Risk Of Cardiovascular Events Research Articles

"Extreme sports" in patients with heart disease: an informative approach to patient counseling

The term "extreme sports" includes a range of sporting activities, predominantly individual, practised outdoors in a wild and non-competitive environment, which have in common the critical role of environmental variables, the importance of qualitative parameters in evaluating performance, the centrality of technological elements and the high perceived risk which, together with the spectacularity, attracts the attention of the media, favoring its popularity. Despite their diversity, these disciplines share specific risks and physiological and pathophysiological aspects. The average age of participants is generally higher than that of traditional and competitive sports, and the prevalence of male subjects implies a higher likelihood of cardiological evaluation whose path has yet to be codified like that of traditional sports. The risk of severe injuries in these sports is not higher than that of traditional sports and non-sporting activities. In contrast, the risk of cardiovascular events is documented only for some sports practised in the mountains, such as mountaineering, skiing and mountain biking, and it does not appear to be higher than that of equivalent physical activities performed at low altitudes. The diagnostic and prognostic criteria for cardiological counseling of enthusiasts are not defined. Environmental exposure to extremes of temperature, altitude, wind and humidity, and dehydration are typical characteristics of these activities, which should be addressed with adequate experience, preparation and equipment to minimize the potential impact on health. Finally, many of these activities are often conducted in "remote areas" compared to the possibility of emergency response, which should be considered in the risk assessment of an acute cardiovascular event. The definition of cardiovascular risk constitutes an open area of research to allow the practice of these sports to an increasing number of participants.

The burden of cardiovascular disease and risk for subsequent major adverse cardiovascular events in survivors of childhood cancer: a prospective, longitudinal analysis from the St Jude Lifetime Cohort Study

The burden of cardiovascular disease and risk for subsequent major adverse cardiovascular events in survivors of childhood cancer: a prospective, longitudinal analysis from the St Jude Lifetime Cohort Study

Temporal trends in use of antisecretory agents among patients administered clopidogrel-based dual antiplatelet therapy after percutaneous coronary intervention.

Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after percutaneous coronary intervention (PCI). However, omeprazole and esomeprazole (inhibiting proton pump inhibitors [PPIs]) may increase cardiovascular event rates on co-administration with clopidogrel. This study aimed to examine trends in the use of antisecretory agents in patients administered clopidogrel-based DAPT and the concomitant use of clopidogrel and inhibiting PPIs. We used National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service from 2009 to 2020. Further, we identified patients who were prescribed clopidogrel-based DAPT after PCI and investigated the concomitant use of antisecretory agents with clopidogrel. To verify the annual trend of drug utilization, we used the Cochran-Armitage trend test. From 2009 to 2020, the percentage of H2 receptor antagonist users decreased steadily (from 82.5% in 2009 to 25.3% in 2020); instead, the percentage of PPI users increased (from 23.7% in 2009 to 82.0% in 2020). The use of inhibiting PPI also increased (from 4.2% in 2009 to 30.7% in 2020). Potassium competitive acid blockers (P-CABs) were rarely used before 2019; however, in 2020, it accounted for 7.8% of the antisecretory users. Our study demonstrates that the use of inhibiting PPIs increased steadily in patients administered clopidogrel-based DAPT therapy. This is a major concern since the concomitant use of inhibiting PPIs with clopidogrel could increase the risk of cardiovascular events.

Eosinophilic esophagitis and risk of incident major adverse cardiovascular events: a nationwide matched cohort study.

Inflammatory diseases have been associated with an increased cardiovascular risk. However, data on incident major adverse cardiovascular events (MACE) from large population-based cohorts of patients with eosinophilic esophagitis (EoE) is lacking. This study included all Swedish adults with EoE without a record of previous cardiovascular disease (CVD) (1990-2017, N = 1546) with follow-up until 2019. Individuals with EoE were identified from prospectively recorded histopathology reports from all Swedish pathology departments (n = 28). EoE patients were matched at index date for age, sex, calendar year and county with up to five general population reference individuals (N = 7281) without EoE or CVD. Multivariable-adjusted hazard ratios (aHRs) for MACE (ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality) were calculated using Cox proportional hazards models. Full sibling comparisons and adjustment for cardiovascular medication were performed. During a median follow-up of 6.0years, we observed 65 incident MACE in patients with EoE (6.4/1000 person-years (PY)) and 225 in reference individuals (4.7/1000 PY). EoE was not associated with a higher risk of MACE (aHR = 1.14, 95% CI = 0.86-1.51) or any of its components. No differences between age, sex and follow-up time were observed. The results remained stable in sensitivity analyses, including when adjusting for relevant cardiovascular medications and a full sibling comparison. In this large population-based cohort study, patients with EoE had no increased risk of MACE compared to reference individuals and full siblings. The results are reassuring for patients with EoE.

