Composite Cardiovascular Outcome Research Articles

Comparative cardiovascular and renal outcomes of Liraglutide versus Dulaglutide in Asian type 2 diabetes patients.

Given the limited head-to-head comparison of cardiovascular and renal outcomes between liraglutide and dulaglutide, our study aimed to investigate the clinical outcomes between dulaglutide and liraglutide in a real-world setting. In this new-user design, comparative and retrospective cohort study, patients with type 2 diabetes mellitus with prescription for GLP-1RAs from January 1, 2016 to December 31, 2022 (n = 8,278) were included. Primary outcome was composite cardiovascular outcomes which was composed of cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke. The composite renal outcome was also interested, including new macroalbuminuria, doubling of serum creatinine, worsening of estimated glomerular filtration rate (eGFR), and progression to dialysis. A total of 3,210 subjects receiving liraglutide and 5,068 subjects receiving dulaglutide were identified. In the adjusted cohort by applying inverse probability of treatment weighting, the incidence of composite cardiovascular outcomes was 18.4 and 18.7 events per 1000 person-years in the liraglutide and dulaglutide groups, respectively. The risk of cardiovascular outcomes did not significantly differ between groups (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.85-1.15). Moreover, the risk of composite renal outcomes was also comparable between groups (subdistribution HR 1.07, 95% CI 0.995-1.16). Liraglutide and dulaglutide demonstrated comparable cardiovascular and renal outcomes in a real-world setting.

Baseline Diastolic BP and BP-Lowering Effects on Cardiovascular Outcomes and All-Cause Mortality: A Meta Analysis.

Lowering blood pressure (BP) in persons with low diastolic BP could be harmful. Hence, we examined whether baseline diastolic BP modifies the effects of BP lowering on clinical outcomes in a meta-analysis of five large BP lowering trials. In a study-level meta-analysis based on individual participant data of the Systolic Blood Pressure Intervention Trial (N = 9361), the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (N = 2362), the Secondary Prevention of Small Subcortical Strokes (N = 3020), the African American Study of Kidney Disease and Hypertension (N = 1094) and the Modification of Diet in Renal Disease (N = 840) studies, we used DerSimonian-Laird random-effects models to examine the dependence of the effect of the BP lowering intervention on baseline diastolic BP for cardiovascular, all-cause mortality and kidney outcomes. Mean baseline age was 65 ± 10 years old. Mean baseline systolic and diastolic BP were 141 ± 17 and 79 ± 12 mm Hg, respectively. More intensive BP control resulted in lower risk of composite cardiovascular outcome (HR 0.79, 95% CI 0.72, 0.87) and all-cause mortality (HR 0.86, 95% CI 0.75, 0.99) without evidence that the BP intervention effects differed by level of baseline diastolic BP (interaction p = 0.76 for cardiovascular composite and 0.85 for all-cause mortality). The mean baseline diastolic BP in the lowest and the upper three quartiles of baseline diastolic BP were 65 ± 6 mm Hg and 84 ± 9 mm Hg, respectively but the effects of the BP interventions on the outcomes were similar in both groups. Furthermore, there was no evidence of interaction of the BP intervention and baseline diastolic BP for kidney outcomes. Within the included diastolic BP range, there was no evidence that baseline diastolic BP modified the beneficial effects of intensive BP lowering.

Impact of procedural and patient-related risks on 1-year outcomes for patients with 1-month DAPT followed by P2Y12 inhibitor monotherapy after biodegradable-polymer drug-eluting stent implantation

Abstract Background While early de-escalation of dual antiplatelet therapy (DAPT) and P2Y12 inhibitor monotherapy following short DAPT are becoming standard treatments for patients after percutaneous coronary intervention (PCI), the impact of procedural and patient-related risks on clinical outcomes of PCI for patients receiving the above DAPT regimen has never been established. Purpose To evaluate the impact of procedural and patient-related risk factors on 1-year cardiovascular and bleeding outcomes in patients with 1-month DAPT followed by P2Y12 inhibitor monotherapy after biodegradable-polymer drug-eluting stent (BP-DES) implantation. Methods Using data from the multi-centre regional-wide REIWA registry, we assessed clinical outcomes according to each risk factor and compared between patients with and without either procedural or patient-related risk factors. The primary end point was net adverse clinical events (NACE), defined as a composite of cardiovascular outcomes (cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic or hemorrhagic stroke) and bleeding outcomes (TIMI major or minor bleeding), which was same with that for STOPDAPT-2 trial. Procedural risk was defined as a factor of complex PCI which was previously published and included the follows: treatment of three vessels, three or more lesions, three or more stents, bifurcation with two stents, long stenting (total stent length >60 mm) and target of chronic total occlusion. Additionally, patient-related risk factors were defined as chronic kidney disease, anaemia, peripheral vascular disease, heart failure and advanced age (≧75 years). Results Among 1,202 patients treated BP-DES with 1-month DAPT, 276 patients (23.0%) had at least one procedural factors and 510 patients (42.4%) had one or more patient-related risks. Compared with each risk factor, patients with patient-related risk factor were more likely to have higher NACE rates, whereas low NACE rates were observed in patients with each procedural risk factor (Figure 1). In addition, during 1-year follow-up, patients with patient-related risk factors had a significantly higher incidence of NACE compared with patients without such risks (4.90 % vs. 1.73 %, p = 0.002) (Figure 2). However, no significant differences in NACE rates was observed between patients with and without procedural risk factors (2.54% vs. 3.24%, p = 0.555). Conclusion In patients undergoing BP-DES implantation and 1 month DAPT followed by P2Y12 inhibitor monotherapy, patient-related risk factors had an impact on 1-year clinical outcomes, while procedural risk factors no longer had small impact on those outcomes.

