Impact of Sex and Gender on Metabolic Syndrome in Adults: A Retrospective Cohort Study From the Canadian Primary Care Sentinel Surveillance Network.

OBJECTIVE: Metabolic syndrome (MetS), a cluster of 5 interconnected factors, is the main contributor to cardiovascular disease. Although sex- and gender-related elements have been linked to MetS and its components, this association has not been explored among Canadians with or without MetS. In this study, we aimed to identify sex and gender differences in characteristics of MetS in the Canadian population. METHODS: This retrospective cohort study used data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) database. The CPCSSN contains de-identified electronic health records of >1.5 million Canadians (2010-2019). Individuals 35 to 75 years of age who had a primary care encounter formed the study sample (N=37,813). Multiple logistic regression models were used to estimate adjusted odds ratios for sex and gender differences among Canadians with and without MetS, which was the primary outcome variable. RESULTS: The estimated prevalence of MetS was 41.9%. The risk of developing MetS was significantly lower among females compared with males (odds ratio 0.73, 95% confidence interval 0.70 to 0.76). However, the risk was higher in females who used antidepressants (odds ratio 1.53, 95% confidence interval 1.42 to 1.65). An equal distribution of deprivation indexes was observed between males and females with MetS, with risk slightly higher for those with material deprivation. Females were found to be the most socially deprived. CONCLUSIONS: This study provides important sex- and gender-specific differences in MetS among Canadians. Targeting sex- and gender-specific risk factors could assist in reversing the trend of adverse cardiovascular outcomes associated with MetS.

Sex Differences in the Association of Age at Hypertension Diagnosis With Brain Structure.

BACKGROUND: Sex differences exist in the likelihood of cognitive decline. The age at hypertension diagnosis is a unique contributor to brain structural changes associated with cerebral small vessel disease. However, whether this relationship differs between sexes remains unclear. Therefore, our objective was to evaluate sex differences in the association between the age at hypertension diagnosis and cerebral small vessel disease-related brain structural changes. METHODS: We used data from the UK Biobank to select participants with a known age at hypertension diagnosis and brain magnetic resonance imaging (n=9430) and stratified them by sex and age at hypertension diagnosis. Control participants with magnetic resonance imaging scans but no hypertension were chosen at random matched by using propensity score matching. For morphological brain structural changes, generalized linear models were used while adjusting for other vascular risk factors. For the assessment of white matter microstructure, principal component analysis led to a reduction in the number of fractional anisotropy variables, followed by regression analysis with major principal components as outcomes. RESULTS: Males but not females with a younger age at hypertension diagnosis exhibited lower brain gray and white matter volume compared with normotensive controls. The volume of white matter hyperintensities was greater in both males and females with hypertension than normotensive controls, significantly higher in older females with hypertension. Compared with normotensive controls, white matter microstructural integrity was lower in individuals with hypertension, which became more prominent with increasing age. CONCLUSIONS: Our study demonstrates that the effect of hypertension on cerebral small vessel disease-related brain structure differs by sex and by age at hypertension diagnosis.

Trimethoprim-sulfamethoxazole prophylaxis during treatment of granulomatosis with polyangiitis with rituximab in the United States of America: a retrospective cohort study.

BACKGROUND: Antibiotic prophylaxis is recommended during ANCA-associated vasculitis (AAV) induction. We aimed to describe the frequency, persistence, and factors associated with trimethoprim-sulfamethoxazole (TMP-SMX) use in an adult population sample with granulomatosis with polyangiitis (GPA) treated with rituximab (RTX). METHODS: We identified adults with GPA treated with RTX within the Merative™ Marketscan® Research Databases (2011-2020). TMP-SMX prophylaxis was defined as a [Formula: see text] 28-day prescription dispensed within a month of starting RTX. We estimated TMP-SMX persistence, allowing prescription refill gaps of 30 days. Multivariable logistic regression and Cox proportional hazards regression assessed the factors associated with baseline TMP-SMX use and persistence, respectively. Covariates included age, sex, calendar year, insurance type, immunosuppressant use, hospitalization, and co-morbidities. RESULTS: Among 1877 RTX-treated GPA patients, the mean age was 50.9, and 54% were female. A minority (n = 426, 23%) received TMP-SMX with a median persistence of 141 (IQR 83-248) days. In multivariable analyses, prophylaxis was associated with prednisone use in the month prior to RTX ([Formula: see text] 20 mg/day vs none, OR 3.96; 95% CI 3.0-5.2; 1-19 mg/day vs none, OR 2.63; 95% CI 1.8-3.8), and methotrexate use (OR 1.48, 95% CI 1.04-2.1), intensive care (OR 1.95; 95% CI 1.4-2.7), and non-intensive care hospitalization (OR 1.56; 95% CI 1.2-2.1) in the 6 months prior to RTX. Female sex (OR 0.63; 95% CI 0.5-0.8) was negatively associated with TMP-SMX use. CONCLUSIONS: TMP-SMX was dispensed to a minority of RTX-treated GPA patients, more often to those on glucocorticoids and with recent hospitalization. Further research is needed to determine the optimal use and duration of TMP-SMX prophylaxis following RTX in AAV.

