Health-Related Quality of Life in Premature Acute Coronary Syndrome: Does Patient Sex or Gender Really Matter?

Background-Limited data exist as to the relative contribution of sex and gender on health-related quality of life (HRQL) among patients with acute coronary syndrome (ACS). This study aims to evaluate the effect of sex and gender-related variables on long-term HRQL among young adults with ACS. Methods and Results-GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond-Premature Acute Coronary SYndrome) is a multicenter, prospective cohort study (January 2009 to August 2013) of adults aged 18 to 55 years, hospitalized with ACS. HRQL was measured at baseline, 1, 6, and 12 months using the Short Form-12 and Seattle Angina Questionnaire (SAQ) among 1213 patients. Median age was 49 years. Women reported worse HRQL than men over time post-ACS, both in terms of physical and mental functioning. Gender-related factors were more likely to be predictors of HRQL than sex. Femininity score, social support, and housework responsibility were the most common gender-related predictors of HRQL at 12 months. We observed an interaction between female sex and social support (beta=0.44 [95% confidence interval, 0.01, 0.88]; P=0.047) for the physical limitation subscale of the SAQ. Conclusions-Young women with ACS report significantly poorer HRQL than young men. Gender appears to be more important than sex in predicting long-term HRQL post-ACS. Specific gender-related factors, such as social support, may be amenable to interventions and could improve the HRQL of patients with premature ACS.CIHRHeart and Stroke Foundation of QuebecHeart and Stroke Foundation of Nova ScotiaHeart and Stroke Foundation of AlbertaHeart and Stroke Foundation of OntarioHeart and Stroke Foundation of YukonHeart and Stroke Foundation of British Columbia, CanadaJames McGill Chair at McGill Universit

A Feasibility Study for CODE-MI: High-Sensitivity Cardiac Troponin - Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women.

Objectives This feasibility study was conducted to inform the design and power evaluation of CODE-MI, a pan-Canadian trial evaluating 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 with symptoms suggestive for myocardial ischemia. Approach CODE-MI is a multi-center, stepped-wedge cluster randomized trial. The cohort and outcomes will be obtained from routinely collected administrative data. Using linked administrative data from 11 hospitals in Ontario from 2014/10 to 2017/09, this feasibility study obtained the following estimates: number of eligible patients, i.e., women presenting to the emergency department with symptoms suggestive of myocardial ischemia and a 24-hour peak hs-cTn value within the female-specific and overall thresholds (i.e. primary cohort); the rate of the 1-year composite outcome of all-cause mortality, re-admission for non-fatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization. Study power was evaluated via simulations. Results Overall, 2,073,849 emergency department 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. Conclusion Routinely collected administrative health data serve as a rich and essential resource for conducting pragmatic trials assessing process change, such as CODE-MI. We demonstrated the strength of using linked administrative health data to guide the design of pragmatic clinical trials and accurately evaluate the study power

Sex Differences in Mortality After Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis

ObjectivesThe aim of this study was to examine sex differences in outcome after transcatheter aortic valve replacement (TAVR) with real-world data from 2 large centers in Canada.BackgroundTranscatheter aortic valve replacement is an effective alternative to surgical valve replacement in symptomatic patients with severe aortic stenosis, but the impact of sex on outcomes remains unclear. The PARTNER (Placement of Aortic Transcatheter Valves) 1A trial demonstrated greater benefit of TAVR over surgery in women, but whether this was due to the poorer surgical outcome of women or better TAVR outcome, compared with men, is unknown.MethodsConsecutive patients (n = 641) undergoing TAVR in Vancouver and Quebec City, Canada, were evaluated. Differences in all-cause mortality were examined with Kaplan-Meier estimates, adjusted logistic regression, and proportional hazards models.ResultsWomen comprised 51.3% of the cohort. Balloon-expandable valves were used in 97% of cases, with transapical approach in 51.7 % women and 38.1% men. Women had more major vascular complications (12.4% vs. 5.4%, p = 0.003) and borderline significantly more major/life-threatening bleeds (21.6% vs. 15.8%, p = 0.08). At baseline, women had higher aortic gradients and worse renal function but better ejection fractions. Men had more comorbidities: prior myocardial infarction, prior revascularization, and chronic obstructive pulmonary disease. The adjusted odds ratio for 30-day all-cause mortality favored women, 0.39 (95% confidence interval: 0.19 to 0.80; p = 0.01), and this benefit persisted for 2 years, hazard ratio 0.60 (95% confidence interval: 0.41 to 0.88; p = 0.008).ConclusionsFemale sex is associated with better short- and long-term survival after TAVR. Added to the PARTNER 1A findings, these results suggest TAVR might be the preferred treatment option for elderly women with symptomatic severe aortic stenosis