Troponin T as a risk marker for recurrent cardiovascular events in the post-discharge setting one month after acute coronary syndrome: a TRACER substudy

Abstract Background Troponin T (TnT) is a protein found in cardiac myocytes that is released during myocardial injury, such as myocardial infarction (MI). TnT levels rapidly rise during an MI, remain elevated for several days, and are a key criterion for diagnosing MI. Additionally, circulating TnT levels may offer prognostic information later, particularly during the rehabilitation phase after an acute coronary syndrome (ACS). Purpose To examine the relationship between circulating TnT at one month after hospitalisation for ACS and subsequent cardiovascular (CV) events. Methods The TRACER trial randomly assigned 12,944 patients diagnosed with non-ST-segment elevation ACS (NSTE-ACS) to receive either vorapaxar or placebo. Plasma samples were obtained after one month, and high-sensitivity (hs)-TnT was measured among 5,313 patients using the Elecsys electrochemiluminescence immunoassays. In this sub-study, the primary composite endpoint was the one-year risk of CV mortality, MI, or ischaemic stroke. Associations with outcomes were evaluated using Cox regression models, both unadjusted and adjusted for clinical baseline characteristics. Results The median concentration of hs-TnT was 11 ng/L one month after hospitalisation for ACS. Higher levels of hs-TnT at one month were associated with older age, coronary artery bypass surgery during the index ACS, male sex, a history of heart failure, renal disease, and diabetes mellitus. The composite outcome of CV mortality, MI, or ischaemic stroke occurred in 381 patients (incidence rate 5.4 per 100 person-years). Hs-TnT at one month after ACS was independently associated with the risk of the composite CV endpoint (relative hazard ratio with 95% confidence interval comparing the third vs. the first sample quartile: 2.40 [1.80 – 3.20]) (see Figure 2). Similarly, hs-TnT, when added to a model including established risk factors, increased the concordance index of the multivariable model from 0.711 to 0.740 (p<0.001). The results were consistent across the different components of the composite endpoint. Conclusions The level of hs-TnT provides useful information on the risk of future CV events in patients when measured one month after an ACS. This information might be useful for optimising secondary preventive treatment following an ACS.Figure.Hs-TnT and composite CV outcome

Delirium and risk of incident cardiovascular events in elderly: data from a global health research network

Abstract Introduction Delirium is a common complication of acute medical disorders. A strong association between cardiovascular events and the occurrence of delirium has been recorded. Thus far, no data are available regarding the risk of incident cardiovascular events after delirium onset in older adults. Methods Using data from TriNetX, a global health federated research network, we performed a propensity score matched (PSM) analysis of older adults (age ≥65 years) admitted to the emergency department (ED) reporting delirium within two weeks, who were compared with those without delirium. We evaluated the occurrence of a composite outcome of cardiovascular events (myocardial infarction, ischemic stroke, heart failure, intracranial haemorrhage, ventricular arrhythmias, takotsubo syndrome, and atrial fibrillation) at 30 days and 1 and 3 years of follow-up. Results 4,480,229 patients were retrieved for the analysis, and 82,693 (1.8%) reported delirium. Before PSM, patients reporting delirium were older, with more prevalent comorbidities. After PSM, a total of 165,386 patients were included in the analysis (mean (SD) age 76.6 (9.0) years, 51.1% females). Throughout the entire follow-up period, the cumulative composite cardiovascular events outcome was significantly higher in patients which reported delirium [Red Line, Figure 1]. Delirium was associated with cardiovascular events at 30 days (HR 1.96, 95% CI 1.92-2.00) ,1 year (HR 1.75, 95% CI 1.72-1.78) and 3 years (HR 1.67, 95% CI 1.64-1.69) of follow-up, as well as for each of its components (Table 1). The presence of delirium was also associated with a higher risk of all-cause death and hospital access (Table 1), evaluated as secondary outcomes. In patients with delirium associated with the occurrence of incident cardiovascular events, there was a higher risk of recurrent cardiovascular events at 1 year (HR 3.11, 95% CI 2.92-3.31) and 3 years (HR 2.84, 95% CI 2.67-3.01) of follow-up. Conclusions In a large, unselected cohort of older adults admitted to ED, occurrence of delirium was associated with a higher risk of cardiovascular events, both in the short and long-term follow-up.Figure 1:Delirium and CV EventsTable 1:Cox Regression Analysis

Superior benefits of sodium-glucose co-transporter-2 inhibitors compared with dipeptidyl peptidase-4 inhibitors for diabetic kidney disease: A cohort study.

