RESULTS: The FRS was recalibrated in 6,938,971 Ontario residents (51.6% women, mean age 48 years) and validated in 71,450 individuals (56.1% women, mean age 52 years). Recalibration reduced overestimation from 109% to 49% for women and 131% to 32% for men. The recalibrated FRS was estimated to reduce statin prescriptions in up to 26 per 1,000 low-risk women and 80 per 1,000 low-risk men, as well as reduce the number needed to treat from 61 to 47 in women and from 53 to 41 in men. In contrast, after recalibration of the PCEs, risk remained overestimated by 217% in women and 128% in men. CONCLUSIONS: Recalibration is a feasible solution to improve risk prediction but is dependent on the model being used. Recalibration of the FRS but not the PCEs reduced overestimation and may improve utilization of statins.

Clinical risk, sociodemographic factors, and SARS-CoV-2 infection over time in Ontario, Canada.

We aimed to determine whether early public health interventions in 2020 mitigated the association of sociodemographic and clinical risk factors with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a population-based cohort study of all adults in Ontario, Canada who underwent testing for SARS-CoV-2 through December 31, 2020. The outcome was laboratory-confirmed SARS-CoV-2 infection, determined by reverse transcription polymerase chain reaction testing. Adjusted odds ratios (ORs) were determined for sociodemographic and clinical risk factors before and after the first-wave peak of the pandemic to assess for changes in effect sizes. Among 3,167,753 community-dwelling individuals, 142,814 (4.5%) tested positive. The association between age and SARS-CoV-2 infection risk varied over time (P-interaction < 0.0001). Prior to the first-wave peak, SARS-CoV-2 infection increased with age whereas this association reversed thereafter. Risk factors that persisted included male sex, residing in lower income neighborhoods, residing in more racially/ethnically diverse communities, immigration to Canada, hypertension, and diabetes. While there was a reduction in infection rates after mid-April 2020, there was less impact in regions with higher racial/ethnic diversity. Immediately following the initial peak, individuals living in the most racially/ethnically diverse communities with 2, 3, or ≥ 4 risk factors had ORs of 1.89, 3.07, and 4.73-fold higher for SARS-CoV-2 infection compared to lower risk individuals in their community (all P < 0.0001). In the latter half of 2020, this disparity persisted with corresponding ORs of 1.66, 2.48, and 3.70-fold higher, respectively. In the least racially/ethnically diverse communities, there was little/no gradient in infection rates across risk strata. Further efforts are necessary to reduce the risk of SARS-CoV-2 infection among the highest risk individuals residing in the most racially/ethnically diverse communities.

Development and validation of a model to categorize cardiovascular cause of death using health administrative data.

Study objective: Develop and evaluate a model that uses health administrative data to categorize cardiovascular (CV) cause of death (COD). Design: Population-based cohort. Setting: Ontario, Canada. Participants: Decedents ≥ 40 years with known COD between 2008 and 2015 in the CANHEART cohort, split into derivation (2008 to 2012; n = 363,778) and validation (2013 to 2015; n = 239,672) cohorts. Main outcome measures: Model performance. COD was categorized as CV or non-CV with ICD-10 codes as the gold standard. We developed a logistic regression model that uses routinely collected healthcare administrative to categorize CV versus non-CV COD. We assessed model discrimination and calibration in the validation cohort. Results: The strongest predictors for CV COD were history of stroke, history of myocardial infarction, history of heart failure, and CV hospitalization one month before death. In the validation cohort, the c-statistic was 0.80, the sensitivity 0.75 (95 % CI 0.74 to 0.75) and the specificity 0.71 (95 % CI 0.70 to 0.71). In the primary prevention validation sub-cohort, the c-statistic was 0.81, the sensitivity 0.71 (95 % CI 0.70 to 0.71) and the specificity 0.75 (95 % CI 0.75 to 0.75) while in the secondary prevention sub-cohort the c-statistic was 0.74, the sensitivity 0.81 (95 % CI 0.81 to 0.82) and the specificity 0.54 (95 % CI 0.53 to 0.54). Conclusion: Modelling approaches using health administrative data show potential in categorizing CV COD, though further work is necessary before this approach is employed in clinical studies.

A feasibility study for CODE-MI: High-sensitivity cardiac troponin-Optimizing the diagnosis of acute myocardial infarction/injury in women.

