Major Adverse Cardiovascular Outcomes Research Articles

#2756 Metabolomic prediction of end stage renal disease in large national biobanks

Abstract Background and Aims Identifying at-risk individuals likely to progress to end-stage renal disease as early as possible is important to effectively concentrate preventative interventions. Existing predictive tools, like the kidney failure risk score, are effective for individuals who already have moderate to severe kidney disease. Here we examine whether comprehensive metabolomics can improve performance in individuals with mildly impaired kidney function. Method Using an NMR metabolomics platform we measured >200 biomarkers including creatinine, albumin, lipids, fatty acids, amino acids, glycolysis metabolites and inflammation markers in blood samples from all 500,000 participants of the UK Biobank, who have >10 years of linked prospective follow-up data. We used machine learning to develop a score to predict kidney disease progression based on biomarkers, age and sex. We compared its performance to eGFR in a held out set of individuals in UK Biobank, and replicated in 200,000 participants of the Estonian Biobank. Results Among individuals with prevalent diabetes, hypertension or eGFR < 90 the biomarker score performs as well as or better than eGFR for all individuals. In particular it outperforms among individuals with only moderate (eGFR 60-75) or mild (eGFR 75-90) impairment of kidney function with an AUC increase from 0.63 to 0.72 and 0.48 to 0.70, respectively (Figure). This improvement is driven by contributions from numerous biomarkers, including lipids and inflammation markers. Furthermore, because these biomarkers capture diverse metabolic risk, the biomarker score also strongly predicts major adverse cardiovascular outcomes. Conclusion This large dataset allows detailed investigation of the value of metabolomics in identifying future risk of severe kidney disease early. In particular these biomarkers can highlight individuals who do not already have very low eGFR.

Sex, racial, ethnic, and geographical disparities in major adverse cardiovascular outcome of glucagon-like peptide-1 receptor agonists among patients with and without diabetes mellitus: A meta-analysis of placebo-controlled randomized controlled trials,

Sex, racial, ethnic, and geographical disparities in major adverse cardiovascular outcome of glucagon-like peptide-1 receptor agonists among patients with and without diabetes mellitus: A meta-analysis of placebo-controlled randomized controlled trials,

A Comparison of 2 Paclitaxel-Coated Balloon Systems in Treatment of De Novo Coronary Artery Lesions

BackgroundIn percutaneous coronary intervention (PCI) of de novo lesions, drug-coated balloons (DCB) have been shown to be a promising strategy to improve clinical outcomes of patients with small vessel disease. Evidence of this strategy in PCI of de novo coronary lesions in a real-world setting is limited. The objective of this study was to compare the 12-month outcomes of 2 paclitaxel-coated balloon systems for the treatment of all de novo coronary artery lesions. MethodsAll patients who were treated for de novo coronary artery stenosis with either SeQuent Please or In.Pact Falcon DCB at a single center from January 2014 to December 2018 were included. The primary end point was the composite of cardiac death, nonfatal myocardial infarction, and target vessel revascularization (3-point major adverse cardiovascular events) at 12 months. ResultsA total of 496 patients with 623 lesions, of which 144 were treated with SeQuent Please and 352 were treated with In.Pact Falcon were included in the study. Baseline patient, lesion and procedural characteristics at baseline were similar between groups. At 12-month follow-up, 3-point major adverse cardiovascular event outcomes were similar (4.2% vs 2.3% respectively; P = .272). Deaths due to cardiovascular events were few and similar between groups (2.7% vs 1.1% respectively; P = .20). ConclusionsBoth paclitaxel DCB systems have similar efficacy and safety outcomes, suggesting that both may be an appropriate treatment choice for patients with de novo lesions. However, a larger randomized controlled study is needed to confirm these findings.

Stabilization of Rapidly Progressive Cardiac Allograft Vasculopathy Using mTOR Inhibition After Heart Transplantation

