FRAX in conjunction with T-score predicts cardiovascular risk in older adults: a retrospective cohort bone density study from Thailand.

Positive airway pressure (PAP) is the first-line treatment for obstructive sleep apnea (OSA), but evidence on its beneficial effect on major adverse cardiovascular events (MACE) and mortality prevention is limited. To determine whether PAP initiation and utilization are associated with lower mortality and incidence of MACE among older adults with OSA living in the central US. This retrospective clinical cohort study included Medicare beneficiaries with 2 or more distinct OSA claims identified from multistate, statewide, multiyear (2011-2020) Medicare fee-for-service claims data. Individuals were followed up until death or censoring on December 31, 2020. Analyses were performed between December 2021 and December 2023. Evidence of PAP initiation and utilization based on PAP claims after OSA diagnosis. All-cause mortality and MACE, defined as a composite of myocardial infarction, heart failure, stroke, or coronary revascularization. Doubly robust Cox proportional hazards models with inverse probability of treatment weights were used to estimate treatment effect sizes controlling for sociodemographic and clinical factors. Among 888 835 beneficiaries with OSA included in the analyses (median [IQR] age, 73 [69-78] years; 390 598 women [43.9%]; 8115 Asian [0.9%], 47 122 Black [5.3%], and 760 324 White [85.5%] participants; median [IQR] follow-up, 3.1 [1.5-5.1] years), those with evidence of PAP initiation (290 015 [32.6%]) had significantly lower all-cause mortality (hazard ratio [HR], 0.53; 95% CI, 0.52-0.54) and MACE incidence risk (HR, 0.90; 95% CI, 0.89-0.91). Higher quartiles (Q) of annual PAP claims were progressively associated with lower mortality (Q2 HR, 0.84; 95% CI, 0.81-0.87; Q3 HR, 0.76; 95% CI, 0.74-0.79; Q4 HR, 0.74; 95% CI, 0.72-0.77) and MACE incidence risk (Q2 HR, 0.92; 95% CI, 0.89-0.95; Q3 HR, 0.89; 95% CI, 0.86-0.91; Q4 HR, 0.87; 95% CI, 0.85-0.90). In this cohort study of Medicare beneficiaries with OSA, PAP utilization was associated with lower all-cause mortality and MACE incidence. Results might inform trials assessing the importance of OSA therapy toward minimizing cardiovascular risk and mortality in older adults.

Introduction: In middle-aged adults, time spent being sedentary is associated with cardiovascular (CV) health risks independent of structured physical activity (PA). However, data are sparse regarding the impact of sedentary behavior on CV risk in older adults. The extent to which the absolute duration or intensity of daily PA reduces CV risk in older adults is also unknown. Objectives: Our objective was to examine the cross-sectional association between objectively-measured sedentary behavior and predicted CV risk among older adults in the Lifestyle Interventions and Independence for Elders (LIFE) study. The secondary objective was to evaluate associations between the duration/intensity of daily PA and predicted CV risk. Methods: LIFE is a randomized clinical trial to determine if regular PA prevents mobility disability among mobility-limited older adults. Activity data were collected by hip-worn accelerometer at baseline prior to participation in study interventions. Only participants with at least three days of accelerometry data (≥ 10 hrs wear time) were included. Unadjusted and adjusted linear regression was used to model the relationship between accelerometry measures and predicted 10-year Framingham risk of Hard Coronary Heart Disease (HCHD; i.e. myocardial infarction or coronary death). Adjusted models included demographic confounders (e.g. education, race, income) and health parameters (e.g. depression, cognition, arthritis) not in the risk score. Accelerometry cut-points were (in counts/min): sedentary behavior: < 100; low-intensity activity: 100-499; higher intensity activity: > 500. Results: Participants (n = 1170; 78.7 ± [SD] 5.3 years; 66.1% female) had a median HCHD risk of 10.3% (25 th -75 th %: 5.7-18.6). Over a mean accelerometer wear time of 8.1 ± 3.2 days, participants spent 77.0 ± 8.2% of their time sedentary. They also spent 16.6 ± 5.0% of their time in low-intensity PA and 6.4 ± 4.4% in higher-intensity PA. For all PA performed (> 100 counts/min), participants achieved a median of 393.4 (337.8-473.5) counts/min. In the unadjusted model, time spent sedentary (β = 2.41; 95% CI : 1.94, 2.89), in low-intensity PA (-2.56; -3.03, -2.08), and in higher-intensity PA (-1.60; -2.09, -1.11) were all associated with HCHD risk (all p’s < 0.001). These associations remained significant after adjustment. The mean intensity of daily PA was not significantly associated with HCHD risk in any model (p > 0.05). Conclusions: Daily time spent being sedentary is positively associated with predicted 10-year HCHD risk among mobility-limited older adults. Duration, but not mean intensity, of daily PA is inversely associated with HCHD risk score in this population.