To compare cardiorenal outcomes of dipeptidyl peptidase-4 inhibitors (DPP-4is) and sodium-glucose co-transporter-2 inhibitors (SGLT-2is) in a national diabetic kidney disease (DKD) population. A cohort study was conducted using Taiwan's National Health Insurance Research Database and Laboratory Databases. Propensity score-matched prevalent new users of SGLT-2is (n = 1524) and DPP-4is (n = 6005) during 2017-2018 were selected from adults with DKD and an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2. Composite renal outcomes included sustained eGFR decrease, renal failure and renal mortality. Composite cardiovascular (CV) outcomes included acute myocardial infarction, stroke, hospitalization for heart failure and CV death. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Compared with DPP-4i users, SGLT-2i users had a reduced risk of composite renal endpoint (HR: 0.16; CI: 0.12-0.24), consistently for a prolonged time to 50% or higher eGFR decrease (HR 0.17; CI: 0.11-0.27), renal failure (HR: 0.14; CI: 0.08-0.23) and decreased renal death (HR: 0.10; CI: 0.01-0.70). SGLT-2i users had a better composite CV outcome than DPP-4i users (HR: 0.74; CI: 0.64-0.85), and lower risks of stroke (HR: 0.76; CI: 0.62-0.92) and hospitalization for heart failure (HR: 0.68; CI: 0.55-0.84). Findings were consistent in analyses stratified by concomitant antidiabetic agents or intervals between DKD diagnosis and study drug initiation. This study shows the superior cardiorenal benefits of SGLT-2is compared with DPP-4is in the DKD population, regardless of concomitant antidiabetic agents or time from DKD onset to study drug initiation. SGLT-2is should be prioritized in adult patients with DKD.

Hypokalaemia in patients with type 2 diabetes and chronic kidney disease: the effect of finerenone - a FIDELITY analysis.

Hypokalaemia is associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). This exploratory FIDELITY analysis, a prespecified pooled patient-dataset from FIDELIO-DKD and FIGARO-DKD, investigated the incidence and effect of hypokalaemia in patients with CKD and type 2 diabetes (T2D) treated with finerenone vs. placebo. Outcomes include the incidence of treatment-emergent hypokalaemia (serum potassium<4.0 or<3.5mmol/L) and the effect of finerenone on cardiovascular composite outcome (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure) and arrhythmia composite outcome (new diagnosis of atrial fibrillation/atrial flutter, hospitalization due to arrhythmia, or sudden cardiac death) by baseline serum potassium subgroups. In the FIDELITY population, treatment-emergent hypokalaemia with serum potassium<4.0 and<3.5mmol/L occurred in 41.1% and 7.5%, respectively. Hazards of cardiovascular and arrhythmia composite outcomes were higher in patients with baseline serum potassium<4.0vs. 4.0-4.5mmol/L (hazard ratio [HR] 1.16; 95% confidence interval [CI] 1.02-1.32, P=0.022 and HR 1.20; 95% CI 1.00-1.44, P=0.055, respectively). Finerenone reduced the incidence of hypokalaemia with serum potassium<4.0mmol/L (HR 0.63; 95% CI 0.60-0.66) and<3.5mmol/L (HR 0.46; 95% CI 0.40-0.53) vs. placebo. Finerenone lessened the hazard of cardiovascular and arrhythmia events vs. placebo, irrespective of baseline serum potassium. A substantial proportion of patients with CKD and T2D experienced hypokalaemia, which was associated with an increased hazard of adverse cardiovascular outcomes. Finerenone reduced the incidence of hypokalaemia. Finerenone reduced the hazard of cardiovascular and arrhythmia outcomes irrespective of serum potassium subgroups. Clinical trials registration: FIDELIO-DKD and FIGARO-DKD are registered with ClinicalTrials.gov, numbers NCT02540993 and NCT02545049, respectively (funded by Bayer AG).

Cardiac Effects of Renin-Angiotensin System Inhibitors in Nonproteinuric CKD.