Inhibition of the mammalian target of rapamycin (mTor) pathway after heart transplantation has been associated with reduced progression of coronary allograft vasculopathy (CAV). The application of low-dose mTOR inhibition in the setting of modern immunosuppression, including tacrolimus, remains an area of limited exploration. This retrospective study included patients who received heart transplantation between January 2009 and January 2019 and had baseline, 1-year and 2-3-year coronary angiography with intravascular ultrasound (IVUS). Intimal thickness in 5 segments along the left anterior descending artery was compared across imaging time points in patients who were transitioned to low-dose mTOR inhibitor (sirolimus) vs standard treatment with mycophenolate on a background of tacrolimus. Long-term adverse cardiovascular outcomes (revascularization, severe CAV, retransplant, and cardiovascular death) were also assessed. Among 216 patients (mean age 51.5 ± 11.9 years, 77.8% men, 80.1% white), 81 individuals (37.5%) were switched to mTOR inhibition. mTOR inhibition was associated with a reduction in intimal thickness by 0.05 mm (95% CI 0.02-0.07; P < 0.001). This reduction was driven by patients who met the criteria for rapidly progressive CAV 1-year post-transplant (0.12 mm; P = 0.016 for interaction). After a median follow-up of 8.6 (IQR 6.6-11) years, 40 patients had major adverse cardiovascular outcomes. The use of mTOR inhibitors was not significantly associated with cardiovascular outcomes (P = 0.669). Transitioning patients after heart transplantation to an immunosuppression regimen composed of low-dose mTOR inhibition and tacrolimus was associated with a lack of progression of CAV, particularly in those with rapidly progressive CAV at 1 year, but not with long-term cardiovascular outcomes.

Beyond MACE: a multidimensional approach to outcomes in clinical trials for older adults with stable ischemic heart disease.

The global population of older adults is expanding rapidly resulting in a shift towards managing multiple chronic diseases that coexist and may be exacerbated by cardiovascular illness. Stable ischemic heart disease (SIHD) is a predominant contributor to morbidity and mortality in the older adult population. Although results from clinical trials demonstrate that chronological age is a predictor of poor health outcomes, the current management approach remains suboptimal due to insufficient representation of older adults in randomized trials and the inadequate consideration for the interaction between biological aging, concurrent geriatric syndromes, and patient preferences. A shift towards a more patient-centered approach is necessary for appropriately and effectively managing SIHD in the older adult population. In this review, we aim to demonstrate the distinctive needs of older adults who prioritize holistic health outcomes like functional capacity, cognitive abilities, mental health, and quality of life alongside the prevention of major adverse cardiovascular outcomes reported in cardiovascular clinical trials. An individualized, patient-centered approach that involves shared decision-making regarding outcome prioritization is needed when any treatment strategy is being considered. By prioritizing patients and addressing their unique needs for successful aging, we can provide more effective care to a patient population that exhibits the highest cardiovascular risks.

Prognostic value of left ventricular hypertrophy in patients with myocardial fibrosis by ECV mapping on cardiac MRI

Abstract Background Cardiovascular magnetic resonance (CMR) can noninvasively identify myocardial fibrosis using extracellular volume (ECV) mapping. In patients with elevated ECV, and without hypertrophic cardiomyopathy (HCM) or cardiac amyloidosis, the prognostic significant of mild-to-moderate left ventricular hypertrophy (LVH) has not been well established. Purpose To determine if the presence of mild to moderate LVH has an impact on major adverse cardiovascular outcomes (MACE) in patients with elevated ECV without HCM or cardiac amyloidosis. Methods This was a retrospective cohort study assessing a group of patients referred for CMR between July 2019 and January 2023 to Mount Sinai Morningside. Patients with ECV&amp;gt;30% and left ventricular wall thickness &amp;lt;1.6 cm (to exclude patients with the possible diagnosis of HCM or cardiac amyloidosis) were considered for inclusion. Those with an established diagnosis of HCM or cardiac amyloidosis were also excluded. The LVH group comprised of patients with mild-to-moderate LVH, defined as a maximum wall thickness of 1.2-1.5 cm. The control group included patients without LVH (wall thickness &amp;lt;1.2 cm). Patients were further stratified by ECV, using the median value for our sample, as "high ECV" (≥35%) or "low ECV" (&amp;lt;35%). The outcome of interest was time-to-first MACE (all-cause death, or incident acute coronary syndrome, acute heart failure, or arrhythmia). Time-to-first MACE within 1 year was compared among groups using unadjusted Kaplan-Meier curves. Additional Cox regression analyses were performed to adjust for significant univariate analysis, including hypertension, hyperlipidemia, diabetes mellitus, use of beta-blocker, use of diuretic, and category of glomerular filtration rate. The results are presented as hazard ratios and 95% confidence intervals. All analyses were performed in SAS Enterprise using α&amp;lt;0.05. Results Out of the cohort, we identified 186 patients that met our selection criteria. The mean age was 61.1 ± 15.5 years, and 58.1% of patients were female. The median follow-up was 175 days in the control group and 115 days in the LVH group. There were 61 MACE (32.8%) in our sample. After adjusting for covariates, mild-to-moderate LVH was associated with 2.2 times the risk of MACE (95%CI 1.3 to 3.8; p=0.0047) at 1 year, compared to patients without LVH. A higher ECV (≥35%) was not significantly associated with worse outcomes within each study arm (p=0.3450). Kaplan Meier survival curves for patients with and without LVH are shown in Figure 1 (p=0.0002). Conclusions In patients with evidence of elevated ECV without underlying cardiac amyloidosis or hypertrophic cardiomyopathy, mild-to-moderate LVH is associated with 2.2 times the risk of MACE compared to normal left ventricular wall thickness.Figure 1