Correlation of hematocrit and cardiovascular events in peritoneal dialysis patients

Objective: To investigate the correlation between hematocrit (HCT) and cardiovascular events in peritoneal dialysis (PD) patients. Methods: Patients undergoing maintenance PD in the PD center of Guizhou Provincial People's Hospital from March 19, 2012 to July 9, 2020 were included. Demographic, baseline clinical and laboratory data of the patients were collected and patients were followed up until April 8, 2022. The primary endpoint was the first occurrence of a cardiovascular event. According to the tertiles of baseline HCT, the patients were divided into group Q1 (HCT≤26.6%), group Q2 (HCT>26.6%-32.4%), and group Q3 (HCT>32.4%). Laboratory indexes and cardiovascular events were compared among the three groups. Kaplan-Meier survival curve, Cox regression analysis and sensitivity analysis were used to analyze the effect of HCT on cardiovascular outcomes. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of HCT for cardiovascular events in PD patients. Results: A total of 860 PD patients were included, including 494 males (57.4%) and 366 females (42.6%), with a mean age of (41.5±15.0) years. There were 287 cases in group Q1, 289 cases in group Q2, and 284 cases in group Q3, respectively. A total of 265 (30.8%) patients experienced first cardiovascular events during the follow-up period. The incidence of cardiovascular events in groups Q1, Q2 and Q3 was 36.2% (104/287), 34.3% (99/289), and 21.8% (62/284), respectively, with a statistically significant difference (P<0.001). The incidence of cardiovascular events decreased with the increase of HCT. Multivariate Cox proportional hazards regression model analysis showed that decreased HCT was a risk factor for cardiovascular events. Compared with group Q3, the risk of cardiovascular events in group Q1 increased by 50.7% (group Q2: HR=1.444, 95%CI: 1.029-2.028, P=0.034; group Q1: HR=1.570, 95%CI: 1.096-2.250, P=0.014). In the sensitivity analysis, using kidney transplantation as the competition event, the risk of cardiovascular events was lower in group Q3 than that in group Q1 (subdistributional HR=1.413, 95%CI: 1.006-1.990, P=0.046). Kaplan-Meier survival curve showed that compared with the other two groups, the cardiovascular events-free survival rate of patients in group Q1 was significantly lower (log-rank χ2=9.722, P=0.008). ROC analysis showed that the area under the curve (AUC) of HCT for predicting cardiovascular events in PD patients was 0.583 (95%CI: 0.542-0.623, P<0.001), with the sensitivity of 40.6% and the specificity of 75.1%. Conclusion: Low-level HCT is associated with an increased risk of the first cardiovascular event in PD patients.

Platelet-fibrin clot strength and platelet reactivity predicting cardiovascular events after percutaneous coronary interventions.

Platelet-fibrin clot strength (PFCS) is linked to major adverse cardiovascular event (MACE) risk. However, the association between PFCS and platelet reactivity and their prognostic implication remains uncertain in patients undergoing percutaneous coronary intervention (PCI). In PCI-treated patients (n = 2512) from registry data from January 2010 to November 2018 in South Korea, PFCS using thromboelastography and platelet reactivity using VerifyNow were measured. High PFCS (PFCSHigh) was defined as thromboelastography maximal amplitude ≥ 68 mm, and high platelet reactivity (HPR) was defined as >208 P2Y12 reaction units. Patients were stratified into four groups according to maximal amplitude and P2Y12 reaction unit levels: (i) normal platelet reactivity (NPR)-PFCSNormal (31.8%), (ii) HPR-PFCSNormal (29.0%), (iii) NPR-PFCSHigh (18.1%), and (iv) HPR-PFCSHigh (21.1%). Major adverse cardiovascular event (all-cause death, myocardial infarction, or stroke) and major bleeding were followed up to 4 years. High platelet reactivity and PFCSHigh showed an additive effect for clinical outcomes (log-rank test, P < .001). Individuals with NPR-PFCSNormal, NPR-PFCSHigh, HPR-PFCSNormal, and HPR-PFCSHigh demonstrated MACE incidences of 7.5%, 12.6%, 13.4%, and 19.3%, respectively. The HPR-PFCSHigh group showed significantly higher risks of MACE compared with the NPR-PFCSNormal group [adjusted hazard ratio (HRadj) 1.89; 95% confidence interval (CI) 1.23-2.91; P = .004] and the HPR-PFCSNormal group (HRadj 1.60; 95% CI 1.12-2.27; P = .009). Similar results were observed for all-cause death. Compared with HPR-PFCSNormal phenotype, NPR-PFCSNormal phenotype was associated with a higher risk of major bleeding (HRadj 3.12; 95% CI 1.30-7.69; P = .010). In PCI patients, PFCS and platelet reactivity demonstrated important relationships in predicting clinical prognosis. Their combined assessment may enhance post-PCI risk stratification for personalized antithrombotic therapy.

Cardiovascular safety of dihydroergotamine mesylate delivered by precision olfactory delivery (INP104) for the acute treatment of migraine.