In contrast to proteinuric chronic kidney disease (CKD), the relative cardioprotective benefits of antihypertensive medications in nonproteinuric CKD are unknown. We examined long-term cardiovascular outcomes and mortality in patients with nonproteinuric CKD treated with renin-angiotensin system inhibitors (RASIs) versus other antihypertensive medications. Among participants of the CRIC study (Chronic Renal Insufficiency Cohort) without proteinuria, we used intention-to-treat analyses with inverse probability of treatment weighting and Cox proportional hazards modeling to determine the association of RASIs versus other antihypertensive medications with a composite cardiovascular outcome (myocardial infarction, stroke, heart failure hospitalization, and death) and mortality. Secondary analyses included per-protocol analyses accounting for continuous adherence and time-updated analyses accounting for the proportion of time using RASIs during follow-up. A total of 2806 participants met the inclusion criteria. In the intention-to-treat analyses, RASIs versus other antihypertensive medications were not associated with an appreciable difference in cardiovascular events (adjusted hazard ratio [aHR], 0.94 [95% CI, 0.80-1.11]) or mortality (aHR, 1.06 [95% CI, 0.88-1.28]). In the per-protocol analyses, RASIs were associated with a lower risk of adverse cardiovascular events (aHR, 0.78 [95% CI, 0.63-0.97]) and mortality (aHR, 0.64 [95% CI, 0.48-0.85]). Similarly, in the time-updated analyses, a higher proportion of RASI use over time was associated with a lower mortality risk (aHR, 0.33 [95% CI, 0.14-0.86]). Among individuals with nonproteinuric CKD, after accounting for time-updated use, RASIs are associated with fewer cardiovascular events and a lower mortality risk compared with other antihypertensive medications. Patients with nonproteinuric CKD may benefit from prioritizing RASIs for hypertension management.

Impact of TNF-α inhibitor therapy on cardiovascular outcomes in ankylosing spondylitis: a nationwide population-based study.

This study aimed to evaluate the association between tumor necrosis factor-α inhibitor (TNFi) therapy and cardiovascular (CV) outcomes, as well as all-cause mortality, in patients with ankylosing spondylitis (AS). This retrospective cohort study included 24,986 patients newly diagnosed with AS between 2010-2019 without a history of CV diseases, using data from the Korean National Health Insurance Service. CV events were observed through the end of 2021. After exposure density sampling (1:1), we investigated the association among use of TNFi, duration of TNFi use, and risk of the composite CV outcome (ischemic stroke, heart failure, ischemic heart disease, or CV death) and all-cause mortality. Overall, TNFi users (N = 8,650) and non-users (N = 8,580) had a comparable risk of the composite CV outcome. However, prolonged TNFi use (≥ 1 year) was associated with a significantly lower risk of the composite CV outcome [adjusted hazard ratio (aHR): 0.72, 95% CI: 0.55-0.93, p = 0.012] and all-cause mortality (aHR: 0.37, 95% CI: 0.21-0.66, p < 0.001) compared to discontinued TNFi use (< 1 year), with adjustments made for age, sex, disease duration, hypertension, diabetes, hyperlipidemia, chronic kidney disease, non-steroidal anti-inflammatory drug (NSAID) use, body mass index (BMI), and smoking status. TNFi therapy did not reduce CV events in AS patients. However, long-term TNFi therapy is likely to be beneficial in reducing CV events and all-cause mortality compared to discontinuing TNFi therapy in patients with AS.

Finerenone and left ventricular hypertrophy in chronic kidney disease and type 2 diabetes.

Left ventricular hypertrophy (LVH) has been associated with an increased risk of cardiovascular (CV) disease and linked to increased morbidity and mortality. In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), hypertension is common, and patients with these co-morbidities additionally have a high prevalence of LVH. This analysis of the prespecified pooled FIDELITY analysis comprising the randomized, double-blind, placebo-controlled, multicentre FIDELIO-DKD and FIGARO-DKD phase III studies aimed to explore the CV and kidney effects of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in patients with CKD and T2D stratified by a diagnosis of LVH at baseline. A diagnosis of LVH in the FIDELITY patient population was determined at baseline using investigator-reported electrocardiogram (ECG) findings. The two efficacy outcomes, assessed by baseline LVH, were the composite CV outcome of time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure (HHF), and a composite kidney outcome of time to onset of kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR)≥57% from baseline over ≥4weeks, or kidney-related death. Safety outcomes by baseline LVH were reported as treatment-emergent adverse events. At baseline out of 13026 patients in FIDELITY, 96.5% had hypertension and 9.6% had investigator-reported LVH. The relative risk reduction for the composite CV and kidney outcomes with finerenone versus placebo was lower in the LVH subgroup; however, the treatment effect of finerenone was not modified by baseline LVH for either outcome (Pinteraction=0.1075 for composite CV outcome and Pinteraction=0.1782 for composite kidney outcome). Analysis of the composite CV outcome components showed a greater reduction in the risk of HHF versus placebo for patients with baseline LVH compared with those without (Pinteraction=0.0024). Overall safety events were comparable between the LVH subgroups and treatment arms. Treatment-emergent hyperkalaemia was observed more frequently with finerenone versus placebo, but discontinuation rates were low in both treatment arms and between LVH subgroups. In conclusion, the overall CV and kidney benefits of finerenone versus placebo were not modified by the presence of LVH at baseline, with overall safety findings being similar between LVH subgroups. A greater benefit was observed for HHF in patients with versus without LVH, suggesting that LVH may be a predictor of the treatment effect of finerenone on HHF.

