Risk Of Major Adverse Cardiovascular Events Research Articles

Vitiligo is associated with an increased risk of cardiovascular diseases: a large-scale, propensity-matched, US-based retrospective study

Vitiligo is an autoimmune disease, characterized by specific destruction of melanocytes. While associations with numerous comorbid conditions, which potentially increase the risk of cardiovascular diseases have been described, data on the risk for cardiovascular disease is inconclusive. To address this relevant knowledge gap, this study aims to identify the risk of cardiovascular disease in vitiligo. The US Collaborative Network was accessed using the TriNetX platform, allowing retrospective data retrieval from electronic health records (EHRs) from 57 US based health care organizations (HCOs). Patients with vitiligo and controls were identified by their respective ICD10 codes. Risk of onset of several cardiovascular diseases was determined in patients within 15 years after diagnoses. A total of 94 diagnoses with a prevalence of ≥1% in both cohorts, which consisted of 96,581 individuals per group after propensity-score-matching, were identified. Of those, 54 displayed an increased risk in vitiligo. None of the cardiovascular diseases investigated were associated with a decreased risk in patients with vitiligo. Specifically, cerebral infarction occurred in 1.3% of patients with vitiligo, and 1.0% in controls. This difference translated into a hazard ratio (HR) of 1.21 (95% confidence interval [CI] 1.11-1.32, padj<0.001). Venous thromboembolism was recorded in 1.34% of cases and 1.02% of controls without vitiligo, resulting in an increased HR of 1.27 (95% CI 1.171-1.38, padj<0.001). Further, major adverse cardiovascular events (MACE) as a composite endpoint was evaluated. The risk for MACE was increased following a vitiligo diagnosis (HR 1.28, 95% CI 1.22-1.35, padj<0.001), which persisted in both sensitivity analyses. Patients with vitiligo display an increased risk of onset of cardiovascular diseases as compared to healthy individuals. Thus, vitiligo might require more precise monitoring and systemic treatment. This research was supported by the Schleswig-Holstein Excellence-Chair Program from the State of Schleswig Holstein, by the Excellence Cluster Precision Medicine in Chronic Inflammation (DFG, EXC 2167), and by DFG Individual Grant LU 877/25-1.

Association between achieved cholesterol levels and the risk of major adverse cardiovascular events after acute coronary syndromes

Abstract Background European guidelines recommend reducing lipid levels to defined targets to lower cardiovascular risk after acute coronary syndromes (ACS). Purpose This study aims to evaluate the association of achieved and reduced lipid levels one year post-ACS with the risk of subsequent major adverse cardiovascular events (MACE) in a real-world setting. Methods Data from SPUM-ACS, a Swiss multicentric cohort of patients hospitalized with ACS between 2007 and 2021, were used to assess the association between lipid levels (LDL-C, non-HDL-C, HDL-C, triglycerides), relative difference from baseline lipid levels, and lipid targets achievement (LDL-C &amp;lt;1.8 and ≥50% reduction from baseline, non-HDL-C &amp;lt;2.2 and triglycerides &amp;lt;1.7mmol/l) one year after ACS with the risk of MACE (myocardial infarction, stroke, coronary revascularization, and cardiovascular death). The observation period for MACE started after a follow-up visit one year post-ACS, during which lipid levels were measured, extending over a median duration of 5.5 years. Cox proportional hazards models, adjusted age, sex, BMI, smoking status, statin therapy intensity, diabetes, systemic inflammatory disease, and creatinine were used. Predicted adjusted hazard ratios (HR) were represented graphically for continuous exposures. Analyses were repeated with interaction terms for predefined subgroups. Results 2579 ACS survivors (mean age 62 years; 80% male), primarily undergoing percutaneous revascularization, attended a follow-up visit one year after ACS and were followed up for a median of 5.5 years. 98% were prescribed statin therapy (59% high-intensity) at discharge. During the first year post-ACS, median LDL-C decreased from 3.7 to 2.4 mmol/l (-34%, p&amp;lt;0.001), non-HDL-C from 3.9 to 2.6 mmol/l (-32%, p&amp;lt;0.001), and triglycerides from 1.21 to 1.16 mmol/l (-6%, p&amp;lt;0.001); HDL-C increased from 1.1 to 1.2 mmol/l (+6%, p&amp;lt;0.001). 92% of patients were on statin therapy (50% high-intensity) one year after ACS. In log-linear models, one year after ACS, a 1 mmol/l reduction of LDL-C, non-HDL-C, and triglycerides levels to the target was associated with a lower risk of subsequent MACE by 23%, 24%, and 14%, respectively (p values &amp;lt;0.001). A 10% relative reduction from baseline levels of LDL-C, non-HDL-C and triglycerides was associated with a lower risk of MACE by 8%, 9%, and 4%, respectively (p values &amp;lt;0.001). Achieving LDL-C &amp;lt;1.8 mmol/l (21%, HR=0.71 [0.54, 0.93]), LDL-C reduction ≥50% from baseline (26%, HR=0.63 [0.48, 0.84]), non-HDL-C &amp;lt;2.2 mmol/l (30%, HR=0.65 [0.51, 0.83]), and triglycerides &amp;lt;1.7 mmol/l (76%, HR=0.76 [0.62, 0.94]) were all associated with a reduction in the risk of MACE. Neither age, sex, BMI, diabetes, or smoking status affected the results (p for interaction ≥0.05). Conclusion These findings affirm current recommendations and underscore lipid reduction and targets achievement as critical strategies for mitigating residual cardiovascular risk in patients with ACS.