Sex Differences in the Effectiveness of Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Sacubitril-Valsartan for the Treatment of Heart Failure.

Background PARAGON-HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) suggested a potential benefit of sacubitril-valsartan in women with preserved ejection fraction. Among patients with heart failure previously treated with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), we studied whether effectiveness of treatment with sacubitril-valsartan compared with ACEI/ARB monotherapy differed between men and women for both preserved and reduced ejection fraction. Methods and Results Data were derived from the Truven Health MarketScan Databases between January 1, 2011, and December 31, 2018. We included patients with a primary diagnosis of heart failure on treatment with ACEIs, ARBs, or sacubitril-valsartan on the basis of the first prescription after diagnosis. A total of 7181 patients treated with sacubitril-valsartan, 25 408 patients using an ACEI, and 16 177 patients treated with ARBs were included. A total of 790 readmissions or deaths occurred among 7181 patients in the sacubitril-valsartan group and 11 901 events in 41 585 patients treated with an ACEI/ARB. Adjusted for covariates, the hazard ratio (HR) for treatment with sacubitril-valsartan compared with an ACEI or ARB was 0.74 (95% CI, 0.68-0.80). The protective effect of sacubitril-valsartan was evident for men and women (women: HR, 0.75 [95% CI, 0.66-0.86]; P<0.01; men: HR, 0.71 [95% CI, 0.64-0.79]; P<0.01; P interaction 0.03). A protective effect for both sexes was seen only among those with systolic dysfunction. Conclusions Treatment with sacubitril-valsartan is more effective at reducing death and admission to the hospital for heart failure compared with ACEIs/ARBs similarly among men and women with systolic dysfunction; sex differences in the effectiveness of sacubitril-valsartan in diastolic dysfunction requires further investigation.

Sex and Gender Influence on Cardiovascular Health in Sub-Saharan Africa: Findings from Ghana, Gambia, Mali, Guinea, and Botswana.

Background: There is an upsurge of cardiovascular diseases (CVDs) in sub-Saharan Africa (SSA). Irrespective of biological sex, gender-related factors could be the precursor of these conditions. Objective: To examine the associations between biological sex, gender-related variables, and cardiovascular health (CVH) risk factors in SSA countries. Methods: We used data from the STEPwise approach to surveillance of risk factors for non-communicable disease survey, conducted in adults from Ghana, Gambia, Mali, Guinea, and Botswana. The main outcome was CVH, measured through the health index with values ranging from 0 (worst) to 5 (best or ideal) CVH. Multivariable logistic regression was applied to determine the gender-related factors related to poorer CVH (index less than 4). Results: Data included 15,356 adults (61.4% females, mean age 36.9 years). The prevalence of hypertension (21.6% vs. 13.8%) and overweight/obesity (48.3% vs. 27.5%) was higher among females as compared to males. Females were more likely to be unemployed (17.3% vs. 9.7%) or reported unpaid work (36.8% vs. 15.2%). Overall, females showed worse CVH than males (ORfemale = 0.95, 95% CI:0.91-0.99). Being married was associated with better CVH compared with being single, more so for males (ORmale = 1.09, 95% CI:0.96-1.24, pinteraction < 0.01). Males with unpaid work (ORmale = 1.28, 95% CI:1.12-1.47) had better CVH than their unpaid female counterparts (ORfemale = 1.08, 95% CI:1.01-1.17). Conclusion: In SSA populations, being female was associated with poorer CVH given the disproportionate burden of hypertension and overweight/obesity. Gender-related factors such as marital status and unpaid work were associated with better CVH in males compared to females.