Low-dose azithromycin prophylaxis in patients with atrial fibrillation and chronic obstructive pulmonary disease.

Low-dose azithromycin prophylaxis is associated with improved outcomes in people suffering frequent exacerbations of chronic obstructive pulmonary disease (COPD), but the use of macrolides in patients with cardiovascular disease has been debated. To investigate the risk of adverse events after COPD exacerbations in patients with atrial fibrillation (AF) treated with azithromycin prophylaxis. Retrospective cohort study within the TriNetX Platform, including AF patients with COPD exacerbations. Risks of primary and secondary outcomes were recorded up to 30days post-COPD exacerbations and compared between azithromycin users and azithromycin non-users. The primary outcomes were the risks for a composite of (1) cardiovascular (all-cause death, heart failure, ventricular arrhythmias, ischemic stroke, myocardial infarction, and cardiac arrest), and (2) hemorrhagic events (intracranial hemorrhage (ICH), and gastro-intestinal bleeding). Cox-regression analyses compared outcomes between groups after propensity score matching (PSM). After PSM, azithromycin users (n = 2434, 71 ± 10years, 49% females) were associated with a lower 30-day risk of post-exacerbation cardiovascular (HR 0.67, 95% CI 0.61-0.73) and hemorrhagic composite outcome (HR 0.45, 95% CI 0.32-0.64) compared to azithromycin non-users (n = 2434, 72 ± 11years, 51% females). The beneficial effect was consistent for each secondary outcomes, except ICH. On sensitivity analyses, the reduced risk of adverse events in azithromycin users was irrespective of smoking status, exacerbation severity, and type of oral anticoagulation. Azithromycin prophylaxis is associated with a lower risk of all-cause death, thrombotic and hemorrhagic events in AF patients with COPD. The possible role of azithromycin prophylaxis as part of the integrated care management of AF patients with COPD needs further study.

Abstract P152: Association of Cannabis Use with Atherosclerotic Cardiovascular Diseases Outcomes: Insights from a Meta-Analysis of a Multinational Cohort of 1.9 Million Individuals

Background: Despite numerous reports suggesting a link between cannabis use and the risk of atherosclerotic cardiovascular diseases (ASCVD), the nature of this relationship—whether causal or not—remains uncertain. Objective: We aimed to consolidate data from observational studies to examine the association between cannabis use and ASCVD outcomes compared to non-users or controls. Methods: RevMan 5.4 was used for statistical analyses employing a random effects model, and outcomes were presented as risk ratios (RR) with corresponding 95% confidence intervals (CI). The study protocol has been registered with PROSPERO (CRD42024530366). Results: Our analysis integrated data from 17 studies, including 1,902,481 individuals aged 18 to 74, with a mean follow-up duration of 8.5 years. The pooled analysis revealed no statistically significant association between cannabis use and the risk of myocardial infarction compared to non-users, with an RR of 1.25 (95% CI: 0.91 to 1.71, p = 0.17). Similarly, the risk of stroke did not show a significant association with cannabis use (RR: 1.38, 95% CI: 0.88 to 2.16, p = 0.16). However, a statistically significant association was found between cannabis use and the composite outcome of any adverse cardiovascular events (RR: 1.48, 95% CI: 1.16 to 1.90, p = 0.002). Conclusion: The statistical correlations between cannabis use and composite adverse cardiovascular outcomes underscore its potential as a risk factor for cardiovascular disease. With rising trends in medical cannabis use and cannabis use disorder across age demographics, heightened risk awareness, CVD screening, and informed decision-making regarding cannabis consumption are critical priorities in healthcare and public health initiatives.

Acute changes in kidney function and outcomes following an acute myocardial infarction: Insights from PARADISE-MI.

Pharmacologic blockade of neurohormonal pathways in patients with acute myocardial infarction (MI) can result in acute changes in biomarkers of kidney function. We evaluated the effect of sacubitril/valsartan versus ramipril on initial changes in serum creatinine and the association of these changes with longer-term outcomes among participants in PARADISE-MI. In this randomized, double-blind, active-controlled, event-driven trial, 5661 patients with an acute MI were assigned to receive sacubitril/valsartan or ramipril, with no run-in. The frequency of an initial pre-specified increase in serum creatinine (≥26.5 or ≥44 μmol/L) from baseline to week 1 was compared between arms. Multivariable Cox regression models were fit to examine the association of acute changes in serum creatinine with the primary cardiovascular composite outcome (cardiovascular death, first heart failure hospitalization, or outpatient heart failure), all-cause mortality, and longer-term changes in estimated glomerular filtration rate (eGFR). An initial increase in serum creatinine ≥26.5 μmol/L occurred in 155 of 2604 (6.0%) patients assigned to sacubitril/valsartan and 120 of 2603 (4.6%) patients assigned to ramipril (odds ratio [OR] 1.32; 95% confidence interval [CI] 1.03-1.68). The corresponding numbers for an increase ≥44 μmol/L were 57 (2.2%) and 42 (1.6%), respectively (OR 1.37; 95% CI 0.92-2.05). A higher odds of increased serum creatinine ≥26.5 and ≥44 μmol/L for sacubitril/valsartan versus ramipril appeared to be restricted to patients who had a greater decline in systolic blood pressure over the same period (p-interaction = 0.05 and 0.001, respectively). In multivariable analyses, neither an acute increase in serum creatinine ≥26.5 or ≥44 μmol/L was associated with a higher risk of cardiovascular outcomes, all-cause mortality, or differences in longer-term eGFR slope. Findings were similar across the randomized treatment arms (p-interaction >0.6 for all). Following acute MI, patients assigned to sacubitril/valsartan had a higher frequency of initial increases in serum creatinine at 1 week, compared with ramipril. In adjusted models, initial increases in serum creatinine with either treatment were not associated with adverse cardiovascular outcomes or changes in longer-term kidney function.