Association of HbA1C with mortality and cardiovascular outcome in patients with type 2 diabetes using drugs with different hypoglycemic risk

Abstract Background Previous clinical trials showed that intensive glucose control did not reduce macrovascular events and mortality. It was speculated that severe hypoglycaemia contributed to these adverse outcomes. More contemporary clinical trials using newer anti-diabetic agents with less hypoglycaemic potential showed a linear relationship between major adverse cardiovascular events (MACE) and HbA1c reduction according to a meta-regression analysis. Purpose The aim of this study was to examine the association between clinical outcomes and HbA1c under different treatment backgrounds in the real-world setting. We hypothesised that when using drugs with minimal hypoglycaemic risk, lower HbA1c would be associated with better outcomes. Methods This was a retrospective population-based cohort study using a multi-centre electronic medical record database. Eligible patients were those diagnosed with type 2 diabetes between 2009 and 2020 who received non-insulin antidiabetic drugs. Patients were stratified into two groups based on the drugs received: drugs with high hypoglycaemic risk (sulphonylurea, meglitinide) and drugs with low hypoglycaemic risk (thiazolidinediones, acarbose, DPP4 inhibitors, GLP1 agonists, SGLT-2 inhibitors). Patients were excluded if they had received these drugs for less than 180 days or had received both high and low hypoglycaemic risk oral drugs simultaneously. HbA1c levels were assessed from the index date to the date of the interested outcome or the end of the study period (31 December 2021), whichever came first. The relationship between HbA1c and clinical outcomes was examined using a Cox proportional hazards model. The outcomes of interest included all-cause mortality and MACE. Results The study population consisted of 6,923 patients, including 3,639 high hypoglycaemic risk drug users and 3,284 low hypoglycaemic risk drug users. Patients with lower HbA1c levels during the follow-up period were older and frailer. After adjusting for baseline covariates, the association between the risk of death and HbA1c presented a U-shaped pattern, and this U-shaped association was similar in the two treatment cohorts (Table 1). On the other hand, the association between the risk of MACE and HbA1c presented a J-shaped pattern. In the high hypoglycaemic risk drug cohort, patients with the highest HbA1c levels (mean HbA1c 9.6%) were associated with a higher risk of MACE compared to the group with a mean HbA1c of 7.2% (hazard ratio [HR] 4.16, 95% confidence interval [CI] 2.07-8.37); lower HbA1c levels were not associated with a lower risk of MACE (Table 2). In contrast, in the low hypoglycaemic risk drug cohort, lower HbA1c levels were associated with a higher risk of MACE (HR 3.82, 95% CI 1.29-11.28). Conclusion Lower HbA1c levels were not associated with a lower risk of all-cause mortality and MACE. Furthermore, this phenomenon was independent of the hypoglycaemic risk of anti-diabetic drugs.

High intensity statin-ezetimibe combination therapy reduces mortality in patients with ischaemic heart disease and elevated Lipoprotein(a)

Abstract Background Early and prompt reduction of low-density lipoprotein cholesterol concentrations (LDL-C) using combination lipid-lowering therapy (LLT) is recommended to lower cardiovascular risk in patients with ischaemic heart disease (IHD) and elevated LDL-C. Lowering LDL-C is also an important cardiovascular risk mitigation strategy in patients with elevated lipoprotein(a) [Lp(a)]. However, it is unknown if combination LLT reduces mortality in patients with elevated Lp(a). Aim To undertake an observational study to investigate the effect of combination LLT using high intensity statin with ezetimibe on cardiovascular outcomes in patients with and without elevated Lp(a). Methods Serum Lp(a) concentrations were measured in 520 consecutively recruited patients with IHD admitted to hospital, half of whom were admitted for acute myocardial infarction. Patients treated with high intensity statin and ezetimibe within the 1st year from admission to hospital (‘HI statin-ezetimibe group’, n=157) were compared with the rest of patients who had less intensive lipid lowering regimen (‘Others group’, n=363) for cardiovascular outcomes. Results During the 2-year follow-up period, 14.6%, 6.5%, and 53.1% of patients had all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE) respectively. Median age was 63.5 years and 82.3% were male. Multivariable Cox regression showed that baseline Lp(a) ≥70 nmol/L was associated with increased risk of all-cause mortality (HR 1.97, 95% CI 1.20-3.22, P=0.007). Compared with a less intensive regimen, HI statin-ezetimibe was associated with reduced risk of all-cause mortality (HR 0.44 [0.21-0.89], P=0.023) and MACE (HR 0.71 [0.52-0.95], P=0.027), with no statistically significant effect on cardiovascular mortality (HR 0.43, P=0.142). Notably, the cardiovascular benefits of HI statin-ezetimibe were more pronounced in patients with elevated Lp(a); a greater reduction in risk of MACE was seen for patients with Lp(a) ≥70 nmol/L (HR 0.51, P=0.007) or Lp(a) ≥100 nmol/L (HR 0.36, P=0.009), and in all-cause mortality risk for those with Lp(a) ≥70 nmol/L (HR 0.24, P=0.025). Although LDL-C reduction &amp;gt;50% was associated with reduced risk of all-cause mortality (p=0.027), this could not fully explain the overall cardiovascular benefit of HI statin-ezetimibe use in patients with or without elevated Lp(a). Conclusion Intensification of lipid-lowering therapy with high-intensity statin and ezetimibe improves cardiovascular outcomes in patients at very high cardiovascular risk, particularly those with elevated Lp(a). Larger studies are required to confirm our findings that this cardiovascular benefit is partially independent of LDL-C lowering.

Relation of apolipoprotein C3 to risk of major adverse cardiovascular events and death after acute coronary syndrome on a background of optimized statin treatment

Abstract Background Apolipoprotein C3 (ApoC3), a component of triglyceride-rich lipoproteins and some low-density lipoprotein and high-density lipoprotein particles, has been shown to predict incident coronary heart disease (CHD) and major adverse cardiovascular events (MACE). However, it is unknown whether ApoC3 predicts risk in patients with acute coronary syndrome (ACS) receiving contemporary therapies including optimized statin treatment, and if any such association is independent of apolipoprotein B (ApoB) levels. Purpose We assessed the association of ApoC3 with first MACE (CHD death, nonfatal myocardial infarction, fatal or nonfatal ischaemic stroke, or hospitalization for unstable angina) and all-cause death in patients with recent ACS treated with high-intensity or maximum-tolerated statin and blinded PCSK9 inhibitor (alirocumab, ALI) or placebo (PBO). Methods ApoC3 was measured by mass spectrometry at baseline (n=11,956) and after 4 months (M4; n=11,176) of treatment with ALI or PBO in the ODYSSEY OUTCOMES trial (which had 18,924 total participants). In continuous and spline analyses adjusted for treatment group and ApoB, we assessed the association of baseline ApoC3 with risk of MACE and death. In the ALI group we determined association of change in ApoC3 from baseline to M4 with risk of MACE and death after M4 in a model adjusted for baseline ApoC3 and ApoB, and the change in ApoB from baseline to M4. Results Median (Q1, Q3) baseline ApoC3 concentration was in a normal range [85 (65, 113) mg/L]. Continuous ApoC3 was not related to MACE (p=0.50) or death (p=0.51); spline analysis showed a slight curvilinear association of baseline ApoC3 with risk of MACE and death, but no clinically meaningful relationship (Figure). Findings were similar in the PBO group alone, and without adjustment for ApoB (data not shown). At M4, the median (Q1, Q3) change from baseline in ApoC3 was -10 (-27, -5; p&amp;lt;0.0001) mg/L with ALI and 2 (-14, 18; P = NS) mg/L with PBO. Overall, ALI significantly reduced the incidence of MACE (10.1% vs 12.1%; p=0.0006) and death (3.5% vs 4.2%; p=0.045) compared with PBO among those with available baseline ApoC3. However, the change in ApoC3 on treatment with ALI did not predict the risk of MACE or death after M4. Findings were qualitatively similar without adjustment for ApoB or its change. Conclusion In a cohort with recent ACS receiving optimized statin therapy and with median baseline ApoC3 in a normal range, ApoC3 did not provide clinically meaningful prediction of cardiovascular events or death. A modest reduction of ApoC3 by ALI did not associate with subsequent risk of MACE or death. It remains uncertain whether targeted therapies producing larger reductions in ApoC3 from higher baseline levels will affect cardiovascular risk.