Differentiating Sex and Gender Among Older Men and Women.

OBJECTIVE: This study aimed to paradigmatically show the development of a gender score that can be used as either an adjustment or a matching variable to separate the effects of gender versus biological sex in a sample of older adults. METHODS: Our sample comprised 1100 participants from the Berlin Aging Study II (52% women, mean [standard deviation] age = 75.6 [3.8] years). The gender score included a multitude of gender-related variables and was constructed via logistic regression. In models of health outcomes, it was used as an adjustment variable in regression analyses as well as a matching variable to match older men and women according to their gender. RESULTS: Matching by gender substantially reduced sample size to n = 340. Analyses (either adjusting for gender or matching men and women according to gender) revealed that female sex was independently associated with lower grip strength (B = -14.47, 95% confidence interval [CI] = -15.51 to -13.44), better cognitive performance (B = 3.47, 95% CI = 1.94 to 5.0), higher pulse wave velocity (B = 0.19, 95% CI = 0.06 to 0.31), lower body mass index (B = -0.97, 95% CI = -1.74 to -0.21), and lower rates of metabolic syndrome (odds ratio = 0.53, 95% CI = 0.37 to 0.77). In addition, both sex and gender were independently associated with cognitive performance and depression. CONCLUSIONS: Calculating a gender score allows for the inclusion of a large number of variables, creating parsimonious models that are adaptable to different data sets and alternative gender definitions. Depending on the research question and the sample properties, the gender score can be used as either an adjustment or a matching variable.Trial Registration: DRKS-Deutsches Register Klinischer Studien (Study ID: DRKS00016157).

Variations in Quality of Care by Sex and Social Determinants of Health Among Younger Adults With Acute Myocardial Infarction in the US and Canada.

Importance: Quality of care of young adults with acute myocardial infarction (AMI) may depend on health care systems in addition to individual-level factors such as biological sex and social determinants of health (SDOH). Objective: To examine whether the quality of in-hospital and postacute care among young adults with AMI differs between the US and Canada and whether female sex and adverse SDOH are associated with a low quality of care. Design, Setting, and Participants: This retrospective cohort analysis used data from 2 large cohorts of young adults (aged ≤55 years) receiving in-hospital and outpatient care for AMI at 127 centers in the US and Canada. Data were collected from August 21, 2008, to April 30, 2013, and analyzed from July 12, 2019, to March 10, 2021. Exposures: Sex, SDOH, and health care system. Main Outcomes and Measures: Opportunity-based quality-of-care score (QCS), determined by dividing the total number of quality indicators of care received by the total number for which the patient was eligible, with low quality of care defined as the lowest tertile of the QCS. Results: A total of 4048 adults with AMI (2345 women [57.9%]; median age, 49 [interquartile range, 44-52] years; 3004 [74.2%] in the US) were included in the analysis. Of 3416 patients with in-hospital QCS available, 1061 (31.1%) received a low QCS, including more women compared with men (725 of 2007 [36.1%] vs 336 of 1409 [23.8%]; P < .001) and more patients treated in the US vs Canada (962 of 2646 [36.4%] vs 99 of 770 [12.9%]; P < .001). Conversely, low quality of post-AMI care (748 of 2938 [25.5%]) was similarly observed for both sexes, with a higher prevalence in the US (678 of 2346 [28.9%] vs 70 of 592 [11.8%]). In adjusted analyses, female sex was not associated with low QCS for in-hospital (odds ratio [OR], 1.05; 95% CI, 0.87-1.28) and post-AMI (OR, 1.07; 95% CI, 0.88-1.30) care. Conversely, being treated in the US was associated with low in-hospital (OR, 2.93; 95% CI, 2.16-3.99) and post-AMI (OR, 2.67; 95% CI, 1.97-3.63) QCS, regardless of sex. Of all SDOH, only employment was associated with higher quality of in-hospital care (OR, 0.72; 95% CI, 0.59-0.88). Finally, only in the US, low quality of in-hospital care was associated with a higher 1-year cardiac readmissions rate (234 of 962 [24.3%]). Conclusions and Relevance: These findings suggest that beyond sex, health care systems and SDOH that depict social vulnerability are associated with quality of AMI care. Taking into account SDOH among young adults with AMI may improve quality of care and reduce readmissions, especially in the US.