Late-Breaking Science Abstracts From the American Heart Association's Scientific Sessions 2018 and Late-Breaking Abstracts in Resuscitation Science From the Resuscitation Science Symposium 2018.

Introduction:Osteoporosis is a prevalent metabolic bone disorder, particularly affecting the elderly, and is often linked to cardiovascular morbidity. This study investigated the associations among osteoporosis, biochemical markers, bone mineral density (BMD), and cardiovascular disease (CVD).Materials and Methods:A cross-sectional analysis was conducted among 280 individuals diagnosed with osteoporosis and 182 without osteoporosis to assess the relationship between osteoporosis and serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and homocysteine (HCY). Correlations between these biochemical indices and BMD were evaluated. CVD prevalence was compared between osteoporosis and non-osteoporosis groups, and receiver operating characteristic curve analysis was used to assess the predictive potential of BMD for CVD risk.Results:Higher triglyceride, TC, and LDL levels were positively associated with osteoporosis, while elevated HDL and HCY levels showed inverse associations. Triglyceride levels correlated negatively with BMD, whereas TC and HDL demonstrated positive correlations. LDL showed a weak negative association, and HCY exhibited a strong inverse correlation with BMD. Individuals with osteoporosis had lower BMD and a higher incidence of CVD compared to those without osteoporosis. Logistic regression confirmed that reduced BMD significantly increased cardiovascular risk.Conclusion:This study highlights significant associations among osteoporosis, lipid profiles, HCY levels, BMD, and CVD. The findings suggest that dyslipidemia and altered HCY metabolism may contribute to both bone loss and cardiovascular pathology. BMD may serve as a potential biomarker for identifying individuals at increased cardiovascular risk. Further longitudinal research is needed to establish causal relationships and assess long-term clinical outcomes.

Background Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine that plays an important role in the regulation of the inflammatory response, growth and cell differentiation. An elevated GDF-15 was found in various conditions including cigarette smoking and stable coronary artery disease (CAD), and it was reported to predict mortality and cardiovascular (CV) events in general population and in patients with established CAD. However, the impact of smoking status on the relationships of GDF-15 with mortality and CV events in patients with suspected or known CAD is unclear. Methods Serum GDF-15 levels were measured in 2,418 patients with suspected or known CAD undergoing elective coronary angiography, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict CV events (ANOX) study, and followed up for 3 years. Patients were divided into 3 groups according to the smoking status: current (n=428), past (n=1,035), and never smokers (n=955). The outcomes were total death, CV death, and major adverse CV events (MACE) defined as a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. Results During the follow-up, 48 current, 120 past, and 86 never smokers died from any cause, 17 current, 47 past, and 24 never smokers died from CV disease, and 35 current, 80 past, and 50 never smokers developed MACE. After adjustment for established risk factors, GDF-15 levels were significantly associated with total death (hazard ratio [HR] for 1-SD increase, 1.30; 95% confidence interval [CI], 1.03–1.65), but not with CV death (HR, 1.09; 95% CI, 0.69–1.62) or MACE (HR, 0.95; 95% CI, 0.64–1.34) in current smokers; GDF-15 levels were significantly associated with total death (HR, 1.73; 95% CI, 1.46–2.05) and CV death (HR, 1.41; 95% CI, 1.09–1.85), but not with MACE (HR, 1.20; 95% CI, 0.96–1.48) in past smokers; GDF-15 levels were significantly associated with total death (HR, 1.62; 95% CI, 1.32–1.95), CV death (HR, 1.76; 95% CI, 1.22–2.46), and MACE (HR, 1.64; 95% CI, 1.27–2.07) in never smokers. Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of GDF-15 levels further improved the prediction of total death (P<0.001 for continuous net reclassification improvement [NRI], P=0.001 for integrated discrimination improvement [IDI]) and MACE (P<0.001 for NRI, P=0.045 for IDI), but not that of CV death, in never smokers, while it did not significantly improved the prediction of total death, CV death, or MACE either in current or in past smokers. Conclusions The GDF-15 level was independently associated with total death and MACE in never, but not in current or past smokers with suspected or known CAD. The relationships of GDF-15 with mortality and CV events seem to be attenuated by the presence of current and past smoking. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization.