Association of Cardiovascular Outcomes With Low-Dose Glucocorticoid Prescription in Patients With Rheumatoid Arthritis.

Many guidelines recommend limiting glucocorticoids in patients with rheumatoid arthritis (RA), but 40% of patients remain on glucocorticoids long term. We evaluated the cardiovascular risk of long-term glucocorticoid prescription by studying patients on stable disease-modifying antirheumatic drugs (DMARDs). Using two claims databases, we identified patients with RA on stable DMARD therapy for >180 days. Proportional hazards models with inverse-probability weights and clustering to account for multiple observations were used to estimate the effect of glucocorticoid dose on composite cardiovascular outcomes (stroke or myocardial infarction [MI]). There were 135,583 patients in Medicare and 39,272 in Optum's de-identified Clinformatics Data Mart (CDM) database. Medicare and CDM patients had an incidence of 1.3 and 0.8 composite cardiovascular outcomes per 100 person-years, respectively. In the older, comorbid Medicare cohort, glucocorticoids were associated with a dose-dependent increase in composite cardiovascular outcomes in adjusted models with predicted one-year incidence of 1.4% (95% confidence interval [CI] 1.2%-1.6%) for ≤5 mg, 1.6% (95% CI 1.4%-1.9%) for >5 to 10 mg, and 1.8% (95% CI 1.2%-2.5%) for >10 mg versus 1.1% (95% CI 1.1%-1.2%) among patients not receiving glucocorticoids. There was no significant association among the CDM cohort. However, in the subgroup of younger patients with RA and higher cardiovascular risk, glucocorticoids were associated with a dose-dependent increase in composite cardiovascular outcomes. Among older patients with more comorbidities and younger patients with higher cardiovascular risk with RA on stable DMARD therapy, glucocorticoids were associated with a dose-dependent increased risk of MI and stroke, even at doses ≤5 mg/day. By contrast, no association was noted among younger, healthier patients with RA.

Relation between blood pressure time in range and composite cardiovascular outcomes in patients with primary aldosteronism: a retrospective case study.

To investigate the association between blood pressure (BP) time in range (TIR) and composite cardiovascular outcomes in patients with primary aldosteronism (PA). Between January 2019 and December 2021, 47 patients with PA were recruited from the First Affiliated Hospital of Xiamen University. Twenty-four-hour ambulatory BP monitoring (ABPM) and cardiovascular outcomes were assessed in all patients during the first diagnosis of PA. The mean age of the patients was 48.8 ± 11.4 years. Compared to PA without composite cardiovascular outcomes, the nighttime systolic BP TIR [31.2% (6.2%, 81.2%) vs. 11.5% (0.0%, 29.7%), p = 0.02] and defined daily dose (DDDs) of antihypertensive medication [2.0 (1.0, 2.8) vs. 1.0 (1.0, 2.0), p = 0.03] were lower in PA patients with composite cardiovascular outcomes, while higher glucose (5.0 ± 1.0 mmol/L vs. 5.9 ± 1.5 mmol/L) and prevalence of a history of alcohol intake was higher in PA patients with composite cardiovascular outcomes. There were no differences in age, sex, BMI, smoking, duration of hypertension, lipid levels, aldosteronism, clinic BP, 24-hour mean BP, daytime or nighttime BP, percentage of nocturnal SBP or DBP decline, 24-hour BP TIR, daytime BP TIR, or nighttime DBP TIR between the two groups. After adjusting for confounding factors, nighttime systolic BP TIR was significantly associated with composite cardiovascular outcomes (adjusted OR = 0.92 [95% CI 0.86, 0.99]) in multiple logistic regression analysis. Nighttime systolic BP TIR was significantly associated with composite cardiovascular outcomes in patients with PA.

Heterogeneous Effects of Intensive Glycemic and Blood Pressure on Cardiovascular Events Among Diabetes by Living Arrangements.