To report the cardiovascular (CV) safety of dihydroergotamine mesylate (DHE) administered by precision olfactory delivery (INP104) from two clinical trials. Although the absolute risk is low, migraine is associated with an increased risk of CV events. DHE is a highly effective acute treatment for migraine, but due to its theoretical risk of promoting arterial vasoconstriction, DHE is contraindicated in patients with CV disease or an unfavorable risk factor profile. The INP104 is a novel drug-device combination product approved for acute treatment of migraine that delivers DHE to the upper nasal space using precision olfactory delivery (POD®). The STOP 101 was a Phase 1 open-label study that assessed the safety, tolerability, and bioavailability of INP104 1.45 mg, intravenous DHE 1.0 mg, and MIGRANAL (nasal DHE) 2.0 mg in healthy participants. The STOP 301 was a pivotal Phase 3, open-label study that assessed the safety, tolerability, and exploratory efficacy of INP104 1.45 mg over 24 and 52 weeks in patients with migraine. In both studies, active or a history of CV disease, as well as significant CV risk factors, were exclusion criteria. In STOP 101, 36 participants received one or more doses of investigational product. Treatment with intravenous DHE, but not INP104 or nasal DHE, resulted in clinically relevant changes from baseline in systolic blood pressure (BP; 11.4 mmHg, 95% confidence interval [CI] 7.9-15.0) and diastolic BP (13.3 mmHg, 95% CI 9.4-17.1) at 5 min post-dose, persisting up to 30 min post-dose for systolic BP (6.3 mmHg; 95% CI 3.0-9.5) and diastolic BP (7.9 mmHg, 95% CI 3.9-11.9). None of the treatments produced any clinically meaningful electrocardiogram (ECG) changes. In STOP 301, 354 patients received one or more doses of INP104. Over 24 weeks, five patients (1.4%) experienced a non-serious, vascular treatment-emergent adverse event (TEAE). Minimal changes were observed for BP and ECG parameters over 24 or 52 weeks. Off-protocol concomitant use of triptans and other ergot derivatives did not result in any TEAEs. In two separate studies, INP104 demonstrated a favorable CV safety profile when used in a study population without CV-related contraindications.

Dietary habits and compliance with dietary guidelines in patients with established cardiovascular disease.

Unhealthy dietary habits are an important risk factor for cardiovascular disease (CVD) and adopting a healthy diet is a central recommendation in CVD prevention. This study assessed the dietary habits of patients with established CVD, their compliance to dietary guidelines, and the relationship between guideline-compliance and recurrent cardiovascular event risk. 2656 patients with established CVD from the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (UCC-SMART) prospective cohort study, were included between 1996 and 2022. Data on dietary intake was retrospectively collected for all participants in December 2022 using a 160-item food frequency questionnaire. Compliance with dietary guidelines was quantified using an amended version of the Dutch Healthy Diet 2015 (DHD-15) index (range: 0-135). Cox proportional hazard models were used to quantify the relationship with cardiovascular events (stroke and myocardial infarction). Among 2656 CVD patients (77% male, mean age 59 ± 9 years), median energy intake was 1922 [IQR: 1536-2351] kcal/day. The median DHD-15 index was 81.7 [IQR 71.2-92.0], with high compliance scores for recommendations on legumes and fish, and low scores for recommendations on whole grains, red meat, processed meat, and dairy. A higher DHD-15 score was associated with lower stroke risk (HR 0.78, 95% CI 0.66-0.92 per 10-point increase) but not with myocardial infarction. Compliance with dietary guidelines was suboptimal in patients with established CVD. High compliance was associated with a clinically significant reduction in stroke risk in patients with established CVD, emphasizing the importance of dietary counseling.

Renal artery stenosis increases the risk of incident atrial fibrillation and cardiovascular events incorporating death

Abstract Background Renal artery stenosis (RAS) remains an under-recognized clinical risk factor for cardiovascular complications. Its long-term impact on AF arrhythmogenesis is unclear. Objective To investigate the role of RAS on incident AF and related adverse cardiovascular events Methods We performed a retrospective cohort study that comprised 100 patients with ultrasonographically-confirmed atherosclerotic RAS, and 50 age- and sex-matched controls who were healthy renal transplant donors (age 52.6 ±5.6 vs 50.1 ±10.7years, women 59% vs 70%). Incident AF was ascertained from clinical records. Primary endpoint was defined as the composite of incident AF, myocardial infarction, unstable angina, heart failure, ischemic stroke, peripheral arterial disease, end-stage renal failure, and cardiovascular death. Results Over a follow-up duration of 4818 ± 2751 days, RAS was significantly associated with incident AF (9.4% versus 0%, P=0.025). Kaplan-Meier analyses showed that RAS was associated with reduced incident AF event-free survival (Log-rank Mantel-Cox=4.6 P=0.032, Figure). Multivariable logistic regression showed that after adjustment for potential confounders (including age, sex, smoking, alcohol use, history of hypertension, diabetes mellitus, myocardial infarction, heart failure, ischemic stroke, renal function and serum low-density lipoprotein level), RAS was independently associated with substantially increased risk of the primary endpoint (OR=27.8, 95%CI [2.3 – 333.9], P=0.009), Conclusions RAS is an important and under-recognized independent risk factor for AF and cardiovascular events incorporating death. Its pathophysiological implications with a view to potential interventions need to be further explored.

Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes.