Impact of Race on the In-Hospital Quality of Care Among Young Adults With Acute Myocardial Infarction.

Background The extent to which race influences in-hospital quality of care for young adults (≤55 years) with acute myocardial infarction (AMI) is largely unknown. We examined racial disparities in in-hospital quality of AMI care and their impact on 1-year cardiac readmission. Methods and Results We used data from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study enrolling young Black and White US adults with AMI (2008-2012). An in-hospital quality of care score (QCS) was computed (standard AMI quality indicators divided by the total a patient is eligible for). Multivariable logistic regression was performed to identify factors associated with the lowest QCS tertile, including interactions between race and social determinants of health. Among 2846 young adults with AMI (median 48 years [interquartile range 44-52], 67.4% women, 18.8% Black race), Black individuals, especially women, exhibited a higher prevalence of cardiac risk factors and social determinants of health and were more likely to experience a non-ST-segment-elevation myocardial infarction than White individuals. Black individuals were more likely in the lowest QCS tertile than White individuals (40.8% versus 34.7%; P=0.003). The association between Black race and low QCS (odds ratio [OR], 1.25; 95% CI, 1.02-1.54) was attenuated by adjustment for confounders. Employment was independently associated with better QCS, especially among Black participants (OR, 0.76; 95% CI, 0.62-0.92; P-interaction=0.02). Black individuals experienced a higher rate of 1-year cardiac readmission (29.9% versus 20.0%; P<0.0001). Conclusions Black individuals with AMI received lower in-hospital quality of care and exhibited a higher rate of cardiac readmissions than White individuals. Black individuals had a lower quality of care if unemployed, highlighting the intersection of race and social determinants of health.

Gender score development in the Berlin Aging Study II: a retrospective approach.

In addition to biological sex, gender, defined as the sociocultural dimension of being a woman or a man, plays a central role in health. However, there are so far few approaches to quantify gender in a retrospective manner in existing study datasets. We therefore aimed to develop a methodology that can be retrospectively applied to assess gender in existing cohorts. We used baseline data from the Berlin Aging Study II (BASE-II), obtained in 2009-2014 from 1869 participants aged 60 years and older. We identified 13 gender-related variables and used them to construct a gender score by using primary component and logistic regression analyses. Of these, nine variables contributed to a gender score: chronic stress, marital status, risk-taking behaviour, personality attributes: agreeableness, neuroticism, extraversion, loneliness, conscientiousness, and level of education. Females and males differed significantly in the distribution of the gender score, but a significant overlap was also found. Thus, we were able to develop a gender score in a retrospective manner from already collected data that characterized participants in addition to biological sex. This approach will allow researchers to introduce the notion of gender retrospectively into a large number of studies.

Anticoagulant Use and the Risk of Thromboembolism and Bleeding in Postoperative Atrial Fibrillation After Noncardiac Surgery.

BACKGROUND: An effective and safe oral anticoagulation (OAC) strategy for patients with new postoperative AF (POAF) after noncardiac surgery remains unclear. We aimed to determine the association between OAC use and 1) thromboembolic events and 2) major bleeding in patients with POAF after noncardiac surgery. METHODS: A retrospective cohort (1999-2015) was used to identify patients with new POAF after inpatient noncardiac surgery. Initiation of OAC was defined as prescription of an OAC within 30 days following hospital discharge. Times to first hospital admission or emergency department visit for a thromboembolic or major bleeding event were compared using Cox proportional hazards models. RESULTS: We identified 22,007 patients with new POAF after inpatient noncardiac surgery. The majority of patients had intermediate (CHA2DS2-VASc 2-3: 45%) to high (CHA2DS2-VASc ≥ 4: 42%) thromboembolic risk. During a mean follow-up of 4 years, a total of 1099 (5%) thromboembolic and 3250 (15%) bleeding events occurred. Compared with patients not on anticoagulation, anticoagulation did not reduce the risk for thromboembolic events (adjusted hazard ratio [aHR] 0.89, 95% CI 0.73-1.07). In patients initiated on anticoagulation, there was an association with a higher risk for major bleeding (aHR 1.14, 95% CI 1.04-1.25). CONCLUSIONS: In patients with new POAF after noncardiac surgery, anticoagulation was not associated with a reduction in long-term thromboembolic events; however, this was accompanied by an overall increased risk for major bleeding. Future prospective clinical studies are needed to better address the role for anticoagulation therapy in the setting of POAF after noncardiac surgery to understand the efficacy and safety of treatment.