Change in hbA1c following treatment with and the short-term risk of major adverse cardiovascular outcomes

Abstract Background Post-hoc analyses from glucagon-like peptide-1 receptor agonist (GLP1-RA) trial populations have shown a benefit on cardiovascular outcomes from reduction in glycated hemoglobin (HbA1c). It is of interest to see if this finding translates into a cohort of real-world GLP1-RA users. Purpose To study among new GLP1-RA users, how reaching a Hba1c below 53 mmol/mol six months after initiation affects the risk of major adverse cardiovascular outcomes (MACE), compared with a HbA1c above 53 mmol/mol. Methods We included new GLP1-RA users six months after initiation of treatment, with an available HbA1c value 0-6 months before and 0-6 months after GLP1-RA initiation, from the Danish registries between 2010-2022. HbA1c levels pre- and post-treatment were categorized as above 53 mmol/mol or below 53mmol/mol. The primary outcome was defined as a composite of myocardial infarction, stroke, and all-cause death. Patients were followed from index (6 months after GLP1-RA initiation) until the outcome, a total of 1 years, or end-of-study (31.12.21), whichever comes first. Crude 1-year risks were compared using the Kaplan Meier estimator, or the Aalen Johansen estimator if competing risk was present. The effect of HbA1c below 53 mmol/mol versus a HbA1c above 53 mmol/mol on MACE was estimated using a Cox regression model adjusted for age, sex, educational level, baseline comorbidities, type 2 diabetes duration, and baseline cardiovascular disease including heart failure. Hospitalization for hyperglycemia was also evaluated using a Cox regression. Results A total of 4,081 new GLP1-RA users (median age: 58y [IQR:50;66], 52% males) were included, 3,090 had a post-treatment HbA1c below 53 mmol/mol and 991 had a post-treatment Hba1c above 53 mmol/mol. During a median follow-up of 1 year (IQR:1.0,1.0), the crude 1-year risk of MACE in persons with a HbA1c below 53 mmol/mol was 6.4% (95% confidence interval [CI]: 5.5;7.2) and 9.5% (7.7;11.3) in persons with HbA1c above 53 mmol/mol, yielding a hazard rate of 0.69 (0.54;0.88). No interaction between pre-and post HbA1c was found (p=0.59). The hazard rate of hospitalization for hypoglycemia was 0.76 (0.45:1.23) for persons reaching HbA1c level below 53 mmol/mol compared to patients with a HbA1c above 53 mmol/mol, with no interaction between pre- and post HbA1c observed (p =0.052). Conclusion A HbA1c level below 53 mmol/mol, among GLP1-RA users reduced the 1-year rate of MACE and did not significantly increase the 1-year rate of hospitalization for hypoglycemia.

Impact of oral anticoagulants in frail atrial fibrillation patients: a report from an observational registry of european patients

Abstract Background The last years showed a substantial increase of interest about the clinical issue of frailty among patients with cardiovascular diseases. Impact of frailty in atrial fibrillation (AF) has been examined in terms of management, quality of life and increased risk of outcomes; nonetheless, the impact of treatment with oral anticoagulants (OAC) remains suboptimally understood. Purpose To analyse the impact of OAC in a cohort of frail AF patients. Methods We used data from a European-wide prospective observational AF registry. Frailty was evaluated with a 40-items frailty index (FI) built according to the cumulative deficit method proposed by Rockwood and Mitnitski. OAC treatment was evaluated at baseline. A net clinical outcome (NCO) of all-cause death, major adverse cardiovascular outcomes, and major bleeding, as well as the single components were the study outcomes. Results Among 10,172 patients available for this analysis, 2,171 (21.3%) were frail. AF frail patients had a mean (SD) age of 71.7 (9.8) years and were 1,073 (49.4%) females. Overall, 1,801 (83.0%) were treated with OAC, of which 1,232 (68.4%) prescribed with vitamin K antagonist (VKA) and 569 (31.6%) prescribed with non-vitamin K antagonist oral anticoagulants (NOACs). Over a mean (SD) follow-up time of 1.56 (0.74) years there were 571 (26.3%) NCO events. Frail patients prescribed with OAC had a lower rate of NCO compared to those not prescribed (27.1% vs. 44.6%, p&amp;lt;0.001). After adjustments, use of OAC was associated with lower risk of NCO and all the other secondary outcomes (Table 1). Regarding the type of OAC, patients prescribed with NOACs reported a lower rate of NCO compared to those prescribed with VKAs (22.7% vs. 29.1%). After adjustments, use of NOACs was associated with a lower risk of NCO and all the other secondary outcomes, except for major bleeding (Table 1). When comparing patients with FI &amp;lt;80th percentile with those with FI ≥80th percentile, adjusted analysis showed that in the FI &amp;lt;80th group the use of OAC was consistently associated with lower risk of all outcomes (except for major bleeding), with a non-statistically significant trend seen in those with FI ≥80th percentile treated with OAC (Table 1). Conclusions In frail AF patients, use of OAC was associated with a lower risk of outcomes, as well as the use of NOACs compared with VKAs. In patients with a very high frailty burden the benefits of OAC may be attenuated.