Background Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine that plays an important role in the regulation of the inflammatory response, growth and cell differentiation. An elevated GDF-15 was found in various conditions including anemia and stable coronary artery disease (CAD), and it was reported to predict mortality and cardiovascular (CV) events in general population and in patients with established CAD. However, the impact of anemia on the relationships of GDF-15 with mortality and CV events in patients with suspected or known CAD is unclear. Methods Serum GDF-15 levels were measured in 2,418 patients with suspected or known CAD undergoing elective coronary angiography, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict CV events (ANOX) study, and followed up for 3 years. Anemia was defined as a hemoglobin level of less than 13 g/dL in men and <12 g/dL in women. Patients were divided into 2 groups according to the presence (anemic, n=882) or absence (non-anemic, n=1,536) of anemia. The primary outcome was all-cause death. The secondary outcomes were CV death, and major adverse CV events (MACE) defined as a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. Results During the follow-up, 164 anemic and 90 non-anemic patients died from any cause, 64 anemic and 24 non-anemic patients died from CV disease, and 96 anemic and 69 non-anemic patients developed MACE. After adjustment for established risk factors, GDF-15 levels were significantly associated with all-cause death (hazard ratio [HR] for 1-SD increase, 1.75; 95% confidence interval [CI], 1.51–2.04), CV death (HR, 1.67; 95% CI, 1.30–2.13), and MACE (HR, 1.46; 95% CI, 1.18–1.81) in anemic, while GDF-15 levels were also significantly associated with all-cause death (HR, 1.47; 95% CI, 1.27–1.69), CV death (HR, 1.56; 95% CI, 1.18–1.99), and MACE (HR, 1.25; 95% CI, 1.004–1.50) in non-anemic patients. Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of GDF-15 levels further improved the prediction of all-cause death (P<0.001 for continuous net reclassification improvement [NRI], P<0.001 for integrated discrimination improvement [IDI]), CV death (P=0.026 for NRI, P=0.023 for IDI), and MACE (P=0.025 for NRI, P=0.042 for IDI) in anemic, whereas it did not improved the prediction of all-cause death (P=0.072 for NRI, P=0.079 for IDI), CV death (P=0.289 for NRI, P=0.179 for IDI) or MACE (P=0.397 for NRI, P=0.230 for IDI) in non-anemic patients. Conclusions The GDF-15 level significantly improved the prediction of all-cause death, CV death, and MACE in anemic, but not in non-anemic patients with suspected or known CAD. The relationships of GDF-15 with mortality and CV events seem to be remarkable in the presence of anemia. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization.