Novel glucose lowering agents are associated with a lower risk of cardiovascular and adverse events in type 2 diabetes: A population based analysis.

BACKGROUND: Recent randomized control trials have described a protective cardiovascular effect of novel glucose lowering drugs in patients at high cardiovascular risk. Whether these second-line agents have similar effects in the general population is unknown. We aimed to compare the risk of major cardiovascular and adverse events in new users of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), dipeptidyl peptidase-4 inhibitor (DPP-4i), glucagon-like peptide 1 agonist (GLP-1a), and sulfonylurea in T2DM patients not controlled on metformin therapy. METHODS: Retrospective cohort study using the MarketScan database (2011-2015). We selected T2DM individuals who were newly dispensed sulfonylureas, SGLT-2i, DPP-4i, or GLP-1a, as second-line therapy, added to metformin. Cohort entry was defined by date of first prescription of the second-line agent. Time to first non-fatal cardiovascular or adverse event was compared using Cox regression models adjusted for confounders. RESULTS: Among 118,341 T2DM patients using metformin (mean age: 56), most were at low cardiovascular risk (4% with previous cardiovascular or cerebrovascular event). During a median follow-up of 10 months compared with sulfonylureas users, cardiovascular risk was lower in users of SGLT-2i (aHR = 0.61; 95% CI: 0.40-0.97), DPP-4i (aHR = 0.79; 95% CI: 0.69-0.90) and GLP-1a (aHR = 0.65; 95% CI: 0.48-0.89). Serious adverse events were rare but compared with sulfonylurea, the risk was lower in new users of novel glucose lowering agents. CONCLUSION: In our analyses, which included patients with and without prior cardiovascular disease, initiating novel glucose lowering drugs as second-line therapy for T2DM was associated with a lower risk of cardiovascular and adverse events than sulfonylurea initiation.

Sex Differences in Cardiovascular Effectiveness of Newer Glucose-Lowering Drugs Added to Metformin in Type 2 Diabetes Mellitus.

Background Randomized controlled trials showed that newer glucose-lowering agents are cardioprotective, but most participants were men. It is unknown whether benefits are similar in women. Methods and Results Among adults with type 2 diabetes mellitus not controlled with metformin with no prior use of insulin, we assessed for sex differences in the cardiovascular effectiveness and safety of sodium-glucose-like transport-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors, initiated as second-line agents relative to sulfonylureas (reference-group). We studied type 2 diabetes mellitus American adults with newly dispensed sulfonylureas, SGLT-2i, GLP-1RA, or dipeptidyl peptidase-4 inhibitors (Marketscan-Database: 2011-2017). We used multivariable Cox proportional hazards models with time-varying exposure to compare time to first nonfatal cardiovascular event (myocardial infarction/unstable angina, stroke, and heart failure), and safety outcomes between drugs users, and tested for sex-drug interactions. Among 167 254 type 2 diabetes mellitus metformin users (46% women, median age 59 years, at low cardiovascular risk), during a median 4.5-year follow-up, cardiovascular events incidence was lower in women than men (14.7 versus 16.7 per 1000-person-year). Compared with sulfonylureas, hazard ratios (HRs) for cardiovascular events were lower with GLP-1RA (adjusted HR-women: 0.57, 95% CI: 0.48-0.68; aHR-men: 0.82, 0.71-0.95), dipeptidyl peptidase-4 inhibitors (aHR-women: 0.83, 0.77-0.89; aHR-men: 0.85, 0.79-0.91) and SGLT-2i (aHR-women: 0.58, 0.46-0.74; aHR-men: 0.69, 0.57-0.83). A sex-by-drug interaction was statistically significant only for GLP-1RA (P=0.002), suggesting greater cardiovascular effectiveness in women. Compared with sulfonylureas, risks of adverse events were similarly lower in both sexes for GLP-1RA (aHR-women: 0.81, 0.73-0.89; aHR-men: 0.80, 0.71-0.89), dipeptidyl peptidase-4 inhibitors (aHR-women: 0.82, 0.78-0.87; aHR-men: 0.83, 0.78-0.87) and SGLT-2i (aHR-women: 0.68, 0.59-0.78; aHR-men: 0.67, 0.59-0.78) (all sex-drug interactions for adverse events P>0.05). Conclusions Newer glucose-lowering drugs were associated with lower risk of cardiovascular events than sulfonylureas, with greater effectiveness of GLP-1RA in women than men. Overall, they appeared safe, with a better safety profile for SGLT-2i than for GLP-1RA regardless of sex.

Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events.

BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD. RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction <0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09). CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.

Anticoagulant Use and Risk of Ischemic Stroke and Bleeding in Patients With Secondary Atrial Fibrillation Associated With Acute Coronary Syndromes, Acute Pulmonary Disease, or Sepsis.

OBJECTIVES: The purpose of this study was to determine if anticoagulation of patients with new onset secondary atrial fibrillation (AF) occurring with acute coronary syndromes (ACS), acute pulmonary disease, or sepsis is associated with a reduction in ischemic stroke or an increase in bleeding risk. BACKGROUND: Studies evaluating the benefits and risks of anticoagulation in secondary AF are infrequent, and the optimal management of these patients is not well understood. METHODS: A retrospective study cohort was identified of 2,304 patients age 65 years or older, hospitalized with a primary diagnosis of ACS, acute pulmonary disease (chronic obstructive pulmonary disease, pneumonia/influenza, pulmonary embolism, or pleural effusion) or sepsis, and a complication of new-onset AF during admission from 1999 to 2015. RESULTS: Over a follow-up of ∼3 years, we did not identify any association between anticoagulation and a lower incidence of ischemic stroke in patients with new-onset AF occurring with ACS, acute pulmonary disease, or sepsis (odds ratio [OR]: 1.22 [95% confidence interval (CI): 0.65 to 2.27], OR: 0.97 [95% CI: 0.53 to 1.77], and OR: 1.98 [95% CI: 0.29 to 13.47]), after adjusting for confounders. However, anticoagulation was associated with a higher risk of bleeding in patients with AF associated with acute pulmonary disease (OR: 1.72 [95% CI: 1.23 to 2.39]), but not in ACS or sepsis (OR: 1.42 [95% CI: 0.94 to 2.14], OR: 0.96 [95% CI: 0.29 to 3.21]). CONCLUSIONS: Our study demonstrates that the benefit of anticoagulation in secondary AF is not strong and can be associated with a higher risk of bleeding. Careful individual assessment regarding decisions on anticoagulation is warranted in these patients.

Long-term risk of stroke and bleeding post-atrial fibrillation ablation.

BACKGROUND: Catheter ablation (CA) is an established therapy for atrial fibrillation (AF). Studies regarding long-term real-world outcomes post-CA have inconsistently accounted for oral anticoagulation (OAC). OBJECTIVES: To describe patterns of OAC use post-CA and to compare the OAC-adjusted long-term risk of stroke and major bleeding in AF patients with and without CA. METHODS: A population-based cohort of AF patients was constructed in Quebec and Ontario, Canada (1999-2014). Propensity score matching was performed to determine the incidence rates of stroke and major bleeding among those undergoing CA, adjusted for time-dependent OAC use. RESULTS: From the entire cohort, 6391 patients were identified as having undergone CA as compared to 482 977 patients who did not. Of these, 1240 patients with government medical insurance undergoing CA were matched with 2427 patients without CA. Post-CA, 78%, 65%, and 61% remained on an OAC at 1, 2, and 5 years, while 75%, 71%, and 68% of patients not undergoing CA were on OACs at 1, 2, and 5 years. At follow-up, there was no statistically significant difference for stroke (adjusted hazard ratio [HR], 0.88; 95% CI, 0.63 to 1.21) or major bleeding (adjusted HR, 0.88; 95% CI, 0.73 to 1.06). CONCLUSION: No evidence was found that CA significantly decreases the risk of stroke or major bleeding when adjusting for OAC use over time. It may be prudent to continue anticoagulation post-CA based on patient-risk profile until randomized trials demonstrate both reduced stroke rates with CA, and improved safety (balancing stroke and bleeding risk) with OAC discontinuation post-CA.

