Hyperphosphatemia, but Not Hypercalcemia, Predicts Cardiovascular Risk After Kidney Transplantation

Although cardiovascular disease is known to be one of the leading causes of death after kidney transplantation (KT), evidence on the risk difference of de novo major adverse cardiovascular events (MACEs) in kidney transplant recipients (KTRs) compared with that in dialysis patients or the general population (GP) remains rare. We identified KTRs using the nationwide health insurance database in South Korea and then 1:1 matched them with the dialysis and GP controls without a pre-existing MACE. The primary endpoint was defined as de novo MACEs consisting of myocardial infarction, coronary revascularization and ischemic stroke. The secondary endpoints were all-cause mortality and death-censored graft failure (DCGF) in KTRs. We included 4156 individuals in each of the three groups and followed them up for 4.7 years. De novo MACEs occurred in 3.7, 21.7 and 2.5 individuals per 1000 person-years in the KTRs, dialysis controls and GP controls, respectively. KTRs showed a lower MACE risk {adjusted hazard ratio (aHR) 0.16 [95% confidence interval (CI) 0.12-0.20], P<.001}than dialysis controls, whereas a similar MACE risk to GP controls [aHR 0.81 (95% CI 0.52-1.27), P=.365]. In addition, KTRs showed a similar MACE risk compared with the GP group, regardless of age, sex and the presence of comorbidities, including hypertension, diabetes and dyslipidemia. Among KTRs, de novo MACEs were associated with an increased risk of all-cause mortality, but not with DCGF. De novo MACEs in KTRs were much lower than that in dialysis patients and had a similar risk to the GP, but once it occurred it caused elevated mortality risk in KTRs.

Association of electrocardiographic abnormalities with major adverse cardiovascular events in kidney transplant recipients.

There is little robust data about the cardiovascular safety of hydroxychloroquine in patients with rheumatoid arthritis (RA), who often have cardiovascular comorbidities. We examined the association between use of hydroxychloroquine (HCQ) in patients with RA and major adverse cardiovascular events (MACE). In a retrospective cohort of Medicare beneficiaries aged ≥ 65years with RA, we identified patients who initiated HCQ (users) and who did not initiate HCQ (non-users) between January 2015-June 2017. Each HCQ user was matched to 2 non-users of HCQ using propensity score derived from patient baseline characteristics. The primary outcome was the occurrence of MACE, defined as acute admissions for stroke, myocardial infarction, or heart failure. Secondary outcomes included all-cause mortality and the composite of MACE and all-cause mortality. Cox proportional hazards model was used to compare outcomes between HCQ users to non-users. The study included 2380 RA patients with incident HCQ use and matched 4633 HCQ non-users over the study period. The mean follow-up duration was 1.67 and 1.63years in HCQ non-users and users, respectively. In multivariable models, use of HCQ was not associated with the risk of MACE (hazard ratio 1.1; 95% CI: 0.832-1.33). However, use of HCQ was associated with a lower risk of all-cause mortality (HR: 0.54; 95% CI: 0.45-0.64) and the composite of all-cause mortality and MACE (HR 0.67; 95% CI: 0.58-0.78). HCQ use was independently associated with a lower risk of mortality in older adults with RA but not with incidence of MACE events. Key Points • Using an incident user design (to avoid the biases of a prevalent user design) and a population-based approach, we examined the effect of hydroxychloroquine (HCQ) on the risk of major cardiovascular events (MACE) in older patients with RA. • We did not find an association between HCQ use and incident MACE. We did, however, find a significant association with the composite outcome (MACE and all-cause mortality) driven by a significant reduction in all-cause mortality with HCQ use.

Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials

Left atrial (LA) volume and strain parameters have been associated with cardiovascular outcomes in several cardiac pathologies, yet their role in predicting major adverse cardiovascular events (MACE) in kidney transplant (KT) recipients has not been explored. We retrospectively reviewed the records of adult KT recipients from our institution (2015-2024). We utilized baseline echocardiograms routinely acquired during KT workup to measure LA volumetrics and strain. MACE was the study's primary endpoint, defined as cardiovascular death, nonfatal myocardial infarction, stroke, major arrhythmias or heart failure hospitalization. Logistic regression, Kaplan-Meier and Cox proportional hazards regression were performed to evaluate the association between LA parameters and MACE. Of 518 patients who underwent kidney transplant, 377 were in sinus rhythm with an acceptable quality echocardiogram (male, 56.7%; mean age 53.7 ± 13.1 years). Over a median follow up duration of 5.3 ± 2.3 years from KT, 82 patients reached the study endpoint. Kaplan-Meier analysis showed significantly lower MACE-free survival in patients with abnormal LA strain. After adjusting for confounding variables in the Cox Proportional Hazards model, of all LA parameters, lower LAScd (HR 0.94, 95% CI 0.89-0.98, p = 0.003), and LASr (HR 0.97, 95% CI 0.94-0.995, p = 0.02) were independently associated with MACE. In this retrospective single center study, LA strain parameters particularly LASr and LAScd were independently associated with MACE after KT. LA strain might have a role in risk stratification in this population.

We examined the incidence of myocardial ischemia (MI) in kidney transplant recipients (KTR) using myocardial perfusion imaging (MPI), and its association with long-term outcomes after transplantation. A retrospective observational study was conducted of asymptomatic KTRs who underwent post-transplant MPI screening for MI, as defined by moderate to severe myocardial perfusion defects, post-stress myocardial stunning or balanced ischemia. A composite outcome of all-cause mortality, graft loss, and major adverse cardiovascular events (MACE) was examined over minimum 5years. We studied 135 KTRs who underwent 226 MPIs, with follow-up duration of 10 (7-13) years. 110 (81%) patients had normal MPIs, 11 (8%) had mild perfusion defects, and 14 (10%) had MI. Correspondingly, composite outcome developed in 6%, 27%, and 43% (p = 0.04), and MACE occurred in 7%, 0%, and 21% (p = 0.11), of the respective subgroups. Twenty-six patients developed the composite outcome after 5 (3-7) years post-transplantation, including 11 patients with MACE. On multivariate analysis, MI, higher low-density lipoprotein levels, and proteinuria > 0.3g/day independently predicted the composite outcome; only MI predicted MACE (all p < 0.05). Ninety-one patients had two serial MPIs, which increased the positive predictive value for MACE from 17 to 25%. Absence of MI had negative predictive value of 83% for MACE and 93% for the composite outcome. MI that is detected early post-kidney transplantation predicts long-term mortality, graft loss, and MACE in KTRs, with excellent negative but poor positive predictive values.

Background and Aims Based on intervention thresholds [1], statins are recommended in kidney transplant recipients (KTRs) who are at high risk for major cardiovascular (CV) events. However, in this population, evidence of statin effectiveness is sparse and non-conclusive. The objective of this study is to assess the effect of statins on CV events in KTRs. Method 613 consecutive KTRs from a single-center cohort were retrospectively included between 2006 and 2019. Exposure to statins (indicated in primary or secondary CV prevention) and atherosclerotic CV events during the study period were comprehensively documented. The primary outcome was the incidence of CV events in all statin users compared to that of non-users, based on the Cardiovascular and Stroke Endpoint Definitions for Clinical Trials [2]. In this study, only atherosclerotic events were selected (peripheral vascular stenosis, stroke, myocardial infarction, angina pectoris and transitional ischemic attack). The secondary outcomes were the incidence of CV events (i) in KTRs using statins indicated in primary CV prevention and (ii) in KTRs using statins indicated in secondary CV prevention compared to that of non-users. Cox proportional hazard models including statin exposure as a time-dependent covariate and fitted with inverse probability treatment weighting (IPTW) were used, as well as a multivariable Cox proportional hazard model. Results During a median [interquartile range (IQR)] follow-up period of 4.6 [2.7–10.0] years, CV events occurred in 88 KTRs: 48 (55.5%) KTRs had peripheral vascular stenosis, 24 (27.3%) had myocardial infarction, 12 (13.6%) had stroke, three (3.5%) had angina pectoris and one (1.1%) had a transitional ischemic attack. The incidence of CV events was 24.8 per 1000 person-years. In the Cox models fitted with IPTW, exposure to statins, regardless of the indication or indicated in primary and secondary CV prevention, was not associated with a decrease in CV events: Hazard Ratio (HR) [95% confidence interval (CI)]: 1.22 [0.73–2.03] (P = .435), HR: 1.12 [0.66–1.89] (P = .672), and HR: 2.78 [1.19–6.53] (P = .018), respectively. In the multivariable Cox model, diabetes mellitus was strongly associated with CV events (HR: 4.39 [2.79–6.90], p&amp;lt;0.001), and statin exposure was not (HR: 1.25 [0.78–2.03]). In a subgroup of KTRs exposed to statins after kidney transplantation but not before (n=314), the median [IQR] levels of LDL-c was 3.48 [2.89–4.08] mmol/L when starting statins and 2.74 [2.14–3.35] mmol/L after one year of statin exposure, i.e. a significant decrease of 0.74 [0.60–0.85] mmol/L (p&amp;lt;0.001). The median [IQR] levels of triglyceride was 1.99 [1.47–2.91] mmol/L when starting statins and 1.72 [1.20–2.50] mmol/L after one year of statin exposure, i.e. a significant decrease of 0.27 [0.17–0.42] mmol/l (p&amp;lt;0.001). There were no significant changes in HDL-c levels. Conclusion Despite an improvement in the lipid profile including a reduction of LDL-c and triglyceride levels, statin exposure was not associated with a decrease in CV events in a long-term KTR cohort. Other CV risk factors than dyslipidemia, such as diabetes mellitus, were more likely related to such events.