Background: The relationship between Positive Airway Pressure (PAP) therapy and its implications for mortality and cardiovascular risk among older adults with sleep apnea has garnered increasing attention in recent years. This literature review synthesizes findings from various studies to illuminate the multifaceted impacts of PAP therapy on health outcomes in this demographic. Literature Review: The literature on Positive Airway Pressure (PAP) therapy reveals a complex relationship between its use, mortality, and cardiovascular risk in older adults with sleep apnea. The studies reviewed provide substantial evidence that while PAP therapy is a cornerstone treatment for obstructive sleep apnea syndrome (OSAS), its efficacy in improving cardiovascular outcomes and reducing mortality is influenced by factors such as patient adherence and the severity of the condition. Conclusion: In conclusion, the literature collectively underscores the significance of PAP therapy in managing obstructive sleep apnea and its associated cardiovascular risks in older adults. While there is evidence supporting its benefits, particularly in reducing mortality and improving cardiovascular health, the overall effectiveness is heavily contingent upon patient adherence to treatment. Future research is essential to clarify the long-term benefits of PAP therapy and to develop strategies that enhance compliance, ultimately aiming to mitigate mortality and cardiovascular risks in this vulnerable population.

Background Osteoporosis related fractures cause significant morbidity and mortality. FRAX score uses clinical risk factors and country-specific data in addition to Bone Mineral Density (BMD) to assess patients with high 10-year risk of hip (>3%) or major osteoporotic (>20%) fracture. We noticed discrepancies between radiologist reported and physician calculated FRAX scores at our hospital. We hypothesized that providers are calculating FRAX score differently as BMD in the FRAX calculator is an optional input variable. Objectives This study was initiated to see the differences in results when FRAX score is calculated using T-score, BMD and no BMD and how this difference can influence treatment. Methods Retrospective chart review of 1200 DEXA reports from 2013 to 2015 was done. Patients between ages of 40-90 years with T-score ranging from -2.5 at femoral neck were included in the study. Patients already on osteoporosis therapy and/or with T-score -1 were excluded. Pertinent risk factors were obtained from chart review. 237 patients met inclusion criteria and 3 separate FRAX scores were calculated using a) Femoral neck BMD b) T-score c) no BMD value. FRAX score reported by radiologist in the chart was also reviewed. Subsequently, FRAX scores obtained using T-score, no BMD value and radiology reported scores were compared against FRAX score calculated using femoral neck BMD (gold standard) Results When FRAX score calculated using BMD was compared with FRAX score calculated without BMD, number of patients with high 10-year fracture probability decreased from 49 to 11 patients, which was a statistically significant decrease of 77.6% (p When data was stratified according to age, there was significant overestimation of risk in patients >65 years(p Conclusion FRAX score calculation without BMD leads to both statistically and clinically significant overdiagnosis especially in elderly. Interchanging T score and BMD to calculate FRAX score leads to same treatment decision. Further education of providers regarding FRAX score is needed. Many providers are not aware that if BMD column is left blank, it defaults the calculation to no BMD. A pop up alerting the user “no machine was selected so the calculation will default to no BMD which can lead to overestimation of risk” in FRAX tool might be helpful to avoid miscalculation.

We compared the predictive power for a major adverse cardiovascular event (MACE) of four home blood pressure (BP) indices (systolic BP, diastolic BP, mean BP, and pulse pressure (PP)) obtained at baseline before treatment and during the on-treatment follow-up period in 3147 patients with essential hypertension (women: 50.1%, mean age: 59.5 years). Associations between MACE and each index were determined using Cox proportional hazard models and the likelihood ratio (LR) test. During a median follow-up of 5.4 years, 46 patients experienced MACE, which was a composite of cardiovascular death, non-fatal stroke, and non-fatal myocardial infarction. The LR test showed that systolic, diastolic, and mean BP during follow-up was more closely associated with cardiovascular risk than the corresponding indices at baseline (LR χ2 for baseline versus follow-up: systolic BP, (6.0, P = 0.014) versus (11.3, P = 0.0008); diastolic BP, (0.4, P = 0.53) versus (12.4, P = 0.0004); mean BP, (3.2, P = 0.074) versus (15.0, P = 0.0001)), whereas neither PP at baseline nor that during follow-up was significantly associated with MACE risk. Among home BP indices during follow-up, mean BP further improved prediction models in which systolic or diastolic BP was already included (P ≤ 0.042), but neither systolic nor diastolic BP improved models with mean BP (P = 0.80). In addition to home systolic and diastolic BP, mean BP during follow-up period provides essential information in predicting future cardiovascular diseases, whereas its utilization should be further assessed by an intervention trial targeting mean BP levels.