Increased Lipoprotein (a) and familial hypercholesterolemia: a dangerous combination.Data from a 12-year follow-up study

Abstract Background Lipoprotein (a)[Lp(a)] is a molecule characterized by very increased atherogenicity. Mounting evidence support the causal link between high Lp(a) concentration and atherosclerotic cardiovascular (CV) disease in the general population. Purpose The role of Lp (a) in specific categories of patients at high CV risk, such as patients with familial hypercholesterolaemia (FH), is also of special importance. The aim of our study was to investigate the prognostic role of Lp (a) regarding major adverse CV outcomes in subjects with heterozygous FH. Methods 155 patients from the outpatient lipid clinic of our hospital (56 males,mean age 41.2±14.2 years, 26% smokers, 16% with diabetes mellitus), without history of CV disease, who fulfilled the FH criteria participated in the study. Participants were evaluated for a mean follow-up period of 12.4±7.1 years with at least one annual visit. Venous blood samples were obtained at baseline in all patients for the determination of plasma glucose, lipid profile and levels of Lp(a). All subjects were on lipid-lowering medication during the follow-up period. The endpoint of our study was the composite of major CV events (coronary artery disease events and stroke). Results The incidence of the composite endpoint of major CV events during the follow-up period was 9% (n=14). In the total population, the mean baseline Lp (a) levels were 34.9±33.7 mg/dl, while 42% had increased Lp (a) levels ≥30mg/dl. The group of FH patients with new-onset CV disease had higher levels of Lp(a) at baseline compared to those without new-onset CV disease (48.1±37.3 vs 33.6±33.1 mg/dl, p=0.01). Also, those with new-onset CV disease had higher percentage of increased Lp(a) levels (≥30mg/dl) at baseline compared to those without development of CV disease (71% vs 39%, p=0.02).Multiple Cox regression analysis revealed that during the follow-up period independent predictors of major adverse CV events were:increased baseline Lp(a) levels(≥30mg/dl)(HR 5.61, 95% CI 1.51-10.92, p=0.01), male sex (HR 8.11, 95% CI 2.02-12.48, p&amp;lt;0.01), baseline low-density cholesterol levels (HR 1.01, 95% CI 1.00-1.02, p=0.04) and the presence of hypertension at baseline (HR 3.59, 95% CI 1.03-12.49, p=0.04), after adjustment for confounding factors. Conclusions In patients with FH, increased baseline Lp(a) is an independent predictor of adverse CV events, after a 12-year follow-up period. FH patients with Lp (a)levels ≥30mg/dl have an almost 5-fold greater CV risk compared to those with lower Lp (a) levels. It seems that Lp (a) reclassifies the already increased CV risk of FH subjects into an even higher level.

Impact of intracoronary imaging-guided percutaneous coronary intervention on procedural outcomes among complex patient groups