Obesity paradox, weight-free anthropometric measures, and major adverse cardiovascular events in the elderly: Insight from the Northern Shanghai Study

Abstract Aims Many studies have investigated the obesity paradox in the elderly. However, besides body mass index (BMI), many other anthropometric measures, such as the waist-to-hip ratio (WHR), provide a better indication of body fat distribution and may be more useful in a geriatric population. Methods 3285 participants aged over 65 years old from the Northern Shanghai Study were included in this analysis. Eight anthropometric measures, including weight-related measures (BMI, weight-adjusted-waist index, body shape index and body surface area) and weight-free measures (WHR, waist-to-height ratio, body roundness index, relative fat mass) were measured and calculated with standard methods. Major adverse cardiovascular events (MACEs) included the non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Results Participants had an average age of 71.4 years and 1428 (43.47%) were men. The median follow-up was 5.4 years (IQR, 4.4-7.3 years) and 218 events occurred. Participants with obesity (BMI ≥ 28 kg/m2) were associated with a higher risk of MACEs compared with the normal (adjusted Hazard ratio = 1.54, 95% confidence interval (CI): 1.07-2.22, P=0.020). Restricted cubic splines also highlighted the robust correlation between high BMI and high MACEs risk (Pfor overall=0.025, Pfor nonlinear=0.339). Similarly, the aHR for the incidence of MACEs in WHR quartile 4 versus quartile 1 was 1.96 (95% CI: 1.26-3.05, P=0.003). When WHR was examined as a continuous variable, the result remained unaltered (Pfor overall=0.020, Pfor nonlinear=0.353). In adjusted model, all four weight-free measures were significantly associated with increased risk of MACEs (all P&amp;lt;0.05), while only two weight-related measures were related to the risk of MACEs. Conclusion In the elderly, BMI and alternative anthropometric measures showed no evidence of an "obesity paradox". Weight-free measures were more relevant to a risk of MACEs.Take home message

Renal hyperfiltration as risk factor of major adverse cardiovascular events in patients with acute myocardial infarction

Abstract Objectives While the interaction between heart and kidney potentially contributes the development of renal hyperfiltration (RHF), its clinical consequence of is not clear in patients with acute myocardial infarction (AMI). Methods A total of 9,561 AMI patients with estimated GFR (eGFR) ≥60 mL/min/1.73 m² were enrolled from a large nationwide, multi-center, prospective, observational cohort between November 2011 and December 2015. RHF was defined as eGFR &amp;gt;90th percentile after multiple adjustments. The primary endpoint was a combination of 3-year major adverse cardiovascular events (MACEs) after AMI treatment. Results The cumulative event rate of MACEs was significantly higher in patients with RHF. In multivariable Cox-regression analysis, RHF increased the 1.34-fold risk of MACE (95% confidence interval [CI] 1.12-1.62) compared to those without RHF. Patients with RHF had a significantly higher risk of all-cause mortality (hazard ratio [HR] 1.64; 95% CI 1.25-2.14) and cardiac death (HR 1.78; 95% CI 1.26-2.51). There was a linear correlation between the adjusted risk of MACEs and eGFR, with the risk increasing as eGFR exceeded approximately 100 mL/min/1.73 m². In the 1:1 propensity-score matched population, the cumulative event rate of MACEs, all-cause mortality, and cardiac death were consistently higher in patients with RHF (all p &amp;lt;0.05). Conclusion RHF was significantly associated with an increased risk of MACEs, all-cause mortality, and cardiac death following AMI compared to patients without RHF. Our study offers new insights into the risk stratification of AMI patients presenting with RHF.

Impact of neutrophil-to-lymphocyte ratio on clinical outcomes in patients with acute or chronic coronary syndrome undergoing percutaneous coronary intervention

Abstract Background Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as an inflammatory biomarker associated with atherosclerosis and cardiovascular events. However, its role in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear. Purpose We aimed to evaluate the clinical impact of baseline NLR in patients undergoing PCI for acute coronary syndrome (ACS) and chronic coronary syndrome (CCS). Methods We retrospectively evaluated all consecutive patients undergoing PCI between 2012-2022 in a large tertiary US hospital. We excluded patients for whom NLR was not available and those who were deemed to have active hematological or infective diseases, including patients presenting with extremely low or high lymphocyte and neutrophil counts or with hs-CRP above 10 mg/L. Quartiles of NLR were derived in the overall population and patients were stratified according to clinical presentation. Within each group, we estimated the risk of 12-month adverse events using the lowest NLR quartile as reference. The primary endpoint was major adverse cardiovascular events (MACE), defined as the composite of all-cause death, myocardial infarction (MI), or stroke. Secondary endpoints were MACE individual components and any periprocedural or post-discharge clinically relevant bleeding. Results A total of 7,201 patients were included in the analysis; of these 3,975 (55.2%) had ACS and 3,226 (44.8%) CCS. Patients in the 4th quartile (NLR &amp;gt; 5.0) were more frequently male, older, and presented more often with chronic kidney disease and complex coronary artery disease. Smoking, diabetes and history of CAD, as well as triglycerides, LDL, non-HDL and total cholesterol levels were lower in the 4th NLR quartile. In patients presenting with CCS, the risk of MACE, all-cause death, MI was similar across NLR quartiles, while the risk of bleeding increased stepwise (Figure 1). In patients presenting with ACS, the 4th NLR quartile had the highest adjusted risk of MACE (HRadj 1.82, 95% CI 1.25-2.67; P=0.002), all cause death (HRadj 2.56, 95% CI 1.41-4.66; P&amp;lt;0.001), and bleeding (HRadj 1.82 95% CI 1.25-2.63, P&amp;lt;0.001) at 1 year, as compared to the lowest quartile (Table 1). Conclusions Among patients undergoing PCI, elevated NLR is strongly associated with risk of MACE and all-cause mortality in patients presenting with ACS but not in those with CCS. Conversely, the risk of bleeding was augmented with higher NLR in both ACS and CCS patients undergoing PCI. In this setting, NLR may inform risk stratification at the time of PCI.

