Major Cardiovascular Events Research Articles

An aspirin-free strategy for percutaneous coronary intervention in patients with diabetes: a pre-specified subgroup analysis of the STOPDAPT-3 trial.

Safety of aspirin-free strategy immediately after percutaneous coronary intervention (PCI) for cardiovascular events in patients with diabetes was unknown. We conducted the prespecified subgroup analysis on diabetes in the STOPDAPT-3 trial, which randomly compared prasugrel (3.75mg/day) monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The co-primary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) at 1 month. Of 5966 study patients, there were 2715 patients (45.5%) with diabetes. Patients with diabetes more often had chronic coronary syndrome, heart failure or cardiogenic shock, and comorbidities than those without. Patients with diabetes compared to those without had higher incidences of major bleeding and cardiovascular events. Regardless of diabetes, the effect of no-aspirin relative to DAPT was not different for the co-primary bleeding (diabetes: 5.05% versus 5.47%; HR, 0.92; 95%CI, 0.66-1.28 and non-diabetes: 3.99% versus 4.07%; HR, 0.98; 95%CI, 0.69-1.38; P for interaction=0.81) and cardiovascular (diabetes: 5.54% versus 5.15%; HR, 1.08; 95%CI, 0.78-1.49 and non-diabetes: 2.95% versus 2.47%; HR, 1.20; 95%CI, 0.79-1.82; P for interaction=0.70) endpoints. The incidences of subacute definite or probable stent thrombosis and any coronary revascularization were higher in the no-aspirin group than in the DAPT group regardless of diabetes. The effects of an aspirin-free prasugrel monotherapy (3.75mg/day) relative to DAPT for major bleeding and cardiovascular events were not different regardless of diabetes. Clinical trial registration: ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111.

Can Coronary Artery Calcium Predict the Risk of Major Cardiovascular Events from Radiotherapy?

Can Coronary Artery Calcium Predict the Risk of Major Cardiovascular Events from Radiotherapy?

The combined effects of depression or anxiety with high-sensitivity C-reactive protein in predicting the prognosis of coronary heart disease patients

BackgroundDepression, anxiety and high-sensitivity C-reactive protein (hs-CRP) are individually associated with poor prognosis in patients with coronary heart disease (CHD). However, the combined effects of depression with inflammation or anxiety with inflammation on the prognosis have been rarely explored.MethodsThis prospective cohort study included 414 patients diagnosed with CHD. The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to assess depression and anxiety. A score ≥ 5 points was defined as elevated depression or anxiety. High hs-CRP was defined as ≥ 3 mg/L. Follow-up was performed 2 years after the patients were discharged. The clinical results included noncardiac readmission, cardiac readmission, major cardiovascular events (MACEs), and composite events. The composite events included noncardiac readmission and MACEs. The Cox proportional hazard regression model was used to analyze the prognostic risk.ResultsAfter full adjustment, patients with elevated depression and high hs-CRP had a higher risk in predicting noncardiac readmission (hazard ratio (HR) = 3.87, 95% confidence interval (CI) = 1.10–9.02, p = 0.002) and composite events (HR = 1.93, 95% CI = 1.13–3.30, p = 0.016) than those with high hs-CRP alone. For the anxiety and hs-CRP group, high hs-CRP alone predicted a higher risk of noncardiac readmission (HR = 3.32, 95% CI = 1.57–7.03, p = 0.002) and composite events (HR = 1.75, 95% CI = 1.12–2.76, p = 0.015) than references. Elevated anxiety had no significant effects on all the endpoints. Furthermore, we didn’t find interactions between depression and hs-CRP or anxiety and hs-CRP.ConclusionIn patients with CHD, elevated depression with high hs-CRP was found to be significant in predicting the risk of noncardiac readmission and composite events. Early diagnosis and treatment of depression with inflammation are necessary in CHD patients.