Treatment Discontinuation and Clinical Events in Type 2 Diabetes Patients Treated with Dipeptidyl Peptidase-4 Inhibitors or NPH Insulin as Third-Line Therapy.

OBJECTIVE: To compare dipeptidyl peptidase-4 (DPP-4) inhibitors with neutral protamine Hagedorn (NPH) insulin, in terms of effectiveness and safety for the management of patients with type 2 diabetes mellitus (DM2) not controlled on metformin and sulfonylureas. METHODS: A retrospective cohort study of individuals with DM2 newly dispensed with either DPP-4 inhibitors or NPH as third-line therapy, after metformin and sulfonylurea. Treatment discontinuation, macrovascular outcomes, and hypoglycemia were compared using multivariable Cox regression models, adjusted for sex, age, year of cohort entry, place of residence, hypertension, past history of hypoglycemia, diabetic ketoacidosis, comorbidities, and number of visits to emergency departments, outpatient physician, and hospitalizations. RESULTS: Treatment discontinuation and hypoglycemia occurred more frequently with NPH than with DPP-4 inhibitor users. In the adjusted Cox model, the use of NPH compared to that of DPP-4 inhibitors was associated with a higher risk of discontinuation (HR: 1.33; 95% CI 1.27-1.40) and hypoglycemia (HR: 2.98; 95% CI 2.72-3.28). Risk of cardiovascular events was similar across groups. CONCLUSIONS: This real-world analysis suggests that DM2 patients initiating third-line therapy with NPH have poorer control of diabetes when compared to DPP-4 inhibitor initiators.

An exploration of the subjective social status construct in patients with acute coronary syndrome.

BACKGROUND: Perception of low subjective social status (SSS) relative to others in society or in the community has been associated with increased risk of cardiovascular disease. Our objectives were to determine whether low SSS in society was associated with barriers to access to care or hospital readmission in patients with established cardiovascular disease, and whether perceptions of discordantly high SSS in the community modified this association. METHODS: We conducted a prospective cohort study from 2009 to 2013 in Canada, United States, and Switzerland in patients admitted to hospital with acute coronary syndrome (ACS). Data on access to care and SSS variables were obtained at baseline. Readmission data were obtained 12 months post-discharge. We conducted multivariable logistic regression to model the odds of access to care and readmission outcomes in those with low versus high societal SSS. RESULTS: One thousand ninety patients admitted with ACS provided both societal and community SSS rankings. The low societal SSS cohort had greater odds of reporting that their health was affected by lack of health care access (OR 1.48, 95% CI 1.11, 1.97) and of experiencing cardiac readmissions (1.88, 95% CI 1.15, 3.06). Within the low societal SSS cohort, there was a trend toward fewer access to care barriers for those with discordantly high community SSS though findings varied based on the outcome variable. There were no statistically significant differences in readmissions based on community SSS rankings. CONCLUSION: Low societal SSS is associated with increased barriers to access to care and cardiac readmissions. Though attenuated, these trends remained even when adjusting for clinical and sociodemographic factors, suggesting that perceived low societal SSS has health effects above and beyond objective socioeconomic factors. Furthermore, high community SSS may potentially mitigate the risk of experiencing barriers to access to health care in those with low societal SSS, though these associations were not statistically significant. Subjective social status relative to society versus relative to the community seem to represent distinct concepts. Insight into the differences between these two SSS constructs is imperative in the understanding of cardiovascular health and future development of public health policies.

Comparative effectiveness of antihypertensive drugs in nondiabetic patients with hypertension: A population-based study.

The authors compared the effectiveness of thiazide diuretic (TD), angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and calcium channel blocker (CCB) monotherapies for the treatment of nondiabetic hypertension using MarketScan Databases 2010-2014. Multivariable Cox regression models assessed whether the addition of a new antihypertensive drug, treatment discontinuation, or switch and major cardiovascular or cerebrovascular events varied across groups. A total of 565 009 patients started monotherapy with ACEIs (43.6%), CCBs (23.6%), TDs (18.8%), or ARBs (14.0%). Patients who took TDs had a higher risk for either drug addition or discontinuation than patients who took ACEIs (hazard ratio [HR], 0.69 [95% CI, 0.68-0.70] vs HR, 0.81 [95% CI, 0.80-0.81]), ARBs (HR, 0.67 [95% CI, 0.66-0.68] vs HR, 0.66 [95% CI, 0.65-0.67]), and CCBs (HR, 0.85 [95% CI, 0.84-0.87] vs HR, 0.94 [95% CI, 0.93-0.95]). Conversely, patients who took TDs experienced a lower risk of clinical events compared with patients who took ACEIs (HR, 1.24 [95% CI, 1.15-1.33]), ARBs (HR, 1.28 [95% CI, 1.18-1.39]), and CCBs (HR, 1.35 [95% CI, 1.25-1.46]). Our results provide a strong rationale for choosing TDs as first-line monotherapy for the control of hypertension.