Clinical characteristics and predictors of adverse cardiovascular events from the australia-new zealand spontaneous coronary artery dissection (ANZ-SCAD) registry

Abstract Background Spontaneous coronary artery dissection (SCAD) is an increasingly recognised cause of acute coronary syndrome (ACS), predominantly affecting women. Our understanding of SCAD remains incomplete with limited prospective data on determinants of major adverse cardiovascular events (MACE). Purpose We aimed to describe the clinical characteristics of patients with SCAD from a large, multicentre SCAD registry. We aimed to identify the predictors of MACE (defined as the composite of all-cause death, non-fatal myocardial infarction, stroke, heart failure, and revascularisation). Methods Observational, multi-centre prospective and retrospective cohort study recruiting patients with SCAD from 23 hospitals in Australia and New Zealand. Patients aged=&amp;gt;18 years with SCAD and an ACS were eligible for inclusion. Prospectively recruited patients gave their informed consent with a waiver of consent for retrospectively recruited patients. All invasive coronary angiography imaging was adjudicated by an independent core laboratory to confirm the diagnosis of SCAD. Cox proportional hazard analysis was used to evaluate the association between MACE and SCAD recurrence with predefined clinical variables. Results From a total 487 patients recruited, 423 (132 prospective and 291 retrospective) patients with SCAD confirmed on core laboratory review were included for analysis. Mean age was 52.4±10.7 years, 89.7% were female and 73.1% were Caucasian. Percutaneous coronary intervention (PCI) was performed in 10.6% of patients. On discharge, 64% of conservatively managed patients were on dual antiplatelet therapy (DAPT). At 15 (interquartile range 5-36) months median follow-up, the accumulated MACE rate was 6.6%. On multivariate analysis, percutaneous coronary intervention (PCI) was associated with a higher risk of MACE [hazard ratio (HR) 3.50, 95% confidence interval (CI) 1.56-7.89, p=0.002], while discharge on at least one antiplatelet medication was associated with a lower risk of MACE (HR 0.13, 95% CI, 0.05-0.36, p&amp;lt;0.001). In patients managed conservatively (n=353), discharge on at least one antiplatelet medication (n=337) was associated with lower MACE (HR 0.27, 95% CI 0.1-0.73, p=0.01), with no difference between single and dual antiplatelet therapy (DAPT) (p=0.74). In patients managed conservatively and on DAPT (n=226), aspirin and clopidogrel was associated with a lower risk of MACE (HR 0.31, 95% CI 0.10-0.93, p=0.038) compared with DAPT consisting of aspirin and ticagrelor (HR 3.25, 95%CI 1.07-9.85 p=0.038) on multivariate analysis. Conclusion Patients with SCAD are at significant risk of MACE. In conservatively managed patients treated with DAPT, aspirin and clopidogrel was independently associated with a lower risk of MACE than aspirin and ticagrelor

Pre-discharge prediction of long-term prognosis in patients after ST-segment elevation myocardial infarction - the ValAMI-P risk score

Abstract Background Despite contemporary management of ST-segment elevation myocardial infarction (STEMI) patients, cardiovascular death (CV death) and re-admission for acute heart failure (aHF) are frequent complications during follow-up. Several clinical, electrocardiographic, and echocardiographic variables have been identified as risk factors of major adverse cardiovascular events (MACE) in this setting. We aim to study the usefulness of a risk score using universally available clinical, electrocardiographic, and echocardiographic variables at discharge to stratify the risk of MACE during follow-up. Methods We prospectively included 712 patients treated with primary percutaneous coronary intervention after STEMI. We registered clinical, ECG and echocardiography-derived pre-discharge data. Left ventricular ejection fraction (LVEF) was categorized according to current recommendations. The primary endpoint was time to first MACE, defined as CV death or aHF, whichever occurred first. We created a risk score (ValAMI-P) including variables independently associated with MACE in multivariable analysis. Patients were classified in three groups (low, intermediate, and high risk) according to the ValAMI-P score. Results Mean age was 60±12 years, most patients (78.5%) were male, and smoking was the most prevalent risk factor (54.4%). During an 8.1-year median follow-up, 154 MACE (21.6%) were registered. In multivariable analysis, age (HR 1.03 [1.01-1.05], p=0.001), previous hypertension (HR 1.49 [1.04-2.12], p=0.029), GRACE score (HR 1.01 [1.01-1.02], p&amp;lt;0.001), mildly reduced LVEF (41-49%; HR 1.92 [1.18-3.11], p=0.008), reduced LVEF (≤40%; HR 5.2 [3.53-7.65], p&amp;lt;0.001) and the number of leads with Q-wave and residual ST-segment elevation at pre-discharge ECG (Q-STE; HR 1.13 [1.03-1.25], p=0.013) associated with long-term MACE. After classification according to the ValAMI-P risk score, patients with intermediate (8-13 points) and high (≥14 points) score depicted an increased risk of MACE (31% and 50%, respectively) compared to patients with low ValAMI-P risk score (≤7 points; 13%; p&amp;lt;0.001 for all comparisons). Conclusions The ValAMI-P risk score, which comprises widely available clinical, ECG and echocardiographic variables at discharge, can identify patients at increased long-term risk of MACE after STEMI.ValAMI-P risk score after STEMI