Framingham Risk Score (FRS) is an insufficient cardiovascular event predictor in unselected kidney transplant recipients. Its role in different risk subgroups and the value of adding novel risk factor candidates to FRS is unknown. We reviewed patients who underwent transplantation from 1998 to 2008 with minimum 3 months graft function, determining FRS-ascertained 10-year risk at 3 months along with relevant clinical and laboratory information. Major adverse cardiac events (MACE) (myocardial infarction, coronary artery revascularization, or cardiac death) 3 months posttransplant were captured. Time-to-MACE multivariate Cox modeling with FRS and novel risk factors (C-reactive protein, uric acid, urine albumin-to-creatinine ratio) as independent variables was performed. Of 956 patients, 89 experienced MACE (2.17 events/100 patient-years). FRS-predicted 10-year risk was 14.7% ± 10.0% in males with and 9.2% ± 8.2% in those without subsequent MACE (P < 0.0001), although FRS substantially underestimated MACE (actual-to-predicted event ratio 1.2-8.4 in different subgroups, all P < 0.0001). Although patients with MACE had a higher C-reactive protein (5.4 ± 6.0 vs. 3.8 ± 2.5 mg/L, P = 0.026) and uric acid (417 ± 109 vs. 386 ± 101 μmol/L, P = 0.012) level as well as lower 3-month estimated glomerular filtration rate (50.1 ± 20.1 vs. 54.8 ± 18.3 mL/min/1.73 m(2), P = 0.022), only FRS more than or equal to 10% (hazard ratio 2.313, 95% confidence interval 1.49-3.58, P = 0.0002) and estimated glomerular filtration rate less than 50 mL/min/1.73 m(2) (hazard ratio 2.291, 95% confidence interval 1.06-4.94, P = 0.034) predicted MACE in multivariate analysis. Adding novel risk factors to FRS did not improve FRS prediction. FRS substantially underpredicts MACE in kidney transplant recipients among all risk subgroups. Commonly available novel risk factors do not improve FRS predictive value.

Cardioprotective Effect of SGLT2 Inhibitor in Diabetic Kidney Transplant Recipients: A Multicenter Propensity Score Matched Study

The effects of lipid-lowering drugs (LLDs) on cardiovascular and renal outcomes in patients with advanced chronic kidney disease (CKD) and dyslipidemia are not completely understood. We conducted a retrospective cohort study to evaluate the effect of LLDs on end-stage kidney disease (ESKD), major adverse cardiovascular events (MACEs), and mortality in adult patients with CKD stage 3b, 4, or 5, and dyslipidemia. Participants were recruited between January 1, 2008, and December 31, 2018, and classified as LLD or non-LLD users; the final follow-up date was December 31, 2020. The primary outcome was time to ESKD or death due to renal failure. Sub-distribution hazard regression models adjusted for multivariables, including time-varying lipid profile covariates, were used for the analysis. Among the 6,740 participants, 4,280 patients with CKD and dyslipidemia, including 872 using LLDs and 3,408 not using LLDs, completed the primary analysis. The multivariable analyses showed that LLD users had a significantly lower risk of time to the composite renal outcome (adjusted hazard ratio [aHR], 0.76, 95% confidence interval [CI], 0.65-0.89), and MACE incidence (aHR, 0.75, 95% CI, 0.62-0.93) than did non-LLD users. After adjusting for time-varying covariates of the lipid profile, there was a significant difference in the composite renal outcome (aHR, 0.78, 95% CI, 0.65-0.93) and MACEs (aHR, 0.77, 95% CI, 0.60-0.98). Among adult patients with advanced CKD and dyslipidemia, LLD users had a significantly lower risk of composite renal outcomes and MACEs than non-LLD users. In addition to reducing lipid profile, the use of LLD is associated with renal and cardiovascular protective effects.

Effects of Preoperative Intravenous Erythropoietin Plus Iron on Outcome in Anemic Patients After Cardiac Valve Replacement

Introduction Kidney transplantation helps reduce cardiovascular mortality in patients receiving renal replacement therapy but the incidence of cardiovascular disorders in kidney transplant recipients remains significantly higher than in the general population. Metabolic syndrome is a combination of cardiovascular risk factors that can reinforce each other and increase the risk of cardiovascular disease and death in the general population. Purpose To study the incidence of the preceding metabolic syndrome in kidney transplant recipients with adverse cardiovascular events. Methods 237 recipients six months after kidney transplantation were included in the study. 79 (33.3%) of them had adverse cardiovascular events during three years of observation. Other patients had no cardiovascular complications. The study groups were comparable by gender, age and traditional cardiovascular risk factors. Results The average waist circumference in kidney transplant recipients with adverse cardiovascular events was 98±14 cm, which was higher than in kidney transplant recipients without adverse cardiovascular events – 94±13 cm, p&amp;lt;0.05. The triglyceride level in the group of kidney transplant recipients with adverse cardiovascular events was 1.70 (1.30–2.50) mmol/L, which was higher than in kidney transplant recipients without cardiovascular complications – 1.45 (1.08–1.80) mmol/L, p&amp;lt;0.01. Hypertriglyceridemia was more frequently diagnosed in recipients with adverse cardiovascular events – 44.3% (n=35) versus 27.8% (n=44), p&amp;lt;0.05. In the study groups no statistically significant differences were found in the level of high-density lipoproteins and the incidence of their reduced level depending on the occurrence of adverse cardiovascular events – 1.30 (1.21–1.42) mmol/L and 20.3% (n=16) versus 1.31 (1.21–1.45) mmol/L and 8.4% (n=29). The blood pressure level and the incidence of arterial hypertension was comparable in the study groups – 77.2% (n=61) and 69.6% (n=110). Blood glucose levels and the incidence of hyperglycemia did not differ in the study groups, but post-transplant impaired glucose tolerance or post-transplant diabetes mellitus in recipients with adverse cardiovascular events were more common – 20.3% (n=16) versus 9.5% (n=15), p&amp;lt;0.05. So 41.8% (n=99) of the study patients had metabolic syndrome. The previous metabolic syndrome was more frequent in recipients with adverse cardiovascular events – 58.2% (n=46) versus 33.5% (n=53), p&amp;lt;0.001. Conclusion Based on the study it was found that the metabolic syndrome increases the risk of adverse cardiovascular events in kidney transplant recipients. The main components of metabolic syndrome that have prognostic value in kidney transplant recipients were an increase in waist circumference, high blood triglyceride levels and the incidence of hypertriglyceridemia, a high incidence of post-transplant impaired glucose tolerance or post-transplant diabetes mellitus. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Belarusian State Medical UniversityMinsk Scientific and Practical Center of Surgery, Transplantology and Hematology

Diabetes mellitus (DM) and cardiovascular disease (CVD) are major public health challenges and also leading causes of post-transplant mortality following renal transplantation. In transplant patients, pre-transplant diabetes as well as newly developed diabetes after transplantation is associated with poor post-transplant outcomes. In this study, we aimed to investigate the effect of pre-transplant diabetes (Pre-DM) and post-transplant diabetes (PTDM) on cardiovascular events in kidney transplant recipients. We analyzed 1930 patients who underwent kidney transplantation at tertiary care hospital between 1979 and 2020. Subjects were classified into the 3 groups (Pre-DM, PTDM, Non-DM) according to whether diabetes was diagnosed and the date of diagnosis was before or after surgery. A Cox proportional hazard model was used to investigate the association between the type of DM (vs. Non-DM) and the incidence of four-point major adverse cardiovascular events (4P-MACE) . During the study follow-up period (median 6.5 years) , 4P-MACE occurred in 36 (3.1%) patients with Non-DM, 65 patients (14.3%) with Pre-DM and 33 (10.7%) patients with PTDM. Pre-DM was significantly associated with increasing risk of cardiovascular events after adjustment for confounding factors including age, sex, BMI, waiting time, ABO incompatibility, number of HLA mismatch, previous cardiovascular disease, donor age and donor type (living or deceased) (hazard ratio (HR) 3.62, 95% confidence interval (CI) 2.29-5.74, p&amp;lt;0.001) . In the Kaplan-Meier curve of the cumulative incidence of 4P-MACE, subjects with Pre-DM had the highest risk of cardiovascular events and those with PTDM had intermediate risk of events. The presence of both Pre-DM or PTDM significantly increased the risk of cardiovascular events in kidney transplant recipients. This suggests the need for management to minimize the long-term impact of pre-existing DM and PTDM in transplant patients. Disclosure S.Lee: None. S.Hong: None. M.Lee: None. Y.Kim: None. H.Kim: None. H.Lee: None. J.Lee: None. E.Kang: None. Funding Severance Hospital Research fund for Clinical excellence (SHRC) (C-2021-0007)

Pulmonary hypertension (PH) frequently complicates end-stage kidney disease, contributing significantly to cardiovascular morbidity and mortality. Some of the pathophysiologic effects of PH may persist even after kidney transplantation (KT). We investigated the association between pre-transplant PH and long-term major adverse cardiovascular events (MACE) after KT. This retrospective cohort study included 468 adult KT recipients from an academic medical center between January 2015 and January 2024. We excluded patients who did not follow up at our institution and those with no adequate pre-transplant assessment of pulmonary artery (PA) pressures. Patients were stratified based on the presence of pre-transplant PH, defined as PA systolic pressure > 35 mmHg on echocardiography or mean PA pressure > 20 mmHg via right heart catheterization. The primary outcome was the occurrence of MACE after KT, defined as cardiovascular death, nonfatal myocardial infarction, stroke, or hospitalization for heart failure. Kaplan-Meier cumulative incidence curves and Multivariable Cox proportional hazards models were used. Of the 468 recipients who qualified for the study, 86 (18.4%) had pre-transplant PH. Over a mean follow-up of 54.7 ± 28.4 months, 89 patients (19.0%) experienced MACE. The incidence of MACE was significantly higher in the PH group at one- (8.1 vs 2.9%, p = 0.03) and five-year (22.0 vs 11.0%, p = 0.01). After adjusting for age, sex, and relevant confounders, PH remained independently associated with MACE (HR 2.15; 95% CI 1.25-3.70; p = 0.01). In this retrospective single-center study, pre-transplant PH was independently associated with an increased risk for MACE following KT. These findings highlight the importance of identifying PH in KT candidates. Enhanced cardiovascular risk surveillance may be warranted in this population. Not applicable as this is a retrospective cohort study.

S924 Cardiovascular Outcome and Cancer Risk in Adult Patients With Ulcerative Colitis in Routine Clinical Care: The Effect of Cardiovascular Risk-Enrichment Factors