BACKGROUND: CODE-MI is a pan-Canadian, multicentre, stepped-wedge, cluster randomized trial that evaluates the impact of using the female-specific 99th percentile threshold for high-sensitivity cardiac troponin (hs-cTn) on the diagnosis, treatment and outcomes of women presenting to the emergency department (ED) with symptoms suggestive for myocardial ischemia. A feasibility study was conducted to estimate the number of eligible patients, the rate of the study's primary outcome under control conditions, and the statistical power to detect a clinically important difference in the primary outcome. METHODS: Using linked administrative data from 11 hospitals in Ontario, Canada, from October 2014 to September 2017, the following estimates were obtained: number of women presenting to the ED with symptoms suggestive of myocardial ischemia and a 24-hour peak hs-cTn value within the female-specific and overall thresholds (ie, primary cohort); the rate of the 1-year composite outcome of all-cause mortality, re-admission for nonfatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization. Study power was evaluated via simulations. RESULTS: Overall, 2,073,849 ED visits were assessed. Among women, chest pain (with or without cardiac features) and shortness of breath were the most common complaints associated with a diagnosis of acute coronary syndrome. An estimated 7.7% of women with these complaints are eligible for inclusion in the primary cohort. The rate of the 1-year outcome in the primary cohort varied significantly across hospitals with a median rate of 12.2% (95%CI: 7.9%-17.7%). With 30 hospitals, randomized at 5-month intervals in 5 steps, approximately 19,600 women are expected to be included in CODE-MI, resulting in >82% power to detect a 20% decrease in the odds of the primary outcome at a 0.05 significance level. CONCLUSIONS: This feasibility study greatly enhanced the design of CODE-MI, allowed accurate evaluation of the study power, and demonstrated the strength of using linked administrative health data to guide the design of pragmatic clinical trials.

Regional health care services and rates of lower extremity amputation related to diabetes and peripheral artery disease: an ecological study.

BACKGROUND: The care necessary to prevent amputation from diabetes and peripheral artery disease (PAD) remains disjointed in many jurisdictions. To help inform integrated regional care, this study explores the correlation between regional health care services and rates of lower extremity amputation. METHODS: This ecological study included 14 administrative health regions in Ontario, Canada. All diabetes- or PAD-related major (above ankle) amputations (Apr. 1, 2007, to Mar. 31, 2017) were identified among residents 40 years of age and older. For each region, age-and sex-adjusted amputation rates were calculated as well as per capita counts of key health providers (podiatrists and chiropodists, as well as surgeons) and health care utilization among study patients in the year before the first major amputation (physician visits, publicly funded podiatry visits, emergency department visits, hospital admissions, home care nursing, minor amputation, limb revascularization). RESULTS: A total of 11 658 patients with major amputation were identified (of whom 79.2% had diabetes and 96.5% had PAD). There was wide regional variation in amputation rates: 2.53 to 11.77 per 100 000 person-quarters. At a regional level, the proportion of study patients who received revascularization showed the strongest negative correlation with amputation rates. The regional proportion of study patients who saw a vascular surgeon showed the strongest negative correlation with amputation rates, relative to other health provider visits. Other measures of health care utilization among patients correlated poorly with regional amputation rates, as did the regional provider counts. The results were similar when we restricted the analysis to diabetes-related amputations. INTERPRETATION: Amputation rates related to diabetes and PAD vary widely across Ontario. Access to vascular assessment and revascularization must be integrated into regional amputation prevention efforts.

Impact of Appropriate Use Criteria for Transthoracic Echocardiography in Valvular Heart Disease on Clinical Outcomes.

BACKGROUND: The association between appropriate use criteria for transthoracic echocardiography (TTE) and clinical outcomes is unknown for patients with valvular heart disease (VHD). The aim of this study was to identify the association of TTE appropriateness with downstream cardiac tests and clinical outcomes in patients with VHD over 365 days. METHODS: A subset of 2,297 patients with VHD across six Ontario academic hospitals was selected from the Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen Significantly) trial and linked to administrative databases. Each patient's index TTE was classified as "rarely appropriate" (rA) versus "appropriate" (comprising "appropriate" and "may be appropriate" TTE according to the 2011 appropriate use criteria). Overall, 431 of 452 patients with rA TTE were matched 1:1 with patients with appropriate TTE using propensity scores to account for measured confounding. RESULTS: Matched patients with rA TTE were less likely to undergo repeat TTE (relative risk, 0.46; 95% CI, 0.33-0.66) or cardiac catheterization (relative risk, 0.27; 95% CI, 0.16-0.47) at 90 days compared with patients with appropriate TTE. rA TTE was significantly associated with a decreased hazard of aortic valve intervention (hazard ratio, 0.40; 95% CI, 0.14-0.42), all-cause hospitalization (hazard ratio, 0.44; 95% CI, 0.34-0.57), and death (hazard ratio, 0.31; 95% CI, 0.15-0.66) over 365 days of follow-up. CONCLUSIONS: Patients with appropriate TTE for VHD were more likely to undergo subsequent cardiac testing within 90 days and valve intervention within 1 year than those with a rA TTE. The 2011 appropriate use criteria for TTE have important clinical implications for outcomes in patient with VHD.

Clinical Effectiveness of Cardiac Noninvasive Diagnostic Testing in Outpatients Evaluated for Stable Coronary Artery Disease.