Abstract Background Intracoronary imaging (ICI) has been previously shown to improve survival and clinical outcomes after percutaneous coronary intervention (PCI). However, whether this prognostic benefit is sustained across different indications/patient groups remains unclear. Methods All PCI procedures performed in England and Wales between 1st April 2014 and 31st March 2020 were retrospectively analysed. The association between ICI use and in-hospital MACCE (major adverse cardiovascular and cerebrovascular outcomes; composite of all-cause mortality, stroke and reinfarction) and mortality was examined using multivariable logistic regression analysis for each imaging-recommended indication (stent thrombosis (ST), in-stent restenosis, stent length&amp;gt;60mm, acute coronary syndrome (ACS) indications, chronic total occlusion, left main stem (LMS) intervention, renal failure and bioresorbable vascular scaffolds (BVS)). Results Of 555,398 PCI procedures, 10.8% (n=59,752) were performed under ICI guidance. ICI use doubled between 2014 (7.8%) and 2020 (17.5%). ICI use was highest for BVS (44.7%) and LMS PCI (41.2%) cases and lowest in ACS (9%). Overall, the odds ratios (OR) of in-hospital MACCE and mortality were only reduced with ICI-guided PCI in cases with an imaging-recommended indication (OR 0.75 95% confidence interval (CI) 0.69-0.81 and OR 0.69 95%CI 0.63-0.76, respectively). Only specific imaging-recommended indications were associated with reduced MACCE and mortality, including LMS PCI (OR 0.45 95%CI 0.39-0.52 and 0.41 95%CI 0.35-0.48, respectively), ACS (OR 0.76 95%CI 0.70-0.82 and 0.70 95%CI 0.63-0.77), stent length&amp;gt;60mm (OR 0.75 95%CI 0.59-0.94 and 0.72 95%CI 0.54-0.95). ST was only associated with lower mortality (OR: 0.69 95%CI 0.52-0.91) while renal failure was associated with reduced MACCE (OR 0.77 95%CI 0.60-0.99) but not mortality. (Figure 1) Conclusion The utilisation of ICI has more than doubled over a seven-year period at a national level but remains low, with less than 1-in-5 procedures performed under ICI guidance. In-hospital survival was better with ICI-guided than angiography-guided PCI, albeit only for specific indications.Figure 1

Long-term outcomes of patients with late presentation STEMI undergoing percutaneous coronary revascularization

Abstract Background/Introduction Patients with late-presentation ST-segment myocardial infarction (STEMI) (12-48hr of symptom onset) tend to have worse clinical outcomes compared to early presenters (&amp;lt;12hr of symptom onset). The optimal management and decision for primary percutaneous coronary intervention (PCI) is limited by the current evidence, particularly in the modern revascularisation era. Purpose The aim of this study was to assess the short- and long-term clinical outcomes of primary PCI in patients with STEMI who present late following symptom onset (12-48hr) compared to those who present early (&amp;lt;12hr). Methods Data from 4265 consecutive patients undergoing PCI for STEMI within 48hr of presentation were analysed from the Melbourne Interventional Group registry between 2014 and 2020. Patients were categorised based upon symptom-to-door time (early &amp;lt;12hr vs late 12-48hr).. The primary endpoints were in-hospital, 30-day and long-term mortality. Secondary outcomes were major adverse cardiovascular events (MACE; composite of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke or repeat revascularisation), procedural outcomes and medications at 30-day. Results 4044 patients were early presentation and 221 patients were late presentation. The median symptom-to-door time was 1.73hr (interquartile range (IQR) 1.2, 2.8) for early presenters and 14.8hr (IQR 13.2, 18.1) for late presenters. Late presenters were less likely to have out-of-hospital cardiac arrest and require inotropic support (all p&amp;lt;0.01). There was no significant difference in in-hospital mortality (6.5% vs 5.4%, p=0.53) and MACE (9.0% vs 7.7%, p=0.52), nor 30-day mortality (7.4% vs 7.3%, p=0.94) and MACE (11.1% vs 10.5%, p=0.77). Long-term mortality did not differ between early and late presenters with hazard ratio 1.17 (95% confidence interval 0.71-1.95, p=0.54). There was no difference in major bleeding at 30-days (p=0.42). Conclusions Primary PCI in patients following late presentation STEMI is not associated with worse short- or long-term clinical outcomes compared to those who present early . Further, randomised controlled trials in the modern revascularisation era are needed to guide clinical practice.

Prevalence of SELECT-eligibility and incidence of 5-year major adverse cardiovascular outcomes in non-diabetic patients with myocardial infarction