Diabetes mellitus and adverse clinical events in patients with atrial fibrillation: implications of insulin treatment: a report from the GLORIA-AF Registry Phase III

Abstract Background Atrial Fibrillation (AF) and diabetes mellitus (DM) are both associated with adverse clinical events, but the associations has not been fully elucidated, especially in relation to insulin use. Purpose To analyze the associations between DM and the risk of clinical adverse events in patients with AF, and second, explore the impact of insulin treatment in these patients. Methods We studied patients with AF from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry with 3-years follow-up. Clinical events included all-cause death, major bleeding, myocardial infarction (MI), stroke, thromboembolism (TE), and major adverse cardiovascular events (MACE). MACE was defined as a composite of stroke, MI and major bleeding. Kaplan-Meier curves were used to estimate the cumulative incidence of clinical events. Multivariable cox regression models with subgroups were used to estimate the association between DM and the risk of mortality and clinical events. Results A total of 15,861 AF patients were included (mean age 70.00 ± 10,21 years old; 55% male, 20% Asia), of which 3,666 had DM (mean age 70.04 ± 9.54 years old; 59% male, 21% Asia). Kaplan-Meier curves showed that AF patients with DM had higher cumulative hazard of all outcomes, including all-cause death (OR: 1.56, 95%CI: 1.38-1.77), CVD (OR: 1.72, 95%CI: 1.44-2.06), major bleeding (OR: 1.4, 95%CI: 1.17-1.67), stroke (OR: 1.29, 95%CI: 1.04-1.61), TE (OR: 1.26, 95%CI:1.02-1.56), MI (OR: 1.88, 95%CI: 1.48-2.39) and MACE (OR: 1.61, 95%CI: 1.41-1.84). After adjustment by prior disease and drugs, the outcomes of stroke (OR: 1.19, 95%CI: 0.95-1.49) and TE (OR: 1.22, 95%CI: 0.98-1.52) showed not significant. Subgroup analysis found that increased risks of stroke were found in female (OR: 1.43, 95%CI: 1.03-1.98, Pinteraction = 0.062) and non-Asian patients (OR: 1.39, 95%CI: 1.06-1.82, Pinteraction = 0.175) with DM. For all cause death, subgroup results were similar with overall patients. In addition, insulin use increased the risk of all cause death (OR: 1.82, 95%CI: 1.45-2.29), CVD (OR: 1.70, 95%CI: 1.22-2.37), major bleeding (OR: 1.54, 95%CI: 1.08-2.18), MI (OR: 1.72, 95%CI: 1.12-2.64), MACE (OR: 1.65, 95%CI: 1.28-2.11) in patients with AF and DM. Multivariable model showed similar result. Conclusions DM was independently associated with higher risk of all-cause death, CVD, MI, major bleeding, and MACE in patients with AF. Insulin use was associated with higher risk of all-cause death, CVD, MI, major bleeding, and MACE in patients with AF and DM.Figure 1Figure 2

The relationship between retinal vascular parameters measured by artificial intelligence and the risk of new-onset cardiovascular disease in a Chinese community-based population

Abstract Background Studies on the association between retinal vascular diameter and tortuosity and the risk of new-onset cardiovascular disease (CVD) are controversial. The predictive value of retinal vascular parameters, measured through artificial intelligence (AI), for incident CVD risk in the community population, remains to be explored. Objectives Our study aims to investigate the association between retinal vascular parameters (diameter and tortuosity) measured through AI, and the risk of new-onset CVD in the Chinese community-based population. Methods We conducted a prospective cohort study on subjects from a Beijing community in China who were free of prevalent stroke or myocardial infarction and underwent retinal photography at baseline. By deep-learning algorithm, quantitative retinal vascular parameters were measured 0.5 to 1 disc diameter from the optic disc margin, including central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriolar-to-venular ratio (AVR), curvature tortuosity arteriole (cTORTa), and curvature tortuosity venule (cTORTv). The primary endpoint was a new-onset major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, first non-fatal stroke, and first non-fatal acute myocardial infarction (AMI). The secondary endpoints included cardiovascular death, first stroke, and first AMI. Cox proportional-hazards regression analyses were performed. Results A total of 3,585 participants were included. The mean age was 56.49 ± 8.94 years, and 2,335 (65.1%) were female. Prevalence of prior hypertension and diabetes was 1594 (44.5%) and 676 (18.9%), respectively. During the follow-up (median, 7.53 years), there were 293 cases of new-onset MACE (8.2%), 44 cardiovascular deaths (1.2%), 226 strokes (6.3%), and 57 AMIs (1.6%). The Kaplan–Meier curves showed significant differences in cumulative hazards of new-onset MACE among tertiles of CRAE, CRVE, AVR, and cTORTa, but not for cTORTv (Figure 1). In Cox proportional-hazards models (Figure 2) adjusting for covariates, CRAE was negatively associated with the risk of new-onset MACE (per 10 μm increase, hazard ratio [HR]=0.95, 95% confidence interval [CI]: 0.92-0.99, P=0.009) and the risk of new-onset stroke (per 10 μm increase, HR=0.96, 95%CI: 0.92-1.00, P=0.04). Similarly, AVR was negatively associated with new-onset MACE risk (per 0.1 increase, HR=0.82, 95%CI: 0.72-0.94, P&amp;lt;0.001) and new-onset stroke risk (per 0.1 increase, HR=0.84, 95%CI: 0.73-0.98, P=0.022). No significant associations were observed between CAVE, cTORTa, and cTORTv with any of the primary or secondary endpoints. Conclusions CRAE and AVR, measured through AI, are associated with the risk of new-onset MACE in the Chinese population. These findings suggest the potential for AI-measured parameters in retinal vasculature to aid in stratifying CVD risk in the general population.