The triglyceride-glucose (TyG) index, a surrogate marker for insulin resistance, has been shown to be closely associated with cardiovascular risk. However, it remains unclear whether diabetes status affects the association between the TyG index and the risk of major adverse cardiovascular events (MACEs) in patients with coronary heart disease (CHD). The aim of this study is to systematically evaluate the relationship between the TyG index and MACEs among CHD patients with different diabetes statuses. We systematically searched PubMed, the Cochrane Library, Web of Science, and Embase from inception to March 13, 2025, for cohort studies examining the association between TyG and MACEs in patients with CHD with different diabetes statuses. The outcomes included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, and revascularization. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were extracted for the TyG index as both categorical and continuous variables. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). All the statistical analyses were performed using Stata (version 17.0) and R (version 4.4.1). Depending on heterogeneity, either a fixed-effect or random-effects model was used to pool the data. Subgroup analysis and meta-regression are used to explore the sources of heterogeneity. This study was registered in PROSPERO (CRD: 420251018545). A total of 36 longitudinal cohort studies comprising 173,851 participants (119,232 with diabetes and 54,619 without diabetes) were included, with 9159 MACEs reported during the follow-up period. In diabetic patients, a higher TyG index significantly increased the risk of MACEs (categorical HR = 1.98, 95% CI 1.61-2.43; continuous HR = 1.57, 95% CI 1.38-1.78), all-cause mortality (HR = 1.74, 95% CI 1.45-2.08), nonfatal myocardial infarction (HR = 2.05, 95% CI 1.52-2.77), nonfatal stroke (HR = 1.73, 95% CI 1.12-2.66), and revascularization (HR = 2.52, 95% CI 1.26-5.04). In nondiabetic patients, a higher TyG index also significantly increased the risk of MACEs (categorical HR = 1.65, 95% CI 1.33-2.05; continuous HR = 1.74, 95% CI 1.46-2.06), all-cause mortality (HR = 1.50, 95% CI 1.18-1.90), nonfatal myocardial infarction (HR = 2.46, 95% CI 1.11-5.47), and revascularization (HR = 2.09, 95% CI 1.57-2.76). However, no association was observed between the TyG index and nonfatal stroke (HR = 1.66, 95% CI 0.88-3.12) in nondiabetic patients. Higher TyG index values appear to be associated with an increased risk of adverse cardiovascular events, all-cause mortality, nonfatal myocardial infarction, and revascularization in both diabetic and nondiabetic patients with CHD. However, no significant association was found between the TyG index and the risk of nonfatal stroke in nondiabetic patients. These findings suggest that the TyG index may offer potential prognostic value in CHD, but further high-quality prospective studies are warranted to confirm these associations and clarify their clinical implications.

Meta-Analysis of Multiple Primary Prevention Trials of Cardiovascular Events Using Aspirin