Although living alone versus with others is a key social element for cardiovascular prevention in diabetes, evidence is lacking about whether the benefit of intensive glycemic and blood pressure (BP) control differs by living arrangements. We thus aim to investigate heterogeneity in the joint effect of intensive glycemic and BP control on cardiovascular events by living arrangements among participants with diabetes. This study included 4731 participants with diabetes in the ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes-Blood Pressure) trial. They were randomized into 4 study arms, each with glycated hemoglobin target (intensive, <6.0% versus standard, 7.0-7.9%) and systolic BP target (intensive, <120 mm Hg versus standard <140 mm Hg). Cox proportional hazard models were used to estimate the joint effect of intensive glycemic and BP control on the composite cardiovascular outcome according to living arrangements. At a mean follow-up of 4.7 years, the cardiovascular outcome was observed in 445 (9.4%) participants. Among participants living with others, intensive treatment for both glycemia and BP showed decreased risk of cardiovascular events compared with standard treatment (hazard ratio [HR], 0.68 [95% CI, 0.51-0.92]). However, this association was not found among participants living alone (HR, 0.96 [95% CI, 0.58-1.59]). P for interaction between intensive glycemic and BP control was 0.53 among participants living with others and 0.009 among those living alone (P value for 3-way interaction including living arrangements was 0.049). We found benefits of combining intensive glycemic and BP control for cardiovascular outcomes among participants living with others but not among those living alone. Our study highlights the critical role of living arrangements in intensive care among patients with diabetes.

R2-CHA2DS2-VASc Score for Cardiovascular Event Prediction After Bioprosthetic Valve Replacement - Subanalysis From the BPV-AF Registry.

There are few studies evaluating the prognostic prediction method in atrial fibrillation (AF) patients after bioprosthetic valve (BPV) replacement. The R2-CHA2DS2-VASc score is increasingly used for the prediction of cardiovascular (CV) events in patients with AF, device implantation, and acute coronary syndrome. We aimed to evaluate the predictive value of the R2-CHA2DS2-VASc score for future CV events in AF patients after BPV replacement. The BPV-AF, an observational, multicenter, prospective registry, enrolled AF patients who underwent BPV replacement. The primary outcome measure was a composite of stroke, systemic embolism, CV events including heart failure requiring hospitalization, and cardiac death. A total of 766 patients was included in the analysis. The mean R2-CHA2DS2-VASc score was 5.7±1.8. Low (scores 0-1), moderate (scores 2-4), and high (scores 5-11) R2-CHA2DS2-VASc score groups consisted of 12 (1.6%), 178 (23.2%), and 576 (75.2%) patients, respectively. The median follow-up period was 491 (interquartile range 393-561) days. Kaplan-Meier analysis showed a higher incidence of the composite CV events in the high R2-CHA2DS2-VASc score group (log rank test; P<0.001). Multivariate Cox proportional hazards regression analysis revealed that the R2-CHA2DS2-VASc score as a continuous variable was an independent predictor of composite CV outcomes (hazard ratio 1.36; 95% confidence interval 1.18-1.55; P<0.001). The R2-CHA2DS2-VASc score is useful for CV risk stratification in AF patients after BPV replacement.

Association of cardiovascular events with central systolic blood pressure: A systemic review and meta-analysis.

Central blood pressure confers cardiovascular risk prediction ability, but whether the association between central systolic blood pressure (cSBP) and cardiovascular endpoints is independent of peripheral systolic blood pressure (pSBP) remains controversial. This systematic review and meta-analysis aim to investigate the associations between cSBP and cardiovascular endpoints in models including and excluding pSBP, respectively. Observational studies assessing the risk of composite cardiovascular endpoints with baseline cSBP were searched in PubMed, Embase, Scopus, Web of Science, and Cochrane Library to May 31, 2022. Risk of bias was assessed by the Newcastle-Ottawa Quality Assessment Scale, and random-effects models were used to pool estimates. Finally, 48 200 participants from 19 studies with a mean age of 59.0±6.9 years were included. Per 10mmHg increase of cSBP was associated with higher risk of composite cardiovascular outcomes (risk ratio [RR]: 1.14 [95%CI 1.08-1.19]) and cardiovascular death (RR: 1.18 [95%CI 1.08-1.30]), and the associations still existed after adjusting for pSBP (RR: 1.13 [95%CI 1.05-1.21] for composite cardiovascular endpoints; RR: 1.25 [95%CI 1.09-1.43] for cardiovascular death). In pSBP-unadjusted studies, increased cSBP was also associated with higher risk of all-cause mortality and stroke, but not in the pSBP-adjusted studies. Both cSBP and pSBP were similarly significantly associated with composite cardiovascular endpoints in models containing them separately and simultaneously. cSBP was significantly associated with cardiovascular events, independently of pSBP. Central or peripheral SBP could supplement cardiovascular risk assessment besides each other.