Impact of neutrophil-to-lymphocyte ratio on clinical outcomes in patients with or without chronic kidney disease undergoing percutaneous coronary intervention

Abstract Background Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as inexpensive inflammatory biomarker associated with worse cardiovascular outcomes. However, little is known about its role in risk stratification of patients with both chronic kidney disease (CKD) and coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Purpose We aimed to evaluate the clinical impact of baseline NLR in patients with and without CKD undergoing PCI. Methods We retrospectively evaluated all consecutive patients undergoing PCI between 2012-2022 in a large tertiary US center. We excluded patients without available NLR and those who were deemed to have active hematological or infective diseases, including patients with extremely low or high lymphocyte and neutrophil counts or with hs-CRP above 10 mg/L. Quartiles of NLR were derived in the overall population and patients were stratified according to presence of CKD (eGFR &amp;lt; 60 ml/min). Within each group, we estimated the risk of adverse events using the lowest NLR quartile as reference. The primary endpoint was 12-month incidence of major adverse cardiovascular events (MACE), defined as the composite of all-cause death, myocardial infarction, or stroke. Secondary endpoints included incidence of clinically relevant bleeding and contrast-associated acute kidney injury (CA-AKI), defined as ≥ 0.3 mg/dL or ≥ 50% serum creatinine increase from baseline. Results A total of 7,287 patients were included in the analysis; of these 2,008 (27.6%) had CKD and 5,279 (72.4%) did not. CKD patients (mean eGFR 40.8±16.1 ml/min) were older, had more comorbidities, and presented with higher hs-CRP levels and a greater estimated risk of CA-AKI. Overall, patients with elevated NLR had more severe CAD and underwent more complex PCI. In CKD patients, incidence of adverse events increased stepwise and those in the 4th NLR quartile had the highest adjusted risks of MACE (HRadj 1.86, 95% CI 1.12-3.08; P=0.012), all cause death (HRadj 2.44, 95% CI 1.18-5.05; P=0.003) and bleeding (HRadj 1.74, 95% CI 1.07-2.84; P=0.002) at 1 year, as compared to those in the lowest quartile (Table 1). In patients without CKD, MACE and all-cause death incidences were numerically higher in the 4th quartile but risk estimates were no longer statistically significant after adjustment. The overall incidence of CA-AKI was much greater in the CKD group. When compared to the lowest quartile, patients in the 4th NLR quartile showed a trend for higher risk of CA-AKI in CKD group, while they had a significant increased risk in non-CKD group (Figure 1). Conclusions Elevated NLR is strongly associated with higher risk of MACE and all-cause mortality in CKD patients. Conversely, the risk of bleeding and CA-AKI is increased with elevated NLR in both CKD and non-CKD patients. Thus, NLR may further inform risk stratification of CKD patients undergoing PCI.

AI-ECG sex-estimation discordances predict cardiovascular events

Abstract Background Cardiovascular disease remains the leading cause of death and burden globally, warranting the need to explore novel predictors of major adverse cardiovascular events (MACE) using new technologies. Artificial Intelligence (AI)-enhanced ECG (AI-ECG) algorithms can provide information on cardiovascular health of individuals, independent of conventional risk factors. Purpose The current study aimed to understand whether a previously described AI-ECG sex estimation algorithm could be applied for risk stratification of major adverse cardiovascular events (MACE), with a focus on a population without previous history of MACE. Methods Patients having 12-lead ECGs between 2018-2019 were included and followed up until August 2023. Exclusion criterion was a prior history of MACE. AI-ECG sex estimation was determined using a previously described algorithm predicting sex based on 12-lead ECGs. The algorithm generates outputs ranging from 0 to 1, representing the estimated probability of being male. Outputs above 0.5 were considered as AI-ECG-estimated male, and below as AI-ECG-estimated female. This was compared with biological sex to determine whether the two matched. Inconsistency between AI-ECG estimated sex and biological sex was defined as discordance. MACE was defined as myocardial infarction, coronary revascularization, non-fatal stroke, and all-cause death. Results Among 80,578 subjects (mean age 59.1 ± 16.1 years, 52.4% female), 9.7% exhibited sex discordance in AI-ECG estimation. Discordance was associated with a 56% higher risk of MACE (HR, 1.56, 95% CI 1.46-1.65, p &amp;lt;0.001), and remained significant in multivariable analysis with traditional risk factors (HR 1.35, 95% CI 1.27-1.43, p &amp;lt;0.001) (Figure 1). Sex-specific analysis showed increased MACE risk in both discordant males and females (Figure 2). Conclusion In patients with no history of MACE, discordance in AI-ECG sex estimation is associated with increased risk of MACE. These findings suggest the potential of AI-ECG sex estimation algorithm for risk assessment, especially in patients with no history of MACE.Figure 1.Cox proportional hazard modelFigure 2.Kaplan-Meier of MACE by sex

Measuring only sitting blood pressure without considering supine blood pressure underestimates cardiovascular risk in the elderly

Abstract Background and Objective Elderly individuals exhibit greater variability in blood pressure (BP) readings between sitting and supine positions. Nocturnal hypertension (supine position) is closely associated with cardiovascular diseases and mortality. However, the relationship between supine BP and cardiovascular risk remains unclear. This study aims to investigate the association between the occurrence of major adverse cardiovascular events (MACEs) with BP in sitting and supine positions. Methodologies A total of 3363 participants aged 65 years or older from the Northern Shanghai Study were included. Each participant is given 3 consecutive sitting SBP readings (SBP1, SBP2, SBP3) at 2-minute intervals, we then calculated the SBP1-2 (average of SBP1 and SBP2), SBP2-3 (average of SBP2 and SBP3), SBP1-2-3 (average of SBP1, SBP2 and SBP3). we also collected two supine BP readings (S-SBP1, S-SBP2). Kaplan-Meier and Cox proportional hazard regression were used to investigate the association of sitting and supine BP with MACEs (composite of nonfatal myocardial infarction, nonfatal stroke, or death). Results The mean age of participants was 71.5 years, and 1467(43.6%) were men. After a median of 6.4-year follow-up, a total of 362 events were recorded. Among 3 successive BP readings, SBP2-3 had strongest association with MACEs incidence (hazard ratio, 1.12 [1.00-1.26] per SD). Multiple cox proportional hazard regression showed supine BP had significant value in predicting MACEs, acute myocardial infarction (AMI) and mortality compared to sitting BP. Kaplan-Meier revealed significant differences in MACEs rates among participants without hypertension (HTN) in both sitting and supine positions, with HTN in both positions, or those with HTN in either position (Log rank P &amp;lt; 0.01). Compared to participants without HTN in both sitting and supine positions, those with HTN in both positions had a 1.4-fold (hazard ratio,1.40[1.08-1.82]) higher risk of MACEs and 2-fold (hazard ratio,2.01[1.24-3.26]) higher risk of stroke. Conclusion Supine BP measurements are more valuable than sitting BP in predicting MACEs in elderly individuals. Hypertension in both positions significantly increases the risk of MACEs. Taken together, supine BP may also need to be emphasized in the elderly.central illustration

Can the presence of aortic or coronary artery calcifications in the standard of care baseline CT or PET-CT scan of patients with Hodgkin or non-Hodgkin lymphoma be used as a predictor of MACE?