Use of Beta-Blockers as a First-Line Treatment for Primary Hypertension

Background: Even though beta-blockers had been used as a first-line therapy for hypertension, since the late 1960s, the Eighth Joint National Committee, JNC 8, decided to recommend them no longer. This decision was based on relatively weak evidence from previous studies, which found that first-line beta-blockers were less effective in reducing stroke and heart failure, the main outcomes of hypertension. Despite the general perception, the most common events caused by hypertension are death and MI, not stroke or heart failure. Therefore, this study aimed to clarify beta-blocker efficacy by incorporating the data from all relevant beta-blocker trials, using the composite outcome of major cardiovascular events. Method: A search was conducted on MEDLINE, PubMed, Embase, and the Cochrane Library, restricted to published, peer-reviewed, human, meta-analysis, and controlled clinical trials. The term words used were “beta-blockers or adrenergic beta antagonists”, “hypertension”, and “death or coronary heart disease or stroke or congestive heart failure or myocardial infarction”. For this research, we selected six randomized controlled trials, and three meta-analyses were also chosen. Results: The results showed that beta-blockers were as effective as other first-line medications in younger hypertensive patients. On the other hand, in the patients aged above 60, the results were mixed. Beta-blockers were more effective than diuretics, but inferior to angiotensin receptor blockers. Also, beta-blockers were as safe and effective as angiotensin-converting enzyme inhibitors in reducing coronary heart disease, myocardial infarction, heart failure, and sudden death. However, beta-blockers were inferior to calcium channel blockers in reducing strokes. Conclusions: Beta-blockers were found to be the most effective in many aspects except for strokes. Further studies are needed to assess beta-blockers’ effectiveness in treating primary hypertension.

Perioperative management of antithrombotic therapy in elderly patients undergoing lumbar discectomy: a retrospective study on 163 patients.

The prevalence of lumbar disc herniation (LDH) has risen alongside the aging population, often necessitating neurosurgical intervention. However, managing antithrombotic medications in elderly patients with a history of major cardiovascular events (MACE) presents challenges, as treatment may require modification or cessation. This study aims to compare surgical outcomes among elderly patients receiving antithrombotic drugs and assess their impact and potential complications. The findings aim to inform the management of elderly patients with cardiovascular and spinal conditions undergoing neurosurgery. This retrospective, observational study was conducted at a single center. A total of 163 patients aged 60 or above who underwent lumbar discectomy for LDH were included. Patients were categorized into three groups based on their antithrombotic drug management: Group A (46 patients) replaced antiplatelet agents with low-dose aspirin for secondary prevention, Group B (54 patients) discontinued antiplatelet agents for primary prevention one week preoperatively and replaced them with LMWH, and Group C (63 patients) did not receive antithrombotic medication. Intraoperative blood loss, surgical time, and postoperative hospitalization were analyzed across all three groups. Continuous variables were compared between groups using the two-tailed Mann-Whitney test, with significance set at p < 0.05. No significant differences were found in intraoperative blood loss or surgical time among groups A, B, and C. Similarly, no significant differences were observed between groups B and C across all analyzed variables. No early or delayed hemorrhagic complications occurred perioperatively or during the 3-month postoperative follow-up period. The study suggests that elective discectomy surgery in patients receiving anticoagulant and antiplatelet therapies may proceed without early complications and can be safely continued perioperatively. These findings have implications for the management of elderly patients requiring neurosurgical intervention in the context of cardiovascular comorbidities.

Development and validation of a chronic kidney disease progression model using patient-level simulations

Chronic disease progression models are available for several highly prevalent conditions. For chronic kidney disease (CKD), the scope of existing progression models is limited to the risk of kidney failure and major cardiovascular (CV) events. The aim of this project was to develop a comprehensive CKD progression model (CKD-PM) that simulates the risk of CKD progression and a broad range of complications in patients with CKD. A series of literature reviews informed the selection of risk factors and identified existing risk equations/algorithms for kidney replacement therapy (KRT), CV events, other CKD-related complications, and mortality. Risk equations and transition probabilities were primarily sourced from publications produced by large US and international CKD registries. A patient-level, state-transition model was developed with health states defined by the Kidney Disease Improving Global Outcomes categories. Model validation was performed by comparing predicted outcomes with observed outcomes in the source cohorts used in model development (internal validation) and other cohorts (external validation). The CKD-PM demonstrated satisfactory modeling properties. Accurate prediction of all-cause and CV mortality was achieved without calibration, while prediction of CV events through CKD-specific equations required implementation of a calibration factor to balance time-dependent versus baseline risk. Predicted annual changes in estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio were acceptable in comparison to external values. A flexible eGFR threshold for KRT equations enabled accurate prediction of these events. This CKD-PM demonstrated reliable modeling properties. Both internal and external validation revealed robust outcomes.

The Role of Natriuretic Peptides in the Management of Heart Failure with a Focus on the Patient with Diabetes.

Natriuretic peptides (NPs) are polypeptide hormones involved in the homeostasis of the cardiovascular system. They are produced by cardiomyocytes and regulate circulating blood volume and sodium concentration. Clinically, measurements of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are recommended by international guidelines as evidence is accumulating on their usefulness. They have a high negative predictive value, and in the setting of low NPs, a diagnosis of heart failure (HF) can be safely excluded in both emergency (BNP < 100 pg/mL, NT-proBNP < 300 pg/mL) and outpatient settings (BNP < 35 pg/mL and NT-proBNP < 125 pg/mL). Moreover, the 2023 consensus from the European Society of Cardiology suggests threshold values for inclusion diagnosis. These values are also associated with increased risks of major cardiovascular events, cardiovascular mortality, and all-cause mortality whether measured in inpatient or outpatient settings. Among patients without known HF, but at high risk of developing it (e.g., in the setting of diabetes mellitus, hypertension, or atherosclerotic cardiovascular disease), NPs may be useful in stratifying cardiovascular risk, optimizing therapy, and reducing the risk of developing overt HF. In the diabetes setting, risk stratification with the use of these peptides can guide the physician to a more informed and appropriate therapeutic choice as recommended by guidelines. Notably, NP levels should be carefully interpreted in light of certain conditions that may affect their reliability, such as chronic kidney disease and obesity, as well as demographic variables, including age and sex. In conclusion, NPs are useful in the diagnosis and prognosis of HF, but they also offer advantages in the primary prevention setting.

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

When does metabolic memory start? Insights from the AMD Annals Initiative on stringent HbA1c targets.

Early, intensive glycemic control in T2D patients is associated with long-term benefits on cardiovascular disease (CVD) development. Evidence on benefits of achieving HbA1c targets close to normal values is scant. Subjects with newly-diagnosed T2D, without CVD at baseline, were identified in an Italian clinical registry (N=251,339). We adopted three definitions of early exposure periods (0-1, 0-2 and 0-3 years). Mean HbA1c was categorized into HbA1c < 5.7%, 5.7-6.4%, 6.5-7.0%, 7.1-8.0%, and >8.0%. The outcome was the incidence of major cardiovascular events. After a mean follow-up of 4.6±2.9 years, at multivariate Cox regression analysis, compared with mean HbA1c <5.7% during the first year after diagnosis, the increase in the risk of CVD was 24%, 42%, 49% and 56% for patients with HbA1c of 5.7%-6.4%, 6.5%-7.0%, 7.1%-8.0%, and >8.0%, respectively. The same trend was documented in all exposure periods. In conclusion, our data support that an early achievement of stringent targets of HbA1c <5.7% is worthy for CVD prevention.

Association of positive airway pressure termination with mortality and non-fatal cardiovascular events in patients with obstructive sleep apnoea

Background and aimsThe recurrence of obstructive sleep apnoea (OSA) after positive airway pressure (PAP) therapy termination has physiological consequences that may increase cardiovascular (CV) risk. We aimed to determine whether...

Coronary artery calcium measurement on attenuation correction computed tomography using artificial intelligence: correlation with coronary flow capacity and prognosis.

This study aimed to test whether the coronary artery calcium (CAC) burden on attenuation correction computed tomography (CTac), measured using artificial intelligence (AI-CACac), correlates with coronary flow capacity (CFC) and prognosis. We retrospectively enrolled patients who underwent [13N]ammonia positron emission tomography (PET) between September 2021 and May 2023. CTac data were obtained from all the patients. Patients with (history of) acute coronary syndrome, previous coronary stent insertion or bypass surgery, or left ventricular ejection fraction < 40% were excluded. The total Agatston score measured using a dedicated AI-CAC quantification software on CTac was defined as AI-CACac. The correlations between AI-CACac and PET-measured myocardial blood flow (MBF) and CFC and significant ischaemia (summed difference score ≥ 7) were analysed. Their prognostic values for major cardiovascular events (MACE), including death, nonfatal myocardial infarction, hospitalisation due to angina pectoris or heart failure, and late (> 90 days) revascularisation, were also evaluated. In total, 289 patients were included in this study. Significant negative correlations were found between AI-CACac and stress MBF (ρ = -0.363, p < 0.001) and MFR (ρ = -0.305, p < 0.001). AI-CACac > 10 was associated with a significantly higher prevalence of impaired CFC (31% vs. 7%, p < 0.001) and significant ischaemia (20% vs. 7%), which remained significant after adjusting for other risk factors. MACE occurred in 49 (17%) patients (median follow-up, 284 days), and those who experienced MACE had significantly higher AI-CACac (median, 166 vs. 56; p = 0.039). However, multivariable analysis revealed an independent prognostic association among impaired CFC, diabetes, smoking, but not for AI-CACac. AI-measured CACac correlates well with PET-measured MBF and CFC, but its prognostic significance requires further validation.

Importance of the Hemoglobin Glycation Index for Risk of Cardiovascular and Microvascular Complications and Mortality in Individuals with Type 2 Diabetes.

This study investigated the prognostic importance of the hemoglobin glycation index (HGI) for macrovascular and microvascular outcomes, mortality, and hypoglycemia occurrence in a type 2 diabetes cohort and compared it to glycated hemoglobin (HbA1c). Baseline and mean first-year HGI and HbA1c, and the variability thereof, were assessed in 687 individuals with type 2 diabetes (median follow-up, 10.6 years). Multivariable Cox regression was conducted to evaluate the associations of HGI and HbA1c parameters with macrovascular (total and major cardiovascular events) and microvascular outcomes (microalbuminuria, advanced renal failure, retinopathy, and peripheral neuropathy), mortality (all-cause and cardiovascular), and moderate/severe hypoglycemia occurrence. During follow-up, there were 215 total cardiovascular events (176 major) and 269 all-cause deaths (131 cardiovascular). Microalbuminuria developed in 126 patients, renal failure in 104, retinopathy in 161, and neuropathy in 177. There were 90 hypoglycemia episodes. Both HGI and HbA1c predicted all adverse outcomes, except microalbuminuria and hypoglycemia. Their adjusted risks were roughly equivalent for all outcomes. For example, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), estimated for 1 standard deviation increments, of mean first-year HGI were 1.23 (1.05 to 1.44), 1.20 (1.03 to 1.38), 1.36 (1.11 to 1.67), 1.28 (1.09 to 1.67), and 1.29 (1.09 to 1.54), respectively, for cardiovascular events, all-cause mortality, renal failure, retinopathy, and neuropathy; whereas the respective HRs (95% CIs) of mean HbA1c were 1.31 (1.12 to 1.53), 1.28 (1.11 to 1.48), 1.36 (1.11 to 1.67), 1.33 (1.14 to 1.55), and 1.29 (1.09 to 1.53). HGI was no better than HbA1c as a predictor of adverse outcomes in individuals with type 2 diabetes, and its clinical use cannot be currently advised.

Impact of vascular biomarkers and supine hypertension on cardiovascular outcomes in hypertensive patients: first results from the Cardiovascular Prognostic COUPLING Study in Japan.

The prognostic impact of vascular biomarkers and supine blood pressure (BP) is not well understood. The multicenter, prospective Coupling study determined the prognostic impact of vascular biomarkers and supine BP in outpatients aged ≥30 years with ≥1 cardiovascular risk factor. Occurrence of major cardiovascular events during follow-up was recorded. The primary outcome was time to onset of a major cardiovascular event. Office and supine BP, the cardio-ankle vascular index (CAVI), and the ankle-brachial index (ABI) were determined annually. Of the 5109 participants in the Coupling study, 4716 were analyzed (51.9% male, mean age 68.5 ± 11.4 years); participants mostly had hypertension treated based on seated office/home BP according to relevant guidelines. During a median follow-up of 5.0 years (interquartile range 3.6-5.2), 231 major cardiovascular events occurred. After adjustment for age, sitting office systolic BP, and other covariates, a 1-unit increase in CAVI (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.01-1.24) and a 0.1-unit decrease in ABI (HR 1.41, 95% CI 1.18-1.68) were significantly associated with cardiovascular event risk; risk was greatest when CAVI was ≥8.0 and ABI was ≤1.10. Uncontrolled supine hypertension (≥140/90 mmHg) was also significantly associated with adjusted cardiovascular event risk (HR 1.36, 95% CI 1.02-1.81); seated office BP control was not significantly associated with cardiovascular event risk. Increased arterial stiffness, mildly lower ABI, and supine hypertension are risk factors for cardiovascular events during standard clinical practice. Supine evaluation of BP and vascular biomarkers has highlighted a blind spot in current hypertension management (Clinical trial registration: University Hospital Medical Information Network Clinical Trials Registry, UMIN000018474).

Dietary strategies and nutritional supplements in the management of heart failure: a systematic review.

Heart failure (HF) is a syndrome of increased intracardiac pressure or decreased cardiac output. There is a lack of conclusive evidence to recommend the regular use of any dietary supplement in patients with HF. However, certain studies have shown nutritional interventions to be beneficial for patients with HF. Therefore, the purpose of this systematic review was to understand and map the updates of dietary interventions and nutritional supplementation measures related to patients with HF over the past 5 years. A systematic review. The PubMed, Web of Science, Scopus, and Cochrane Library databases were searched for randomized clinical trials on the association between dietary interventions and nutritional supplements and HF published between 2018 and 2023. A total of 1755 documents were retrieved, of which 19 were finalized for inclusion. The findings suggest that individualized nutritional support reduces mortality and risk of major cardiovascular events in chronic heart failure inpatients at high nutritional risk. The Mediterranean diet improves functionality, quality of life, and cardiac function. Additionally, supplementation with thiamine, ubiquinol, D-ribose, and L-arginine enhances left ventricular ejection fraction. Probiotic yogurt may effectively improve the inflammatory and antioxidative status of chronic heart failure. Whey protein and melatonin have a positive effect on improving endothelial function in HF patients. Certain dietary interventions and nutritional supplements may provide some benefit to patients with HF. However, there is no relevant definitive evidence on the impact of nutritional interventions on the prognosis of HF, and more high-quality clinical trials are needed for further in-depth studies. Identifier, CRD42024510847.

PCSK9 Monoclonal Antibodies Have Come a Long Way.

This review examines the pivotal role of monoclonal antibodies against PCSK9 in lipid-lowering therapy, emphasizing their biological and clinical impact. Randomized controlled trials have validated that PCSK9 monoclonal antibodies (Mabs) effectively reduce LDL-c levels by approximately 50%, even when added to maximal statin therapy. They moreover produce a notable 15-20% relative decrease in major cardiovascular events, with a greater reduction among high-risk patients and no evidence for serious adverse effects, assuaging previous concerns. This review highlights the benefits of PCSK9 Mabs in high cardiovascular risk patients. Despite their efficacy and safety, these therapies are hindered by limited access, and require broader integration into clinical practice to optimize therapeutic outcomes.

A register-based cohort study on the effectiveness and Safety of anti-PCSK9 treatment in persons with hyperlipidemia.

Dyslipidemia is a known risk factor for cardiovascular disease. While statins are the primary treatment, some individuals require additional lipid-lowering therapies, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Alirocumab and evolocumab have shown efficacy in reducing low-density lipoprotein cholesterol (LDL-C) levels and reduce the risk of major cardiovascular events (MACE) but have not been directly compared in clinical trials. This study aims to assess the effects of PCSK9 inhibitors on LDL-C levels and evaluate the impact of a mandated switch from alirocumab to evolocumab. Taking advantage of the mandated switch in PCSK9 treatment in Denmark, we conducted a register-based cohort study of 907 individuals with dyslipidemia treated with PCSK9 inhibitors in the Capital Region of Denmark from 2016 to 2022. We analyzed LDL-C levels, treatment retention, and MACE, adjusting for variables such as age, sex, dose, and concurrent lipid-lowering medications. We show that PCSK9 inhibitors treatment resulted in a 49% reduction in LDL-C levels. Following a mandated switch from alirocumab to evolocumab, no significant difference was observed in LDL-C levels or adverse clinical outcomes, including MACE. Treatment discontinuation was most likely within the first 100 days, and no significant difference in discontinuation rates was found between the two drugs. Our study demonstrates that both alirocumab and evolocumab are effective in significantly reducing LDL-C levels in individuals with dyslipidemia. The mandated switch from alirocumab to evolocumab did not result in significant changes in LDL-C or clinical outcomes, suggesting that these treatments can be used interchangeably. These findings support the clinical equivalence of the two PCSK9 inhibitors and may guide therapeutic decisions in lipid management.

Effect of frail phenotype on cardiorenal risk and healthcare utilization in older patients with chronic kidney disease.

Introduction Limited data have addressed frailty's role in cardiorenal risk among older adult patients with chronic kidney disease (CKD). We investigated whether frailty could predict major renal and cardiovascular events, healthcare utilization, and mortality in these patients. Methods We conducted a prospective cohort enrolling patients ≥ 75 years with a stable estimated glomerular filtration rate (eGFR) &lt; 60 mL/min/1.73 m2. Frailty phenotype consists of shrinking, low activity, exhaustion, weakness, and slowness, scored 0 to 5. The primary composite renal outcome was a ≥ 25 % decrease in eGFR concurrent with CKD stage progression or dialysis initiation. Secondary outcomes included major adverse cardiovascular events (MACE), emergency room (ER) visits, all-cause mortality, and hospitalization. Using multivariate Cox models with/without competing risk analyses, we explored frailty's impact on these outcomes. Results Among 203 older CKD patients (mean age 81.6 ± 5.0 years, female 40.9 %, diabetes 33.0 %, body mass index 24.9 ± 3.7 kg/m2), 67.9% were frail. Over 3.47 years, 38.9% faced composite renal outcomes, 13.3% MACE, 15.3% mortality, and more than half utilized healthcare. Every one-point frailty elevated composite renal outcome risk by 28.0 % (HR: 1.28, 95% CI:1.03-1.59) and significantly increased secondary outcomes (hospitalization [HR: 1.24, 95% CI: 1.06-1.46], unexpected ER visit [HR: 1.20, [95% CI:1.03-1.39], and mortality [HR: 1.51, 95% CI: 1.06-2.16]) but not for MACE [HR: 1.43, 95% CI: 0.99-2.08]. Results were consistent across subgroups and competing risk analysis. Conclusion In CKD patients ≥ 75 years, frailty was associated with progressive kidney disease, increased mortality and healthcare utilization.

The Influence of Remnant Cholesterol on Cardiovascular Risk and Mortality in Patients with Non-Functional Adrenal Incidentalomas and Mild Autonomous Cortisol Secretion: A Retrospective Cohort Study.

Background: Increased cardiovascular risk has been described in individuals with adrenal incidentalomas. The aim of the present study is to assess the effect of remnant cholesterol (RC) on the cardiovascular risk and mortality of patients with adrenal incidentalomas. Methods: A retrospective cohort study was conducted with patients with adrenal incidentalomas between 2001 and 2024. One hundred thirty-seven patients (mean age of 61.2 ± 11.5 years; 56.6% women) with non-functioning adrenal incidentalomas and with mild autonomous cortisol secretion (MACS) (cortisol post-dexamethasone suppression test ≥1.8 µg/mL) were included. The patients were divided into two groups using 30 mg/dL as the cut-off for RC. Logistic regression models were used to study the impact of RC on major adverse cardiovascular events and mortality (MACEs). Results: Patients with RC ≥ 30 mg/dL exhibited a higher prevalence of type 2 diabetes mellitus (T2D) (p < 0.001), lower HDL-C (p < 0.001) and LDL-C (p = 0.025) levels, a higher frequency of treatment with statins (p = 0.032), and a higher rate of non-fatal major cardiovascular events (p = 0.038) and MACEs (p = 0.038). Patients with MACS showed no differences in RC or complications during the follow-up. The relative risk of high RC was 2.65 (1.04-6.77) for cardiovascular events and 2.27 (1.05-4.92) for MACEs, with p < 0.05 in both cases. The only variables independently affecting MACEs were age ([odds ratio] OR = 1.13 [p = 0.004]), female sex (OR = 0.20; p = 0.016), LDL-C (OR = 1.02; p = 0.029), and RC (OR = 1.06; p = 0.014). T2D and HDL-C were not independently associated with MACEs. Conclusions: RC ≥30 mg/dL in patients with adrenal incidentalomas was associated with a higher prevalence of T2D, lower HDL-C levels, and a higher risk of MACEs. MACS was not associated with RC or MACEs during the follow-up.

12213 Is Atrial Fibrillation An Adverse Cardiovascular Effect Of Romosozumab

Abstract Disclosure: S. Martinez: None. D. Anez: None. M. Shahid: None. Osteoporosis and cardiovascular disease are both common in older populations. Therefore, it is not uncommon to find the two disorders in a single individual and yet it may be difficult to establish whether the diseases are coincident or the result of complex hormonal processes interacting with multiple systems, including possibly sclerostin. Indeed, pre-existent cardiovascular disease predisposes to osteoporotic bone loss and increased fracture risk. To date, a number of studies have linked the incidence of major adverse cardiovascular events (MACE) with various osteoporosis treatments while other treatments have demonstrated no associated or a reduced cardiovascular risk. Here we discuss the possibility of romosozumab-induced sudden, new onset atrial fibrillation (a fib) in a 70-year-old female with no known risk factors other than age. A 70-year-old female with a 20-year history of osteoporosis presented to establish care. After 5 years of alendronate therapy, she was switched to denosumab injections, 60 mg every 6 months. During Covid the patient’s physicians closed their office and denosumab therapy was interrupted for approximately 18 months. Therefore, when the patient established care with a new rheumatologist she was started on romosozumab. After 6 months of romosozumab the patient developed new onset atrial fibrillation. The cardiovascular safety of romosozumab, in particular, has been adjudicated in two large trials describing predominantly major cardiovascular events such as myocardial infarction, stroke, heart failure and cardiovascular death. In one of those trials, two reports of atrial fibrillation were also included in the adverse events but further details were not available. These increased MACEs prompted a safety warning from the FDA such that use of romosozumab in patients who have experienced a myocardial infarction or stroke within the year prior to its use is contraindicated. Recently atrial fibrillation and congestive heart failure were documented in 78-year-old woman who had been receiving romosozumab for three months for the treatment of osteoporosis. Our case represents a second report of a temporal relationship between the initiation of romosozumab and the onset of atrial fibrillation raising the question of a possible cause and effect. Disclaimer: This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities. Presentation: 6/3/2024

The role of aryl hydrocarbon receptor agonists in the treatment of vitiligo.

Vitiligo is a chronic autoimmune disorder characterized by progressive skin depigmentation. Vitiligo significantly impacts patients' quality of life, contributing to psychological and social burdens. Despite readily available therapeutic options, many cases remain refractory to treatment, highlighting the critical need for safer and more effective therapies. Currently, ruxolitinib is the only FDA-approved medication for vitiligo; however, it carries a black box warning for serious adverse effects, including infections, malignancy, and major cardiovascular events, limiting its use. Recent studies have identified the aryl hydrocarbon receptor (AhR) as a promising therapeutic target, suggesting that AhR agonists could address the multifaceted pathogenesis of vitiligo. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search to analyze the role of AhR agonists in the treatment of vitiligo on PubMed, Cochrane, Embase, MEDLINE, and Web of Science databases on April 15, 2024. Fourteen studies met the inclusion criteria, comprising two clinical trials, two case reports, and nine basic science studies. Our search revealed that culturing AhR agonists with melanocytes upregulates melanin-synthesizing enzymes, reduces reactive oxygen species, and modulates pro-inflammatory cytokines such as IL-17A and IL-22. Tapinarof, a topical AhR agonist used commonly for the treatment of psoriasis, demonstrated clinical efficacy in repigmentation with a favorable safety profile compared to long-term steroid use. Although limited by the number of clinical studies, this review underscores the potential of using AhR agonists, such as tapinarof, as a transformative approach to vitiligo management. Future clinical trials are necessary to evaluate the safety, efficacy, and long-term outcomes of AhR agonists.