Abstract Background The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) trial has randomized 17,605 non-diabetic patients with a body mass index (BMI) ≥27 kg/m2 to treatment with semaglutide versus placebo. Follow-up will be terminated on March 31, 2023. In consecutive myocardial infarction (MI) patients representing daily clinical practice, the prevalence of SELECT-eligible patients and the incidence of the three-point major adverse cardiovascular events (MACE; MI, ischemic stroke, and cardiovascular death) are not known. Purpose To assess the prevalence of SELECT-eligibility and the incidence of 5-year MACE in SELECT-eligible patients in a contemporary semi-nationwide European MI cohort representing daily clinical practice. Methods We identified 34,385 patients with a first-time MI and followed the in- and exclusion criteria for the SELECT trial as outlined in the Figure. Concordant with the SELECT trial, follow-up started on day 60 and maximum follow-up time was 5 years. We estimated adjusted hazard ratios (aHR) for the SELECT-eligible cohort using patients with a BMI from 20 to &amp;lt;27 kg/m2 as reference group. Moreover, we stratified the SELECT-eligible cohort by BMI ≥27 to &amp;lt;33 kg/m2 and ≥33 kg/m2. Results As depicted in the Figure, 10,769 patients with a BMI ≥27 kg/m2 were eligible for SELECT (SELECT-eligible cohort), which corresponds to a prevalence of 31% in the entire 34,385 MI cohort. The normoweight reference group included 11,011 patients. At baseline, the median age was 64 years for the SELECT-eligible cohort and 68 years for the reference group. Stratification of the SELECT-eligible cohort showed median age of 65 years for the BMI ≥27 to &amp;lt;33 kg/m2 and 63 years for the BMI ≥33 kg/m2 subgroups. The cumulative 5-year incidence of MACE was 10.7% for SELECT-eligible and 13.2% for reference patients (aHR 0.96, 95% CI 0.88-1.04). When stratifying the SELECT-eligible cohort, those with BMI ≥27 to &amp;lt;33 and ≥33 kg/m2 had cumulative 5-year incidence of 10.9% (aHR 0.95, 95% CI 0.87-1.04) and 9.9% (aHR 0.99, 95% CI 0.84-1.16). Conclusions In a large contemporary semi-nationwide cohort of consecutive MI patients, approximately 3 out of 10 were eligible for the SELECT trial and the estimated 5-year MACE incidence in SELECT-eligible patients was just above 10%. SELECT-eligible patients experienced the index MI up to 7 years earlier than the reference group. However, the 5-year incidence of MACE did not suggest that overweight/obese patients fulfilling SELECT eligibility criteria were associated with an excess MACE risk when compared to a normoweight reference group.

Time to Benefit of Surgery vs Targeted Medical Therapy for Patients With Primary Aldosteronism: A Meta-analysis.

Primary aldosteronism (PA) is one of the most common causes of secondary hypertension, but the comparative outcomes of targeted treatment remain unclear. To compare the clinical outcomes in patients treated for primary aldosteronism over time. Medline and EMBASE were searched. Original studies reporting the incidence of mortality, major adverse cardiovascular outcomes (MACE), progression to chronic kidney disease, or diabetes following adrenalectomy vs medical therapy were selected. Two reviewers independently abstracted data and assessed study quality. Standard meta-analyses were conducted using random-effects models to estimate relative differences. Time to benefit meta-analyses were conducted by fitting Weibull survival curves to estimate absolute risk differences and pooled using random-effects models. 15 541 patients (16 studies) with PA were included. Surgery was consistently associated with an overall lower risk of death (hazard ratio [HR] 0.34, 95% CI 0.22-0.54) and MACE (HR 0.55, 95% CI 0.36-0.84) compared with medical therapy. Surgery was associated with a significantly lower risk of hospitalization for heart failure (HR 0.48 95% CI 0.34-0.70) and progression to chronic kidney disease (HR 0.62 95% CI 0.39-0.98), and nonsignificant reductions in myocardial infarction and stroke. In absolute terms, 200 patients would need to be treated with surgery instead of medical therapy to prevent 1 death after 12.3 (95% CI 3.1-48.7) months. Surgery is associated with lower all-cause mortality and MACE than medical therapy for PA. For most patients, the long-term surgical benefits outweigh the short-term perioperative risks.

Abstract 14567: Lipid Variability as a Risk Factor of Major Adverse Cardiovascular Outcomes. Meta-Analysis of Observational Studies

Introduction: Serum lipids variability has been described as a risk factor for cardiovascular disease. However, there is no published systematic review in the literature at the moment. The purpose is to evaluate the association between lipid variability and outcomes related to cardiovascular disease. Methods: We made a systematic search in Pubmed, Science Direct, Clinical Key, CINAHL, Lilacs, and Google Scholar using: lipids, variability, death, stroke, myocardial infarction, and cholesterol variability as keywords. Two independent researchers selected and made an extraction of the data. Non-agreement was solved by a third researcher. Non-language limitations were made. Exposure factors were coefficient of variation (CV), standard deviation (SD), and variability independent of the mean (VIM) from LDL, HDL, Non-HDL, Total Cholesterol, and Triglycerides. MACE was the outcome of interest. We made a forest plot and heterogeneity analysis using I2. All analyses were made using STATA v. 14.2 Results: Eight papers from the initial 9785 met the inclusion criteria. All papers were cohort studies and a high heterogeneity was identified in the majority of them. The main heterogeneity causes were the difference in the number of participants in the studies, the years following, and the age of the participants included in the studies. In relation to the studies of low heterogeneity (&lt;40%), we found that the high variability of HDL analyzed with CV increases the risk of myocardial infarction (RR=1.39 [95% CI 1.35-1.42, I2 0%]). On the other hand, there were found significative relations between the variability of HDL analyzed with VIM to cardiovascular disease (RR=1.26 [95% CI 1.20-1.33], however, it had a high heterogeneity (I2 68.4%). Conclusions: The comparisons of the studies that analyze lipid variability have a high heterogeneity due to population differences. A relationship was found in the variability of HDL and myocardial infarction.