An administrative data merging solution for dealing with missing data in a clinical registry: adaptation from ICD-9 to ICD-10

<p>Abstract</p> <p>Background</p> <p>We have previously described a method for dealing with missing data in a prospective cardiac registry initiative. The method involves merging registry data to corresponding ICD-9-CM administrative data to fill in missing data 'holes'. Here, we describe the process of translating our data merging solution to ICD-10, and then validating its performance.</p> <p>Methods</p> <p>A multi-step translation process was undertaken to produce an ICD-10 algorithm, and merging was then implemented to produce complete datasets for 1995–2001 based on the ICD-9-CM coding algorithm, and for 2002–2005 based on the ICD-10 algorithm. We used cardiac registry data for patients undergoing cardiac catheterization in fiscal years 1995–2005. The corresponding administrative data records were coded in ICD-9-CM for 1995–2001 and in ICD-10 for 2002–2005. The resulting datasets were then evaluated for their ability to predict death at one year.</p> <p>Results</p> <p>The prevalence of the individual clinical risk factors increased gradually across years. There was, however, no evidence of either an abrupt drop or rise in prevalence of any of the risk factors. The performance of the new data merging model was comparable to that of our previously reported methodology: c-statistic = 0.788 (95% CI 0.775, 0.802) for the ICD-10 model versus c-statistic = 0.784 (95% CI 0.780, 0.790) for the ICD-9-CM model. The two models also exhibited similar goodness-of-fit.</p> <p>Conclusion</p> <p>The ICD-10 implementation of our data merging method performs as well as the previously-validated ICD-9-CM method. Such methodological research is an essential prerequisite for research with administrative data now that most health systems are transitioning to ICD-10.</p

Identifying priorities in methodological research using ICD-9-CM and ICD-10 administrative data: report from an international consortium

BACKGROUND: Health administrative data are frequently used for health services and population health research. Comparative research using these data has been facilitated by the use of a standard system for coding diagnoses, the International Classification of Diseases (ICD). Research using the data must deal with data quality and validity limitations which arise because the data are not created for research purposes. This paper presents a list of high-priority methodological areas for researchers using health administrative data. METHODS: A group of researchers and users of health administrative data from Canada, the United States, Switzerland, Australia, China and the United Kingdom came together in June 2005 in Banff, Canada to discuss and identify high-priority methodological research areas. The generation of ideas for research focussed not only on matters relating to the use of administrative data in health services and population health research, but also on the challenges created in transitioning from ICD-9 to ICD-10. After the brain-storming session, voting took place to rank-order the suggested projects. Participants were asked to rate the importance of each project from 1 (low priority) to 10 (high priority). Average ranks were computed to prioritise the projects. RESULTS: Thirteen potential areas of research were identified, some of which represented preparatory work rather than research per se. The three most highly ranked priorities were the documentation of data fields in each country's hospital administrative data (average score 8.4), the translation of patient safety indicators from ICD-9 to ICD-10 (average score 8.0), and the development and validation of algorithms to verify the logic and internal consistency of coding in hospital abstract data (average score 7.0). CONCLUSION: The group discussions resulted in a list of expert views on critical international priorities for future methodological research relating to health administrative data. The consortium's members welcome contacts from investigators involved in research using health administrative data, especially in cross-jurisdictional collaborative studies or in studies that illustrate the application of ICD-10

Assay precision and risk of misclassification at rule-out cut-offs for high-sensitivity cardiac troponin

Clinical trials and guidelines support the use of very low high-sensitivity cardiac troponin (hs-cTn) results to rule-out a myocardial infarction (MI) ( 1) ). The International Federation of Clinical Chemistry and Laboratory Medicine Committee on Clinical Applications of Cardiac Biomarkers committee, through a modeling approach, suggests assays need to have a lower limit near 3 ng/L and an analytical variation of 10% below 7 ng/L if these low values are to perform consistently in practice ( 2) ). Our objectives for the present study were to assess: i) if any type of instrument or individual instrument could achieve a coefficient of variation (CV) of ≤10% at very low hs-cTn cut-offs (i.e., targets) recommended in clinical pathways; ii) the frequency of results at the hs-cTn target, above the target and below the target, with the latter group representing potential misclassification to the low risk group where the target level would in the intermediate risk range.<br/

Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration

To evaluate the associations of emergent genome-wide-association study-derived coronary heart disease (CHD)-associated single nucleotide polymorphisms (SNPs) with established and emerging risk factors, and the association of genome-wide-association study-derived lipid-associated SNPs with other risk factors and CHD events

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Abstract: Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate