Major Cardiovascular Events In Patients Research Articles

Patient-specific multifactorial mortality risk assessment using classification and regression tree analysis in the context of ambulatory blood pressure monitoring.

Ambulatory blood pressure monitoring is essential for understanding blood pressure patterns beyond clinical visits, aiding in risk assessment, treatment evaluation, and managing hypertension. This retrospective cohort study aimed to identify risk factors for all-cause mortality and major cardiovascular events in patients who underwent ambulatory blood pressure monitoring. Eligible participants aged 18 or older, with an estimated glomerular filtration rate (eGFR) > 60ml/min/1.73m2, who underwent ambulatory blood pressure monitoring for various reasons, were included in the study. Data were gathered through telephone interviews, electronic health records, and the national health record system. Descriptive analysis and classification and regression tree modeling were used to uncover significant risk factors related to all-cause mortality and cardiovascular events, and to assess the model's performance compared to traditional Cox survival analysis. The study included 1291 patients, primarily male (51.8%) with a mean age of 61.1 ± 15.2years. During a mean follow-up of 46.9months, 76 (5.9%) patients died of any cause, and 195 (15.1%) had a cardiovascular event. The highest survival rates were observed in patients with a diastolic blood pressure (BP) dipping percentage between -2% and 29%, nighttime systolic BP variability below 32mmHg, and age below 72. Conversely, smokers with a diastolic BP dipping percentage below -10% showed the lowest survival rates. The best cardiovascular outcomes were observed in patients with diastolic BP dipping above -11%, nighttime mean systolic BP < 144mmHg, no statin use, normotensive status, and daytime mean heart rate ≥ 60bpm. Conversely, the worst outcomes were seen in patients with diastolic BP dipping below -11% and a morning surge ≥ 14mmHg. In all-cause mortality and cardiovascular event analysis, the combined model demonstrated excellent calibration and predictive power, like the classification and regression tree model and traditional analysis. These findings highlight the potential of a combined model for assessing mortality and cardiovascular event risk in patients who have undergone ambulatory blood pressure monitoring.

Effects of the Strong Hearts program at two years post program completion.

This is a follow-up to the original published article, Effects of the Strong Hearts Program after a Major Cardiovascular Event in Patients with Cardiovascular Disease. This study evaluated the long-term efficacy of the Strong Hearts program up to 2 years after program completion. All study participants who initially completed the Strong Hearts program between 2020 and 2021 (n=128) were contacted at 12months and 24months following the date of program completion. A phone survey was conducted to see if any significant post-cardiovascular events or readmissions to the hospital occurred, and self-reported dates of any occurrences were recorded. Hospital readmissions and cardiac-related procedures were cross-referenced with the hospital's electronic medical record. A chi-square goodness-of-fit analysis was utilized to compare the observed rates of categorical outcomes vs. expected rates yielded from the empirical literature. The rate of all-cause readmission at 6months post-program completion was 2/120 (1.7 %), compared to the expected rate of 50 %, χ2(1) = 112.13, p<0.001. The readmission rate at 1 year post-program completion was 17/120 (14.2 %), vs. the expected rate of 45 %, χ2(1) = 46.09, p<0.001, and at 2 years post-program completion, the readmission rate was 24/120 (20.0 %) compared to the expected rate of 53.8 %, χ2(1) = 56.43, p<0.001. Ten participants (8.3 %) had a subsequent cardiac procedure within 2 years of completing the program, including two requiring percutaneous coronary intervention (1.7 %) and eight requiring coronary artery bypass grafting (CABG, 6.7 %), compared to the expected rates of 13.4 and 57.74 %, χ2(1)=153.08, p<0.001, respectively. Mortality at 2 years post-program completion was 2/128 (1.6 %), compared to 23.4 %, χ2(1)=34.13, p<0.001. Efficacy of the Strong Hearts program continued at 6months, 1 year, and 2 years post-program completion in terms of all-cause readmission, subsequent cardiac event, and all-cause mortality.

Remnant cholesterol predicts major cardiovascular events in coronary artery disease patients with NAFLD

Abstract Remnant cholesterol has attracted interest as a marker of cardiovascular event risk. The power of remnant cholesterol to predict major cardiovascular events (MACE) in patients with non-alcoholic fatty liver disease (NAFLD) is unclear and is addressed in the present study. We enrolled a high-risk cohort of 913 patients with coronary artery disease (CAD). NAFLD was diagnosed using the validated fatty liver index (FLI). Prospectively, MACE including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke were recorded over a mean follow-up period of 9.5±5.2 years. At baseline, remnant cholesterol was significantly higher in patients with NAFLD (n=419) than in patients who did not have NAFLD (30±28 mg/dl vs. 18±17 mg/dl; p&amp;lt;0.001). During follow-up, 379 of our patients suffered MACE. Remnant cholesterol in Cox regression models adjusting for age, sex, hypertension, smoking, diabetes mellitus, body mass index and LDL cholesterol independently predicted MACE in the total study population (standardized adjusted HR 1.18 [1.08-1.30], p&amp;lt;0.001), and both in patients with NAFLD as well as in those who did not have NAFLD (standardized adjusted HRs 1.19 [1.05-1.35], p=0.006 and 1.24 [1.03-1.49], p=0.023, respectively). From our data we conclude that remnant cholesterol is a predictor of MACE in patients with CAD with and without NAFLD.

The triglyceride-glucose index, ventricular arrhythmias and major cardiovascular events in patients at high risk of sudden cardiac death

BackgroundThe association between the triglyceride-glucose (TyG) index and ventricular arrhythmias (VAs) is unclear. This study aimed to investigate the relationship between the TyG index, VAs, and major cardiovascular events in patients at high risk of sudden cardiac death (SCD).MethodsWe enrolled 1046 patients at high risk of SCD with an indication for implantable cardioverter-defibrillator (ICD) implantation at the Chinese National Center for Cardiovascular Diseases. The primary outcome was VAs, defined as sustained ventricular tachycardia and ventricular fibrillation documented by the ICD. The secondary outcomes were cardiac mortality, heart transplantation, and rehospitalization for heart failure.ResultsThe mean (± SD) age was 59.6 ± 14.0 years old, and 25.7% were female. During the mean follow-up of 36.1 months, 342 (32.7%) patients had VAs, and 185 (17.7%) patients had major cardiovascular events. The mean fasting glucose and triglyceride levels were 111.9 ± 42.7 mg/dL and 140.0 ± 95.4 mg/L, respectively, with a TyG index range of 6.96–11.8. In the Fine-Gray subdistribution hazard model analysis, an increase in the TyG index was associated with a significant increase in the VAs (per 1 TyG index, hazard ratio [HR] 2.95; 95% confidence interval [CI], 2.29–3.80) and secondary outcome (HR 2.84; 95% CI 1.86–4.34). When stratified into tertiles, the risk of VAs was significantly higher in the highest tertile (HR 4.08; 95% CI, 2.81–5.92) than in the lowest tertile. Analysis of the secondary outcome revealed similar findings (HR 3.18; 95% CI, 1.73–5.85).ConclusionsIn our cohort, the pre-operational TyG index is significantly associated with VAs and major cardiovascular events for patients with high risk of SCD.

One-year risk of all-cause death and major cardiovascular events in patients presenting with hypertensive crisis. A report from a global federated research health network

Abstract Background Few data are available about the clinical course of patients presenting with hypertensive crisis who are discharged alive from hospital. Purpose To assess the long-term risk of adverse events in patients with hypertensive crises. Methods Retrospective study utilizing a research health network. Based on the ICD-10-CM codes recorded between 2000 and 2022, from 85 health care associations mainly located in the United States, patients with hypertensive crisis were subdivided into hypertensive urgencies (I16.0) and hypertensive emergencies (I16.1). In those with hypertensive emergencies, the type of target organ damage was reported, ie. central nervous system (ischemic stroke, hypertensive encephalopathy, intracerebral hemorrhages), cardiovascular (CVS: myocardial infarction (MI), heart failure (HF), aorta dissection (AD)), or renal (acute kidney failure). Primary outcomes were the one-year risks of all-cause death, and major cardiovascular events (MACE: MI, stroke, cardiac arrest, AD, and HF). Secondary outcomes were the risks for each type of MACE. Cox regression analysis after propensity score matching (PSM) 1:1 was used to produce hazard ratios (HRs) and 95% Confidence Intervals (95%CIs). Results Overall, we identified 25 294 patients with hypertensive emergency (age 62.4±15.7, 46.1% females) and 21,737 patients with hypertensive urgency (age 63.5±17.2, 55.5% females). Patients with hypertensive emergency were more likely males, Black or African American origin and showed a higher prevalence of chronic hypertensive-related complications, vs. those with hypertensive urgency. After PSM, patients with hypertensive emergency showed a higher risk of all-cause death (HR, 1.34, 95%CI 1.25-1.44) and MACE (HR 4.09, 95%CI 3.87-4.33), vs. those with hypertensive urgency. Of the secondary outcomes, patients with hypertensive emergency had increased risks of MI (HR 3.33, 95%CI 3.03-3.67), stroke (HR 4.73, 95%CI 4.33-5.17), cardiac arrest (HR 1.30, 95%CI 1.07-1.58), AD (HR 5.49, 95%CI 3.90-7.73), and HF (HR 3.01, 95%CI 2.74-3.14). All the different types of organ involvement during the hypertensive emergency were each associated with similar long-term risks of adverse events (Figure 1). Conclusion Patients with hypertensive emergency have a high long-term risk of MACE and all-cause death. Preventing the onset of target organ damage in patients with hypertensive crisis is crucial to mitigate their long-term risk of adverse events.

Unseen threat: how subclinical atherosclerosis increases mortality risk in patients with type 1 diabetes

BackgroundCardiovascular disease (CVD), particularly ischemic heart disease, remains the leading cause of death and morbidity in patients with type 1 diabetes. Detecting subclinical atherosclerosis could enhance cardiovascular risk stratification and enable individualised therapies. The aim of this study is to investigate the prevalence and predictors of subclinical atherosclerosis in patients with type 1 diabetes without overt cardiovascular disease (CVD) and to assess its impact on patient survival over a follow-up period of at least 5 years.MethodsThis observational study included 507 patients treated at the Diabetes Unit of the Hospital of Girona Doctor Josep Trueta between 2015 and 2023. The inclusion criteria for patients were as follows: those aged 18 and older with diabetes for a minimum of 10 years or those aged 40 and older with a diabetes for at least 5 years. Subclinical atherosclerosis was identified via ultrasound imaging of the carotid and femoral arteries. Clinical and biochemical evaluations were also conducted. Major cardiovascular events (MACE) and deaths from other causes were monitored, and survival analysis was performed using Kaplan‒Meier methods.ResultsSubclinical atherosclerosis was detected in 218 patients (43%). Multivariate analysis revealed that the male sex, diabetic nephropathy, tobacco exposure, higher HbA1c levels, older age, and longer diabetes duration were significant predictors. During a mean follow-up of 70.64 ± 27.08 months, 19 patients experienced MACE, and 13 died from any cause. The probability of MACE or death was greater in patients with subclinical atherosclerosis, with a hazard ratio (HR) of 25.1 (95% CI 5.81–108, p < 0.001) for MACE and an odds ratio (OR) of 7.57 (95% CI 1.97–53.9, p = 0.004) for death.ConclusionSubclinical atherosclerosis is independently associated with increased overall mortality and MACE in patients with type 1 diabetes. Identifying clinical predictors can improve risk stratification and personalised therapeutic strategies to prevent MACEs in this high-risk population.Graphical

Nonalcoholic fatty liver disease is associated with ventricular arrhythmias and major cardiovascular events in patients with implantable cardioverter-defibrillators

BackgroundPatients with nonalcoholic fatty liver disease (NAFLD) are at risk for cardiovascular diseases. Less is known about the relationship between NAFLD, ventricular arrhythmias (VAs), and cardiovascular events. ObjectiveWe sought to evaluate the association between NAFLD and VAs and major cardiovascular events in patients with implantable cardioverter-defibrillators (ICDs). MethodsA total of 921 patients at high risk of sudden cardiac death who received ICDs were retrospectively analyzed. NAFLD is diagnosed by the presence of hepatic steatosis and lack of secondary causes of hepatic fat accumulation. The primary end points were VAs, defined as sustained ventricular tachycardia and ventricular fibrillation documented by the device. The secondary end points were cardiac mortality, heart transplantation, and rehospitalization for heart failure. ResultsThe prevalence of NAFLD in patients with ICDs was 24.2% (223/921). The mean age was 58.5 ± 12.7 years, and 25.7% were female. During the mean follow-up of 34.8 months, 272 (29.5%) patients achieved primary end points and 171 (18.6%) achieved secondary end points. Kaplan-Meier analysis revealed that NAFLD was associated with an increased risk of VAs (hazard ratio [HR], 3.90; 95% confidence interval [CI], 2.87–5.29; log-rank P < .0001) and secondary end points (HR, 2.04; 95% CI, 1.72–2.94; log-rank P < .0001). In adjusted Cox regression models, NAFLD was an independent risk factor for VAs (HR, 3.84; CI, 2.87–5.12; P < .001) and secondary end points (HR, 2.26; CI, 1.55–3.28; P < .001). ConclusionIn our retrospective cohort, NAFLD is significantly associated with VAs and major cardiovascular events in patients with ICDs.

No Increased Risk of Major Adverse Cardiovascular Events following Nicotinamide Exposure.

Nicotinamide metabolites have recently been implicated in increased risk of major cardiovascular events (MACE). Supportive data about clinical risk of MACE for nicotinamide users is lacking. To determine whether nicotinamide use results in an increase of MACE. Retrospective cohort study of two patient cohorts, Vanderbilt University Medical Center (VUMC) and Military Veteran Program (MVP). The risk of MACE in patients exposed to nicotinamide was compared to the risk of MACE in unexposed patients. In the VUMC cohort, 1228 patients were exposed to nicotinamide based on keyword entry for "nicotinamide" or "niacinamide" and hand-review of charts, while 253 were unexposed but had documented recommendation for use. In the MVP cohort, there were 1594 with exposure to nicotinamide propensity score matched to 2694 without exposure. The primary exposure for the VUMC cohort was a confirmed exposure to nicotinamide in chart review. The primary exposure for the MVP cohort was medication entry for "nicotinamide" or "niacinamide". The primary outcome was development of MACE based on a validated phenotype. Between both cohorts, 6039 patients were included, of whom 5125 were male with a mean age of 63.2 years. Neither cohort had significant differences in mean age, sex, race and ethnicity between the nicotinamide exposed and unexposed groups. In the VUMC cohort, there was no significant association between nicotinamide exposure and the primary outcome of MACE (HR 0.76, 95% CI 0.46 - 1.25, p = 0.28). MACE prior to nicotinamide exposure was strongly associated with subsequent MACE (HR 9.01, 95% CI 5.90 - 13.70, p < 0.001). In the MVP cohort, we adjusted for MACE risk factors as potential confounding variables and saw no significant association between nicotinamide exposure and MACE (HR 1.00 95% CI 0.75 - 1.32), while history of prior MACE remained strongly associated with subsequent MACE (HR 9.50, 95% CI 6.38 - 14.1). In this retrospective cohort study of 6039 adults from two different patient populations, we found no increased risk of MACE in patients with nicotinamide exposure.

Abstract P106: Association of long term blood pressure variability and Major Cardiovascular events in patients with primary aldosteronism

Objective: Long-term blood pressure variability (BPV) is associated with an increased risk of major cardiovascular events (MACE), but it is rarely reported in patients with primary aldosteronism (PA). We aim to investigate the association between long-term BPV and cardiovascular events in patients with PA. Methods: This was a retrospective cohort study which conducted at the Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region from January 2006 to December 2021. The study included patients with PA aged over 30 years. The primary outcome was the incidence of major cardiovascular events during the follow-up, which extended until June 2023. The BPV index encompassed four parameters: standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and maximum and minimum blood pressure difference (MMD). Multivariate analysis using logistic regression was performed, adjusting for demographic variables such as age, sex, body mass index, as well as clinical characteristics including smoking and alcohol consumption. Results: A total of 2,380 patients with PA were ultimately enrolled in this study. Access to clinic blood pressure was ensured at least three times during follow-up visits, with a minimum follow-up interval of 1 month. During a median follow-up of3.6 years, there were 124 cases of MACE. The mean age of the participants was 49.36 years, with men accounting for 1,288 cases. The average blood pressure recorded was 135 mmHg. After adjusting for confounding factors such as age, sex, smoking, alcohol consumption, BMI and cardiovascular risk factors, the systolic BPV (SD, CV, ARV) was found to be significantly associated with MACE (OR= 1.03, CI 1.02-1.05; P&lt;0.05). In the group of mean SBP≥130mmHg, SBP variability had a significant association with MACE (OR: 1.03; CI: 1.01-1.06; P&lt;0.05). However, no significant correlation between SBP variability and MACE in group of mean SBP &lt;130mmHg (P&gt;0 .05). Conclusion: Focusing on long-term systolic BP SD, CV, and ARV in patients with primary aldosteronism may help to prevent the occurrence of cardiovascular events.

Inhibition of the RXRA-PPARα-FABP4 signaling pathway alleviates vascular cellular aging by an SGLT2 inhibitor in an atherosclerotic mice model.

Atherosclerosis is the pathological cause of atherosclerotic cardiovascular disease (ASCVD), which rapidly progresses during the cellular senescence. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce major cardiovascular events in patients with ASCVD and have potential antisenescence effects. Here, we investigate the effects of the SGLT2 inhibitor dapagliflozin on cellular senescence in atherosclerotic mice. Compared with ApoE-/- control mice treated with normal saline, those in the ApoE-/- dapagliflozin group, receiving intragastric dapagliflozin (0.1 mg kg-1 d-1) for 14 weeks, exhibited the reduction in the total aortic plaque area (48.8%±6.6% vs. 74.6%±8.0%, P<0.05), the decrease in the lipid core area ((0.019±0.0037) mm2vs. (0.032±0.0062) mm2, P<0.05) and in the percentage of senescent cells within the plaques (16.4%±3.7% vs. 30.7%±2.0%, P<0.01), while the increase in the thickness of the fibrous cap ((21.6±2.1) µm vs. (14.6±1.5) µm, P<0.01). Transcriptome sequencing of the aortic arch in the mice revealed the involvement of the PPARα and the fatty acid metabolic signaling pathways in dapagliflozin's mechanism of ameliorating cellular aging and plaque progression. In vitro, dapagliflozin inhibited the expression of PPARα and its downstream signal FABP4, by which the accumulation of senescent cells in human aortic smooth muscle cells (HASMCs) was reduced under high-fat conditions. This effect was accompanied by a reduction in the intracellular lipid content and alleviation of oxidative stress. However, these beneficial effects of dapagliflozin could be reversed by the PPARα overexpression. Bioinformatics analysis and molecular docking simulations revealed that dapagliflozin might exert its effects by directly interacting with the RXRA protein, thereby influencing the expression of the PPARα signaling pathway. In conclusion, the cellular senescence of aortic smooth muscle cells is potentially altered by dapagliflozin through the suppression of the RXRA-PPARα-FABP4 signaling pathway, resulting in a deceleration of atherosclerotic progression.

The Effect of Low-Dose Colchicine on the Phenotype and Function of Neutrophils and Monocytes in Patients with Chronic Coronary Artery Disease: A Double-Blind Randomized Placebo-Controlled Cross-Over Study.

Recent landmark trials showed that colchicine provides a substantial benefit in reducing major cardiovascular events in patients with coronary artery disease. Yet, its exact mechanism of action is still poorly understood. This study aimed to unravel the effect of colchicine on monocyte and neutrophil phenotype and function. A randomized double-blind placebo-controlled cross-over intervention study was executed in patients with a history of myocardial infarction. In neutrophils, colchicine treatment decreased CD62L expression and NGAL release upon ex vivo stimulation and increased PMA-induced ROS production. The effects of colchicine on monocytes were limited to a decrease in HLA-DR expression in the intermediate and nonclassical monocytes. Also, on the level of RNA expression, colchicine did not affect monocyte phenotype, while affecting various immunomodulating genes in neutrophils. Overall, our study suggests that treatment with colchicine affects neutrophil function, particularly by reducing neutrophil recruitment, lowering concentrations of NGAL, and changing the expression of various genes with immunomodulatory potential, whereas the effect on monocytes is limited.

Anticoagulant and antiplatelet treatment effects on the incidence of major cardiovascular events in patients with coronary artery ectasia: An updated systematic review

IntroductionCoronary artery ectasia (CAE), widenings in sections of the arteries, is a rare condition found in up to 3–5% of angiography cases. Sometimes recurrence of major adverse cardiac events (MACE) has been reported in the CAE subjects. The present systematic review aims to collect and summarize reports on whether the use of anticoagulants in addition to single antiplatelet/dual antiplatelet therapy (SAPT/DAPT) in CAE patients with significant occlusion/heavy thrombus is efficient and safe in decreasing the incidence/recurrence of MACE. Material and methodsA systematically comprehensive search was performed covering PubMed, Scopus, ISI Web of Science, and Google Scholar databases. ResultsTwenty-five studies were found including 20 case reports, four case series, and one randomized clinical trial. Of 20 case reports 15 were male (75 %), and five were female (25 %). Of the four the case series, all showed positive outcomes after DAPT plus anticoagulant in more than 50 % of patients; two took only DAPT and 13 took anticoagulant ± DAPT, and five compared both. Cases received DAPT only experienced recurrences of MACE. The other cases were uneventful with less MACE and better outcomes after the use of anticoagulant ± DAPT. Results of these case-series included 457 CAE patients showed that more than 80 % of subjects were male, and in all studies tailored pharmacological interventions, including antiplatelet and anticoagulant (warfarin) therapies, resulted in less MACE and mortality. ConclusionIt can be concluded that antiplatelet (SAPT/DAPT) must be applied in combination with anticoagulants to provide more efficient protection against MACE in CAE patients. However, further high-quality randomized clinical trials are needed to confirm the results.

The Role of Family or Community Nurse in Dealing with Frail and Chronic Patients in Italy: A Scoping Review.

Even though Family and Community Nurses (FCNs) were introduced into the Italian healthcare system in 2000, to date, there is a substantial knowledge gap regarding the implementation of these professional figures within the Primary Care (PC) system. This scoping review aims to provide a comprehensive picture of the role of FCNs in managing older adults and the elderly with chronic conditions within the Italian PC system. A search on Medline, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Embase, and Scopus was conducted including studies published until 7 April 2023. Among 141 potential articles, only 4 met our inclusion criteria. Each of these studies attributed their findings to the presence of FCNs. They reported a significant decrease in the prevalence of several behaviours among patients diagnosed with hypertension, a reduction in metabolic complications among frail patients receiving home enteral nutrition, a decline in hospital readmissions or emergency services utilization among patients >65 years of ages with at least one chronic disease, and, notably, a high level of effectiveness in detecting major cardiovascular events in patients with cardiac implantable electronic devices. Despite the effectiveness of interventions managed by FCNs, comprehensive information and research on the integration of this role within the PC setting are still lacking in the Italian healthcare system.

Deaths and major cardiovascular events in patients with lymphoma: Analysis from a French nationwide hospitalization database

BackgroundThere are few data assessing the risk of death and cardiovascular events in patients with lymphoma. AimUsing a nationwide hospitalization database, we aimed to address cardiovascular outcomes in patients with lymphoma. MethodsFrom 01 January to 31 December 2013, 3,381,472 adults were hospitalized in French hospitals; 22,544 of these patients had a lymphoma. The outcome analysis (all-cause or cardiovascular death, myocardial infarction, ischaemic stroke, bleedings, new-onset heart failure and new-onset atrial fibrillation) was performed over a 5-year follow-up period. Each patient with lymphoma was matched with a patient without a lymphoma or other cancer (1:1). A competing risk analysis was also performed. ResultsAfter adjustment on all risk factors, cardiovascular and non-cardiovascular co-morbidities, the subdistribution hazard ratios for all-cause death, major bleeding, intracranial bleeding, new-onset heart failure and new-onset atrial fibrillation were higher in patients with lymphoma; conversely, the subdistribution hazard ratios for cardiovascular death, myocardial infarction and ischaemic stroke were lower in patients with lymphoma. In the matched analysis, the risk of all-cause death (subdistribution hazard ratio 1.936, 95% confidence interval 1.881–1.992) and major bleeding (subdistribution hazard ratio 1.117, 95% confidence interval 1.049–1.188) remained higher in patients with lymphoma. ConclusionIn this large nationwide cohort study, patients with lymphoma had a higher incidence of all-cause death and major bleeding.

Impact of inflammation and anti-inflammatory therapies on the incidence of major cardiovascular events in patients with ankylosing spondylitis: A population-based study

ObjectiveTo examine the independent effect of inflammatory burden and various treatments on the risk of incident major adverse cardiovascular events (MACE) in ankylosing spondylitis (AS) patients. MethodsAS patients were retrospectively selected from a territory-wide database between 2006 and 2015, and were followed until the end of 2018. The primary outcome was the first occurrence of MACE. Multivariate time-varying Cox proportional hazard models were used to determine the associations between inflammatory burden (measured by c-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and different therapies with incident MACE, after adjusting for traditional cardiovascular (CV) risk factors. ResultsA total of 3827 patients with AS (mean age: 45.2 ± 15.0 years, male: 2911 [76.1 %]) were recruited. After a follow-up of 23,275 person-years, 135 patients (3.5 %) developed a first MACE. Univariate analyses showed that elevated ESR and CRP levels, and the use of glucocorticoids were associated with a significantly higher risk of MACE, while the use of sulfasalazine (SLZ), biologic DMARDs and non-cyclooxygenase-2 inhibitors (non-COX-IIi) were associated with reduced risk of MACE. After adjusting for CV risk factors in the multivariable models, only ESR (HR: 1.02; ESR ≥30 mm/h, HR:1.94) and CRP level (HR: 1.14; CRP >3 mg/dl HR:5.43) remained significantly associated with increased risk of MACE, while SLZ use (HR: 0.41–0.52) was protective against MACE. ConclusionHigh inflammatory burden was an independent predictor associated with an increased risk of MACE, while the use of SLZ might reduce risk of incident MACE in patients with AS.

#2437 Association between iron deficiency and risk of major events in chronic kidney disease—CKD-REIN Cohort

Abstract Background and Aims Iron deficiency (ID) is common in patients with chronic kidney disease (CKD) but remains under-diagnosed and its prognosis poorly documented in the absence of anemia. Data from CKDopps showed low TSAT levels were associated with increased risk of all-cause mortality and incidence of major cardiovascular events in patients with moderate to advanced CKD, an effect that was not modified by the presence of anemia [1]. Additionally, patients with both low TSAT and high ferritin levels displayed the highest risk of all-cause mortality. The aim of the study was to assess the relationship between ID and the risk of major adverse outcomes in patients with CKD in France. Method Using data from the French CKD-REIN cohort which included and followed over 5 years, 3,033 nephrology outpatients with CKD stage 2 to 5 CKD [2], we estimated the prevalence of ID, defined by a ferritin level &amp;lt; 100 mg/L and/or a transferrin saturation (TSAT) &amp;lt; 20%, and associated hazard ratios (HR) of kidney failure with replacement therapy, kidney failure defined by an eGFR &amp;lt; 15 ml/min per 1.73 m2 or initiation of kidney replacement therapy, all-cause mortality, all-cause hospitalization and death or hospitalization for heart failure. The analysis was conducted using a Cox model in which ID was included as a time-dependent variable and adjusted for identified confounders (socio-demographic characteristics, comorbidities, and biological measures) and hemoglobin level. Results A total of 2 914 patients with at least one ferritin or TSAT measurement at baseline or during follow-up were included in the analysis. The majority were men (66%), with a mean age of 67 ± 13 years; 49.6%, 41.2%, and 9.2%, had CKD stage 2/3, 4, and 5, respectively. Baseline prevalence of ID in the cohort was 50% [48-52]. Mean hemoglobin was 13 ± 1.7 g/dL, and only 31% of patients with ID also had a hemoglobin &amp;lt; 12 g/dL. Of the 2 914 patients included in the analysis, 627 (22%) required dialysis or transplantation, and 382 (13%) died before kidney replacement therapy. The incidence rate of kidney failure with replacement therapy was 6.76 versus 3.53 per 100 person-years in patients with and without ID. ID was associated with significant increased risk of kidney failure with replacement therapy, with adjusted HRs for confounders and hemoglobin level of 1.51 [1.24-1.82] (Fig. 1). A total of 836 patients (29%) progressed to kidney failure during the study period, and 341 (12%) died before this stage. The incidence rate of kidney failure was 8.66 versus 6.43 per 100 person-years in patients with and without ID. ID was associated with significant increased risk of kidney failure, with adjusted HRs for confounders and hemoglobin level of 1.19 [1.02-1.38] (Fig. 1). Adjusted HRs for all-cause mortality, for all-cause hospitalization, and for hospitalization or death for heart failure, were 1.31 [1.04-1.66], 1.04 [0.93-1.15], and 1.38 [1.07-1.80], respectively (Fig. 2). Conclusion This study confirms that ID is common in patients with CKD and shows that ID is significantly associated with the risk for kidney failure, all-cause mortality, and heart failure, independent of the presence of anemia. An intervention trial would be needed to assess whether correction of this ID in CKD patients is associated with a reduction in associated risks.

Elevated carbonylated proteins are associated with major cardiovascular events in patients with chronic coronary syndrome: A cohort study.

Protein carbonylation is reported in atherosclerosis, but its predictive value is unknown. We evaluated plasma carbonylated protein (PC) levels in association with clinical outcomes in coronary artery disease (CAD) in long-term follow-up. In patients with advanced stable CAD, we assessed plasma PC content along with fibrin clot properties, i.e., permeability (Ks) and clot lysis time, and its determinants: plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor. We recorded a composite of myocardial infarction, ischemic stroke, systemic embolism, and cardiovascular death during a follow-up of 8.3 (1.8) years. The analysis involved 178 patients aged 64.0 (57.0-70.0) years. The baseline PC content was 2.9 (2.2-3.7) nmol/mg protein and was elevated above the reference value obtained for a control group (2.03 nmol/mg protein) in 82.6% of patients. In linear regression models, high PC adjusted for age was associated with lower Ks, longer clot lysis time, and elevated PAI-1 and thrombin-activatable fibrinolysis inhibitor. Baseline PC was 48% higher in patients with the composite endpoint (n = 67, 37.6%) compared with others (P <0.001). Patients with PC in the highest quartile (3.7-5.1 nmol/mg protein) were more likely to develop the composite endpoint compared to the lowest quartile (hazard ratio [HR] 4.9; 95% confidence interval, 2.1-11.3; P <0.001). This is the first study showing that in CAD the extent of protein carbonylation, in part via its antifibrinolytic effects, predisposes to cardiovascular events in long-term follow-up, highlighting the role of persistent oxidative protein modifications in atherosclerotic vascular disease.

Major cardiovascular events in patients with cardiovascular monosodium urate deposits in atherosclerotic plaques.

To determine the association of cardiovascular atherosclerotic plaque monosodium urate deposits with the occurrence of major cardiovascular events in gout and hyperuricemia patients. This retrospective cohort study included patients with clinically suspicion of gout, who performed a dual energy computed tomography of the affected limb and thorax between June 1st, 2012 and December 5th, 2019. Clinical and laboratory parameters were retrieved from patientś charts. Established cardiovascular risk factors were evaluated. Medical history review identified the presence of major adverse cardiac events with a median follow up time of 33 months (range 0-108 months) after the performed computed tomography scan. Full data sets were available for 189 patients: 131 (69.3%) gout patients, 40 (21.2%) hyperuricemia patients, and 18 (9.5%) controls. Patients with cardiovascular monosodium urate deposits (n = 85/189, 45%) revealed increased serum acute phase reactants, uric acid levels and calcium scores in computed tomography compared with patients without cardiovascular monosodium urate deposits. Major adverse cardiac events were observed in 35 patients (18.5%) with a higher prevalence in those patients revealing cardiovascular monosodium urate deposits (n = 22/85, 25.9%) compared with those without cardiovascular monosodium urate deposits (n = 13/104, 12.5%, OR 2.4, p= 0.018). This is the first study demonstrating the higher hazard of major adverse cardiac events in patients with dual energy computed tomography-verified cardiovascular monosodium urate deposits. The higher prevalence of cardiac events in patients with cardiovascular monosodium urate deposits may facilitate risk stratification of gout patients, as classical cardiovascular risk scores or laboratory markers fail in their proper identification.

Cost-effectiveness of low-dose colchicine in patients with chronic coronary disease in the netherlands.

Recent trials have shown that low-dose colchicine (0.5 mg once daily) reduces major cardiovascular events in patients with acute and chronic coronary syndromes. We aimed to estimate the cost-effectiveness of low-dose colchicine therapy in patients with chronic coronary disease when added to standard background therapy. This Markov cohort cost-effectiveness model used estimates of therapy effectiveness, transition probabilities, costs and quality of life obtained from the Low-dose Colchicine 2 (LoDoCo2) trial, as well as meta-analyses and public sources. In this trial, Low-dose colchicine was added to standard of care and compared to placebo. The main outcomes were cardiovascular events including myocardial infarction, stroke and coronary revascularisation, quality-adjusted life-year (QALY), the cost per QALY gained (incremental cost-effectiveness ratio), and net monetary benefit. In the model, low-dose colchicine therapy yielded 0.04 additional QALYs compared with standard of care at an incremental cost of €455 from a societal perspective and €729 from a healthcare perspective, resulting in a cost per QALY gained of €12,176/QALY from a societal perspective and €19,499/QALY from a healthcare perspective. Net monetary benefit was €1,414 from a societal perspective and €1,140 from a healthcare perspective. Low-dose colchicine has a 96% and 94% chance of being cost effective, from respectively a societal and healthcare perspective when using a willingness to pay of €50,000/QALY. Net monetary benefit would decrease below zero when annual low-dose colchicine costs would exceed an annual cost of €221 per patient. Adding low-dose colchicine to standard of care in patients with chronic coronary disease is cost-effective according to commonly accepted thresholds in Europe and Australia and compares favourably in cost-effectiveness to other drugs used in chronic coronary disease.

Machine Learning-Based Discrimination of Cardiovascular Outcomes in Patients With Hypertrophic Cardiomyopathy

BackgroundCurrent risk stratification strategies for patients with hypertrophic cardiomyopathy (HCM) are limited to traditional methodologies. ObjectivesThe authors aimed to establish machine learning (ML)-based models to discriminate major cardiovascular events in patients with HCM. MethodsWe enrolled consecutive HCM patients from 2 tertiary referral centers and used 25 clinical and echocardiographic features to discriminate major adverse cardiovascular events (MACE), including all-cause death, admission for heart failure (HF-adm), and stroke. The best model was selected for each outcome using the area under the receiver operating characteristic curve (AUROC) with 20-fold cross-validation. After testing in the external validation cohort, the relative importance of features in discriminating each outcome was determined using the SHapley Additive exPlanations (SHAP) method. ResultsIn total, 2,111 patients with HCM (age 61.4 ± 13.6 years; 67.6% men) were analyzed. During the median 4.0 years of follow-up, MACE occurred in 341 patients (16.2%). Among the 4 ML models, the logistic regression model achieved the best AUROC of 0.800 (95% CI: 0.760-0.841) for MACE, 0.789 (95% CI: 0.736-0.841) for all-cause death, 0.798 (95% CI: 0.736-0.860) for HF-adm, and 0.807 (95% CI: 0.754-0.859) for stroke. The discriminant ability of the logistic regression model remained excellent when applied to the external validation cohort for MACE (AUROC = 0.768), all-cause death (AUROC = 0.750), and HF-adm (AUROC = 0.806). The SHAP analysis identified left atrial diameter and hypertension as important variables for all outcomes of interest. ConclusionsThe proposed ML models incorporating various phenotypes from patients with HCM accurately discriminated adverse cardiovascular events and provided variables with high importance for each outcome.