Background Despite more than 4 million cardiac noninvasive diagnostic tests (NIT) being performed annually for stable coronary artery disease in the United States, it is unclear whether they are associated with downstream improvements in outcomes when compared with no testing. We sought to determine whether NIT was associated with reduced downstream major adverse cardiovascular events when compared with not testing. Methods and Results We conducted a population-based study of ≈1.5 million patients undergoing chest pain evaluation in Ontario, Canada. Patients were categorized into NIT and no-testing groups. Cause-specific proportional hazards models were used to compare the rate of major adverse cardiovascular events (composite outcome of unstable angina, acute myocardial infarction or cardiovascular mortality and each constituent) between the 2 groups after adjusting for clinically relevant covariates. The rate of the composite outcome was ≈25% lower for patients undergoing noninvasive testing (hazard ratio [HR], 0.77; 95% CI, 0.75-0.79). The benefits of testing were consistent for all 3 constituents of the composite; unstable angina (HR, 0.87; 95% CI, 0.82-0.93 for the NIT versus the no-testing group), myocardial infarction (HR, 0.83; 95% CI, 0.79-0.86 for the NIT versus the no-testing group) and cardiovascular mortality (HR, 0.68; 95% CI, 0.65-0.72 for the NIT versus the no-testing group). Conclusions Our large population-based study reports an ≈25% reduction in major adverse cardiovascular events that was independently associated with NIT in outpatients being evaluated for stable angina. This study demonstrates the prognostic importance of NIT versus no testing on the health of contemporary populations.

Calibration and discrimination of the Framingham Risk Score and the Pooled Cohort Equations.

BACKGROUND: Although accurate risk prediction is essential in guiding treatment decisions in primary prevention of atherosclerotic cardiovascular disease, the accuracy of the Framingham Risk Score (recommended by a Canadian guideline) and the Pooled Cohort Equations (recommended by US guidelines) has not been assessed in a large contemporary Canadian population. Our primary objective was to assess the calibration and discrimination of the Framingham Risk Score and Pooled Cohort Equations in Ontario, Canada. METHODS: We conducted an observational study involving Ontario residents aged 40 to 79 years, without a history of atherosclerotic cardiovascular disease, who underwent cholesterol testing and blood pressure measurement from Jan. 1, 2010, to Dec. 31, 2014. We compared predicted event rates generated by the Framingham Risk Score and the Pooled Cohort Equations with observed event rates at 5 years using linkages from validated administrative databases. RESULTS: Our study cohort included 84 617 individuals (mean age 56.3 yr, 56.9% female). Over a maximum follow-up period of 5 years, we observed 2162 (2.6%) events according to the outcome definition of the Framingham Risk Score, and 1224 (1.4%) events according to the outcome definition of the Pooled Cohort Equations. The predicted event rate of 5.78% by the Framingham Risk Score and 3.51% by the Pooled Cohort Equations at 5 years overestimated observed event rates by 101% and 115%, respectively. The degree of overestimation differed by age and ethnicity. The C statistics for the Framingham Risk Score (0.74) and Pooled Cohort Equations (0.73) were similar. INTERPRETATION: The Framingham Risk Score and Pooled Cohort Equations significantly overpredicted the actual risks of atherosclerotic cardiovascular disease events in a large population from Ontario. Our finding suggests the need for further refinement of cardiovascular disease risk prediction scores to suit the characteristics of a multiethnic Canadian population.

Making Informed CHOICES: The Launch of a "Big Data" Pragmatic Trial to Improve Cholesterol Management and Prevent Heart Disease in Ontario.

Cholesterol-lowering statin medications are a safe and effective therapy to lower cholesterol and reduce the risk of cardiovascular events. Yet physician prescribing patterns and patient adherence remain suboptimal in Canada and the United States, often due to pervasive misconceptions. The Community Heart Outcomes Improvement and Cholesterol Education Study (CHOICES) is a pragmatic, registry-based, cluster randomized controlled trial that aims to improve cholesterol management through appropriate statin use in adults and to ultimately reduce cardiovascular events in high-risk communities across Ontario. The trial uses an innovative, multicomponent intervention and implementation approach that includes audit and feedback reports for family physicians and educational materials and tools for patients.

Association Between Physicians' Appropriate Use of Echocardiography and Subsequent Healthcare Use and Outcomes in Patients With Heart Failure.