Patients with type 2 diabetes and chronic kidney disease are at high risk for kidney failure, cardiovascular events, and death. Whether treatment with semaglutide would mitigate these risks is unknown. We randomly assigned patients with type 2 diabetes and chronic kidney disease (defined by an estimated glomerular filtration rate [eGFR] of 50 to 75 ml per minute per 1.73 m2 of body-surface area and a urinary albumin-to-creatinine ratio [with albumin measured in milligrams and creatinine measured in grams] of >300 and <5000 or an eGFR of 25 to <50 ml per minute per 1.73 m2 and a urinary albumin-to-creatinine ratio of >100 and <5000) to receive subcutaneous semaglutide at a dose of 1.0 mg weekly or placebo. The primary outcome was major kidney disease events, a composite of the onset of kidney failure (dialysis, transplantation, or an eGFR of <15 ml per minute per 1.73 m2), at least a 50% reduction in the eGFR from baseline, or death from kidney-related or cardiovascular causes. Prespecified confirmatory secondary outcomes were tested hierarchically. Among the 3533 participants who underwent randomization (1767 in the semaglutide group and 1766 in the placebo group), median follow-up was 3.4 years, after early trial cessation was recommended at a prespecified interim analysis. The risk of a primary-outcome event was 24% lower in the semaglutide group than in the placebo group (331 vs. 410 first events; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.88; P = 0.0003). Results were similar for a composite of the kidney-specific components of the primary outcome (hazard ratio, 0.79; 95% CI, 0.66 to 0.94) and for death from cardiovascular causes (hazard ratio, 0.71; 95% CI, 0.56 to 0.89). The results for all confirmatory secondary outcomes favored semaglutide: the mean annual eGFR slope was less steep (indicating a slower decrease) by 1.16 ml per minute per 1.73 m2 in the semaglutide group (P<0.001), the risk of major cardiovascular events 18% lower (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P = 0.029), and the risk of death from any cause 20% lower (hazard ratio, 0.80; 95% CI, 0.67 to 0.95, P = 0.01). Serious adverse events were reported in a lower percentage of participants in the semaglutide group than in the placebo group (49.6% vs. 53.8%). Semaglutide reduced the risk of clinically important kidney outcomes and death from cardiovascular causes in patients with type 2 diabetes and chronic kidney disease. (Funded by Novo Nordisk; FLOW ClinicalTrials.gov number, NCT03819153.).

Physical activity change after early rhythm control after new-onset atrial fibrillation and major adverse cardiovascular event risk

Abstract Background There is paucity of information about major adverse cardiovascular event (MACE) related to physical activity change after early rhythm control (ERC) after new-onset atrial fibrillation (AF). We investigated the association between physical activity after ERC and clinical outcomes in new-onset AF patients. Methods This study was performed based on the Korean National Health Insurance Service database. We included adults with new-onset AF between 2009 and 2018. Patients who received national health screening examination before and after AF diagnosis within 2-year were finally included (n=161,379). Among these, 48,243 patients were received rhythm control within 2-year after AF diagnosis. Patients were categorized into 4 groups as follows: persistent non-exerciser, new exerciser (after AF diagnosis and ERC), exercise maintainer, and exercise quitter (after AF diagnosis and ERC). The primary outcome was MACE defined as the composite of ischemic stroke, myocardial infarction, and hospitalization for heart failure. Multivariable Cox analysis was performed. Results Among 48,243 patients receiving ERC, 63% (n=30,540) was persistent non-exerciser, 13% (n=6260) was new exerciser, 11% (n=5102) was exercise maintainer, and 13% (n=6341) was exercise quitter. After multivariable adjustment, compared to persistent non-exerciser, new exerciser and exercise maintainer with ERC showed lower risk of MACE by 10% and 19%, respectively (adjusted hazard ratio [aHR], 95% confidence interval [95% CI], 0.903 [0.802-0.994] for new exerciser, and 0.810 [0.725-0.906] for exercise maintainer) (Table 1). However, exercise quitter did not show significant benefit compared to persistent non-exerciser (Table 1). To assess the synergistic effect of ERC and starting or maintaining physical activity, we performed exploratory analysis including patients who did not receive ERC. Compared to persistent non-exerciser without ERC, persistent non-exerciser with ERC was associated with a significantly lower risk of MACE (0.832 [0.797-0.868], Table 2). Patients who received ERC and started or maintained physical activity with ERC showed greatest risk reduction for MACE by 27% and 36%, respectively (0.732 [0.668-0.802] for new exerciser and 0.641 [0.576-0.713] for exercise maintainer) (Table 2). Conclusion Even in context with beneficial effect of ERC in patients with new-onset AF, maintaining or starting regular physical activity after ERC might bring greater reduction on the risk of MACE. Physician should emphasize healthy lifestyle behavior with rhythm control in patients with new-onset AF.

#233 Marine n-3 polyunsaturated fatty acids and cardiovascular events in patients with end-stage renal disease receiving hemodialysis