Catheter ablation for the treatment of atrial fibrillation is associated with a reduction in health care resource utilization.

BACKGROUND: Catheter ablation (CA) is superior to antiarrhythmic therapy at reducing recurrence of atrial fibrillation (AF); however, there are limited data regarding whether this decrease translates into a reduction in health care resource utilization. OBJECTIVE: To evaluate the impact of AF ablation on long-term health care resource utilization. METHODS: A population-based cohort was constructed to include patients who underwent CA for AF in Quebec, Canada, between April 2005 and March 2011. Resource utilization was evaluated 24 months pre- and postindex CA procedure. RESULTS: In a cohort of 1,556 patients, resource utilization increased progressively over the 24-month period leading to index CA (P for trend <0.05 for hospitalizations, ER visits, outpatient visits, cardioversions, and echocardiograms). After index CA, all-cause hospitalizations, hospitalizations for AF, ER visits, cardioversions, and echocardiograms were reduced 12 months post-CA compared to 12 months prior (all-cause hospitalizations 0.8-0.6 per patient per year; hospitalizations for AF 0.4-0.3; ER visits 2.9-1.8; cardioversions 0.5-0.2; echocardiograms 0.8-0.5; P < 0.05 for all trends). Resource utilization continued to decline at 24 months post-CA (vs. 12 months prior) for all-cause hospitalizations (0.4), cardioversions (0.1), and echocardiograms (0.3) (per patient year; P < 0.05 for all trends). CONCLUSION: In conclusion, the pattern of increasing health care resource utilization preceding CA for AF reverses after CA to lower than preablation levels up to 24 months post-CA.

Early non-persistence with dabigatran and rivaroxaban in patients with atrial fibrillation.

OBJECTIVE: Dabigatran and rivaroxaban are novel oral anticoagulants (NOACs) approved for stroke prevention in atrial fibrillation (AF). Although NOACs are more convenient than warfarin, their lack of monitoring may predispose patients to non-persistence. Limited information is available on NOAC non-persistence rates and related clinical outcomes in clinical practice. METHODS: We conducted a retrospective cohort study using administrative data from Ontario, Canada, from January 1998 to March 2014 of patients with AF who were dispensed dabigatran or rivaroxaban. Non-persistence was defined as a gap in dabigatran or rivaroxaban prescriptions ≥14 days. A multivariable Cox proportional hazards model was used to estimate the primary composite outcome of stroke, transient ischaemic attack (TIA) and mortality associated with non-persistence. RESULTS: The cohort consisted of 15 857 dabigatran (age 80.7±6.7 year) and 10 119 rivaroxaban users (age 77.0±7.1 year) with women comprising 52% of each medication group. At 6 months, 36.4% of patients were non-persistent to dabigatran, while 31.9% of patients were non-persistent to rivaroxaban. Stroke/TIA/death was significantly higher for those non-persistent to dabigatran (HR 1.76 (95% CI 1.60 to 1.94); p<0.0001) or rivaroxaban (HR 1.89 (95% CI 1.64 to 2.19); p<0.0001) compared with those who were persistent. Risk of stroke/TIA was markedly higher in non-persistent patients to dabigatran (HR 3.75 (95% CI 2.59 to 5.43); p<0.0001) and rivaroxaban (HR 6.25 (95% CI 3.37 to 11.58); p<0.0001) than those persistent. CONCLUSIONS: NOAC non-persistence rates are high in clinical practice, with approximately one in three patients becoming non-persistent to dabigatran or rivaroxaban within 6 months after drug initiation. Non-persistence with either dabigatran or rivaroxaban is significantly associated with worse clinical outcomes of stroke/TIA/death.