Abstract Background Major adverse cardiovascular events (MACE), commonly defined as acute myocardial infarction, acute coronary syndrome/ischemic heart disease requiring revascularization, stroke, and heart failure, represent a significant cause of mortality among patients with cancer. With increased rates of both cancer and cancer survivorship, the identification of new predictive markers for the development of MACE in this population is crucial for implementing effective preventive and risk-mitigation strategies. Purpose To determine whether the presence of calcifications in the coronary arteries (CAC) or aorta (CA) of lymphoma patients, as reported in standard-of-care PET-CT (Positron Emission Tomography-Computed Tomography) or chest CT (Computed Tomography) scan, can predict the occurrence of MACE. Methods A Retrospective analysis was conducted on a cohort of patients diagnosed with Hodgkin or non-Hodgkin lymphoma and treated with anthracycline-based chemotherapy. Patients were diagnosed from January 1, 2013, and followed through to June 30, 2023. The reference point for the study was the radiologist’s report of the PET-CT or chest CT conducted before the initiation of anthracycline therapy. Patients who did not undergo a PET-CT or CT before the start of treatment, and/or developed MACE before treatment initiation were excluded. Univariate and multivariate adjusted Cox regression models were employed to assess whether the presence of CA and CAC was associated with the development of MACE. Associations with outcomes were evaluated using the Kaplan-Meier method and Cox regression. Results 326 patients were included with a mean age of 55 years (range: 52-60), predominantly male 201 (61%) and white 314 (96%), CAC was reported in 75 patients (23%) and CA in 18 (6%). In the univariate regression model, a statistically significant association was found between the presence of both CA and CAC with the risk of MACE. CAC showed a stronger association with the development of MACE than CA (HR: 3.7 [1-7.9], p=0.0005 vs HR: 2.9 [1- 8.5], p=0.050). In multivariable analysis CAC emerged as the strongest predictor of MACE (HR: 2.9 [1.3 – 6.4], p=0.01), after accounting for hypertension, diabetes, dyslipidemia, and GFR &amp;lt;60 (Table 1), while the association with CA attenuated (HR: 2.01 [0.7-6.5], p=0.2010) and was no longer significant (Table 2). Conclusion CAC in the standard-of-care PET/-CT scans was a predictor of MACE in lymphoma patients treated with anthracyclines, while the association with CA weakened in multivariable analyses and was likely underpowered given the small number of patients with CA. If replicated, this finding warrants closer surveillance of this group of patients and can be considered as a non-invasive cardiovascular risk marker.

Adverse cardiovascular events in patients with cancer: a biomarker-enhanced clinical risk score

Abstract Background/Introduction Continuously improving cancer-specific survival puts a growing proportion of cancer patients at risk of major adverse cardiovascular events (MACE), but reliable tools for cardiovascular risk prediction remain unavailable (1). Purpose To assess a broad panel of cardiovascular biomarkers and clinical risk factors and to provide a novel risk score for the prediction of MACE in cancer patients. Methods Among 2’192 patients with newly diagnosed or recurrent cancer, a broad panel of cardiovascular biomarkers, including NT-proBNP, P-/E-/L-selectins, ICAM-1, VCAM-1, sLOX-1, CRP, and Lp(a) were measured by blinded study personnel. Patients were followed prospectively for the occurrence of 2-year MACE and 5-year cardiovascular death (2,3). Uni- and multivariable competing risk models were fit to assess independent associations of cardiovascular risk factors and biomarkers with MACE, and a risk score was developed. Results Beyond clinical risk factors, ICAM-1, P-/E-/L-selectins and NT-proBNP levels were independently linked to 2-year MACE risk, though shape of associations differed markedly. A clinical risk score was derived, assigning +1 point for male sex, smoking, and age ≥60 years, and +2 points for ASCVD history, yielding a bootstrapped C-statistic of 0.76 (95%CI:0.71-0.81). Implementation of cardiovascular biomarkers conferred improved performance (0.83, 95%CI:0.78-0.88). A simplified model, solely informed by clinical variables and readily available NT-proBNP (+1 point for NT-proBNP≥230pg/mL), achieved similar performance (0.80, 95%CI:0.74-0.86), with a cumulative 2-year MACE incidence of 0% in low- and 11.0% in high-risk patients. Conclusions Cancer patients are at substantial MACE risk. The herein presented first-of-its-kind risk score, integrating traditional cardiovascular risk factors and biomarkers, including NT-proBNP, effectively predicts 2-year MACE and 5-year cardiovascular death.

Nomogram-based prediction of MACE in older adults with STEMI

Abstract Introduction Despite the significant progress made in diagnosing and treating patients with ST elevation myocardial infarction (STEMI), high-risk subgroups such as older adults (those over 65 years-old) still face considerable residual risk of major adverse cardiovascular events (MACE) following treatment for their index event. Thus, it is crucial to create accurate, validated, and actionable tools to stratify patients according to their risk of MACE after admission for STEMI. Purpose Utilizing clinical data obtained from a registry of patients diagnosed with STEMI, this study aims to develop a nomogram that can reliably predict the likelihood of MACE incidence. Methods Using a large electronic single-center registry, all consecutive patients with STEMI, undergoing primary percutaneous coronary intervention (PCI), and aged 65 and above were identified. Demographic, laboratory, clinical and intra-procedural variables were examined. Univariate and multivariate logistic regression analyses were utilized to identify those factors which were independently associated with MACE incidence in the post PCI follow-up period. A nomogram was developed in a training set, and performance metrics such as receiver operating curves (ROC), calibration plots, and decision curve analysis were used for validation in a testing set. Analyses were performed using tidyverse and rms packages in R programming language. Results 1946 patients were included in the study and split into 70% training and 30% testing sets. Both groups were similar in terms of baseline demographic and clinical characteristics. Mean follow-up period was 17 months. Total MACE incidence in the post PCI follow-up period was 18%. Thirty-eight factors with limited missing information (&amp;lt;5%) were examined for their relationship with MACE incidence and after performing univariate and multivariate analysis 8 were selected for construction of the nomogram: left-ventricular ejection fraction (LVEF), serum creatinine, hemoglobin and fasting blood glucose levels, presence of valvular heart disease, post PCI TIMI flow grade, diameter of the stent placed in the culprit lesion, and presence of shock in the post PCI setting. The area under the curve (AUC) for MACE prediction in post PCI follow-up period showed acceptable discrimination (c-statistic=73%, 95%CI 71.2% to 76.3%). Calibration plots demonstrated that the nomogram model was well-calibrated, and its predictions were closely aligned with observed outcomes. Additionally, decision curve analysis indicated that the model exhibited strong discriminatory ability in predicting MACE. Conclusions A nomogram developed using a combination of laboratory, clinical, and procedural parameters reliably predicts future risk for MACE in older adults following STEMI. Future implementation of this model may identify the highest risk individuals to target more aggressive preventive efforts in a vulnerable cohort of patients.Plot 1Plot 2