Abstract Background and Aims Cardiovascular (CV) disease is the leading cause of death in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD). The two major marine n-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may have cardioprotective effects. This study aimed to investigate the predictive value of plasma n-3 PUFAs on CV events and all-cause mortality in patients with ESRD receiving HD. Method A validated prospective multicenter cohort study of 336 patients with ESRD receiving HD with 5 years of follow-up was conducted. Blood samples were collected at baseline and analyzed for the plasma levels of EPA and DHA expressed as a weight percentage (wt%) of total plasma fatty acids. The primary outcome was CV events defined as acute myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, peripheral artery disease (PAD), or cardiovascular mortality. The secondary outcomes were all-cause mortality and each individual component of CV events. The sum of EPA and DHA (EPA+DHA) was used in all analyses and expressed as n-3 PUFAs in wt%. The population was divided into three groups according to n-3 PUFA tertiles. Kaplan-Meier curves and multivariable Cox regressions adjusted for relevant confounders were used to analyze the association between plasma n-3 PUFA levels and study outcomes. Results Median follow-up time was 5.05 years (IQR, 5.02-5.07). Mean age was 65 ± 15 years and plasma n-3 PUFA levels ranged from 2.1 to 16.8 wt%, with a median of 5.7 wt% (IQR, 4.72-6.96 wt%). During follow-up 60% of the cohort died, 17% died of CV disease, and 42% had a CV event. Figure 1 shows the unadjusted associations between the plasma n-3 PUFA tertiles and the risk of CV events. A n-3 PUFA level between 5.06-6.52 wt% was associated with a 36% lower risk of CV events [unadjusted HR 0.64 (95% CI 0.43-0.96)]. Additionally, a n-3 PUFA level above 6.52 wt% was associated with a 34% lower risk of CV events [unadjusted HR 0.66 (95% CI 0.44-0.98)], both in comparison to levels below 5.06 wt%. After adjusting for relevant confounders, as shown in Figure 2, n-3 PUFA levels between 5.06 to 6.52 wt% were associated with a significantly lower risk of CV events [adjusted HR 0.60 (95% CI 0.40-0.92)], PAD [adjusted HR 0.44 (95% CI 0.22-0.88)], and all-cause mortality [adjusted HR 0.61 (95% CI 0.42-0.86)], when compared to levels below 5.06 wt%. Conclusion In this study of patients with ESRD receiving HD, a low plasma level of n-3 PUFA was associated with a higher risk of CV events, peripheral artery disease, and all-cause mortality.

Combination therapy of beta-blockers and digoxin is associated with increased risk of major adverse cardiovascular events and all-cause mortality in patients with atrial fibrillation: a report from the GLORIA-AF registry.

The effect of digoxin and beta-blockers on cardiovascular outcomes and mortality remains unclear. The study aimed to determine differences in cardiovascular (CV) outcomes and death rates among patients with atrial fibrillation (AF) who were prescribed with beta-blockers, digoxin or combination therapy. Data from phase II/III of the prospective Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) were analysed. The risk of major cardiovascular events (MACE) and death among patients with different prescriptions using COX proportional hazard regression was considered. Propensity score (PS) matching and weighting were further used to adjust for potential confounders of prescription use. A total of 14,201 patients [median age: 71.0 (IQR 64.0-77.0) years; 46.2% female] were recruited. After a median follow-up of 3.0 (IQR 2.4-3.1) years, 864 MACE, and 988 all-cause deaths were recorded. The incidence rate (IR) of MACE was 22.4 (95%CI 21.0-24.0) per 1000 person-years, while the IR of all-cause death was 25.4 (95%CI 23.8-27.0) per 1000 person-years. After multivariate adjustment with Cox regression, the risk of MACE (HR 1.35, 95% CI 1.09-1.68) and the risk of all-cause death (HR 1.28, 95%CI 1.04-1.57) were significantly higher in the combination therapy group, compared to the beta-blockers alone group. The risks of MACE and all-cause death remained significant in both PS matched and PS weighted cohort Among AF patients, combination therapy of beta-blockers and digoxin was associated with higher risks of MACE and all-cause death compared to beta-blockers alone.

#1185 Cardiovascular, renal and mortality risk by the KDIGO risk classification: the first observational study in Japan

Abstract Background and Aims The prevalence of chronic kidney disease (CKD) has been increasing, affecting 850 million people worldwide and 13 million individuals in Japan. CKD is a risk factor for cardiovascular complications including heart failure, and dialysis. KDIGO risk classification is widely used for the management of people with CKD in Japan; however, risk of clinical outcomes by the KDIGO classification in Japanese population is unclear. The aim of this study is to describe the risk of major adverse cardiovascular event (MACE) and renal outcomes according to the KDIGO classification in Japanese clinical practice. Method This study was a cohort study using data collated from the RWD database which includes electronic medical records and claims data from approximately 200 medical institutions across Japan since 2000. Subjects aged ≥18 years with two or more consecutive results of eGFR &amp;lt;90 mL/min/1.73 m2 at least 90 days apart within a 360-day period were included, and those received renal replacement therapy (RRT; dialysis or renal transplantation) before the index date was excluded. The index date was defined as the date of the second eGFR measurement &amp;lt;90 mL/min/1.73 m2 between January 2004 and December 2020. Patients were categorized into KDIGO classification G2-G5 based on their eGFR values and A1-A3 based on urine protein test (quantitative test and urine dipstick) results and into `no urine protein data` if no urine protein test was available. The primary endpoint was MACE that was defined as a composite of myocardial infarction, stroke, heart failure hospitalization, and in-hospital death. The secondary endpoint was renal outcomes defined as a composite of RRT, eGFR decline &amp;gt;50%, eGFR &amp;lt;15 mL/min/1.73 m2, diagnosis of CKD stage 5, and in-hospital death, and was analyzed in the group excluding patients with eGFR &amp;lt;15 mL/min/1.73 m2 or with diagnosis of stage 5 CKD on or before the index date. The risk of MACE and renal outcomes were evaluated using the cox proportional hazards model with G2A1 as a reference. Sensitivity analyses were performed for the population excluding those without urine protein data and for the population with quantitative urine protein test results. Results This study included 543,606 patients who met the criteria. Mean age was 61.6 ± 15.3 years, and 50.1% was male. Of those, 222,246 (40.9%) had no urine protein data. Tables 1 and 2 show hazard ratio (HR) for MACE and renal outcomes, respectively. HR (95% confidence interval) for MACE was 1.17 (1.12-1.21) in G2A2 and 1.16 (1.12-1.20) in G3aA1, showing significantly increased risk in early stages of CKD, and continued to increase as disease advances to 2.83 (2.54-3.15) in G5A3. HR for renal outcomes was similarly significantly increased in early stages of CKD, and further increased to 19.96 (18.62-21.40) in G4A3. Results of two sensitivity analyses, excluding subjects with no urine protein data (n = 321,360, 59.1% of overall population) shown in Table 3 and 4, and excluding patients with no quantitative data (n = 36,615, 6.7% of overall population) showed similar trends, supporting the robustness of primary findings. Conclusion This study is the first to demonstrate the applicability of the KDIGO risk classification in assessing the risk of cardiovascular events, including heart failure, and renal outcomes in Japan. Risk of events was increased from early stages of CKD (G3aA1 and G2A2), suggesting the importance of early diagnosis and therapeutic intervention through appropriate testing. These findings may contribute to better management of people with CKD.