Abstract 18565: Statin Utilization and Outcomes Among Patients With Coronary Artery Disease Undergoing Percutaneous or Surgical Revascularization

Background: Patients undergoing coronary revascularization are at high risk for adverse health outcomes. Accordingly, current guidelines suggest high-intensity use of statin intervention therapy to help mitigate atherosclerotic risk. We analyzed outcomes of patients following coronary revascularization stratified by the level of statin intervention in a large, real-world integrated healthcare system. Methods: Patients were stratified by type of coronary revascularization (percutaneous coronary intervention (PCI) vs coronary artery bypass grafting (CABG)). Statin use was divided as: (1) no statin, (2) less than guideline-directed statin intensity (&lt;GDSI), and GDSI. HRs and incidence rate per 1000-person years were assessed for secondary ASCVD outcomes (MI, ischemic stroke/TIA and all-cause death) in the population. Results: Over a mean follow up of about 5 years, a total of 33,513 patients underwent PCI and 12,436 underwent CABG. Over 35% of patients in both groups received either &lt;GDSI or no statin therapy. Patients who underwent PCI and were given no statin treatment had higher incidence of MI (69 vs 23 per 1000PY), stroke (21 vs 10) and death (69 vs 30) than those on GDSI. Patients who underwent CABG and were given no statin treatment had higher incidence of MI (31 vs 15 per 1000PY), stroke (30 vs 13) and death (79 vs 20) than those on GDSI. Amongst both groups, adjusted analysis showed that patients receiving GDSI had significantly lower risk for all major adverse cardiovascular outcomes (Table). In particular, GDSI in patients undergoing PCI was associated with the most significant reduction in MI, with an HR of 0.42. Conclusions: Underuse of GDSI was highly prevalent in patients undergoing coronary vascularization, both for PCI and CABG, and this was associated with suboptimal outcomes. Further practical interventions should be studied to assure that patients are treated aggressively with guideline directed therapies to lower risk for adverse outcomes.

Abstract 16941: Breast Artery Calcification for Primary Prevention of Major Adverse Cardiovascular Outcomes: A New Risk Stratification Tool for Women

Introduction: Reductions in cardiovascular mortality among women lag behind men. There is a critical need for improved primary prevention of major adverse cardiovascular events (MACE) in women. We examined if breast artery calcification (BAC), detected on screening mammograms, prognosticates long-term MACE. Methods: In this retrospective study of consecutive women age 40-75 years without coronary disease from 2011-12, followed for 10 years at Dartmouth-Hitchcock Medical Center, we recorded baseline mammograms, clinical parameters and 10-year MACE risk was estimated via the pooled cohort equation (PCE). The association of BAC and MACE was examined by a multivariable, interactive logistic regression model with MACE as dependent variable, adjusting for confounders and an interaction of BAC with 3 strata of PCE predicted risk: low (&lt;5%), moderate (5-7.5%) and high (&gt;7.5%). The primary endpoint was MACE over 10 years. Results: Among 1216 women, 19% had BAC. Women with BAC were older, had more hypertension and diabetes, and a higher baseline PCE score. Over 10 years of follow-up, 21% of women with BAC developed MACE compared to 11% women without BAC (p&lt;0.001). This association was independent of risk factors and statin use. Among women with low (&lt; 5%) risk of MACE, those with BAC had an 18% incidence of MACE, compared to 7% in women without BAC (OR 2.8, 95% CI 1.5 - 5.0) (Fig 1A). The incremental increase in MACE in patients with BAC decreased with higher PCE-predicted risk. Peak interaction occurred at a PCE-predicted risk of 10% (Fig 1B). Among women with a PCE-predicted risk &lt;10%, BAC was a strong predictor of MACE with an attributable fraction of 20% (Fig 1B). Conclusions: BAC is a strong, independent predictor of MACE, particularly in women at low risk by PCE. Although PCE is used widely to risk stratify women for MACE, our study suggests it severely underestimates risk in women with a low PCE score. Further prospective trials are needed to validate these findings.

Effectiveness of lipid-lowering therapy on mortality and major adverse cardiovascular event outcomes in patients undergoing percutaneous coronary intervention: a network meta-analysis of randomised controlled trials

BackgroundEmergency percutaneous coronary intervention (PCI) can quickly restore myocardial perfusion after acute coronary syndrome. Whether and which lipid-lowering regimens are effective in reducing major adverse cardiovascular events (MACEs) and mortality...