Design and baseline characteristics of the Finerenone, in addition to standard of care, on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease (FIND-CKD) randomized trial

ABSTRACT Background Finerenone, a non-steroidal mineralocorticoid receptor antagonist, improved kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes in two phase 3 outcome trials. The Finerenone, in addition to standard of care, on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease (FIND-CKD) study investigates the effect of finerenone in adults with CKD without diabetes. Methods FIND-CKD (NCT05047263 and EU CT 2023-506897-11-00) is a randomized, double-blind, placebo-controlled phase 3 trial in patients with CKD of non-diabetic aetiology. Adults with a urinary albumin:creatinine ratio (UACR) ≥200–≤3500 mg/g and an estimated glomerular filtration rate (eGFR) ≥25–&amp;lt;90 ml/min/1.73 m2 receiving a maximum tolerated dose of a renin–angiotensin system inhibitor were randomized 1:1 to once-daily placebo or finerenone 10 or 20 mg depending on eGFR &amp;gt;60 or &amp;lt;60 ml/min/1.73 m2. The primary efficacy outcome is total eGFR slope, defined as the mean annual rate of change in eGFR from baseline to month 32. Secondary efficacy outcomes include a combined cardiorenal composite outcome comprising time to kidney failure, sustained ≥57% decrease in eGFR, hospitalization for heart failure or cardiovascular death, as well as separate kidney and cardiovascular composite outcomes. Adverse events are recorded to assess tolerability and safety. Results Across 24 countries, 3231 patients were screened and 1584 were randomized to study treatment. The most common causes of CKD were chronic glomerulonephritis (57.0%) and hypertensive/ischaemic nephropathy (29.0%). Immunoglobulin A nephropathy was the most common glomerulonephritis (26.3% of the total population). At baseline, mean eGFR and median UACR were 46.7 ml/min/1.73 m2 and 818.9 mg/g, respectively. Diuretics were used by 282 participants (17.8%), statins by 851 (53.7%) and calcium channel blockers by 794 (50.1%). Sodium–glucose co-transporter 2 (SGLT2) inhibitors were used in 16.9% of patients; these individuals had a similar mean eGFR (45.6 versus 46.8 ml/min/1.73 m2) and a slightly higher median UACR (871.9 versus 808.3 mg/g) compared with those not using SGLT2 inhibitors at baseline. Conclusions FIND-CKD is the first phase 3 trial of finerenone in patients with CKD of non-diabetic aetiology.

Long-term prosthetic-associated subclinical thrombotic events evaluation by cardiac CTA after transcatheter aortic valve implantation: incidence and outcomes

ObjectiveTo observe prosthetic-associated subclinical thrombotic events (PASTE) after transcatheter aortic valve implantation (TAVI) by cardiac CTA, and assess their impact on long-term patient outcomes.MaterialsWe prospectively and consecutively enrolled 188 patients with severe aortic stenosis treated with TAVI from February 2014 to April 2017. At 5 years, 61 of 141 survived patients who had completed annual follow-up CTA (≥ 5 years) were included. We analyzed PASTE by CTA, including hypoattenuated leaflet thickening (HALT), sinus filling defect (SFD), and prosthesis filling defect (PFD). The primary outcome was a major adverse cardiovascular composite outcome (MACCO) of stroke, cardiac re-hospitalization, and bioprosthetic valve dysfunction (BVD); the secondary outcomes were bioprosthetic hemodynamics deterioration (PGmean) and cardiac dysfunction (LVEF).ResultsDuring a median follow-up time of 5.25 years, long-term incidence of HALT, SFD, and PFD were 54.1%, 37.7%, and 73.8%, respectively. In the primary outcome, SFD and early SFD were associated with the MACCO (SFD: p = 0.005; early SFD: p = 0.018), and SFD was a predictor of MACCO (HR: 2.870; 95% CI: 1.010 to 8.154, p = 0.048). In the secondary outcomes, HALT was associated with increased PGmean (p = 0.031), while persistent HALT was correlated with ΔPGmean (β = 0.38, p = 0.035). SFD was negatively correlated with ΔLVEF (β = −0.39, p = 0.041), and early SFD was negatively correlated with LVEF and ΔLVEF (LVEF: r = −0.50, p = 0.041; ΔLVEF: r = −0.53, p = 0.030).ConclusionsPASTE were associated with adverse long-term outcomes, bioprosthetic hemodynamics deterioration, and cardiac dysfunction. In particular, SFD was a predictor of MACCO and may be a potential target for anticoagulation after TAVI (NCT02803294).RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT02803294.Critical relevance statementPASTE, especially SFD, after TAVI based on cardiac CTA findings impacts the long-term outcomes of patients which is a predictor of long-term major adverse outcomes in patients and may be a potential target for anticoagulation after TAVI.Key PointsTranscatheter aortic valve implantation is being used more often; associated subclinical thromboses have not been thoroughly evaluated.Prosthetic-associated subclinical thrombotic events were associated with adverse outcomes, bioprosthetic hemodynamics deterioration, and cardiac dysfunction.Studies should be directed at these topics to determine if they should be intervened upon.Graphical