Background There is little understanding of whether a physician's tendency to order an inappropriate cardiac service is associated with the use of other cardiac services and clinical outcomes in their patients with heart failure (HF). Methods and Results We conducted a secondary analysis of 35 Ontario-based cardiologists who participated in the control arm of the Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen Significantly) trial. Transthoracic echocardiograms, ordered during the trial, were classified as rarely appropriate (rA), appropriate, or maybe appropriate on the basis of the 2011 appropriate use criteria. Cardiologists were grouped into tertiles of rA transthoracic echocardiogram ordering frequency: low ordering (bottom tertile), n=11; moderate ordering, n=12; or high ordering (top tertile), n=12. The main outcomes were measures of cardiac service use, including cardiology-related physician visits, tests, and medications. Among 1677 patients with heart failure and an outpatient visit to 1 of 35 cardiologists, we found no significant association between rA transthoracic echocardiogram ordering frequency (by tertile) and cardiac testing use, although patients of cardiologists in the high ordering group had fewer physician visits, on average, than patients seen by low ordering cardiologists. In addition, patients of cardiologists in the highest rA ordering tertile had significantly lower odds of receiving potentially effective interventions, such as ß blockers (odds ratio, 0.62; 95% CI, 0.43-0.89), than the low ordering group. Conclusions Although patients of cardiologists who frequently order rA transthoracic echocardiograms do not appear more (or less) likely to have subsequent cardiac tests, these patients have fewer follow-up visits and lower odds of receiving evidence-based medications. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02038101.

Low-Value Transthoracic Echocardiography, Healthcare Utilization, and Clinical Outcomes in Patients With Coronary Artery Disease.

BACKGROUND: The relationship between ordering frequency of rarely appropriate transthoracic echocardiograms on healthcare utilization and patient outcomes in coronary artery disease (CAD) is not known. Our objective was to investigate practice patterns of cardiologists who order a high frequency of low-value transthoracic echocardiograms in patients with CAD and whether practice behavior influences patient outcomes. METHODS AND RESULTS: A retrospective cohort of outpatient CAD patients was accrued by identifying patients with at least 1 visit to 1 of 35 Ontario-based cardiologists in the EchoWISELY randomized clinical trial (Will Inappropriate Scenarios for Echocardiography Lessen Significantly) control group. The main outcomes of interest were patient-level receipt of diagnostic tests, physician visits, medication prescriptions, and clinical outcomes at 1 year. Our cohort consisted of 3966 patients with CAD (mean [SD] age, 67.8 [12.0] years; 72% men), with an outpatient visit to 1 of 35 eligible cardiologists, stratified into 3 ordering tertiles. Patients of cardiologists in the top ordering tertile of rarely appropriate transthoracic echocardiograms had significantly lower odds of receiving the following services at 1 year compared with patients in the low ordering group: cholesterol assessment (odds ratio [OR], 0.77 [95% CI, 0.65-0.91]); hemoglobin A1c assessment (OR, 0.79 [95% CI, 0.66-0.94]); ß-blocker prescription (OR, 0.70 [95% CI, 0.55-0.90]); and aldosterone receptor antagonist prescription (OR, 0.46 [95% CI, 0.22-0.98]). Patients of high ordering cardiologists had greater odds of all-cause mortality at 1 year (OR, 1.54 [95% CI, 1.04-2.28]), although all other outcomes were similar. CONCLUSIONS: Patients with CAD seen by cardiologist who ordered a high rate of rarely appropriate transthoracic echocardiograms were less likely to receive potentially high-value screening tests and evidence-based medications than low ordering cardiologists. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02038101.

Population-based secular trends in lower-extremity amputation for diabetes and peripheral artery disease.

BACKGROUND: The evolving clinical burden of limb loss secondary to diabetes and peripheral artery disease remains poorly characterized. We sought to examine secular trends in the rate of lower-extremity amputations related to diabetes, peripheral artery disease or both. METHODS: We included all individuals aged 40 years and older who underwent lower-extremity amputations related to diabetes or peripheral artery disease in Ontario, Canada (2005-2016). We identified patients and amputations through deterministic linkage of administrative health databases. Quarterly rates (per 100 000 individuals aged ≥ 40 yr) of any (major or minor) amputation and of major amputations alone were calculated. We used time-series analyses with exponential smoothing models to characterize secular trends and forecast 2 years forward in time. RESULTS: A total of 20 062 patients underwent any lower-extremity amputation, of which 12 786 (63.7%) underwent a major (above ankle) amputation. Diabetes was present in 81.8%, peripheral artery disease in 93.8%, and both diabetes and peripheral artery disease in 75.6%. The rate of any amputation initially declined from 9.88 to 8.62 per 100 000 between Q2 of 2005 and Q4 of 2010, but increased again by Q1 of 2016 to 10.0 per 100 000 (p = 0.003). We observed a significant increase in the rate of any amputation among patients with diabetes, peripheral artery disease, and both diabetes and peripheral artery disease. Major amputations did not significantly change among patients with diabetes, peripheral artery disease or both. INTERPRETATION: Lower-extremity amputations related to diabetes, peripheral artery disease or both have increased over the last decade. These data support renewed efforts to prevent and decrease the burden of limb loss.