LEADER was a landmark cardiovascular outcome trial with the GLP-1 receptor agonist liraglutide, which demonstrated significant reductions in major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke), driven by a reduction in cardiovascular deaths and accompanied by a significant reduction in all-cause mortality. Shortly afterwards, the SUSTAIN-6 trial with once-weekly semaglutide demonstrated non-inferiority for MACE, with a nominal reduction in MACE that was driven by a reduction in the risk of non-fatal strokes. Since then, a further six cardiovascular trials have been published with GLP-1 receptor agonists, with major differences in study design and outcomes. Four trials have been performed with once-weekly formulations. The EXSCEL trial with once-weekly exenatide showed non-inferiority for MACE, but not superiority, with a reduction in all-cause mortality which was an exploratory outcome. The Harmony Outcomes trial with albiglutide demonstrated significant reductions in MACE, driven by reductions in fatal or non-fatal myocardial infarction. REWIND, with dulaglutide, also demonstrated significant reductions in MACE, this time driven by reductions in strokes. The AMPLITUDE-O trial with efpeglenatide showed significant reductions in MACE, but none of the individual components of MACE was significantly reduced as a secondary endpoint, and in contrast to other trials there was also a significant reduction in heart failure events. The fifth trial was the PIONEER 6 trial with the oral formulation of semaglutide, and this showed non-inferiority for MACE, but not superiority, with reductions in cardiovascular deaths and all-cause mortality which were secondary outcomes. Finally, FREEDOM-CVO with a subcutaneous mini-pump of exenatide showed non-inferiority for MACE and MACE plus hospitalisation for unstable angina. A reduction in albuminuria was seen in several of these trials, but there was no definite effect on eGFR or end-stage renal disease. Meta-analysis of the cardiovascular outcome trials with GLP-1 receptor agonists has demonstrated significant reductions in MACE, cardiovascular death, fatal or non-fatal stroke, fatal or non-fatal myocardial infarction, and all-cause mortality. It remains unclear why updated guidance from NICE on the management of T2DM in adults fails to acknowledge these evidence-based cardiovascular benefits.

Background:Osteoporosis (OP) is characterized by compromised bone strength and deterioration of quality, often leading to fragility fractures(1). Dual-energy x-ray absorptiometry (DXA) is the recommended test for OP screening(1). However, there are limitations to perform DXA on all patients, and the clinicians use screening tools to identify those patients with higher risk, like the FRAX score(2). Nevertheless, these scores have showed low to moderate correlation with DXA in RD patients(3).Objectives:To evaluate the fracture risk in RD patients, using different versions of FRAX scores without a bone mineral density (BMD) measure.Methods:An observational prospective study was performed at the Rheumatology Clinic in the University Hospital “Dr. Jose Eleuterio Gonzalez” in Monterrey, Mexico, between August and October 2020. Consecutive patients with a RD were evaluated as part of a “Bone Health Program”(3). Demographics and the risk factors included in FRAX tool was collected from ≥40 years-old patients; FRAX score was calculated online at https://www.sheffield.ac.uk/FRAX/ (algorithm for Mexicans). Four versions were calculated: 1) FRAX score without (w/o) BMD; 2) FRAX score with a T-score of -1.0 (w/Op); 3) FRAX score with a T-score of -2.5 (w/OP) and a FRAX score with positive previous fracture (Fx+). Then were classified as low (<10% for OP or <1% for hip), intermediate (10%-19% for OP or 1%-<3% for hip) and high risk (≥20% for OP or ≥3% for hip). Results are shown in means (SD) or frequency (%). A chi-square test was used to compare groups. Spearman’s correlation test (rho) was done between OP risk and Hip risk in each version of FRAX. P<0.05 was considered statistically significant.Results:One hundred and three patients were included, 93.2% were woman. The most frequent diagnosis was RA in 51.5% of patients, followed by osteoarthritis in 7.8%. 62.1% of patients had a previous BMD measured by DXA. 21.4% had history of previous fracture. 61.2% of patients were taking glucocorticoids. (Table 1). According to FRAX risk w/o BMD, 82 (79.6%) had low risk, 13 (12.6%) had intermediate risk, and 8 (7.8%) had high risk for OP. According to FRAX risk w/o BMD, 59 (57.3%) had low risk, 24 (23.3%) had intermediate risk, and 20 (19.4%) had high risk for hip fracture (Table 2). The correlations between OP risk and Hip risk in each version were as follow: FRAX w/o BMD (rho= .734, P= <.001) FRAX w/Op (rho= .308, P= .002); FRAX w/OP (rho= .476, P= <.001); FRAX with Fx+ (rho= .634, P= <.001).Conclusion:There is a wide variability among the different FRAX risk scores evaluated, and moderate to high correlation between the OP and Hip risk in patients with RD.