Double product derived from exercise stress echocardiography (ESE) or dobutamine stress echocardiography (DSE) in patients with a history of breast cancer and radiotherapy (RXT) exposure and MACE

Abstract Background Breast cancer survivorship has markedly improved in the last two decades due to improved therapies. Among these, adjuvant chest radiotherapy stands out as an integral part of the current treatment. Chest radiotherapy can trigger accelerated atherosclerosis, which, coupled with cardiovascular (CV) risk factors common to this population, can lead to increased rates of coronary artery disease (CAD). ESC 2022 guidelines have established both Exercise Stress Echocardiography (ESE) and Dobutamine Stress Echocardiography (DSE) as cost-efficient and reliable tools for screening this patient population. Recommendations include ESE or DSE 5 years after radiotherapy as a screening tool. Double product (DP), an index common to both tests, parallels myocardial oxygen consumption. It has been used to predict major adverse cardiovascular events (MACE) in other cohorts. Purpose We sought to evaluate if DP could be used as a prognostic indicator for MACE (myocardial infarction, stroke, cardiovascular death, and heart failure) in this population. Methods Breast cancer patients treated with adjuvant radiotherapy from 2000 to 2022 were included. ESE or DSE was done after a mean of 5.4 years (1Q-2.2, 3Q-7.5) post-radiotherapy. Uni and multivariable adjusted Cox regression models were performed to evaluate the association between DP quartiles achieved and the risk of MACE in DSE and ESE groups. MACE-free survival among different quartiles was plotted with the Kaplan Meier method. Results 696 patients were included, with a mean age of 65 (SD 10.0) and 72 (SD 9.4) in ESE and DSE respectively. 61% of patients had ESE. In ESE, we observed increased rates of MACE in the 1st quartile when compared to the other quartiles (Figure 1a). On the other hand, univariate and multivariate Cox models established that for every increase of 1000 units of DP achieved during ESE, there is a risk-reduction of 9% [HR=0.91 (0.86-0.95); p=&amp;lt;0.01] in the future incidence of MACE, thus establishing DP as a protective marker. Additionally, advanced age was shown to be a major risk factor as well [HR=4.58 (1.91-10.9); p=&amp;lt;0.01]. In the DSE cohort however, the development of MACE was equally distributed across DP quartiles even after adjusting for existing comorbidities (Figure 1b). Cox analysis did not establish DP as a prognostic tool in this cohort (Table 1). Conclusion DP is established as an excellent prognostic tool for the detection of MACE in patients who underwent ESE. Patients who achieve higher DP quartiles during these tests have lower future rates of MACE. Regarding DSE, DP is not a good prognostic tool. This could be explained by higher burden of cardiovascular risk factors in this patient population. ESE should be recommended when possible.

Association of a history of acute kidney injury with major adverse cardiovascular events in chronic kidney disease patients

Abstract Background/introduction Acute kidney injury (AKI) is strongly associated with major adverse cardiovascular events (MACE), particularly heart failure, in both general and critically ill populations. A recent study questioned whether this association holds true only for patients without chronic kidney disease (CKD). Purpose To evaluate the association of a history of AKI with MACE in a large real-world CKD population defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Methods A retrospective cohort study was conducted using Merative® Explorys electronic health records (&amp;gt;54 million patients) from Jan 2010 to Dec 2019. Six cohorts of CKD patients (diagnosed or not) were created, one for each stage (1-5). Patients were required to have two consecutive abnormal eGFR, uACR/uPCR results within 3-18 months to determine CKD stage, to have at least a 12-months lookback period, and no history of end-stage kidney disease. CKD classification was not mutually exclusive (individual patients could contribute to multiple stages). Index date was the date of the second abnormal test. History of AKI was defined using ICD diagnosis codes, not through biological changes. We followed each patient until the occurrence of a composite of MACE including death, coronary events [acute coronary syndrome + coronary revascularization], any stroke, hospitalization for heart failure, or loss to follow-up, or for up to 5 years. We used multivariable Cox proportional hazards regression to estimate associations between the history of AKI and the risk of MACE during follow-up, adjusted for the following confounders: age, sex, ethnicity, systolic blood pressure, eGFR, BMI, CV history, diabetes, and any CKD diagnosis at baseline. Results Most of the 969,394 patients included in at least one CKD stage cohort were in stage 3a (see table) and Caucasian. Mean ages were 57-75y and 42%-64% were females across the 5 CKD stages. The prevalence of pre-existing CV disease increased from 24% in stage 1 to 57% in stage 4. The proportion of patients with a history of AKI increased from 4% in stage 1 to 36% in stage 4, as well as, the proportion of patients with a ICD code for CKD diagnosis at baseline (3% to 44%). The 5-year incidence of the composite of MACE increased from 25.1% in stage 1 to 65.8% in stage 5. Death was the most frequent event across all stages. In multivariable analysis, a history of AKI was associated with increased risk of MACE (hazard ratios, HR 1.19 to 1.32), all-cause death (HR 1.12 to 1.86), and hospitalization for Heart Failure (HR 1.59 to 1.98) for all CKD stages, and coronary events for stage 2 to 5 (HR 1.14 to 1.22), but not stroke. Conclusion Patients with CKD and a history of AKI are at higher risk of adverse CV outcomes, especially hospitalization for heart failure. This study suggest that these patients should receive cardio -protective intervention.