#1992 Triglyceride-glucose index and risk of cardiovascular events, graft loss and new onset diabetes after transplantation in renal transplant recipients

Abstract Background and Aims Insulin resistance is prevalent disorder, but its clinical significance remains undetermined in renal transplant recipients. We explored the clinical implication of triglyceride-glucose (TyG) index in renal transplant recipients, recognizing it as a valuable marker for insulin resistance. Method A total of 6354 renal transplant recipients were enrolled from a nationwide, prospective cohort between May 2014 and December 2022. The TyG index was assessed between 6- and 12-months post-transplantation. We evaluated the association between TyG index and the risk of composite of cardiovascular events and death, renal allograft loss, and new onset diabetes after transplantation (NODAT). Results During the mean follow-up period of 39.2 ± 26.1 months, a total of 106 composite events of cardiovascular events and death, 174 events of renal allograft loss, and 438 events of NODAT were observed. The cumulative rate for composite events, graft loss, and NODAT was greater in patients with higher TyG quartile (all P &amp;lt; 0.001). In multivariate analysis, higher quartile of TyG was associated with an increased risk of composite events (HR 1.81, 95% CI 1.14–2.86), renal allograft loss (HR 2.13, 95% CI 1.28–3.55), and NODAT (HR 2.52, 95% CI 1.90–3.34). Higher quartile of TyG was associated with future graft dysfunction (adjusted mean eGFR differences of −4.72, 95% CI −7.39 – −2.04). There was a linear escalation in the risk of composite events and graft loss with the incremental rise in the TyG index, concomitant with an exponential augmentation in the risk of NODAT. Conclusion Renal transplant recipients with higher TyG index are associated with higher risk of composite of cardiovascular event and death, renal allograft loss, and NODAT.

#1564 Clinical implication of hyperfiltration and metabolic syndrome on the cardiovascular events, kidney failure, and all-cause mortality

Abstract Background and Aims Renal hyperfiltration (RHF) and metabolic syndrome (MetS) increase the risk of cardiovascular disease, end stage kidney disease (ESKD), and all-cause mortality. While RHF is strongly related to the metabolic risk, it is little known how the combined association of these two factors affects the risk of MetS-related complication, cardiovascular disease, and all-cause mortality. Method We reviewed the National Health Insurance Service database of Korea for people who received national health screenings between 2009 and 2011. RHF was defined as estimated glomerular filtration rate (eGFR) &amp;gt; 95th percentile after stratification for age, sex, height and weight, and normal renal filtration defined as eGFR 25-75th percentile. MetS was considered as the presence of three or more of the metabolic risks. Individuals were compared based on the presence of RHF and MetS. Age, sex, and Charlson comorbidity index matching were performed to reduce the selection bias in the study population. Finally, a total of 276,952 patients were matched, with 69,238 patients in each group, in a 1:1:1:1 ratio based on both their metabolic status and the presence of RHF. Results In multivariate Cox analysis, in comparison to normal renal filtration without MetS, RHF without MetS does not increase the risk of progression to ESKD. RHF patients increased the risk of progression to ESKD (aHR 2.75, 95% CI 1.38-5.50) only when combined with MetS. Moreover, irrespective of metabolic status, the risk of cardiovascular events (without MetS: aHR 1.08, 95% CI 1.00-1.17), (with MetS: aHR, 1.49; 95% CI, 1.38-1.60) and all-cause mortality (without MetS: aHR 1.29, 95% CI 1.20-1.40), (with MetS: aHR, 1.49; 95% CI, 1.37-1.62) increases significant in RHF patients. Notably, RHF synergistically increases the risk of cardiovascular events when accompanied with MetS (p for interaction = 0.041). However, RHF increases the risk of all-cause mortality more significantly without MetS than with MetS (p for interaction = 0.005). Conclusion The clinical implication of RHF is dependent on MetS status, and a significant interaction between the two factors is observed. To establish a treatment strategy for patients with RHF, MetS status must be considered.