AimsThe CANVAS Program identified the effect of canagliflozin on major adverse cardiovascular events (MACE) differed according to whether participants were using diuretics at study commencement. We sought to further evaluate this finding related to baseline differences, treatment effects, safety, and risk factor changes.Methods and resultsThe CANVAS Program enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk. Participants were randomized to canagliflozin or placebo and followed for a mean of 188 weeks. The primary outcome was major cardiovascular events, a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary outcomes included multiple cardiovascular, renal, and safety events. In this post hoc subgroup analysis, participants were categorized according to baseline use of any diuretic. The effect on outcomes was compared using Cox proportional hazards models, while risk factor changes were compared using mixed‐effect models. At baseline, 4490 (44.3%) participants were using a diuretic. Compared with those not using a diuretic, participants using a diuretic were more likely to be older (mean age ± standard deviation, 64.3 ± 8.0 vs. 62.5 ± 8.3), be female (38.9% vs. 33.4%), and have heart failure (19.6% vs. 10.3%) (all Pdifference < 0.0001). The effect of canagliflozin on major cardiovascular events was greater for those using diuretic at baseline than for those who were not [adjusted hazard ratio 0.65 (95% confidence interval 0.54–0.78) vs. adjusted hazard ratio 1.13 (95% confidence interval 0.93–1.36), Pheterogeneity < 0.0001]. Changes in most risk factors, including blood pressure, body weight, and urine albumin‐to‐creatinine ratio, were similar between groups (all Pdifference > 0.11), although the effect of canagliflozin on haemoglobin A1c reduction was slightly weaker in participants using compared with not using diuretics at baseline (−0.52% vs. −0.64%, Pheterogeneity = 0.0007). Overall serious adverse events and key safety outcomes, including adverse renal events, were also similar (all Pheterogeneity > 0.07).ConclusionsParticipants on baseline diuretics derived a greater benefit for major cardiovascular events from canagliflozin, which was not fully explained by differences in participant characteristics nor risk factor changes.

Background Peripheral artery disease (PAD) increase the risk of comorbidity and mortality in coronary artery disease (CAD). Objectives We evaluate influence of PAD on prognosis in patients undergoing percutaneous coronary intervention (PCI). Methods We analyzed all consecutive patients included in our dedicated local registry for PCI between January 2011 and December 2016. Presence of PAD was defined by decreased ankle-brachial index (&amp;lt;0.9). Major adverse cardiovascular event (MACE) was defined as a composite of cardiovascular death, non-fatal myocardial infarct, revascularization, and ischemic stroke. Major bleeding was defined as Bleeding Academic Research Consortium 3 or 5. Results Among the 4,747 patients who underwent the PCI, 12.9% (n=610) of PAD were identified. Old age (&amp;gt;60 years), renal dysfunction, reduced ejection fraction, and presence of PAD were predictors with both MACE and major bleeding event. Among them, presence of PAD was an independent risk factor of MACE and major bleeding (MACE, HR 8.26, 95% CI 2.33- 29.41, p=0.036; major bleeding, HR 3.11, 95% CI 1.10–10.63, p=0.040, respectively). The MACE and major bleeding rate at 5-year was significantly increased in patients with PAD (MACE, 30.0% vs. 15.8%, log rank test p&amp;lt;0.001; major bleeding, 6.7 vs. 3.6%, log rank test p=0.003, respectively) (Figure). Conclusion Presence of PAD was strongly associated with higher rate of long-term MACE and major bleeding. These findings could have a clinical relevance in requiring individualized pharmacologic strategies to reduce the burden of cardiovascular disease. Funding Acknowledgement Type of funding sources: None.