The effect of fibrates on lowering low-density lipoprotein cholesterol and cardiovascular risk reduction: a systemic review and meta-analysis.

The effect of fibrate treatment on cardiovascular risk is inconsistent. This meta-analysis aimed to assess the effect of fibrates on major adverse cardiovascular outcome (MACE) reduction. PubMed, Embase, and Cochrane library databases were searched up to February 2023 for randomized controlled trials comparing fibrate therapy against placebo and reporting cardiovascular outcomes and lipid profile changes. The primary outcome was the clinical outcomes of each trial that most closely corresponding to MACE, a composite of cardiovascular death, acute myocardial infarction, stroke, and coronary revascularization. A pre-specified meta-regression analysis to examine the relationship between the changes in lipid levels after fibrate treatment and the risk of MACE was also performed. Twelve trials were selected for final analysis, with 25 781 patients and 2741 MACEs in the fibrate group and 27 450 patients and 3754 MACEs in the control group. Overall, fibrate therapy was associated with decreased risk of MACE [RR 0.87, 95% confidence interval (CI) 0.81-0.94] with moderate heterogeneity (I2 = 47%). In meta-regression analysis, each 1 mmol/L reduction in low-density lipoprotein cholesterol (LDL-C) after fibrate treatment reduced MACE (RR 0.71, 95% CI 0.49-0.94, P = 0.01), while triglyceride level changes did not show a significant association (RR per 1mmol/L reduction 0.96, 95% CI 0.53-1.40, P = 0.86). A sensitivity analysis with the composite outcome of cardiovascular death or acute myocardial infarction produced similar results. Treatment with fibrates was associated with decreased risk of MACE. The reduction in MACE risk with fibrate therapy appears to be attributable to LDL-C reduction rather than a decrease in triglyceride levels.

358P Major adverse cardiovascular event outcomes of adjuvant taxane + anthracycline versus taxane-based chemotherapy in older adults with triple-negative breast cancer: A SEER-Medicare study

358P Major adverse cardiovascular event outcomes of adjuvant taxane + anthracycline versus taxane-based chemotherapy in older adults with triple-negative breast cancer: A SEER-Medicare study

Advanced glycation end product signaling and metabolic complications: Dietary approach.

Advanced glycation end products (AGEs) are a heterogeneous collection of compounds formed during industrial processing and home cooking through a sequence of nonenzymatic glycation reactions. The modern western diet is full of heat-treated foods that contribute to AGE intake. Foods high in AGEs in the contemporary diet include processed cereal products. Due to industrialization and marketing strategies, restaurant meals are modified rather than being traditionally or conventionally cooked. Fried, grilled, baked, and boiled foods have the greatest AGE levels. Higher AGE-content foods include dry nuts, roasted walnuts, sunflower seeds, fried chicken, bacon, and beef. Animal proteins and processed plant foods contain furosine, acrylamide, heterocyclic amines, and 5-hydroxymethylfurfural. Furosine (2-furoil-methyl-lysine) is an amino acid found in cooked meat products and other processed foods. High concentrations of carboxymethyl-lysine, carboxyethyl-lysine, and methylglyoxal-O are found in heat-treated nonvegetarian foods, peanut butter, and cereal items. Increased plasma levels of AGEs, which are harmful chemicals that lead to age-related diseases and physiological aging, diabetes, and autoimmune/inflammatory rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis. AGEs in the pathophysiology of metabolic diseases have been linked to individuals with diabetes mellitus who have peripheral nerves with high amounts of AGEs and diabetes has been linked to increased myelin glycation. Insulin resistance and hyperglycemia can impact numerous human tissues and organs, leading to long-term difficulties in a number of systems and organs, including the cardiovascular system. Plasma AGE levels are linked to all-cause mortality in individuals with diabetes who have fatal or nonfatal coronary artery disease, such as ventricular dysfunction. High levels of tissue AGEs are independently associated with cardiac systolic dysfunction in diabetic patients with heart failure compared with diabetic patients without heart failure. It is widely recognized that AGEs and oxidative stress play a key role in the cardiovascular complications of diabetes because they both influence and are impacted by oxidative stress. All chronic illnesses involve protein, lipid, or nucleic acid modifications including crosslinked and nondegradable aggregates known as AGEs. Endogenous AGE formation or dietary AGE uptake can result in additional protein modifications and stimulation of several inflammatory signaling pathways. Many of these systems, however, require additional explanation because they are not entirely obvious. This review summarizes the current evidence regarding dietary sources of AGEs and metabolism-related complications associated with AGEs.