#853 Kidney-protective medication and risk of adverse clinical outcomes in patients with chronic kidney disease: preliminary findings from DISCOVER CKD

Abstract Background and Aims Renin-angiotensin-system inhibitors (RASi) have been a foundational therapy in chronic kidney disease (CKD) for several decades. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have also emerged as a critical disease-modifying therapy in CKD, with contemporary data from trials showing SGLT2i to significantly improve kidney and cardiovascular (CV) outcomes in patients with or without diabetes. Nonetheless, several studies have revealed sub-optimal prescribing of RASi and/or SGLT2i therapy (both herein referred to as kidney-protective medication) in patients with CKD. Using prospective data from the DISCOVER CKD study, we conducted an exploratory analysis to assess the association of kidney-protective medication real-world use with mortality risk, CV events (fatal and non-fatal), and hospitalisation in patients with CKD. Method DISCOVER CKD (NCT04034992) is a multi-country, non-interventional cohort study designed to characterise the epidemiology of CKD, including describing patient characteristics, disease progression, clinical outcomes, patient journey, practice patterns, and clinical management. In the prospective phase, patients with CKD were recruited from the UK, USA, Spain, Italy, Sweden and Japan between September 2019 and June 2022. Clinical data were extracted manually from patients’ health records into a standardised case report form. The current analysis includes 12 months’ follow-up data. A Cox proportional hazards model was used to compare the risk of all-cause mortality and CV events and a negative binomial regression model was used to compare the risk of all-cause hospitalisation between patients receiving and not receiving kidney-protective medication at baseline, with adjustments for age, sex, CKD stage, diabetes mellitus, hyperkalaemia, and heart failure. DISCOVER CKD received research ethics board approval, and informed consent was obtained from all patients. Results Of the 1052 patients enrolled in DISCOVER CKD, 643 (61.1%) were receiving kidney-protective medication in the form of RASi (n = 618) and SGLT2i (n = 147) at baseline. The mean age of participants receiving and not receiving kidney-protective medication was 62.4 years and 62.7 years, respectively; 34.4% and 40.8%, respectively, were female. Most patients had CKD stage 3A (n = 332, 31.6%) or 3B (n = 308, 29.3%), and 8.4% (n = 88) had ongoing dialysis. Body mass index (30.4 vs 29.4 kg/m2) and blood pressure were similar for those receiving kidney-protective medication versus those who were not. Laboratory assessments were also generally similar, although estimated glomerular filtration rate (eGFR; 40.9 vs 33.7 mL/min/1.73 m2) and haemoglobin (132.0 g/L vs 124.0 g/L) were higher in patients receiving kidney-protective medication versus those not. During the follow-up, patients receiving kidney-protective medication had a 67% lower risk of all-cause mortality (hazard ratio [HR] 0.33; 95% confidence interval [CI] 0.12–0.80, p = 0.019), and a 20% lower risk of all-cause hospitalisation (HR, 0.80; 95% CI 0.64–0.99, p = 0.042) compared with patients not receiving kidney-protective medication. In the population without pre-existing CV disease, a trend towards a lower rate of CV events was observed in patients with kidney-protective medication (CV events rates: 2.2 vs 3.2 per 100 person-years; HR, 0.38; 95% CI 0.12–1.08, p = 0.074 (Figure). Conclusion In this multinational CKD cohort, preliminary analysis indicates that using kidney-protective medication was associated with lower risks of adverse outcomes including death. Further analysis to mitigate potential confounding will be performed to confirm these preliminary findings.

#2251 Long-term systolic blood pressure variability as an independent risk factor for cardiovascular events in kidney transplant recipients

Abstract Background and Aims Cardiovascular (CV) events represent the main cause of death in patients undergoing renal transplantation. Several studies have described the role of blood pressure variability (BPV) in predicting all-cause mortality and fatal and non-fatal CV events in the general population and in diabetic patients. Systolic blood pressure variability (SBPV) has recently been proposed as a predictor of clinical outcomes in patients with chronic kidney disease. However, evidence is still scarce about the prognostic role of BPV in the setting of renal transplantation. The aim of the study was to evaluate the role of long-term SBPV in the development of fatal and non-fatal CV events (myocardial infarction, unstable angina or revascularization, stroke and hospitalization for heart failure) in subjects undergoing kidney transplantation. Method We performed a single-center retrospective observational analysis in a cohort of 272 kidney transplant patients (mean age 64 ± 13 years, 66% men), with a transplant duration ≥12 months and with at least 6 blood pressure measurements at defined intervals (3 months ±15 days) over an assessment period of 18 months. BPV was expressed as standard deviation of ambulatory systolic blood pressure (SBP) and patients were accordingly classified in tertiles (low &amp;lt;9.3 mmHg, medium 9.3-13 mmHg, high &amp;gt;13 mmHg). The role of SBPV was analyzed by Kaplan-Meier (logrank) and its independent effect by Cox Regression. Results Over a mean follow-up of 58.7 ± 17.2 months, 27 subjects (9.9%) developed CV events. For each increase of 2.7 mmHg in SBP standard deviation, the risk for fatal or non-fatal CV events increased almost 3-folds (P = 0.02) and patients in the highest tertile of SBP standard deviation showed a 4-fold increased risk (P = 0.01) (Fig. 1). This relationship was maintained even after incremental adjustment for time-averaged pulse pressure, age, diabetes, prior CV event, and dialysis vintage (HR 3.2, 95% CI 1.1–10.0, p 0.04) (Table 1). Conclusion Long-term BPV represents an independent risk factor for CV events in kidney transplant patients. It is therefore essential to seek for stable long-term blood pressure levels in this population in order to minimize the residual CV risk.

#2470 Isolated diastolic hypertension in hemodialysis patients

Abstract Background and Aims Isolated diastolic hypertension (IDH) is relatively rare in the general population (prevalence about 6.5%, Front Cardiovasc Med. 2021;8:810105) and of uncertain etiologic implications. The prevalence of this alteration in the hemodialysis (HD) population and the etiologic implications of IDH have not been studied. Method We investigated the prevalence and the risk for all-cause death and cardiovascular events of isolated diastolic hypertension in a population of 534 HD patients enrolled in 7 centres in 3 European countries (the EURECA-m working group). BP was measured by a golden standard method in this population (48 h ABPM) using well-validated instruments (AAMI/ESH/ISO). Along with recommendations by the European Society of Hypertension guidelines, recordings were made at 15-minute intervals during the day and 30 minutes at night. According to a consensus document by the EURECAm working group (Nephrol Dial Transplant. 2019;34:1542-1548), isolated diastolic hypertension was defined as 48 h diastolic BP &amp;gt; 80 mmHg with a systolic BP &amp;lt;130. Results Among 534 HD patients, thirty-one (5.8%) had isolated diastolic HTN, which is very close to the prevalence estimated in the general population (6.5%). During a mean follow-up of 2.6 years, 138 patients died, 188 had at least one CV event, and 249 experienced the combined event. In univariate analyses, diastolic hypertension was associated with death (HR 0.21; 95% CI: 0.05-0.86, P = 0.03) and the combined outcome of death and CV events (HR 0.42, 95% CI: 0.20-0.88, P = 0.02). However, these associations were no longer significant after adjustment for age and sex (all P &amp;gt; 0.45). Additional sensitivity analyses substantially confirmed these findings. No effect modification by age or gender was observed in these associations. Conclusion In a large cohort of HD patients studied by state-of-the-art 48-hour BP monitoring, the prevalence of isolated diastolic hypertension in HD patients (5.8%) is close to that registered in the general population (6.5%). This alteration predicts the risk for clinical outcomes in unadjusted analyses but not after adjustment for age and sex. Isolated diastolic hypertension is as rare as it is in the general population and unlikely to contribute to the high risk of adverse clinical outcomes in the dialysis population.

#2088 Renal outcome, cardio-vascular events and infections in patients with lupus nephritis: MassiLUP cohort 2001-2022

Abstract Background and Aims Most epidemiological studies in lupus nephritis (LN) report the risk of end-stage kidney disease (ESKD) (10-20% of patients at 10-15 years in developed countries), but less data is available on the long-term risk of chronic kidney disease (CKD), even though CKD is a major risk factor for morbidity and mortality. While immunosuppressive therapy for LN aims to reach and maintain remission in order to prevent CKD, it also exposes patients to cardiovascular, infectious and neoplastic adverse events. We conducted a retrospective cohort study to evaluate survival without CKD and adverse events in patients with LN. Method The MassiLUP cohort comprises all patients who underwent a kidney biopsy for a first flare of LN between 2001 and 2022 in the University Hospital of Marseille, France. We assessed patient survival, renal survival and survival without CKD (defined by an estimated glomerular filtration rate &amp;lt; 60 mL/min/1.73 m2), without cardiovascular event, without severe infection (requiring hospitalization, or zoster), and without cancer. Results A total of 168 patients (82.7% female; mean age 33 years; mean serum creatinine 102 µmol/L at the time of the first kidney biopsy) were included, with a mean follow-up of 9.6 ± 5.7 years. One (0.6%) patient had class I LN (ISN/RPS 2003 classification), 17 (10.1%) class II LN, 45 (26.8%) had class III (± V) LN, 73 (43.5%) had class IV (± V) LN, 29 (17.3%) patients had pure class V LN; 3 biopsies could not be classified. Four patients died during the follow-up (3 of severe infections and 1 of stroke); 41 (24.4%) patients developed CKD, among whom 19 (11.3%) patients reached ESKD; 34 (20.2%) patients presented a cardiovascular event, 59 (35.1%) a severe infection, and 12 (7.1%) a cancer. Survival rates without CKD were 82.9%, 74.6% and 67.3% at 5, 10 and 15 years, respectively. Survival rates without ESKD were 94.4%, 88.6% and 79.9% at 5, 10 and 15 years, respectively. Survival rates without cardiovascular event were 85.7%, 77.3% and 75.5% at 5, 10 and 15 years, respectively. Survival rates without severe infection were 76.3%, 63.8% and 51.8% at 5, 10 and 15 years, respectively. Survival rates without cancer were 96.3%, 92.9% and 85.6% at 5, 10 and 15 years, respectively. Conclusion Despite free access to treatment and care in France, the long-term prognosis of patients with lupus nephritis remains burdened by both a risk of CKD and ESKD, and a significant risk of cardiovascular and infectious events. This calls for continued efforts to improve therapeutic strategies, both in terms of efficacy and toxicity, and to strengthen the therapeutic alliance in the care of patients with LN.